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Sample records for acids glycolic acid

  1. GLYCOLIC - FORMIC ACID FLOWSHEET DEVELOPMENT

    SciTech Connect

    Pickenheim, B.; Stone, M.; Newell, J.

    2010-11-08

    Flowsheet testing was performed to further develop the nitric/glycolic/formic acid flowsheet as an alternative to the nitric/formic flowsheet currently being processed at the DWPF. This new flowsheet has shown that mercury can be removed in the Sludge Receipt and Adjustment Tank (SRAT) with minimal hydrogen generation. All other processing objectives were also met, including greatly reducing the Slurry Mix Evaporator (SME) product yield stress as compared to the baseline nitric/formic flowsheet. Eight runs were performed in total, including the baseline run. The baseline nitric/formic flowsheet run was extremely difficult to process under existing DWPF acceptance criteria with this simulant at the HM levels of noble metals. While nitrite was destroyed and mercury was removed to near the DWPF limit, the rheology of the SRAT and SME products were well above design basis and hydrogen generation far exceeded the DWPF limit. In addition, mixing during the SME cycle was very poor. In this sense, the nitric/glycolic/formic acid flowsheet represents a significant upgrade over the current flowsheet. In the nitric/glycolic/formic flowsheet runs, mercury was successfully removed with almost no hydrogen generation and the SRAT and SME products yield stresses were within process limits or previously processed ranges. It is recommended that DWPF continue to support development of the nitric/glycolic/formic flowsheet. Although experience is limited at this time, this flowsheet meets or outperforms the current flowsheet in many regards, including off-gas generation, mercury removal, product rheology and general ease of processing. Additional flowsheet testing will allow for a more thorough understanding of the chemistry and effectiveness of the flowsheet over a range of sludge compositions and formic/glycolic ratios. This testing will also show whether the REDOX and metal solubility concerns with this change in the flowsheet can be addressed by just adjusting the volumes of

  2. Glycolic acid modulates the mechanical property and degradation of poly(glycerol, sebacate, glycolic acid).

    PubMed

    Sun, Zhi-Jie; Wu, Lan; Huang, Wei; Chen, Chang; Chen, Yan; Lu, Xi-Li; Zhang, Xiao-Lan; Yang, Bao-Feng; Dong, De-Li

    2010-01-01

    The development of biodegradable materials with controllable degradation properties is beneficial for a variety of applications. Poly(glycerol-sebacate) (PGS) is a promising candidate of biomaterials; so we synthesize a series of poly(glycerol, sebacate, glycolic acid) (PGSG) with 1:2:0, 1:2:0.2, 1:2:0.4, 1:2:0.6, 1:2:1 mole ratio of glycerol, sebacate, and glycolic acid to elucidate the relation of doped glycolic acid to the degradation rate and mechanical properties. The microstructures of the polymers with different doping of glycolic acid were dissimilar. PGSG with glycolic acid in the ratio of 0.2 displayed an integral degree of ordering, different to those with glycolic acid in the ratio of 0, 0.4, 0.6, and 1, which showed mild phase separation structure. The number, DeltaH(m), and temperature of the PGSG melting peaks tended to decrease with the increasing ratio of doped glycolic acid. In vitro and in vivo degradation tests showed that the degradation rate of PGSG with glycolic acid in the ratio of 0.2 was slowest, but in the ratio range of 0, 0.4, and 0.6, the degradation rate increased with the increase of glycolic acid. All PGSG samples displayed good tissue response and anticoagulant effects. Our data suggest that doping glycolic acid can modulate the microstructure and degree of crosslinking of PGS, thereby control the degradation rate of PGS.

  3. Glycolic acid peel therapy - a current review.

    PubMed

    Sharad, Jaishree

    2013-01-01

    Chemical peels have been time-tested and are here to stay. Alpha-hydroxy peels are highly popular in the dermatologist's arsenal of procedures. Glycolic acid peel is the most common alpha-hydroxy acid peel, also known as fruit peel. It is simple, inexpensive, and has no downtime. This review talks about various studies of glycolic acid peels for various indications, such as acne, acne scars, melasma, postinflammatory hyperpigmentation, photoaging, and seborrhea. Combination therapies and treatment procedure are also discussed. Careful review of medical history, examination of the skin, and pre-peel priming of skin are important before every peel. Proper patient selection, peel timing, and neutralization on-time will ensure good results, with no side effects. Depth of the glycolic acid peel depends on the concentration of the acid used, the number of coats applied, and the time for which it is applied. Hence, it can be used as a very superficial peel, or even a medium depth peel. It has been found to be very safe with Fitzpatrick skin types I-IV. All in all, it is a peel that is here to stay. PMID:24399880

  4. Millimetre wave rotational spectrum of glycolic acid

    NASA Astrophysics Data System (ADS)

    Kisiel, Zbigniew; Pszczółkowski, Lech; Białkowska-Jaworska, Ewa; Charnley, Steven B.

    2016-03-01

    The pure rotational spectrum of glycolic acid, CH2OHCOOH, was studied in the region 115-318 GHz. For the most stable SSC conformer, transitions in all vibrational states up to 400 cm-1 have been measured and their analysis is reported. The data sets for the ground state, v21 = 1 , and v21 = 2 have been considerably extended. Immediately higher in vibrational energy are two triads of interacting vibrational states and their rotational transitions have been assigned and successfully fitted with coupled Hamiltonians accounting for Fermi and Coriolis resonances. The derived energy level spacings establish that the vibrational frequency of the ν21 mode is close to 100 cm-1. The existence of the less stable AAT conformer in the near 50 °C sample used in our experiment was also confirmed and additional transitions have been measured.

  5. Enhanced bioconversion of ethylene glycol to glycolic acid by a newly isolated Burkholderia sp. EG13.

    PubMed

    Gao, Xiaoxin; Ma, Zhengfei; Yang, Limin; Ma, Jiangquan

    2014-10-01

    Burkholderia sp. EG13 with high ethylene glycol-oxidizing activity was isolated from soil, which could be used for the synthesis of glycolic acid from the oxidation of ethylene glycol. Using the resting cells of Burkholderia sp. EG13 as biocatalysts, the optimum reaction temperature and pH were 30 °C and 6.0, respectively. After 24 h of biotransformation, the yield of glycolic acid from 200 mM ethylene glycol was 98.8 %. Furthermore, an integrated bioprocess for the production of glycolic acid which involved in situ product removal (ISPR) was investigated. Using fed-batch method with ISPR, a total of 793 mM glycolic acid has been accumulated in the reaction mixture after the 4th feed.

  6. GLYCOLIC ACID PHYSICAL PROPERTIES, IMPURITIES, AND RADIATION EFFECTS ASSESSMENT

    SciTech Connect

    Pickenheim, B.; Bibler, N.

    2010-06-08

    The DWPF is pursuing alternative reductants/flowsheets to increase attainment to meet closure commitment dates. In fiscal year 2009, SRNL evaluated several options and recommended the further assessment of the nitric/formic/glycolic acid flowsheet. SRNL is currently performing testing with this flowsheet to support the DWPF down-select of alternate reductants. As part of the evaluation, SRNL was requested to determine the physical properties of formic and glycolic acid blends. Blends of formic acid in glycolic acid were prepared and their physical properties tested. Increasing amounts of glycolic acid led to increases in blend density, viscosity and surface tension as compared to the 90 wt% formic acid that is currently used at DWPF. These increases are small, however, and are not expected to present any difficulties in terms of processing. The effect of sulfur impurities in technical grade glycolic acid was studied for its impact on DWPF glass quality. While the glycolic acid specification allows for more sulfate than the current formic acid specification, the ultimate impact is expected to be on the order of 0.03 wt% sulfur in glass. Note that lower sulfur content glycolic acid could likely be procured at some increased cost if deemed necessary. A paper study on the effects of radiation on glycolic acid was performed. The analysis indicates that substitution of glycolic acid for formic acid would not increase the radiolytic production rate of H{sub 2} and cause an adverse effect in the SRAT or SME process. It has been cited that glycolic acid solutions that are depleted of O{sub 2} when subjected to large radiation doses produced considerable quantities of a non-diffusive polymeric material. Considering a constant air purge is maintained in the SRAT and the solution is continuously mixed, oxygen depletion seems unlikely, however, if this polymer is formed in the SRAT solution, the rheology of the solution may be affected and pumping of the solution may be

  7. GLYCOLIC ACID PHYSICAL PROPERTIES, IMPURITIES, AND RADIATION EFFECTS ASSESSMENT

    SciTech Connect

    Lambert, D.; Pickenheim, B.; Hay, M.

    2011-06-20

    The Defense Waste Processing Facility (DWPF) is pursuing alternative reductants/flowsheets to increase attainment to meet closure commitment dates. In fiscal year 2009, SRNL evaluated several options and recommended the further assessment of the nitric/formic/glycolic acid flowsheet. SRNL is currently performing testing with this flowsheet to support the DWPF down-select of alternate reductants. As part of the evaluation, SRNL was requested to determine the physical properties of formic and glycolic acid blends. Blends of formic acid in glycolic acid were prepared and their physical properties tested. Increasing amounts of glycolic acid led to increases in blend density, viscosity and surface tension as compared to the 90 wt% formic acid that is currently used at DWPF. These increases are small, however, and are not expected to present any difficulties in terms of processing. The effect of sulfur impurities in technical grade glycolic acid was studied for its impact on DWPF glass quality. While the glycolic acid specification allows for more sulfate than the current formic acid specification, the ultimate impact is expected to be on the order of 0.03 wt% sulfur in glass. Note that lower sulfur content glycolic acid could likely be procured at some increased cost if deemed necessary. A paper study on the effects of radiation on glycolic acid was performed. The analysis indicates that substitution of glycolic acid for formic acid would not increase the radiolytic production rate of H{sub 2} and cause an adverse effect in the SRAT or SME process. It has been cited that glycolic acid solutions that are depleted of O{sub 2} when subjected to large radiation doses produced considerable quantities of a non-diffusive polymeric material. Considering a constant air purge is maintained in the SRAT and the solution is continuously mixed, oxygen depletion seems unlikely, however, if this polymer is formed in the SRAT solution, the rheology of the solution may be affected and

  8. Material compatibility evaluation for DWPF nitric-glycolic acid-literature review

    SciTech Connect

    Mickalonis, J.; Skidmore, E.

    2013-06-01

    Glycolic acid is being evaluated as an alternative for formic and nitric acid in the DWPF flowsheet. Demonstration testing and modeling for this new flowsheet has shown that glycolic acid and glycolate has a potential to remain in certain streams generated during the production of the nuclear waste glass. A literature review was conducted to assess the impact of glycolic acid on the corrosion of the materials of construction for the DWPF facility as well as facilities downstream which may have residual glycolic acid and glycolates present. The literature data was limited to solutions containing principally glycolic acid.

  9. GLYCOLIC-FORMIC ACID FLOWSHEET FINAL REPORT FOR DOWNSELECTION DECISION

    SciTech Connect

    Lambert, D.; Pickenheim, B.; Stone, M.; Newell, J.; Best, D.

    2011-03-10

    Flowsheet testing was performed to develop the nitric-glycolic-formic acid flowsheet (referred to as the glycolic-formic flowsheet throughout the rest of the report) as an alternative to the nitric/formic flowsheet currently being processed at the DWPF. This new flowsheet has shown that mercury can be removed in the Sludge Receipt and Adjustment Tank (SRAT) with minimal hydrogen generation. All processing objectives were also met, including greatly reducing the Slurry Mix Evaporator (SME) product yield stress as compared to the baseline nitric/formic flowsheet. Forty-six runs were performed in total, including the baseline run and the melter feed preparation runs. Significant results are summarized. The baseline nitric/formic flowsheet run, using the SB6 simulant produced by Harrell was extremely difficult to process successfully under existing DWPF acceptance criteria with this simulant at the HM levels of noble metals. While nitrite was destroyed and mercury was removed to near the DWPF limit, the rheology of the SRAT and SME products were well above design basis and hydrogen generation far exceeded the DWPF SRAT limit. In addition, mixing during the SME cycle was very poor. In this sense, the nitric/glycolic/formic acid flowsheet represents a significant upgrade over the current flowsheet. Mercury was successfully removed with almost no hydrogen generation and the SRAT and SME products yield stresses were within process limits or previously processed ranges. The glycolic-formic flowsheet has a very wide processing window. Testing was completed from 100% to 200% of acid stoichiometry and using a glycolic-formic mixture from 40% to 100% glycolic acid. The testing met all processing requirements throughout these processing windows. This should allow processing at an acid stoichiometry of 100% and a glycolic-formic mixture of 80% glycolic acid with minimal hydrogen generation. It should also allow processing endpoints in the SRAT and SME at significantly higher

  10. Synthesis and characterization of hydrolytically degradable copolyester biomaterials based on glycolic acid, sebacic acid and ethylene glycol.

    PubMed

    Simitzis, J; Soulis, S; Triantou, D; Zoumpoulakis, L; Zotali, P

    2011-12-01

    Copolyesters of glycolic acid (G) combined with sebacic acid (S) and ethylene glycol were synthesized in different molar ratios (G: 0-100% and S: 100-0%) and their hydrolytic degradation was studied and correlated with their structures. Based on the FTIR spectra of the homopolyesters and copolyesters and the normalized peak intensity of the I(2918), I(2848) and I(1087) for the corresponding wavenumbers, it is concluded that the I(2918) and the I(2848) are in accordance with the mean number degree of polymerization of ethylene sebacate units and the I(1087) is in accordance with the mean number degree of polymerization of glycolate units. Based on the XRD diffractograms, poly(ethylene sebacate) and poly(glycolic acid) belong to the monoclinic and the orthorhombic crystal system, respectively and both have higher crystallinity than the copolyesters. The experimental data of the hydrolytic degradation were fitted with exponential rise to maximum type functions using two-parameter model and four-parameter model. Three regions can been distinguished for the hydrolytic degradation by decreasing the molar feed ratio of sebacic acid, which are correlated with the changes of crystallinity. Two copolyesters are proposed: first the copolyester with high amount of glycolate units (S10G90) having higher hydrolytic degradation than G100 and second the copolyester with equal amount of glycolate and ethylene sebacate units (S50G50), having lower hydrolytic degradation than G100. These hydrolytically degradable copolyesters are soluble in common organic solvents, opposite to poly(glycolic acid) and could have perspectives for biomedical applications.

  11. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... diesters with benzoic acid and diethylene glycol. 721.10111 Section 721.10111 Protection of Environment... diesters with benzoic acid and diethylene glycol. (a) Chemical substance and significant new uses subject... benzoic acid and diethylene glycol (PMN P-04-510; CAS No. 610787-78-5) is subject to reporting under...

  12. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... diesters with benzoic acid and neopentlyl glycol. 721.10110 Section 721.10110 Protection of Environment... diesters with benzoic acid and neopentlyl glycol. (a) Chemical substance and significant new uses subject... benzoic acid and neopentlyl glycol (PMN P-04-509; CAS No. 610787-77-4) is subject to reporting under...

  13. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... diesters with benzoic acid and diethylene glycol. 721.10111 Section 721.10111 Protection of Environment... diesters with benzoic acid and diethylene glycol. (a) Chemical substance and significant new uses subject... benzoic acid and diethylene glycol (PMN P-04-510; CAS No. 610787-78-5) is subject to reporting under...

  14. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... diesters with benzoic acid and neopentlyl glycol. 721.10110 Section 721.10110 Protection of Environment... diesters with benzoic acid and neopentlyl glycol. (a) Chemical substance and significant new uses subject... benzoic acid and neopentlyl glycol (PMN P-04-509; CAS No. 610787-77-4) is subject to reporting under...

  15. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... diesters with benzoic acid and diethylene glycol. 721.10111 Section 721.10111 Protection of Environment... diesters with benzoic acid and diethylene glycol. (a) Chemical substance and significant new uses subject... benzoic acid and diethylene glycol (PMN P-04-510; CAS No. 610787-78-5) is subject to reporting under...

  16. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... diesters with benzoic acid and diethylene glycol. 721.10111 Section 721.10111 Protection of Environment... diesters with benzoic acid and diethylene glycol. (a) Chemical substance and significant new uses subject... benzoic acid and diethylene glycol (PMN P-04-510; CAS No. 610787-78-5) is subject to reporting under...

  17. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... diesters with benzoic acid and neopentlyl glycol. 721.10110 Section 721.10110 Protection of Environment... diesters with benzoic acid and neopentlyl glycol. (a) Chemical substance and significant new uses subject... benzoic acid and neopentlyl glycol (PMN P-04-509; CAS No. 610787-77-4) is subject to reporting under...

  18. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... diesters with benzoic acid and neopentlyl glycol. 721.10110 Section 721.10110 Protection of Environment... diesters with benzoic acid and neopentlyl glycol. (a) Chemical substance and significant new uses subject... benzoic acid and neopentlyl glycol (PMN P-04-509; CAS No. 610787-77-4) is subject to reporting under...

  19. 40 CFR 721.10110 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and neopentlyl glycol.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... diesters with benzoic acid and neopentlyl glycol. 721.10110 Section 721.10110 Protection of Environment... diesters with benzoic acid and neopentlyl glycol. (a) Chemical substance and significant new uses subject... benzoic acid and neopentlyl glycol (PMN P-04-509; CAS No. 610787-77-4) is subject to reporting under...

  20. 40 CFR 721.10111 - Hexanoic acid, 2-ethyl-, mixed diesters with benzoic acid and diethylene glycol.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... diesters with benzoic acid and diethylene glycol. 721.10111 Section 721.10111 Protection of Environment... diesters with benzoic acid and diethylene glycol. (a) Chemical substance and significant new uses subject... benzoic acid and diethylene glycol (PMN P-04-510; CAS No. 610787-78-5) is subject to reporting under...

  1. GLYCOLIC-FORMIC ACID FLOWSHEET SLUDGE MATRIX STUDY

    SciTech Connect

    Lambert, D.; Koopman, D.

    2011-06-30

    Testing was completed to demonstrate the viability of the newly developed glycolic acid/formic acid flowsheet on processing in the Defense Waste Processing Facility's (DWPF) Chemical Process Cell (CPC). The Savannah River National Laboratory (SRNL) initiated a sludge matrix study to evaluate the impact of changing insoluble solid composition on the processing characteristics of slurries in DWPF. Four sludge simulants were prepared to cover two compositional ranges in the waste. The first was high iron/low aluminum versus low iron/high aluminum (referred to as HiFe or LoFe in this report). The second was high calcium-manganese/low nickel, chromium, and magnesium versus low calcium-manganese/high nickel, chromium, and magnesium (referred to as HiMn or LoMn in this report). These two options can be combined to form four distinct sludge compositions. The sludge matrix study called for testing each of these four simulants near the minimum acid required for nitrite destruction (100% acid stoichiometry) and at a second acid level that produced significant hydrogen by noble metal catalyzed decomposition of formic acid (150% acid stoichiometry). Four simulants were prepared based on the four possible combinations of the Al/Fe and Mn-Ca/Mg-Ni-Cr options. Preliminary simulant preparation work has already been documented. The four simulants were used for high and low acid testing. Eight planned experiments (GF26 to GF33) were completed to demonstrate the viability of the glycolic-formic flowsheet. Composition and physical property measurements were made on the SRAT product. Composition measurements were made on the condensate from the Mercury Water Wash Tank (MWWT), Formic Acid Vent Condenser (FAVC), ammonia scrubber and on SRAT samples pulled throughout the SRAT cycle. Updated values for formate loss and nitrite-tonitrate conversion were found that can be used in the acid calculations for future sludge matrix process simulations with the glycolic acid/formic acid flowsheet

  2. Intermediates to ethylene glycol: carbonylation of formaldehyde catalyzed by Nafion solid perfluorosulfonic acid resin

    SciTech Connect

    Hendriksen, D.E.

    1983-01-01

    Details of a series of reactions for the production of ethylene glycol using a catalyst of Nafion solid perfluorosulfonic acid resin was detailed. The reactions included the carbonylation of formaldehyde and esterification and then hydrogenation of the product of the carbonylation, glycolic acid. Other preparations included in the work included methyl glycolate, acetylglycolic acid, methyl acetylglycolate, and methyl methoxyacetate.

  3. The effects of an alpha hydroxy acid (glycolic acid) on hairless guinea pig skin permeability.

    PubMed

    Hood, H L; Kraeling, M E; Robl, M G; Bronaugh, R L

    1999-11-01

    The barrier integrity of hairless guinea pig skin after treatment with an alpha hydroxy acid was assessed through in vivo topical application of an oil-in-water emulsion containing 5 or 10% glycolic acid at pH 3.0. The control was a commercial moisturizing lotion, pH 7.8. A dosing regimen for the glycolic acid formulations that was tolerated by the hairless guinea pigs and significantly decreased stratum corneum turnover time was determined using the dansyl chloride staining technique. Once-daily dosing of hairless guinea pig skin for 3 weeks with the glycolic acid formulations resulted in approximately a 36-39% decrease in stratum corneum turnover time compared with the control lotion. After this treatment, hairless guinea pigs were sacrificed for the in vitro measurement of the percutaneous absorption of [14C]hydroquinone and [14C]musk xylol. No significant differences in the 24-hour absorption of either test compound were found for skin treated with the control lotion or the glycolic acid formulations. There were also no significant differences found in the absorption of [3H]water through skin from the different treatment groups. Although no increase in skin penetration occurred after treatment with the glycolic acid formulations, histology revealed approximately a twofold increase in epidermal thickness. Also the number of nucleated cell layers nearly doubled in skin treated with 5% and 10% glycolic acid compared with the control lotion and untreated skin. These studies demonstrate that substantial changes in the structure of hairless guinea pig epidermis can occur without significant effect on skin permeability of two model compounds.

  4. Degradation and compatibility behaviors of poly(glycolic acid) grafted chitosan.

    PubMed

    Zhang, Luzhong; Dou, Sufeng; Li, Yan; Yuan, Ying; Ji, Yawei; Wang, Yaling; Yang, Yumin

    2013-07-01

    The films of poly(glycolic acid) grafted chitosan were prepared without using a catalyst to improve the degradable property of chitosan. The films were characterized by Fourier transform-infrared spectroscopy and X-ray photoelectron spectroscopy (XPS). The degradation of the poly(glycolic acid) grafted chitosan films were investigated in the lysozyme solution. In vitro degradation tests revealed that the degradation rate of poly(glycolic acid) grafted chitosan films increased dramatically compared with chitosan. The degradation rate of poly(glycolic acid) grafted chitosan films gradually increased with the increasing of the molar ratio of glycolic acid to chitosan. Additionally, the poly(glycolic acid) grafted chitosan films have good biocompatibility, as demonstrated by in vitro cytotoxicity of the extraction fluids. The biocompatible and biodegradable poly(glycolic acid) grafted chitosan would be an effective material with controllable degradation rate to meet the diverse needs in biomedical fields.

  5. 21 CFR 172.856 - Propylene glycol mono- and diesters of fats and fatty acids.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Propylene glycol mono- and diesters of fats and... CONSUMPTION Multipurpose Additives § 172.856 Propylene glycol mono- and diesters of fats and fatty acids. Propylene glycol mono- and diesters of fats and fatty acids may be safely used in food, subject to...

  6. The Mm-Wave Rotational Spectrum of Glycolic Acid

    NASA Astrophysics Data System (ADS)

    Kisiel, Zbigniew; Pszczółkowski, Lech; Białkowska-Jaworska, Ewa; Charnley, Steven B.

    2014-06-01

    Glycolic acid, HOCH_2COOH is the simplest α-hydroxy acid. It is as yet undetected in the interstellar medium, but is known to be present in carbonaceous meteorites and in residues from UV-photolysed interstellar ice analogue mixtures. Prior rotational spectroscopy has been carried out up to 40 GHz for the main, SSC conformer, Presently we report the analysis of the rotational spectrum of glycolic acid on the basis of broadband measurements performed up to 318 GHz, and updated spectroscopic constants for the ground state and the first two excited states of the low-frequency ν21 torsional mode. We have used the AABS package to assign multiple further excited vibrational states of the SSC conformer. In particular, we have been able to assign the highly perturbed triad of ν14, ν20 and 3ν21 states. The triad has been fitted down to experimental accuracy with a coupled fit, which allowed us to pin down the hitherto elusive frequency of the ν21 mode. The experimental results make an interesting comparison with those of anharmonic force field calculations. We have also been able to extend the measurements for the AAT conformer. C.E.Blom, A.Bauder, Chem. Phys. Lett., 82, 492 (1981), J. Am. Chem. Soc., 104, 2993 (1982). H.Hasegawa, O.Ohashi, I.Yamaguchi, J. Mol. Spectrosc., 82, 205 (1982). P.D.Godfrey, F.M.Rodgers, R.D.Brown, J. Am. Chem. Soc., 119, 2232 (1997).

  7. Kinetic Modeling of Esterification of Ethylene Glycol with Acetic Acid

    NASA Astrophysics Data System (ADS)

    Yadav, Vishnu P.; Mukherjee, Rudra Palash; Bantraj, Kandi; Maity, Sunil K.

    2010-10-01

    The reaction kinetics of the esterification of ethylene glycol with acetic acid in the presence of cation exchange resin has been studied and kinetic models based on empirical and Langmuir approach has been developed. The Langmuir based model involving eight kinetic parameters fits experimental data much better compared to empirical model involving four kinetic parameters. The effect of temperature and catalyst loading on the reaction system has been analyzed. Further, the activation energy and frequency factor of the rate constants for Langmuir based model has been estimated.

  8. Kinetic Modeling of Esterification of Ethylene Glycol with Acetic Acid

    SciTech Connect

    Yadav, Vishnu P.; Maity, Sunil K.; Mukherjee, Rudra Palash; Bantraj, Kandi

    2010-10-26

    The reaction kinetics of the esterification of ethylene glycol with acetic acid in the presence of cation exchange resin has been studied and kinetic models based on empirical and Langmuir approach has been developed. The Langmuir based model involving eight kinetic parameters fits experimental data much better compared to empirical model involving four kinetic parameters. The effect of temperature and catalyst loading on the reaction system has been analyzed. Further, the activation energy and frequency factor of the rate constants for Langmuir based model has been estimated.

  9. 21 CFR 172.850 - Lactylated fatty acid esters of glycerol and propylene glycol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Lactylated fatty acid esters of glycerol and... CONSUMPTION Multipurpose Additives § 172.850 Lactylated fatty acid esters of glycerol and propylene glycol. The food additive lactylated fatty acid esters of glycerol and propylene glycol may be safely used...

  10. Synthesis of elastic biodegradable polyesters of ethylene glycol and butylene glycol from sebacic acid.

    PubMed

    Park, Hyung-seok; Seo, Jung-a; Lee, Hye-Young; Kim, Hae-Won; Wall, Ivan B; Gong, Myoung-Seon; Knowles, Jonathan C

    2012-08-01

    High molecular weight biodegradable polyesters were prepared from sebacic acid, ethylene glycol and butylene glycol through a simple non-solvent polycondensation with a low toxicity catalyst. The successful synthesis of the polyesters was confirmed by gel permeation chromatography, (1)H-nuclear magnetic resonance and Fourier transform-infrared spectroscopies and differential scanning calorimetry. The degradation tests were performed at 37 °C in phosphate buffer solution (pH 7.4) and showed a mass loss of ~5% over 12 weeks compared with only 2% for polycaprolactone (PCL). Reverse transcription polymerase chain reaction results following culture of osteoblasts on the polymer surface showed that poly(ethylene sebacate) and poly(butylene sebacate) films were optimal for osteoblast formation in terms of Runx 2 and osteocalcin gene expression.

  11. Clinical Performance of a Dermal Filler Containing Natural Glycolic Acid and a Polylactic Acid Polymer

    PubMed Central

    Macchetto, Pedro Cervantes; Durán Páramo, Rosa Margarita

    2010-01-01

    Lipoatrophy is a condition that affects certain individuals, most commonly those who are infected with the human immunodeficiency virus.1–3 Injectable fillers are used for the treatment of these dermal contour deformities to smooth dermal depressions formed by the loss of volume. These dermal fillers (also known as soft tissue augmentation devices) can correct contour deformities caused by lipoatrophy in patients who are human immunodeficiency virus positive or negative. The product used in this study is a patented, second-generation, injectable, dermal collagen stimulator that combines glycolic acid and polylactic acid. The glycolic acid used is not a polymer, but rather an acid derived from sugar cane. Its chemical structure corresponds to that of an alpha-hydroxy acid. Glycolic acid is a well-characterized agent that is present in a number of cosmetic products. Polylactic acid is a synthetic, biocompatible, biodegradable, inert, synthetic polymer from the poly a-hydroxy-acid family that is believed to stimulate fibroblasts to produce more collagen, thus increasing facial volume. Together, polylactic acid and glycolic acid act in concert to 1) stimulate collagen production and 2) hydrate the outer layers of the skin. A multicenter, clinical investigation authorized by the Mexican Secretariat of Health was conducted between September 20, 2002, and September 19, 2004. This clinical study was conducted in male patients between 32 and 60 years of age with lipoatrophy as a result of highly active antiretroviral therapy for human immunodeficiency virus infection. The study objective was to measure the improvement of contour deformities after the injection of a dermal collagen stimulator containing glycolic acid and polylactic acid. In addition to safety, this dermal filler was assessed when used to correct volume deformities caused by lipoatrophy in subjects who are human immunodeficiency virus positive. Thirty male subjects participated and were treated as follows

  12. Comparative effects of retinoic acid or glycolic acid vehiculated in different topical formulations.

    PubMed

    Maia Campos, Patrícia Maria Berardo Gonçalves; Gaspar, Lorena Rigo; Gonçalves, Gisele Mara Silva; Pereira, Lúcia Helena Terenciane Rodrigues; Semprini, Marisa; Lopes, Ruberval Armando

    2015-01-01

    Retinoids and hydroxy acids have been widely used due to their effects in the regulation of growth and in the differentiation of epithelial cells. However, besides their similar indication, they have different mechanisms of action and thus they may have different effects on the skin; in addition, since the topical formulation efficiency depends on vehicle characteristics, the ingredients of the formulation could alter their effects. Thus the objective of this study was to compare the effects of retinoic acid (RA) and glycolic acid (GA) treatment on the hairless mouse epidermis thickness and horny layer renewal when added in gel, gel cream, or cream formulations. For this, gel, gel cream, and cream formulations (with or without 6% GA or 0.05% RA) were applied in the dorsum of hairless mice, once a day for seven days. After that, the skin was analyzed by histopathologic, morphometric, and stereologic techniques. It was observed that the effects of RA occurred independently from the vehicle, while GA had better results when added in the gel cream and cream. Retinoic acid was more effective when compared to glycolic acid, mainly in the cell renewal and the exfoliation process because it decreased the horny layer thickness.

  13. Poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) thermogel as a novel submucosal cushion for endoscopic submucosal dissection.

    PubMed

    Yu, Lin; Xu, Wei; Shen, Wenjia; Cao, Luping; Liu, Yan; Li, Zhaoshen; Ding, Jiandong

    2014-03-01

    Endoscopic submucosal dissection (ESD) is a clinical therapy for early stage neoplastic lesions in the gastrointestinal tract. It is, however, faced with a crucial problem: the high occurrence of perforation. The formation of a submucosal fluid cushion (SFC) via a fluid injection is the best way to avoid perforation, and thus an appropriate biomaterial is vital for this minimally invasive endoscopic technique. In this study, we introduced an injectable thermogel as a novel submucosal injection substance in ESD. The hydrogel synthesized by us was composed of poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers. The polymer/water system was a low-viscosity fluid at room temperature and thus easily injected, and turned into a non-flowing gel at body temperature after injection. The submucosal injection of the thermogel to create SFCs was performed in both resected porcine stomachs and living minipigs. High mucosal elevation with a clear margin was maintained for a long duration. Accurate en bloc resection was achieved with the assistance of the thermogel. The mean procedure time was strikingly reduced. Meanwhile, no obvious bleeding, perforation and tissue damage were observed. The application of the thermogel not only facilitated the ESD procedure, but also increased the efficacy and safety of ESD. Therefore, the PLGA-PEG-PLGA thermogel provides an excellent submucosal injection system, and has great potential to improve the ESD technique significantly.

  14. Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease

    PubMed Central

    Lee, Jae Min; Keum, Bora; Yoo, In Kyung; Kim, Seung Han; Choi, Hyuk Soon; Kim, Eun Sun; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck; Kim, Myung Gyu; Jo, Sang Kyung

    2016-01-01

    Abstract The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease. We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing. The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients’ reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group. The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function. PMID:27603372

  15. Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease.

    PubMed

    Lee, Jae Min; Keum, Bora; Yoo, In Kyung; Kim, Seung Han; Choi, Hyuk Soon; Kim, Eun Sun; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck; Kim, Myung Gyu; Jo, Sang Kyung

    2016-09-01

    The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease.We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing.The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients' reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group.The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function. PMID:27603372

  16. Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease.

    PubMed

    Lee, Jae Min; Keum, Bora; Yoo, In Kyung; Kim, Seung Han; Choi, Hyuk Soon; Kim, Eun Sun; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck; Kim, Myung Gyu; Jo, Sang Kyung

    2016-09-01

    The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease.We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing.The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients' reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group.The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function.

  17. Efficacy and safety of azelaic acid and glycolic acid combination therapy compared with tretinoin therapy for acne.

    PubMed

    Spellman, M C; Pincus, S H

    1998-01-01

    We conducted a 12-week, multicenter, randomized, double-masked, parallel-group study of the efficacy, safety, and tolerability of azelaic acid 20% cream and glycolic acid lotion compared with tretinoin 0.025% cream and a vehicle lotion to treat mild-to-moderate facial acne vulgaris. Patients treated with azelaic/glycolic acid experienced a significantly greater reduction in the number of papules, as well as a greater reduction in the number of inflammatory lesions, than those treated with tretinoin. Overall global improvement was approximately 25% in both groups. In the physician evaluations, treatment with azelaic/glycolic acid was found to cause significantly less dryness, scaling, and erythema than tretinoin. Patients also reported significantly less dryness, redness, and peeling with azelaic/glycolic acid. Significantly more patients in the azelaic/glycolic acid group than the tretinoin group reported that they felt attractive. The combination of azelaic acid and glycolic acid is a useful alternative to tretinoin, being at least as efficacious as the latter, while offering a superior tolerability and patient approval profile.

  18. 21 CFR 172.856 - Propylene glycol mono- and diesters of fats and fatty acids.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Propylene glycol mono- and diesters of fats and... diesters of fats and fatty acids. Propylene glycol mono- and diesters of fats and fatty acids may be safely used in food, subject to the following prescribed conditions: (a) They are produced from edible...

  19. 21 CFR 172.856 - Propylene glycol mono- and diesters of fats and fatty acids.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Propylene glycol mono- and diesters of fats and... diesters of fats and fatty acids. Propylene glycol mono- and diesters of fats and fatty acids may be safely used in food, subject to the following prescribed conditions: (a) They are produced from edible...

  20. 21 CFR 172.856 - Propylene glycol mono- and diesters of fats and fatty acids.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Propylene glycol mono- and diesters of fats and... diesters of fats and fatty acids. Propylene glycol mono- and diesters of fats and fatty acids may be safely used in food, subject to the following prescribed conditions: (a) They are produced from edible...

  1. Development of a w/o/w emulsion for chemical peeling applications containing glycolic acid.

    PubMed

    Yener, Gülgün; Baitokova, Aida

    2006-01-01

    Glycolic acid is a member of the AHA family, which occurs naturally in foods and has been used for centuries as a cutaneous rejuvenation treatment. It is used in many cosmetic products as an exfoliant and moisturizer. When glycolic acid is used in greater amounts, however, there are greater cosmetic benefits but also potential for skin irritation as far as burning increases. The aim of this work was to investigate the feasibility of a topical delivery system as a multiple emulsion combining glycolic acid, strontium nitrate, and dexpanthenol in order to optimize the acid's cosmetic properties and lowering its side effects. PMID:17256078

  2. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis

    PubMed Central

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min

    2013-01-01

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair. PMID:25206505

  3. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis.

    PubMed

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min

    2013-07-25

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair.

  4. The study of gamma irradiation effects on poly (glycolic acid)

    NASA Astrophysics Data System (ADS)

    Rao Nakka, Rajeswara; Rao Thumu, Venkatappa; Reddy SVS, Ramana; Rao Buddhiraju, Sanjeeva

    2015-05-01

    We have investigated the effects of gamma irradiation on chemical structure, thermal and morphological properties of biodegradable semi-crystalline poly (glycolic acid) (PGA). PGA samples were subjected to irradiation treatment using a 60Co gamma source with a delivered dose of 30, 60 and 90 kGy, respectively. Gamma irradiation induces cleavage of PGA main chains forming ∼OĊH2 and ĊH2COO∼ radicals in both amorphous and crystalline regions. The free radicals formed in the amorphous region abstract atmospheric oxygen and convert them to peroxy radicals. The peroxy radical causes chain scission at the crystal interface through hydrogen abstraction from methylene groups forming the ∼ĊHCOO∼ (I) radical. Consequently, the observed electron spin resonance (ESR) doublet of irradiated PGA is assigned to (I). The disappearance of the ESR signal above 190°C indicates that free radicals are formed in the amorphous region and decay below the melting temperature of PGA. Fourier transform infrared and optical absorption studies confirm that the ? groups are not influenced by gamma irradiation. Differential scanning calorimetry (DSC) studies showed that the melting temperature of PGA decreased from 212°C to 202°C upon irradiation. Degree of crystallinity increased initially and then decreased with an increase in radiation as per DSC and X-ray diffraction studies. Irradiation produced changes in the physical properties of PGA as well as affecting the morphology of the material.

  5. 21 CFR 172.850 - Lactylated fatty acid esters of glycerol and propylene glycol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Lactylated fatty acid esters of glycerol and... DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.850 Lactylated fatty acid esters of glycerol and propylene glycol. The food additive lactylated fatty acid esters of glycerol...

  6. 21 CFR 172.850 - Lactylated fatty acid esters of glycerol and propylene glycol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Lactylated fatty acid esters of glycerol and... DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.850 Lactylated fatty acid esters of glycerol and propylene glycol. The food additive lactylated fatty acid esters of glycerol...

  7. 21 CFR 172.850 - Lactylated fatty acid esters of glycerol and propylene glycol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Lactylated fatty acid esters of glycerol and... DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.850 Lactylated fatty acid esters of glycerol and propylene glycol. The food additive lactylated fatty acid esters of glycerol...

  8. Azelaic acid and glycolic acid combination therapy for facial hyperpigmentation in darker-skinned patients: a clinical comparison with hydroquinone.

    PubMed

    Kakita, L S; Lowe, N J

    1998-01-01

    This multicenter, randomized, double-masked, parallel-group, 24-week clinical study compared the efficacy of the combination of azelaic acid 20% cream and glycolic acid 15% or 20% lotion with hydroquinone 4% in the treatment of facial hyperpigmentation in darker-skinned patients. At week 24, overall improvement and reduction in lesion area, pigmentary intensity, and disease severity were comparable in the two treatment groups. At some visits, patients treated with an azelaic/glycolic acid combination had slightly greater levels of peeling, burning, stinging, or dryness than did patients treated with hydroquinone, although scores for cutaneous signs and symptoms were always low. The present study demonstrated that the combination of azelaic acid 20% cream and glycolic acid 15% or 20% lotion was as effective as hydroquinone 4% cream in the treatment of hyperpigmentation in darker-skinned patients, with only a slightly higher rate of mild local irritation. These findings suggest that the addition of glycolic acid to azelaic acid treatment for hyperpigmentation is an appropriate alternative in selected darker-skinned patients.

  9. Advantages of using glycolic acid as a retardant in a brushite forming cement.

    PubMed

    Mariño, Faleh Tamimi; Torres, Jesús; Hamdan, Mohammad; Rodríguez, Carmen Rueda; Cabarcos, Enrique López

    2007-11-01

    In this study we have compared the effect of using acetic, glycolic, and citric acids on the brushite cement setting reaction and the properties of the resultant cement. The cement solid phase was made by mixing beta-tricalcium phosphate (beta-TCP), monocalcium dihydrogen phosphate anhydrate (MCPA), and sodium pyrophosphate, whereas the cement liquid phase consisted of aqueous solutions of carboxy acids at concentrations ranging from 0.5 to 3.5M. Cements were prepared by mixing the solid phase with the liquid phase to form a workable paste. The cement setting time was longer for glycolic and citric acids. The best mechanical properties in dry environments were obtained using glycolic and citric acid liquid phases. In a wet environment at 37 degrees C, the cement set with glycolic acid was the strongest one. Brushite cement diametral tensile strength seems to be affected by the calcium-carboxyl phase produced in the setting reaction. The acceptable setting time and mechanical properties of cements set in glycolic acid solutions are attributed to the additional hydrophilic groups in the carboxylic acid and the low solubility in water of the calcium salt produced in the reaction. Moreover, at high concentrations, carboxylic acids add chemically to the cement matrix becoming reactants themselves.

  10. Fast determination of ethylene glycol, 1,2-propylene glycol and glycolic acid in blood serum and urine for emergency and clinical toxicology by GC-FID.

    PubMed

    Hložek, Tomáš; Bursová, Miroslava; Čabalaa, Radomír

    2014-12-01

    A simple, cost effective, and fast gas chromatography method with flame ionization detection (GC-FID) for simultaneous measurement of ethylene glycol, 1,2-propylene glycol and glycolic acid was developed and validated for clinical toxicology purposes. This new method employs a relatively less used class of derivatization agents - alkyl chloroformates, allowing the efficient and rapid derivatization of carboxylic acids within seconds while glycols are simultaneously derivatized by phenylboronic acid. The entire sample preparation procedure is completed within 10 min. To avoid possible interference from naturally occurring endogenous acids and quantitation errors 3-(4-chlorophenyl) propionic acid was chosen as an internal standard. The significant parameters of the derivatization have been found using chemometric procedures and these parameters were optimized using the face-centered central composite design. The calibration dependence of the method was proved to be quadratic in the range of 50-5000 mg mL(-1), with adequate accuracy (92.4-108.7%) and precision (9.4%). The method was successfully applied to quantify the selected compounds in serum of patients from emergency units.

  11. 40 CFR 721.6980 - Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols polyglycidyl ethers (generic name). 721.6980... Substances § 721.6980 Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky... reporting. (1) The chemical substance dimer acids, polymer with polyalkylene glycol, bisphenol...

  12. 40 CFR 721.6980 - Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols polyglycidyl ethers (generic name). 721.6980... Substances § 721.6980 Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky... reporting. (1) The chemical substance dimer acids, polymer with polyalkylene glycol, bisphenol...

  13. 40 CFR 721.6980 - Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols polyglycidyl ethers (generic name). 721.6980... Substances § 721.6980 Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky... reporting. (1) The chemical substance dimer acids, polymer with polyalkylene glycol, bisphenol...

  14. Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

    PubMed

    Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-08-01

    In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

  15. Electrospun Poly(lactic acid-co-glycolic acid) Scaffolds for Skin Tissue Engineering

    PubMed Central

    Kumbar, Sangamesh G.; Nukavarapu, Syam Prasad; James, Roshan; Nair, Lakshmi S.; Laurencin, Cato T.

    2008-01-01

    Electrospun fiber matrices composed of scaffolds of varying fiber diameters were investigated for potential application of severe skin loss. Few systematic studies have been performed to examine the effect of varying fiber diameter electrospun fiber matrices for skin regeneration. The present study reports the fabrication of poly[lactic acid-co-glycolic acid] (PLAGA) matrices with fiber diameters of 150–225, 200–300, 250–467, 500–900, 600–1200, 2500–3000 and 3250–6000 nm via electrospinning. All fiber matrices found to have a tensile modulus from 39.23 ± 8.15 to 79.21 ± 13.71 MPa which falls in the range for normal human skin. Further, the porous fiber matrices have porosity between 38–60 % and average pore diameters between 10–14µm. We evaluated the efficacy of these biodegradable fiber matrices as skin substitutes by seeding them with human skin fibroblasts (hSF). Human skin fibroblasts acquired a well spread morphology and showed significant progressive growth on fiber matrices in the 350–1100 nm diameter range. Collagen type III gene expression was significantly up-regulated in hSF seeded on matrices with fiber diameters in the range of 350–1100 nm. Based on the need, the proposed fiber skin substitutes can be successfully fabricated and optimized for skin fibroblast attachment and growth. PMID:18639927

  16. 21 CFR 172.850 - Lactylated fatty acid esters of glycerol and propylene glycol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.850 Lactylated fatty acid esters of glycerol and propylene glycol. The food additive lactylated fatty acid esters of glycerol...

  17. 40 CFR 721.1729 - Boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid (H3BO3), mixed esters with... identified as boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1729...

  18. 40 CFR 721.1729 - Boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Boric acid (H3BO3), mixed esters with... identified as boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1729...

  19. 40 CFR 721.1729 - Boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Boric acid (H3BO3), mixed esters with... identified as boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1729...

  20. 40 CFR 721.1729 - Boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Boric acid (H3BO3), mixed esters with... identified as boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1729...

  1. 40 CFR 721.1729 - Boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Boric acid (H3BO3), mixed esters with... identified as boric acid (H3BO3), mixed esters with polyethylene glycol mono-Bu ether and polyethylene glycol... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1729...

  2. Poly(lactic acid) and poly(lactic-co-glycolic acid) particles as versatile carrier platforms for vaccine delivery.

    PubMed

    Pavot, Vincent; Berthet, Morgane; Rességuier, Julien; Legaz, Sophie; Handké, Nadège; Gilbert, Sarah C; Paul, Stéphane; Verrier, Bernard

    2014-12-01

    The development of safe and effective vaccines for cancer and infectious diseases remains a major goal in public health. Over the last two decades, controlled release of vaccine antigens and immunostimulant molecules has been achieved using nanometer or micron-sized delivery vehicles synthesized using biodegradable polymers. In addition to achieving a depot effect, enhanced vaccine efficacy using such delivery vehicles has been attributed to efficient targeting of antigen presenting cells such as dendritic cells. Biodegradable and biocompatible poly(lactic acid) and poly(lactic-co-glycolic acid) polymers belong to one such family of polymers that have been a popular choice of material used in the design of these delivery vehicles. This review summarizes research findings from ourselves and others highlighting the promise of poly(lactic acid)- and poly(lactic-co-glycolic acid)-based vaccine carriers in enhancing immune responses.

  3. Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid

    PubMed Central

    Keum, Chang-Gu; Noh, Young-Wook; Baek, Jong-Suep; Lim, Ji-Ho; Hwang, Chan-Ju; Na, Young-Guk; Shin, Sang-Chul; Cho, Cheong-Weon

    2011-01-01

    Background Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. Methods Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2–5 minutes of sonication time, 70–130 W sonication power, and 5–25 mg drug loading. Results A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. Conclusion Our research shows that the choice of surfactant is important for controlled release of

  4. 40 CFR 721.6980 - Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Dimer acids, polymer with polyalkylene... Substances § 721.6980 Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky... reporting. (1) The chemical substance dimer acids, polymer with polyalkylene glycol, bisphenol...

  5. 40 CFR 721.6980 - Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky-lenepolyols...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Dimer acids, polymer with polyalkylene... Substances § 721.6980 Dimer acids, polymer with polyalkylene glycol, bisphenol A-diglycidyl ether, and alky... reporting. (1) The chemical substance dimer acids, polymer with polyalkylene glycol, bisphenol...

  6. Cationic poly(lactic-co-glycolic acid) iron oxide microspheres for nucleic acid detection

    NASA Astrophysics Data System (ADS)

    Pandey, Chandra Mouli; Sharma, Aditya; Sumana, Gajjala; Tiwari, Ida; Malhotra, Bansi Dhar

    2013-04-01

    Herein, we envisage the possibility of preparing stable cationic poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating the iron oxide nanoparticles (IONPs; 8-12 nm). The IONPs are incorporated into PLGA in organic phase followed by microsphere formation and chitosan coating in aqueous medium via nano-emulsion technique. The average size of the microspheres, as determined by dynamic light scattering are about 310 nm, while the zeta potential for the composite remains near 35 mV at pH 4.0. These microspheres are electrophoretically deposited onto indium tin oxide (ITO)-coated glass substrate used as cathode and parallel platinum plate as the counter electrode. This platform is utilized to fabricate a DNA biosensor, by immobilizing a probe sequence specific to Escherichia coli. The bioelectrode shows a surface-controlled electrode reaction with the electron transfer coefficient (α) of 0.64 and charge transfer rate constant (ks) of 61.73 s-1. Under the optimal conditions, this biosensor shows a detection limit of 8.7 × 10-14 M and is found to retain about 81% of the initial activity after 9 cycles of use.Herein, we envisage the possibility of preparing stable cationic poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating the iron oxide nanoparticles (IONPs; 8-12 nm). The IONPs are incorporated into PLGA in organic phase followed by microsphere formation and chitosan coating in aqueous medium via nano-emulsion technique. The average size of the microspheres, as determined by dynamic light scattering are about 310 nm, while the zeta potential for the composite remains near 35 mV at pH 4.0. These microspheres are electrophoretically deposited onto indium tin oxide (ITO)-coated glass substrate used as cathode and parallel platinum plate as the counter electrode. This platform is utilized to fabricate a DNA biosensor, by immobilizing a probe sequence specific to Escherichia coli. The bioelectrode shows a surface-controlled electrode reaction with the

  7. [Reaction of bone tissue elements on synthetic bioresorbable materials based on lactic and glycolic acids].

    PubMed

    Kulakov, A A; Grigor'ian, A S

    2014-01-01

    The aim of the study was to evaluate the adverse effects of synthetic polymeric bioresorbable materials based on lactic and glycolic acids on the bone tissue. The study was carried-out on 40 Wister-line rats. Four types of bioresorbable polymeric materials were implanted: PolyLactide Glycolide Acid (PLGA), Poly-L-Lactide Acid (PLLA); Poly-96L/4D-Lactide Acid (96/4 PLDLA); Poly-70L/30D-Lactide Acid (70/30 PLDLA). The results showed connective tissue formation (fibrointegration) bordering bone adjacent to implanted materials. This proved the materials to cause pathogenic influence on the bone which mechanisms are described in the article.

  8. Viscoelasticity of repaired sciatic nerve by poly(lactic-co-glycolic acid) tubes

    PubMed Central

    Piao, Chengdong; Li, Peng; Liu, Guangyao; Yang, Kun

    2013-01-01

    Medical-grade synthetic poly(lactic-co-glycolic acid) polymer can be used as a biomaterial for nerve repair because of its good biocompatibility, biodegradability and adjustable degradation rate. The stress relaxation and creep properties of peripheral nerve can be greatly improved by repair with poly(lactic-co-glycolic acid) tubes. Ten sciatic nerve specimens were harvested from fresh corpses within 24 hours of death, and were prepared into sciatic nerve injury models by creating a 10 mm defect in each specimen. Defects were repaired by anastomosis with nerve autografts and poly(lactic-co-glycolic acid) tubes. Stress relaxation and creep testing showed that at 7 200 seconds, the sciatic nerve anastomosed by poly(lactic-co-glycolic acid) tubes exhibited a greater decrease in stress and increase in strain than those anastomosed by nerve autografts. These findings suggest that poly(lactic-co-glycolic acid) exhibits good viscoelasticity to meet the biomechanical require-ments for a biomaterial used to repair sciatic nerve injury. PMID:25206634

  9. Viscoelasticity of repaired sciatic nerve by poly(lactic-co-glycolic acid) tubes.

    PubMed

    Piao, Chengdong; Li, Peng; Liu, Guangyao; Yang, Kun

    2013-11-25

    Medical-grade synthetic poly(lactic-co-glycolic acid) polymer can be used as a biomaterial for nerve repair because of its good biocompatibility, biodegradability and adjustable degradation rate. The stress relaxation and creep properties of peripheral nerve can be greatly improved by repair with poly(lactic-co-glycolic acid) tubes. Ten sciatic nerve specimens were harvested from fresh corpses within 24 hours of death, and were prepared into sciatic nerve injury models by creating a 10 mm defect in each specimen. Defects were repaired by anastomosis with nerve autografts and poly(lactic-co-glycolic acid) tubes. Stress relaxation and creep testing showed that at 7 200 seconds, the sciatic nerve anastomosed by poly(lactic-co-glycolic acid) tubes exhibited a greater decrease in stress and increase in strain than those anastomosed by nerve autografts. These findings suggest that poly(lactic-co-glycolic acid) exhibits good viscoelasticity to meet the biomechanical require-ments for a biomaterial used to repair sciatic nerve injury.

  10. Separation of glycols from dilute aqueous solutions via complexation with boronic acids

    SciTech Connect

    Randel, L.A.; King, C.J.

    1991-07-01

    This work examines methods of separating low molecular weight glycols from dilute aqueous solution. Extraction into conventional solvents is generally not economical, since, in the literature reviewed, distribution ratios for the two- to four-carbon glycols are all less than one. Distribution ratios can be increased, however, by incorporating into the organic phase an extracting agent that will complex with the solute of interest. The extracting agent investigated in this work is 3-nitrophenylboronic acid (NPBA). NPBA, a boric acid derivative, reversibly complexes with many glycols. The literature on complexation of borate and related compounds with glycols, including mechanistic data, measurement techniques, and applications to separation processes, provides information valuable for designing experiments with NPBA and is reviewed herein. 88 refs., 15 figs., 24 tabs.

  11. Treatment of pseudofolliculitis barbae with topical glycolic acid: a report of two studies.

    PubMed

    Perricone, N V

    1993-10-01

    Pseudofolliculitis barbae (razor bumps) is a foreign-body inflammatory reaction surrounding ingrown facial hair, which results from shaving. The problem occurs in persons with curly hair, with an incidence of over 50 percent in black men. The objective of the two studies described was to assess the effectiveness of topical glycolic acid in the treatment and prevention of razor bumps. The studies consisted of two placebo-controlled trials in thirty-five adult men. The results showed that glycolic acid lotion was significantly more effective than placebo in treating pseudofolliculitis barbae. There was over a 60 percent reduction in lesions on the treated side, which allowed daily shaving with little irritation. Topical application of glycolic acid lotion is an effective therapy for pseudofolliculitis barbae and allows the patient to resume a daily shaving regimen.

  12. Thermosensitivity of bile acid-based oligo(ethylene glycol) stars in aqueous solutions.

    PubMed

    Strandman, Satu; Le Dévédec, Frantz; Zhu, X X

    2011-08-01

    Amphiphilic star-shaped oligo(ethylene glycol)s with a hydrophobic bile acid core and varying number of hydrophilic arms have been made. Their thermal behavior in aqueous solutions depends on the number rather than the length of the arms. The two-armed lithocholate derivative showed the strongest tendency for association and exhibited the lowest cloud point (79 °C) of the oligomers made, as well as another phase separation at a lower temperature (31 °C). The "double thermosensitivity" arising both from the salt-dependent LCST of the oligo(ethylene glycol) segments and the temperature-responsive self-assembly of amphiphilic bile acid derivative provides an interesting path in the design of bile acid-based smart materials.

  13. Thermosensitivity of bile acid-based oligo(ethylene glycol) stars in aqueous solutions.

    PubMed

    Strandman, Satu; Le Dévédec, Frantz; Zhu, X X

    2011-08-01

    Amphiphilic star-shaped oligo(ethylene glycol)s with a hydrophobic bile acid core and varying number of hydrophilic arms have been made. Their thermal behavior in aqueous solutions depends on the number rather than the length of the arms. The two-armed lithocholate derivative showed the strongest tendency for association and exhibited the lowest cloud point (79 °C) of the oligomers made, as well as another phase separation at a lower temperature (31 °C). The "double thermosensitivity" arising both from the salt-dependent LCST of the oligo(ethylene glycol) segments and the temperature-responsive self-assembly of amphiphilic bile acid derivative provides an interesting path in the design of bile acid-based smart materials. PMID:21661073

  14. Near-infrared laser-induced generation of three rare conformers of glycolic acid.

    PubMed

    Halasa, Anna; Lapinski, Leszek; Reva, Igor; Rostkowska, Hanna; Fausto, Rui; Nowak, Maciej J

    2014-07-31

    Structural transformations were induced in conformers of glycolic acid by selective excitation with monochromatic tunable near-infrared laser light. For the compound isolated in Ar matrixes, near-IR excitation led to generation of two higher-energy conformers (GAC; AAT) differing from the most stable SSC form by 180° rotation around the C-C bond. A detailed investigation of this transformation revealed that one conformer (GAC) is produced directly from the near-IR-excited most stable conformer. The other higher-energy conformer (AAT) was effectively generated only upon excitation of the primary photoproduct (GAC) with another near-IR photon. Once these higher-energy conformers of glycolic acid were generated in an Ar matrix, they could be subsequently transformed into one another upon selective near-IR excitations. Interestingly, no repopulation of the initial most stable SSC conformer occurred upon near-IR excitation of the higher-energy forms of the compound isolated in solid Ar. A dramatically different picture of near-IR-induced conformational transformations was observed for glycolic acid isolated in N2 matrixes. In this case, upon near-IR excitation, the most stable SSC form converted solely into a new conformer (SST), where the acid OH group is rotated by 180°. This conformational transformation was found to be photoreversible. Moreover, SST conformer, photoproduced in the N2 matrix, spontaneously converted to the most stable SSC form of glycolic acid, when the matrix was kept at cryogenic temperature and in the dark.

  15. Physicochemical Properties and Applications of Poly(lactic-co-glycolic acid) for Use in Bone Regeneration

    PubMed Central

    Félix Lanao, Rosa P.; Jonker, Anika M.; Wolke, Joop G.C.; Jansen, John A.; van Hest, Jan C.M.

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most often used synthetic polymer within the field of bone regeneration owing to its biocompatibility and biodegradability. As a consequence, a large number of medical devices comprising PLGA have been approved for clinical use in humans by the American Food and Drug Administration. As compared with the homopolymers of lactic acid poly(lactic acid) and poly(glycolic acid), the co-polymer PLGA is much more versatile with regard to the control over degradation rate. As a material for bone regeneration, the use of PLGA has been extensively studied for application and is included as either scaffolds, coatings, fibers, or micro- and nanospheres to meet various clinical requirements. PMID:23350707

  16. FY13 GLYCOLIC-NITRIC ACID FLOWSHEET DEMONSTRATIONS OF THE DWPF CHEMICAL PROCESS CELL WITH SIMULANTS

    SciTech Connect

    Lambert, D.; Zamecnik, J.; Best, D.

    2014-03-13

    Savannah River Remediation is evaluating changes to its current Defense Waste Processing Facility flowsheet to replace formic acid with glycolic acid in order to improve processing cycle times and decrease by approximately 100x the production of hydrogen, a potentially flammable gas. Higher throughput is needed in the Chemical Processing Cell since the installation of the bubblers into the melter has increased melt rate. Due to the significant maintenance required for the safety significant gas chromatographs and the potential for production of flammable quantities of hydrogen, eliminating the use of formic acid is highly desirable. Previous testing at the Savannah River National Laboratory has shown that replacing formic acid with glycolic acid allows the reduction and removal of mercury without significant catalytic hydrogen generation. Five back-to-back Sludge Receipt and Adjustment Tank (SRAT) cycles and four back-to-back Slurry Mix Evaporator (SME) cycles were successful in demonstrating the viability of the nitric/glycolic acid flowsheet. The testing was completed in FY13 to determine the impact of process heels (approximately 25% of the material is left behind after transfers). In addition, back-to-back experiments might identify longer-term processing problems. The testing was designed to be prototypic by including sludge simulant, Actinide Removal Product simulant, nitric acid, glycolic acid, and Strip Effluent simulant containing Next Generation Solvent in the SRAT processing and SRAT product simulant, decontamination frit slurry, and process frit slurry in the SME processing. A heel was produced in the first cycle and each subsequent cycle utilized the remaining heel from the previous cycle. Lower SRAT purges were utilized due to the low hydrogen generation. Design basis addition rates and boilup rates were used so the processing time was shorter than current processing rates.

  17. Comparison of clindamycin 1% and benzoyl peroxide 5% gel to a novel composition containing salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid, citric acid, and dioic acid in the treatment of acne vulgaris.

    PubMed

    Baumann, Leslie S; Oresajo, Christian; Yatskayer, Margarita; Dahl, Amanda; Figueras, Kristian

    2013-03-01

    This study evaluated the tolerance and efficacy of 2 facial skin products in subjects with acne using the following acne treatments: 1) treatment A, a combination of salicylic acid, capryloyl salicylic acid, HEPES, glycolic acid, citric acid, and dioic acid, and 2) treatment B (BenzaClin®, clindamycin 1% and benzoyl peroxide 5% gel). The treatment design included the split-face application of treatment A and treatment B and the full-face application of the cleanser, moisturizer, and sunscreen. Data were collected through physician visual assessments, subject irritation questionnaires and assessments, along with clinical photography. Results showed similar tolerance and efficacy for both treatments.

  18. 40 CFR 721.10661 - Methylenebis [isocyanatobenzene], polymer with alkanedoic acid, alkylene glycols, alkoxylated...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Methylenebis , polymer with alkanedoic acid, alkylene glycols, alkoxylated alkanepolyol and substituted trialkoxysilane (generic). 721.10661 Section 721.10661 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES...

  19. Organics Characterization Of DWPF Alternative Reductant Simulants, Glycolic Acid, And Antifoam 747

    SciTech Connect

    White, T. L.; Wiedenman, B. J.; Lambert, D. P.; Crump, S. L.; Fondeur, F. F.; Papathanassiu, A. E.; Kot, W. K.; Pegg, I. L.

    2013-10-01

    The present study examines the fate of glycolic acid and other organics added in the Chemical Processing Cell (CPC) of the Defense Waste Processing Facility (DWPF) as part of the glycolic alternate flowsheet. Adoption of this flowsheet is expected to provide certain benefits in terms of a reduction in the processing time, a decrease in hydrogen generation, simplification of chemical storage and handling issues, and an improvement in the processing characteristics of the waste stream including an increase in the amount of nitrate allowed in the CPC process. Understanding the fate of organics in this flowsheet is imperative because tank farm waste processed in the CPC is eventually immobilized by vitrification; thus, the type and amount of organics present in the melter feed may affect optimal melt processing and the quality of the final glass product as well as alter flammability calculations on the DWPF melter off gas. To evaluate the fate of the organic compounds added as the part of the glycolic flowsheet, mainly glycolic acid and antifoam 747, samples of simulated waste that was processed using the DWPF CPC protocol for tank farm sludge feed were generated and analyzed for organic compounds using a variety of analytical techniques at the Savannah River National Laboratory (SRNL). These techniques included Ion Chromatography (IC), Gas Chromatography-Mass Spectrometry (GC-MS), Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES), and Nuclear Magnetic Resonance (NMR) Spectroscopy. A set of samples were also sent to the Catholic University of America Vitreous State Laboratory (VSL) for analysis by NMR Spectroscopy at the University of Maryland, College Park. Analytical methods developed and executed at SRNL collectively showed that glycolic acid was the most prevalent organic compound in the supernatants of Slurry Mix Evaporator (SME) products examined. Furthermore, the studies suggested that commercially available glycolic acid contained minor amounts

  20. Glycolic acid chemical peeling improves inflammatory acne eruptions through its inhibitory and bactericidal effects on Propionibacterium acnes.

    PubMed

    Takenaka, Yuko; Hayashi, Nobukazu; Takeda, Mikiko; Ashikaga, Sayaka; Kawashima, Makoto

    2012-04-01

    Glycolic acid chemical peeling is effective for treating comedones, and some clinical data show that it also improves inflammatory eruptions. The purpose of this study was to identify the mechanism of glycolic acid chemical peeling to improve inflammatory acne. To assess growth inhibitory and bactericidal effects of glycolic acid on Propionibacterium acnes in vitro, we used an agar diffusion method and a time-kill method. To reveal bactericidal effects in vivo, we established an agar-attached method which correlated well with the ordinary swab-wash method, and we used the agar-attached method to compare the numbers of propionibacteria on the cheek treated with glycolic acid chemical peeling. Our results show that 30% glycolic acid (at pH 1.5, 3.5 and 5.5) formed growth inhibitory circles in the agar diffusion method, but the diameters of those circles were smaller than with 1% nadifloxacin lotion or 1% clindamycin gel. In the time-kill method, 30% glycolic acid (at pH 1.5 and 3.5) or 1% nadifloxacin lotion reduced the number of P. acnes to less than 100 CFU/mL within 5 min. In contrast, in 30% glycolic acid (at pH 5.5) or in 1% clindamycin gel, P. acnes survived for more than 4 h. Chemical peeling with 35% glycolic acid (at pH 1.2) decreased the number of propionibacteria on the cheeks of patients compared with untreated controls (P < 0.01). Our results demonstrate that glycolic acid has moderate growth inhibitory and bactericidal effects on P. acnes, and that chemical peeling with glycolic acid works on inflammatory acne via those effects. PMID:21950544

  1. Glycolic acid chemical peeling improves inflammatory acne eruptions through its inhibitory and bactericidal effects on Propionibacterium acnes.

    PubMed

    Takenaka, Yuko; Hayashi, Nobukazu; Takeda, Mikiko; Ashikaga, Sayaka; Kawashima, Makoto

    2012-04-01

    Glycolic acid chemical peeling is effective for treating comedones, and some clinical data show that it also improves inflammatory eruptions. The purpose of this study was to identify the mechanism of glycolic acid chemical peeling to improve inflammatory acne. To assess growth inhibitory and bactericidal effects of glycolic acid on Propionibacterium acnes in vitro, we used an agar diffusion method and a time-kill method. To reveal bactericidal effects in vivo, we established an agar-attached method which correlated well with the ordinary swab-wash method, and we used the agar-attached method to compare the numbers of propionibacteria on the cheek treated with glycolic acid chemical peeling. Our results show that 30% glycolic acid (at pH 1.5, 3.5 and 5.5) formed growth inhibitory circles in the agar diffusion method, but the diameters of those circles were smaller than with 1% nadifloxacin lotion or 1% clindamycin gel. In the time-kill method, 30% glycolic acid (at pH 1.5 and 3.5) or 1% nadifloxacin lotion reduced the number of P. acnes to less than 100 CFU/mL within 5 min. In contrast, in 30% glycolic acid (at pH 5.5) or in 1% clindamycin gel, P. acnes survived for more than 4 h. Chemical peeling with 35% glycolic acid (at pH 1.2) decreased the number of propionibacteria on the cheeks of patients compared with untreated controls (P < 0.01). Our results demonstrate that glycolic acid has moderate growth inhibitory and bactericidal effects on P. acnes, and that chemical peeling with glycolic acid works on inflammatory acne via those effects.

  2. Poly(N-vinylimidazole/ethylene glycol dimethacrylate) for the purification and isolation of phenolic acids.

    PubMed

    Schemeth, Dieter; Noël, Jean-Christophe; Jakschitz, Thomas; Rainer, Matthias; Tessadri, Richard; Huck, Christian W; Bonn, Günther K

    2015-07-23

    In this study we report the novel polymeric resin poly(N-vinyl imidazole/ethylene glycol dimethacrylate) for the purification and isolation of phenolic acids. The monomer to crosslinker ratio and the porogen composition were optimized for isolating phenolic acids diluted in acetonitrile at normal phase chromatography conditions, first. Acetonitrile serves as polar, aprotic solvent, dissolving phenolic acids but not interrupting interactions with the stationary phase due to the approved Hansen solubility parameters. The optimized resin demonstrated high loading capacities and adsorption abilities particularly for phenolic acids in both, acetonitrile and aqueous solutions. The adsorption behavior of aqueous standards can be attributed to ion exchange effects due to electrostatic interactions between protonated imidazole residues and deprotonated phenolic acids. Furthermore, adsorption experiments and subsequent curve fittings provide information of maximum loading capacities of single standards according to the Langmuir adsorption model. Recovery studies of the optimized polymer in the normal-phase and ion-exchange mode illustrate the powerful isolation properties for phenolic acids and are comparable or even better than typical, commercially available solid phase extraction materials. In order to prove the applicability, a highly complex extract of rosemary leaves was purified by poly(N-vinyl imidazole/ethylene glycol dimethacrylate) and the isolated compounds were identified using UHPLC-qTOF-MS.

  3. Acid-base equilibria in ethylene glycol--III: selection of titration conditions in ethylene glycol medium, protolysis constants of alkaloids in ethylene glycol and its mixtures.

    PubMed

    Zikolov, P; Zikolova, T; Budevsky, O

    1976-08-01

    Theoretical titration curves are used for the selection of appropriate conditions for the acid-base volumetric determination of weak bases in ethylene glycol medium. The theoretical curves for titration of some alkaloids are deduced graphically on the basis of the logarithmic concentration diagram. The acid-base constants used for the construction of the theoretical titration curves were determined by potentiometric titration in a cell without liquid junction, equipped with a glass and a silver-silver chloride electrode. It is shown that the alkaloids investigated can be determined accurately by visual or potentiometric titration. The same approach for the selection of titration conditions seems to be applicable to other non-aqueous amphiprotic solvents.

  4. Mode of Action: Oxalate Crystal-Induced Renal Tubule Degeneration and Glycolic Acid-Induced Dysmorphogenesis—Renal and Developmental Effects of Ethylene Glycol

    SciTech Connect

    Corley, Rick A.; Meek, M E.; Carney, E W.

    2005-10-01

    Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

  5. Surface Mechanical and Rheological Behaviors of Biocompatible Poly((D,L-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA-PEG) and Poly((D,L-lactic acid-ran-glycolic acid-ran-ε-caprolactone)-block-ethylene glycol) (PLGACL-PEG) Block Copolymers at the Air-Water Interface.

    PubMed

    Kim, Hyun Chang; Lee, Hoyoung; Khetan, Jawahar; Won, You-Yeon

    2015-12-29

    Air-water interfacial monolayers of poly((D,L-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA-PEG) exhibit an exponential increase in surface pressure under high monolayer compression. In order to understand the molecular origin of this behavior, a combined experimental and theoretical investigation (including surface pressure-area isotherm, X-ray reflectivity (XR) and interfacial rheological measurements, and a self-consistent field (SCF) theoretical analysis) was performed on air-water monolayers formed by a PLGA-PEG diblock copolymer and also by a nonglassy analogue of this diblock copolymer, poly((D,L-lactic acid-ran-glycolic acid-ran-caprolactone)-block-ethylene glycol) (PLGACL-PEG). The combined results of this study show that the two mechanisms, i.e., the glass transition of the collapsed PLGA film and the lateral repulsion of the PEG brush chains that occur simultaneously under lateral compression of the monolayer, are both responsible for the observed PLGA-PEG isotherm behavior. Upon cessation of compression, the high surface pressure of the PLGA-PEG monolayer typically relaxes over time with a stretched exponential decay, suggesting that in this diblock copolymer situation, the hydrophobic domain formed by the PLGA blocks undergoes glass transition in the high lateral compression state, analogously to the PLGA homopolymer monolayer. In the high PEG grafting density regime, the contribution of the PEG brush chains to the high monolayer surface pressure is significantly lower than what is predicted by the SCF model because of the many-body attraction among PEG segments (referred to in the literature as the "n-cluster" effects). The end-grafted PEG chains were found to be protein resistant even under the influence of the "n-cluster" effects.

  6. A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres

    PubMed Central

    Wright, Bernice; Parmar, Nina; Bozec, Laurent; Aguayo, Sebastian D

    2015-01-01

    Poly (lactic-co-glycolic) acid microspheres are amenable to a number of biomedical procedures that support delivery of cells, drugs, peptides or genes. Hydrophilisation or wetting of poly (lactic-co-glycolic) acid are an important pre-requisites for attachment of cells and can be achieved via exposure to plasma oxygen or nitrogen, surface hydrolysis with NaOH or chloric acid, immersion in ethanol and water, or prolonged incubation in phosphate buffered saline or cell culture medium. The aim of this study is to develop a simple method for wetting poly (lactic-co-glycolic) acid microspheres for cell delivery applications. A one-step ethanol immersion process that involved addition of serum-supplemented medium and ethanol to PLGA microspheres over 30 min–24 h is described in the present study. This protocol presents a more efficient methodology than conventional two-step wetting procedures. Attachment of human skeletal myoblasts to poly (lactic-co-glycolic) acid microspheres was dependent on extent of wetting, changes in surface topography mediated by ethanol pre-wetting and serum protein adsorption. Ethanol, at 70% (v/v) and 100%, facilitated similar levels of wetting. Wetting with 35% (v/v) ethanol was only achieved after 24 h. Pre-wetting (over 3 h) with 70% (v/v) ethanol allowed significantly greater (p ≤ 0.01) serum protein adsorption to microspheres than wetting with 35% (v/v) ethanol. On serum protein-loaded microspheres, greater numbers of myoblasts attached to constructs wetted with 70% ethanol than those partially wetted with 35% (v/v) ethanol. Microspheres treated with 70% (v/v) ethanol presented a more rugose surface than those treated with 35% (v/v) ethanol, indicating that more efficient myoblast adhesion to the former may be at least partially attributed to differences in surface structure. We conclude that our novel protocol for pre-wetting poly (lactic-co-glycolic) acid microspheres that incorporates biochemical and structural features

  7. A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres.

    PubMed

    Wright, Bernice; Parmar, Nina; Bozec, Laurent; Aguayo, Sebastian D; Day, Richard M

    2015-08-01

    Poly (lactic-co-glycolic) acid microspheres are amenable to a number of biomedical procedures that support delivery of cells, drugs, peptides or genes. Hydrophilisation or wetting of poly (lactic-co-glycolic) acid are an important pre-requisites for attachment of cells and can be achieved via exposure to plasma oxygen or nitrogen, surface hydrolysis with NaOH or chloric acid, immersion in ethanol and water, or prolonged incubation in phosphate buffered saline or cell culture medium. The aim of this study is to develop a simple method for wetting poly (lactic-co-glycolic) acid microspheres for cell delivery applications. A one-step ethanol immersion process that involved addition of serum-supplemented medium and ethanol to PLGA microspheres over 30 min-24 h is described in the present study. This protocol presents a more efficient methodology than conventional two-step wetting procedures. Attachment of human skeletal myoblasts to poly (lactic-co-glycolic) acid microspheres was dependent on extent of wetting, changes in surface topography mediated by ethanol pre-wetting and serum protein adsorption. Ethanol, at 70% (v/v) and 100%, facilitated similar levels of wetting. Wetting with 35% (v/v) ethanol was only achieved after 24 h. Pre-wetting (over 3 h) with 70% (v/v) ethanol allowed significantly greater (p ≤ 0.01) serum protein adsorption to microspheres than wetting with 35% (v/v) ethanol. On serum protein-loaded microspheres, greater numbers of myoblasts attached to constructs wetted with 70% ethanol than those partially wetted with 35% (v/v) ethanol. Microspheres treated with 70% (v/v) ethanol presented a more rugose surface than those treated with 35% (v/v) ethanol, indicating that more efficient myoblast adhesion to the former may be at least partially attributed to differences in surface structure. We conclude that our novel protocol for pre-wetting poly (lactic-co-glycolic) acid microspheres that incorporates biochemical and structural features

  8. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR ETHYLENE GLYCOL AND ITS MAJOR METABOLITE, GLYCOLIC ACID, IN RATS AND HUMANS

    SciTech Connect

    Corley, Rick A.; Bartels, M J.; Carney, E W.; Weitz, Karl K.; Soelberg, Jolen J.; Gies, Richard A.; Thrall, Karla D.

    2005-05-19

    An extensive database on the toxicity and modes of action of the major industrial chemical, ethylene glycol (EG), has been developed over the past several decades. These studies have consistently identified the kidney as a primary target organ, with rats being more sensitive than mice and males more sensitive than females following chronic exposure. Renal toxicity has been associated with the terminal metabolite, oxalic acid which can precipitate with calcium to form crystals. EG also induces developmental toxicity, although these effects appear to require high-doses or accelerated dose-rates, and have been reported only in rats and mice. The developmental toxicity of EG has been attributed to the intermediate metabolite, glycolic acid (GA). The developmental toxicity of EG has been the subject of extensive research and regulatory review in recent years. Therefore, a physiologically based pharmacokinetic (PBPK) model was developed to integrate the extensive mode of action and pharmacokinetic data on EG and GA for use in developmental risk assessment. Metabolic rate constants and partition coefficients for EG and GA were estimated from in vitro studies. Other biochemical constants were optimized from appropriate in vivo pharmacokinetic studies. The resulting PBPK model includes inhalation, oral, dermal, intravenous and subcutaneous routes of administration. Metabolism of EG and GA were described in the liver with elimination via the kidneys. Several rat and human metabolism studies were used to validate the resulting PBPK model. Consistent with these studies, simulations indicated that the metabolism of EG to GA was essentially first-order (linear) up to 2500 mg/kg/day while the metabolism of GA saturated between bolus ethylene glycol doses of 200 and 1000 mg/kg/day. This saturation results in non-linear increases in blood GA concentrations, correlating with the developmental toxicity of EG. Pregnancy had no effect on maternal EG and GA kinetics over a broad dose

  9. Conjugates of unsaturated fatty acids with propylene glycol as potentially less-irritant skin penetration enhancers.

    PubMed

    Ben-Shabat, Shimon; Baruch, Nir; Sintov, Amnon C

    2007-11-01

    Fatty acids (FA) are well known as efficient enhancers for transdermal delivery of drugs; however, their frequent dermal toxicity limits their regular use. In order to utilize the fatty acid as a safe enhancer devoid of its irritant effect, we have synthesized and evaluated a series of fatty acids conjugated to propylene glycol (FA-PG). Each one of the conjugates was prepared as a mono- or di- acyl ester derivative. The effects of the synthetic enhancers on the porcine skin permeability were evaluated in a diffusion cell system using lidocaine as the model drug. In addition, in vivo examinations in rabbits were preformed for skin toxicological evaluation. The results indicate that among the FA-PG conjugates, oleic acid (C18:1(n-9))-PG, linoleic acid (C18:2(n-6))-PG and alpha-linolenic acid (C18:3(n-3))-PG, mono- or di-esters, enhance the penetration of lidocaine relatively to the vehicle (without enhancer). The conjugates of oleic acid (C18:1(n-9)) and linoleic acid (C18:2(n-6)) with PG have demonstrated a similar enhancing effect as the corresponding free fatty acids. Interestingly, although the mono- or the di- conjugates of alpha-linolenic acid (C18:3(n-3)) with PG enhanced the lidocaine flux as the other two fatty acid conjugates, they resulted in a reduced permeability as compared to the action of their free acid. In addition, the mono-conjugates of alpha-linolenic acid (C18:3(n-3)) with PG exhibited elevated skin irritation in rabbits (relative to the fatty acid alone) compared to the significantly reduced irritation of oleate-PG and linoeate-PG mono-conjugates. In conclusion, except saturated FA-PG and alpha-linolenic acid (C18:3(n-3)) - PG mono-conjugates, unsaturated fatty acids (e.g., oleic and linoleic acids) after conjugation to PG may be safe and effective enhancers for delivering topical drugs.

  10. Ferulic Acid-Based Polymers with Glycol Functionality as a Versatile Platform for Topical Applications.

    PubMed

    Ouimet, Michelle A; Faig, Jonathan J; Yu, Weiling; Uhrich, Kathryn E

    2015-09-14

    Ferulic acid-based polymers with aliphatic linkages have been previously synthesized via solution polymerization methods, yet they feature relatively slow ferulic acid release rates (∼11 months to 100% completion). To achieve a more rapid release rate as required in skin care formulations, ferulic acid-based polymers with ethylene glycol linkers were prepared to increase hydrophilicity and, in turn, increase ferulic acid release rates. The polymers were characterized using nuclear magnetic resonance and Fourier transform infrared spectroscopies to confirm chemical composition. The molecular weights, thermal properties (e.g., glass transition temperature), and contact angles were also obtained and the polymers compared. Polymer glass transition temperature was observed to decrease with increasing linker molecule length, whereas increasing oxygen content decreased polymer contact angle. The polymers' chemical structures and physical properties were shown to influence ferulic acid release rates and antioxidant activity. In all polymers, ferulic acid release was achieved with no bioactive decomposition. These polymers demonstrate the ability to strategically release ferulic acid at rates and concentrations relevant for topical applications such as skin care products. PMID:26258440

  11. Performance of AA5052 alloy anode in alkaline ethylene glycol electrolyte with dicarboxylic acids additives for aluminium-air batteries

    NASA Astrophysics Data System (ADS)

    Wang, DaPeng; Zhang, DaQuan; Lee, KangYong; Gao, LiXin

    2015-11-01

    Dicarboxylic acid compounds, i.e. succinic acid (SUA), adipic acid (ADA) and sebacic acid (SEA), are used as electrolyte additives in the alkaline ethylene glycol solution for AA5052 aluminium-air batteries. It shows that the addition of dicarboxylic acids lowers the hydrogen gas evolution rate of commercial AA5052 aluminium alloy anode. AA5052 aluminium alloy has wide potential window for electrochemical activity and better discharge performance in alkaline ethylene glycol solution containing dicarboxylic acid additives. ADA has the best inhibition effect for the self-corrosion of AA5052 anode among the three dicarboxylic acid additives. Fourier transform infrared spectroscopy (FT-IR) reveals that dicarboxylic acids and aluminium ions can form coordination complexes. Quantum chemical calculations shows that ADA has a smaller energy gap (ΔE, the energy difference between the lowest unoccupied orbital and the highest occupied orbital), indicating that ADA has the strongest interaction with aluminium ions.

  12. Culturing primary human osteoblasts on electrospun poly(lactic-co-glycolic acid) and poly(lactic-co-glycolic acid)/nanohydroxyapatite scaffolds for bone tissue engineering.

    PubMed

    Li, Mengmeng; Liu, Wenwen; Sun, Jiashu; Xianyu, Yunlei; Wang, Jidong; Zhang, Wei; Zheng, Wenfu; Huang, Deyong; Di, Shiyu; Long, Yun-Ze; Jiang, Xingyu

    2013-07-10

    In this work, we fabricated polymeric fibrous scaffolds for bone tissue engineering using primary human osteoblasts (HOB) as the model cell. By employing one simple approach, electrospinning, we produced poly(lactic-co-glycolic acid) (PLGA) scaffolds with different topographies including microspheres, beaded fibers, and uniform fibers, as well as the PLGA/nanohydroxyapatite (nano-HA) composite scaffold. The bone-bonding ability of electrospun scaffolds was investigated by using simulated body fluid (SBF) solution, and the nano-HA in PLGA/nano-HA composite scaffold can significantly enhance the formation of the bonelike apatites. Furthermore, we carried out in vitro experiments to test the performance of electrospun scaffolds by utilizing both mouse preosteoblast cell line (MC 3T3 E1) and HOB. Results including cell viability, alkaline phosphatase (ALP) activity, and osteocalcin concentration demonstrated that the PLGA/nano-HA fibers can promote the proliferation of HOB efficiently, indicating that it is a promising scaffold for human bone repair.

  13. Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

    PubMed

    Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

    2014-01-01

    Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

  14. Evaluation of Hanford high level waste vitrification chemistry for an NCAW simulant -- FY 1994: Potential exothermic reactions in the presence of formic acid, glycolic acid, and oxalic acid

    SciTech Connect

    Sills, J.A.

    1995-07-01

    A potential for an uncontrollable exothermic reaction between nitrate and organic salts during preparation of a high level waste melter feed has been identified. In order to examine this potential more closely, the thermal behavior of simulated neutralized current acid waste (NCAW) treated with various organic reductants was studied. Differential scanning calorimetry (DSC) measurements were collected on simulated waste samples and their supernates treated with organics. Organic reductants used were formic acid, glycolic acid, and oxalic acid. For comparison, samples of untreated simulant and untreated simulant with added noble metals were tested. When heated, untreated simulant samples both with and without noble metals showed no exothermic behavior. All of the treated waste simulant samples showed exothermic behavior. Onset temperatures of exothermic reactions were 120 C to 210 C. Many onset temperatures, particularly those for formic acid treated samples, are well below 181 C, the estimated maximum steam coil temperature (considered to be a worst case maximum temperature for chemical process tank contents). The enthalpies of the reactions were {minus}180 {times} 10{sup {minus}3} J/Kg supernate ({minus}181 J/g) for the oxalic acid treated simulant supernate to {minus}1,150 {times} 10{sup {minus}3} J/Kg supernate ({minus}1,153 J/g) for the formic acid treated simulant supernate.

  15. XPS and wettability characterization of modified poly(lactic acid) and poly(lactic/glycolic acid) films.

    PubMed

    Kiss, E; Bertóti, I; Vargha-Butler, E I

    2002-01-01

    Poly(lactic acid) (PLA) and poly(lactic/glycolic acid) copolymers (PLGA) are biodegradable drug carriers of great importance, although successful pharmaceutical application requires adjustment of the surface properties of the polymeric drug delivery system to be compatible with the biological environment. For that reason, reduction of the original hydrophobicity of the PLA or PLGA surfaces was performed by applying a hydrophilic polymer poly(ethylene oxide) (PEO) with the aim to improve biocompatibility of the original polymer. PEO-containing surfaces were prepared by incorporation of block copolymeric surfactants, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic), into the hydrophobic surface. Films of polymer blends from PLA or PLGA (with lactic/glycolic acid ratios of 75/25 and 50/50) and from Pluronics (PE6800, PE6400, and PE6100) were obtained by the solvent casting method, applying the Pluronics at different concentrations between 1 and 9.1% w/w. Wettability was measured to monitor the change in surface hydrophobicity, while X-ray photoelectron spectroscopy (XPS) was applied to determine the composition and chemical structure of the polymer surface and its change with surface modification. Substantial reduction of surface hydrophobicity was achieved on both the PLA homopolymer and the PLGA copolymers by applying the Pluronics at various concentrations. In accordance with the wettability changes the accumulation of Pluronics in the surface layer was greatly affected by the initial hydrophobicity of the polymer, namely, by the lactide content of the copolymer. The extent of surface modification was also found to be dependent on the type of blended Pluronics. Surface activity of the modifying Pluronic component was interpreted by using the solubility parameters. PMID:16290340

  16. Thermal destruction of copolymers of polypropylene glycol maleate with acrylic acid

    NASA Astrophysics Data System (ADS)

    Burkeev, M. Zh.; Sarsenbekova, A. Zh.; Tazhbaev, E. M.; Figurinene, I. V.

    2015-12-01

    The results from thermogravimetric and kinetic studies of copolymers of polypropylene glycol maleate with acrylic acid at different molar ratios are presented. The results from conventional thermogravimetric studies are used to determine kinetic characteristics of the process of thermal decomposition, i.e., activation energy and pre-exponential factors. These parameters are determined in three ways: the Achar, Freeman-Carroll, and Sharp-Wentworth methods. Activation energies calculated using all the three methods confirm the dependence of the destruction process on the ratio of components in a synthesized copolymer. It is shown that the obtained values of the activation energies and thermodynamic characteristics allow us to predict a copolymer's composition.

  17. The Path of Carbon in Photosynthesis XI. The Role of Glycolic Acid

    DOE R&D Accomplishments Database

    Schou, L.; Benson, A. A.; Bassham, J. A.; Calvin, M.

    1950-09-11

    The metabolism of C{sup 14} labeled glycolic acid by Scenedesmus has been studied using radiochromatographic techniques for the separation and identification of products. When the pH of the medium was 2.8, appreciable assimilation occurred. The products were identical to those observed in C{sup 14}O{sub 2} photosynthesis. A major reaction anaerobically in the dark resulted in incorporation of C{sup 14} in almost equal amounts in the glycine and serine reservoirs. When the algae were illuminated, a diminution in the amount of glycine was observed.

  18. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

    PubMed Central

    Makadia, Hirenkumar K.; Siegel, Steven J.

    2011-01-01

    In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release. PMID:22577513

  19. 40 CFR 721.10505 - Phosphoric acid, mixed mono- and diesters with 2-ethyl-1-hexanol and polyethylene glycol mono-C12...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphoric acid, mixed mono- and... Phosphoric acid, mixed mono- and diesters with 2-ethyl-1-hexanol and polyethylene glycol mono-C12-16-alkyl... identified as phosphoric acid, mixed mono- and diesters with 2-ethyl-1-hexanol and polyethylene glycol...

  20. 40 CFR 721.10505 - Phosphoric acid, mixed mono- and diesters with 2-ethyl-1-hexanol and polyethylene glycol mono-C12...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphoric acid, mixed mono- and... Phosphoric acid, mixed mono- and diesters with 2-ethyl-1-hexanol and polyethylene glycol mono-C12-16-alkyl... identified as phosphoric acid, mixed mono- and diesters with 2-ethyl-1-hexanol and polyethylene glycol...

  1. The Effects of Topically Applied Glycolic Acid and Salicylic Acid on Ultraviolet Radiation-Induced Erythema, DNA Damage and Sunburn Cell Formation in Human Skin

    PubMed Central

    Kornhauser, Andrija; Wei, Rong-Rong; Yamaguchi, Yuji; Coelho, Sergio G.; Kaidbey, Kays; Barton, Curtis; Takahashi, Kaoruko; Beer, Janusz Z.; Miller, Sharon A.; Hearing, Vincent J.

    2009-01-01

    Background α-Hydroxy acids (αHA) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that αHA can increase the sensitivity of skin to ultraviolet radiation. More recently, β-hydroxy acids (βHA), or combinations of αHA and βHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing β-HA. Objective To determine whether topical treatment with glycolic acid, a representative αHA, or with salicylic acid, a βHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. Methods Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday - Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all 4 sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Results Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Conclusions Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not. PMID:19411163

  2. Interfacial Fast Release Layer in Monodisperse Poly (lactic-co-glycolic acid) Microspheres Accelerates the Drug Release.

    PubMed

    Wu, Jun; Zhao, Xiaoli; Yeung, Kelvin W K; To, Michael K T

    2016-01-01

    Understanding microstructural evolutions of drug delivery devices during drug release process is essential for revealing the drug release mechanisms and controlling the drug release profiles. In this study, monodisperse poly (lactic-co-glycolic acid) microspheres in different diameters were fabricated by microfluidics in order to find out the relationships between the microstructural evolutions and the drug release profiles. It was found that poly (lactic-co-glycolic acid) microspheres underwent significant size expansion which took place from the periphery to the center, resulting in the formation of interfacial fast release layers. At the same time, inner pores were created and the diffusion rate was increased so that the early stage drug release was accelerated. Due to the different expansion rates, small poly (lactic-co-glycolic acid) microspheres tendered to follow homogeneous drug release while large poly (lactic-co-glycolic acid) microspheres tendered to follow heterogeneous drug release. This study suggests that the size expansion and the occurrence of interfacial fast release layer were important mechanisms for early stage drug release of poly (lactic-co-glycolic acid) microspheres.

  3. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    PubMed Central

    Zhao, Qun; Li, Zhi-yue; Zhang, Ze-peng; Mo, Zhou-yun; Chen, Shi-jie; Xiang, Si-yu; Zhang, Qing-shan; Xue, Min

    2015-01-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury. PMID:26604912

  4. Interaction between bovine collagen and glycolic acid peeling: a proposal of a new protocol.

    PubMed

    Sito, G; Sorrentino, L

    1996-01-01

    For the past 10 years the alfa-hydroxyacids and the bovine collagen injection have been used for peeling and the correction of multiple skin diseases. Until now, such progressive achievement has occurred in separate parallels just like the indications that have been held distinct. However, the studies carried out in order to clarify the mechanical action of the two substances have shown a common and fundamental denominator: the stimulation of synthesis of the new collagen in the patient's skin. On the basis of these results and the existence of common clinical indications of the use of glycolic acid and collagen, the authors have worked out a protocol involving a combined and contemporary application in progressive steps. They developed the rationales of such protocol and analyzed the results of its application on a number of carefully selected patients for a clinical comparison and on a sample of rats for a histological comparison. They have concluded that the contemporary use of glycolic acid and bovine collagen is a simple and safe method whose synergy action leads to more intense and long-lasting effects than the ones observed in the isolated application of the two substances. The authors have also obtained interesting and significant histological results.

  5. Cross-linked polystyrene sulfonic acid and polyethylene glycol as a low-fouling material.

    PubMed

    Alghunaim, Abdullah; Zhang Newby, Bi-min

    2016-04-01

    A negatively charged hydrophilic low fouling film was prepared by thermally cross-linking a blend consisting of polystyrene sulfonic acid (PSS) and polyethylene glycol (PEG). The film was found to be stable by dip-washing. The fouling resistance of this material toward bacterial (Escherichia coli) and colloidal (polystyrene particles) attachment, non-specific protein (fibronectin) adsorption and cell (3T3 NIH) adhesion was evaluated and was compared with glass slides modified with polyethylene glycol (PEG) brushes, oxidized 3-mercaptopropyltrimethoxysilane (sulfonic acid, SA), and n-octadecyltrichlorosilane (OTS). The extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory and thermodynamic models based on surface energy were used to explain the interaction behaviors of E. coli/polystyrene particles-substrate and protein-substrate interactions, respectively. The cross-linked PSS-PEG film was found to be slightly better than SA and PEG toward resisting non-specific protein adsorption, and showed comparable low attachment results as those of PEG toward particle, bacterial and NIH-3T3 cells adhesion. The low-fouling performance of PSS-PEG, a cross-linked film by a simple thermal curing process, could allow this material to be used for applications in aqueous environments, where most low fouling hydrophilic polymers, such as PSS or PEG, could not be easily retained.

  6. Glycolic acid-catalyzed deamidation of asparagine residues in degrading PLGA matrices: a computational study.

    PubMed

    Manabe, Noriyoshi; Kirikoshi, Ryota; Takahashi, Ohgi

    2015-03-31

    Poly(lactic-co-glycolic acid) (PLGA) is a strong candidate for being a drug carrier in drug delivery systems because of its biocompatibility and biodegradability. However, in degrading PLGA matrices, the encapsulated peptide and protein drugs can undergo various degradation reactions, including deamidation at asparagine (Asn) residues to give a succinimide species, which may affect their potency and/or safety. Here, we show computationally that glycolic acid (GA) in its undissociated form, which can exist in high concentration in degrading PLGA matrices, can catalyze the succinimide formation from Asn residues by acting as a proton-transfer mediator. A two-step mechanism was studied by quantum-chemical calculations using Ace-Asn-Nme (Ace = acetyl, Nme = NHCH3) as a model compound. The first step is cyclization (intramolecular addition) to form a tetrahedral intermediate, and the second step is elimination of ammonia from the intermediate. Both steps involve an extensive bond reorganization mediated by a GA molecule, and the first step was predicted to be rate-determining. The present findings are expected to be useful in the design of more effective and safe PLGA devices.

  7. Disposition of glycolic acid into rat and rabbit embryos in vitro.

    PubMed

    Ellis-Hutchings, Robert G; Moore, Nigel P; Marshall, Valerie A; Rasoulpour, Reza J; Carney, Edward W

    2014-07-01

    High dose gavage administration of ethylene glycol (EG) induces teratogenicity in rodents, but not in rabbits, resulting from saturation of intermediate EG metabolism and glycolic acid (GA) accumulation. In vivo, rat embryos sequester GA 2-4-fold higher than maternal blood, a phenomenon absent in rabbits and proposed not to occur in humans. This research explored the mechanisms of GA disposition into rat and rabbit conceptuses using whole embryo culture (WEC). Rat and rabbit embryos concentrated GA from the culture medium. In vitro to in vivo discordance in the rabbit plausibly stemmed from anatomical differences between these models. GA sequestration was attenuated at 4°C in both species. Rat embryos further demonstrated pH-dependence of GA sequestration and inhibition by D-lactic acid. These data suggest GA disposition into rat and rabbit embryos is energy- and pH-dependent, and carrier-mediated. Anatomical and maternal-to-conceptal pH gradient differences likely underlie the lack of enhanced GA disposition in non-rodent species.

  8. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury.

    PubMed

    Zhao, Qun; Li, Zhi-Yue; Zhang, Ze-Peng; Mo, Zhou-Yun; Chen, Shi-Jie; Xiang, Si-Yu; Zhang, Qing-Shan; Xue, Min

    2015-09-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  9. GLYCOLIC-NITRIC ACID FLOWSHEET DEMONSTRATION OF THE DWPF CHEMICAL PROCESSING CELL WITH MATRIX SIMULANTS AND SUPERNATE

    SciTech Connect

    Lambert, D.; Stone, M.; Newell, J.; Best, D.

    2012-05-07

    Savannah River Remediation (SRR) is evaluating changes to its current DWPF flowsheet to improve processing cycle times. This will enable the facility to support higher canister production while maximizing waste loading. Higher throughput is needed in the CPC since the installation of the bubblers into the melter has increased melt rate. Due to the significant maintenance required for the DWPF gas chromatographs (GC) and the potential for production of flammable quantities of hydrogen, reducing or eliminating the amount of formic acid used in the CPC is being developed. Earlier work at Savannah River National Laboratory has shown that replacing formic acid with an 80:20 molar blend of glycolic and formic acids has the potential to remove mercury in the SRAT without any significant catalytic hydrogen generation. This report summarizes the research completed to determine the feasibility of processing without formic acid. In earlier development of the glycolic-formic acid flowsheet, one run (GF8) was completed without formic acid. It is of particular interest that mercury was successfully removed in GF8, no formic acid at 125% stoichiometry. Glycolic acid did not show the ability to reduce mercury to elemental mercury in initial screening studies, which is why previous testing focused on using the formic/glycolic blend. The objective of the testing detailed in this document is to determine the viability of the nitric-glycolic acid flowsheet in processing sludge over a wide compositional range as requested by DWPF. This work was performed under the guidance of Task Technical and Quality Assurance Plan (TT and QAP). The details regarding the simulant preparation and analysis have been documented previously.

  10. GLYCOLIC-NITRIC ACID FLOWSHEET DEMONSTRATION OF THE DWPF CHEMICAL PROCESS CELL WITH SLUDGE AND SUPERNATE SIMULANTS

    SciTech Connect

    Lambert, D.; Stone, M.; Newell, J.; Best, D.; Zamecnik, J.

    2012-08-28

    Savannah River Remediation (SRR) is evaluating changes to its current Defense Waste Processing Facility (DWPF) flowsheet to improve processing cycle times. This will enable the facility to support higher canister production while maximizing waste loading. Higher throughput is needed in the Chemical Process Cell (CPC) since the installation of the bubblers into the melter has increased melt rate. Due to the significant maintenance required for the DWPF gas chromatographs (GC) and the potential for production of flammable quantities of hydrogen, reducing or eliminating the amount of formic acid used in the CPC is being developed. Earlier work at Savannah River National Laboratory has shown that replacing formic acid with an 80:20 molar blend of glycolic and formic acids has the potential to remove mercury in the SRAT without any significant catalytic hydrogen generation. This report summarizes the research completed to determine the feasibility of processing without formic acid. In earlier development of the glycolic-formic acid flowsheet, one run (GF8) was completed without formic acid. It is of particular interest that mercury was successfully removed in GF8, no formic acid at 125% stoichiometry. Glycolic acid did not show the ability to reduce mercury to elemental mercury in initial screening studies, which is why previous testing focused on using the formic/glycolic blend. The objective of the testing detailed in this document is to determine the viability of the nitric-glycolic acid flowsheet in processing sludge over a wide compositional range as requested by DWPF. This work was performed under the guidance of Task Technical and Quality Assurance Plan (TT&QAP). The details regarding the simulant preparation and analysis have been documented previously.

  11. Characterization of perivascular poly(lactic-co-glycolic acid) films containing paclitaxel.

    PubMed

    Jackson, John K; Smith, Janet; Letchford, Kevin; Babiuk, Kelly Anne; Machan, Lindsay; Signore, Pierre; Hunter, William L; Wang, Kaiyue; Burt, Helen M

    2004-09-28

    The objectives of this study were to investigate the use of poly(lactic-co-glycolic acid) (PLGA) for the formulation of paclitaxel loaded films and to characterize these films for potential application as perivascular "wraps" to prevent restenosis. Films were manufactured from PLGA blended with either methoxypolyethylene glycol (MePEG) or a diblock copolymer composed of poly(D,L-lactic acid)-block-methoxypolyethylene glycol, PDLLA-MePEG (diblock) by solvent evaporation on teflon discs. Elasticity was determined by gravimetric stress/strain analysis. Thermal analysis was determined using differential scanning calorimetry (DSC). Changes in film composition and degradation in aqueous media were determined using gel permeation chromatography (GPC). Paclitaxel release from films was measured by incubation of the films in phosphate buffered saline (PBS) with drug analysis by HPLC methods. The addition of MePEG or diblock to PLGA caused a concentration dependent increase in the elasticity of films, due to plasticizing effects. DSC analysis showed that MePEG and diblock caused a concentration dependent decrease in the glass transition temperature (Tg) of PLGA indicating miscibility of the polymers. When placed in aqueous media, more than 75% of MePEG dissolved out of the PLGA films within 2 days, whereas diblock partitioned slowly and in a controlled manner out of the films. Paclitaxel release from PLGA/MePEG films was very slow with less than 5% of the encapsulated drug being released over 2 weeks. The addition of 30% diblock to paclitaxel loaded PLGA films caused a substantial increase (five- to eight-fold) in the release rate of paclitaxel. PLGA films containing 30% diblock and either 1% or 5% paclitaxel were partially or completely degraded following perivascular implantation in rats. PMID:15363506

  12. Poly(L-lactic acid)/poly(glycolic acid) microfibrillar polymer-polymer composites: Preparation and viscoelastic properties

    NASA Astrophysics Data System (ADS)

    Kimble, L. D.; Fakirov, S.; Bhattacharyya, D.

    2015-05-01

    Microfibrillar composites (MFCs) from petrochemical-derived polymers have been investigated for several years and the technique can result in significant improvements in mechanical properties when compared with the neat matrix material of the respective composite. The current work applies the technique to biodegradable, biocompatible polymers for potential applications in bioabsorbable medical devices. MFCs were prepared from melt blended poly(L-lactic acid) (PLLA) and poly(glycolic acid) (PGA) via cold drawing then compression molding of extruded yarn. These MFCs were shown to have higher Young's moduli than that of neat PLLA but for load-bearing applications the creep characteristics are of interest. The MFC sheets resulting from compression molding were subjected to tensile relaxation tests at 37°C in the fiber orientation direction. Specimens were also tested via dynamic mechanical thermal analysis (DMTA). Neat PLLA specimens were subjected to the same tests for comparison. Results indicate that at 37°C PLLA/PGA MFCs exhibit lower creep resistance than that of neat PLLA due to the more rapid relaxation of stress observed. DMTA results elucidate the loss modulus changes in PLLA/PGA MFCs which occur as the material approaches the glass transition temperature of PGA (˜45°C).

  13. Wetting of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams for tissue culture.

    PubMed

    Mikos, A G; Lyman, M D; Freed, L E; Langer, R

    1994-01-01

    Biodegradable foams of hydrophobic polymers can be efficiently wet by two-step immersion in ethanol and water, which overcomes the hindered entry of water into air-filled pores. Ethanol readily enters into the porous polymer, after which it is diluted and replaced by water. This method was evaluated for porous disks of poly(L-lactic acid) (PLLA) and poly(DL-lactic-co-glycolic acid) (PLGA) foams of copolymer ratios 85:15 and 50:50. For PLLA disks of 0.88 porosity and 1730 microns thickness, prewetting with ethanol for 1 h increased the percentage of void volume filled with water after 48 h from 23 to 79%. The same enhanced entry of water was also observed for prewet PLGA 85:15 disks of 0.86 porosity and 1300 microns thickness, which exhibited an increase from 59 to 97% void volume occupied by water. Furthermore, the water entry even after 1 h was very close to its plateau value for all prewet polymers tested. In recent studies, this method has been useful in uniformly seeding three-dimensional biodegradable polymer substrates for cell and tissue culture.

  14. Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

    SciTech Connect

    Corley, R.A.; Saghir, S.A.; Bartels, M.J.; Hansen, S.C.; Creim, J.; McMartin, K.E.; Snellings, W.M.

    2011-02-01

    A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrations exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.

  15. Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.

    PubMed

    Jiang, Tao; Khan, Yusuf; Nair, Lakshmi S; Abdel-Fattah, Wafa I; Laurencin, Cato T

    2010-06-01

    Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications. PMID:19777575

  16. Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin.

    PubMed

    Pradhan, Roshan; Ramasamy, Thiruganesh; Choi, Ju Yeon; Kim, Jeong Hwan; Poudel, Bijay Kumar; Tak, Jin Wook; Nukolova, Natalia; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2015-06-01

    Multiple-drug combination therapy is becoming more common in the treatment of advanced cancers because this approach can decrease side effects and delay or prevent drug resistance. In the present study, we developed hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGA NPs) for co-delivery of docetaxel (DTX) and tanespimycin (17-AAG). DTX and 17-AAG were simultaneously loaded into HA-PLGA NPs using an oil-in-water emulsification/solvent evaporation method. Several formulations were tested. HA-PLGA NPs loaded with DTX and 17-AAG at a molar ratio of 2:1 produced the smallest particle size (173.3±2.2nm), polydispersity index (0.151±0.026), and zeta potential (-12.4±0.4mV). Approximately 60% and 40% of DTX and 17-AAG, respectively, were released over 168h in vitro. Cytotoxicity assays performed in vitro using MCF-7, MDA-MB-231, and SCC-7 cells showed that dual drug-loaded HA-PLGA NPs at a DTX:17-AAG molar ratio of 2:1 exhibited the highest synergistic effect, with combination index values of 0.051, 0.036, and 0.032, respectively, at the median effective dose. Furthermore, synergistic antitumor activity was demonstrated in vivo in a CD44 and RHAMM (CD168) - overexpressing squamous cell carcinoma (SCC-7) xenograft in nude mice. These findings indicated that nanosystem-based co-delivery of DTX and 17-AAG could provide a promising combined therapeutic strategy for enhanced antitumor therapy.

  17. Biodegradability of poly(lactic-co-glycolic acid) after femtosecond laser irradiation

    NASA Astrophysics Data System (ADS)

    Shibata, Akimichi; Yada, Shuhei; Terakawa, Mitsuhiro

    2016-06-01

    Biodegradation is a key property for biodegradable polymer-based tissue scaffolds because it can provide suitable space for cell growth as well as tailored sustainability depending on their role. Ultrashort pulsed lasers have been widely used for the precise processing of optically transparent materials, including biodegradable polymers. Here, we demonstrated the change in the biodegradation of a poly(lactic-co-glycolic acid) (PLGA) following irradiation with femtosecond laser pulses at different wavelengths. Microscopic observation as well as water absorption and mass change measurement revealed that the biodegradation of the PLGA varied significantly depending on the laser wavelength. There was a significant acceleration of the degradation rate upon 400 nm-laser irradiation, whereas 800 nm-laser irradiation did not induce a comparable degree of change. The X-ray photoelectron spectroscopy analysis indicated that laser pulses at the shorter wavelength dissociated the chemical bonds effectively, resulting in a higher degradation rate at an early stage of degradation.

  18. Poly(acrylic acid)-poly(ethylene glycol) nanoparticles designed for ophthalmic drug delivery.

    PubMed

    Vasi, Ana-Maria; Popa, Marcel Ionel; Tanase, Edi Constantin; Butnaru, Maria; Verestiuc, Liliana

    2014-02-01

    Poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG), four-arm, amine-terminated particles with nanometer size and spherical shape were obtained by the polymers cross-linking, via activation with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride, in a w/o emulsion. The morphology and surface charge of the final particles are strongly dependent on the molar ratio of PAA-PEG and the PAA concentration. The physicochemical characteristics correlated with the drug-loading capacity, in vitro and ex vivo release kinetics of pilocarpine hydrochloride and biocompatibility results indicate that these nanoparticles exhibit the prerequisite behavior for use as carriers of ophthalmic drugs. PMID:24357331

  19. Poly(lactic acid) / Poly(ethylene glycol) blends: Mechanical, thermal and morphological properties

    NASA Astrophysics Data System (ADS)

    Bijarimi, M.; Ahmad, S.; Rasid, R.; Khushairi, M. A.; Zakir, M.

    2016-04-01

    The poly(lactic acid) (PLA) was melt blended with linear polyethylene glycol (PEG) in an effort to increase the toughness of PLA. Melt blending was carried out in an internal mixer at 180 °C mixing temperature with 50 rpm for 15 minutes. The blends were characterized in terms of mechanical, thermal and morphological properties. It was found that tensile and flexural strength, stiffness and notched Izod impact strength decreased significantly when the PEG was added to the PLA matrix at 2.5-10% of PEG concentrations. Both glass transition and melting temperatures (Tg and Tm) lowered as the concentration of PEG was increased. Moreover, it was noted that the PLA/PEG blends showed a lower onset and peak degradation temperatures but with lower final degradation temperature as compared to the neat PLA. The morphological analysis revealed that the PEG was dispersed as droplets in the PLA matrix with a clear boundary between PLA matrix and PEG phases.

  20. In Vivo Evaluation of Ibuprofen-Loaded Poly(lactic-co-glycolic) Acid Nanoparticles in Rats

    NASA Astrophysics Data System (ADS)

    Abidin, Suhaili Zainal; Sameni, Javad; Julianto, Tommy; Bukhari, Nadeem Irfan

    2009-06-01

    The aim of our studies was to formulate a nanoparticulate system that delivers the required dose of ibuprofen to the blood serum. The poly (lactic-co-glycolic acid, 50:50) nanoparticles were fabricated using emulsion solvent evaporation technique for the encapsulation of Ibuprofen. After oral administration of Ibuprofen-loaded nanoparticles in rats, drug concentration in blood serum was detected using HPLC. Drug loading and drug entrapment efficiency was detected with different drug loading. The results indicated that drug loading and drug entrapment were increased with increasing drug/PLGA ratio. The concentration profiles of ibuprofen released from nanoparticles indicated that the burst effect was reduced with a sustain drug release after administration. SEM images show the spherical shape and smooth surface of nanoparticles, with low PDI. In conclusion, our studies showed the significant increases in release time of optimum drug loading with a sustain drug release using ibuprofen/PLGA nanoparticles.

  1. Inkjet deposition of itraconazole onto poly(glycolic acid) microneedle arrays.

    PubMed

    Boehm, Ryan D; Jaipan, Panupong; Skoog, Shelby A; Stafslien, Shane; VanderWal, Lyndsi; Narayan, Roger J

    2016-03-11

    Poly(glycolic acid) microneedle arrays were fabricated using a drawing lithography process; these arrays were modified with a drug release agent and an antifungal agent by piezoelectric inkjet printing. Coatings containing poly(methyl vinyl ether-co-maleic anhydride), a water-soluble drug release layer, and itraconazole (an antifungal agent), were applied to the microneedles by piezoelectric inkjet printing. Microscopic evaluation of the microneedles indicated that the modified microneedles contained the piezoelectric inkjet printing-deposited agents and that the surface coatings were released in porcine skin. Energy dispersive x-ray spectrometry aided in confirmation that the piezoelectric inkjet printing-deposited agents were successfully applied to the desired target areas of the microneedle surface. Fourier transform infrared spectroscopy was used to confirm the presence of the component materials in the piezoelectric inkjet printing-deposited material. Itraconazole-modified microneedle arrays incubated with agar plates containing Candida albicans cultures showed zones of growth inhibition.

  2. Preparation and investigation of mefenamic acid - polyethylene glycol - sucrose ester solid dispersions.

    PubMed

    Fülöp, Ibolya; Gyéresi, Árpád; Kiss, Lóránd; Deli, Mária A; Croitoru, Mircea Dumitru; Szabó-Révész, Piroska; Aigner, Zoltán

    2015-12-01

    Mefenamic acid (MA) is a widely used non-steroidal antiinflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives.

  3. Inkjet deposition of itraconazole onto poly(glycolic acid) microneedle arrays.

    PubMed

    Boehm, Ryan D; Jaipan, Panupong; Skoog, Shelby A; Stafslien, Shane; VanderWal, Lyndsi; Narayan, Roger J

    2016-03-01

    Poly(glycolic acid) microneedle arrays were fabricated using a drawing lithography process; these arrays were modified with a drug release agent and an antifungal agent by piezoelectric inkjet printing. Coatings containing poly(methyl vinyl ether-co-maleic anhydride), a water-soluble drug release layer, and itraconazole (an antifungal agent), were applied to the microneedles by piezoelectric inkjet printing. Microscopic evaluation of the microneedles indicated that the modified microneedles contained the piezoelectric inkjet printing-deposited agents and that the surface coatings were released in porcine skin. Energy dispersive x-ray spectrometry aided in confirmation that the piezoelectric inkjet printing-deposited agents were successfully applied to the desired target areas of the microneedle surface. Fourier transform infrared spectroscopy was used to confirm the presence of the component materials in the piezoelectric inkjet printing-deposited material. Itraconazole-modified microneedle arrays incubated with agar plates containing Candida albicans cultures showed zones of growth inhibition. PMID:26869165

  4. Preparation of spherical macroporous poly(lactic-co-glycolic acid) for bone tissue regeneration.

    PubMed

    Bian, Chunhui; Lin, Huiming; Li, Xiaofeng; Ma, Jie; Jiang, Pingping; Qu, Fengyu

    2015-02-01

    Spherical macroporous poly(lactic-co-glycolic acid) (PLGA) has been synthesised using an emulsion method. Polyvinyl alcohol and Pluronic F127 have been used as dispersing and porogen agent, respectively. The diameter of the spherical PLGA is about 20 μm and the pore size of the PLGA macroporous is about 2-2.5 μm observed by scanning electron microscopy. After immersing in simulated body fluid, the PLGA materials can induce the formation of hydroxyapatite (HAP) on their surface. The HAP-PLGA has been obtained and used as the host for drug release. Furthermore, the drug-loaded samples possess the various drug release performance by adjusting the thickness of the HAP layer. This highly satisfied composite material is expected to be promising in the applications in tissue regeneration engineering.

  5. Catalytic biofilms on structured packing for the production of glycolic acid.

    PubMed

    Li, Xuan Zhong; Hauer, Bernhard; Rosche, Bettina

    2013-02-01

    While structured packing modules are known to be efficient for surface wetting and gas-liquid exchange in abiotic surface catalysis, this model study explores structured packing as a growth surface for catalytic biofilms. Microbial biofilms have been proposed as self-immobilized and self-regenerating catalysts for the production of chemicals. A concern is that the complex and dynamic nature of biofilms may cause fluctuations in their catalytic performance over time or may affect process reproducibility. An aerated continuous trickle-bed biofilm reactor system was designed with a 3 L structured packing, liquid recycling and pH control. Pseudomonas diminuta established a biofilm on the stainless steel structured packing with a specific surface area of 500 m2 m-3 and catalyzed the oxidation of ethylene glycol to glycolic acid for over two months of continuous operation. A steady-state productivity of up to 1.6 gl-1h-1 was achieved at a dilution rate of 0.33 h-1. Process reproducibility between three independent runs was excellent, despite process interruptions and activity variations in cultures grown from biofilm effluent cells. The results demonstrate the robustness of a catalytic biofilm on structured packing, despite its dynamic nature. Implementation is recommended for whole-cell processes that require efficient gas-liquid exchange, catalyst retention for continuous operation, or improved catalyst stability. PMID:23412062

  6. Polypropylene Glycol-Silver Nanoparticle Composites: A Novel Anticorrosion Material for Aluminum in Acid Medium

    NASA Astrophysics Data System (ADS)

    Solomon, Moses M.; Umoren, Saviour A.; Israel, Aniekemeabasi U.; Ebenso, Eno E.

    2015-11-01

    Admixture of polypropylene glycol and 1 mM AgNO3 together with natural honey as reducing and stabilizing agent was employed to prepare in situ polypropylene glycol/silver nanoparticle (PPG/AgNPs) composite. The prepared PPG/AgNPs composite was characterized by UV-Vis spectroscopy, FTIR, XRD, and EDS, while the morphology of the Ag nanoparticles in the composite was obtained by TEM. TEM results revealed that the Ag nanoparticles were spherical in shape. The anticorrosion property of PPG/AgNPs composite was examined by electrochemical, weight loss, SEM, EDS, and water contact angle measurements. Results obtained show that PPG/AgNPs are effective in retarding the dissolution of Al in an acid-induced corrosive environment. Inhibition efficiency increased with the increasing composite concentration but decreased with the increasing temperature. Potentiodynamic polarization results revealed that PPG/AgNPs functions as a mixed-type corrosion inhibitor. The adsorption of the composite onto Al surface was found to follow El-Awady et al. adsorption isotherm model. SEM, EDS, and water contact angle results confirmed the adsorption of PPG/AgNPs films onto Al surface.

  7. Antimicrobial biomaterials based on carbon nanotubes dispersed in poly(lactic-co-glycolic acid)

    NASA Astrophysics Data System (ADS)

    Aslan, Seyma; Loebick, Codruta Zoican; Kang, Seoktae; Elimelech, Menachem; Pfefferle, Lisa D.; van Tassel, Paul R.

    2010-09-01

    Biomaterials that inactivate microbes are needed to eliminate medical device infections. We investigate here the antimicrobial nature of single-walled carbon nanotubes (SWNTs) incorporated within the biomedical polymer poly(lactic-co-glycolic acid) (PLGA). We find Escherichia coli and Staphylococcus epidermidis viability and metabolic activity to be significantly diminished in the presence of SWNT-PLGA, and to correlate with SWNT length and concentration (<2% by weight). Up to 98% of bacteria die within one hour on SWNT-PLGA versus 15-20% on pure PLGA. Shorter SWNTs are more toxic, possibly due to increased density of open tube ends. This study demonstrates the potential usefulness of SWNT-PLGA as an antimicrobial biomaterial.Biomaterials that inactivate microbes are needed to eliminate medical device infections. We investigate here the antimicrobial nature of single-walled carbon nanotubes (SWNTs) incorporated within the biomedical polymer poly(lactic-co-glycolic acid) (PLGA). We find Escherichia coli and Staphylococcus epidermidis viability and metabolic activity to be significantly diminished in the presence of SWNT-PLGA, and to correlate with SWNT length and concentration (<2% by weight). Up to 98% of bacteria die within one hour on SWNT-PLGA versus 15-20% on pure PLGA. Shorter SWNTs are more toxic, possibly due to increased density of open tube ends. This study demonstrates the potential usefulness of SWNT-PLGA as an antimicrobial biomaterial. Electronic supplementary information (ESI) available: Raman spectra before and after SWNT cutting via cyclodextrins, and sample images from viability and metabolic activity assays are included. See DOI: 10.1039/c0nr00329h

  8. Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles.

    PubMed

    Pandey, Sanjeev K; Patel, Dinesh K; Maurya, Akhilendra K; Thakur, Ravi; Mishra, Durga P; Vinayak, Manjula; Haldar, Chandana; Maiti, Pralay

    2016-08-01

    Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton's lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17-30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer. PMID:27112980

  9. Effects of material thickness and processing method on poly(lactic-co-glycolic acid) degradation and mechanical performance.

    PubMed

    Shirazi, Reyhaneh Neghabat; Aldabbagh, Fawaz; Ronan, William; Erxleben, Andrea; Rochev, Yury; McHugh, Peter

    2016-10-01

    In this study, the effects of material thickness and processing method on the degradation rate and the changes in the mechanical properties of poly(lactic-co-glycolic acid) material during simulated physiological degradation were investigated. Two types of poly(lactic-co-glycolic acid) materials were considered: 0.12 mm solvent-cast films and 1 mm compression-moulded plates. The experimental results presented in this study were compared to the experimental results of Shirazi et al. (Acta Biomaterialia 10(11):4695-703, 2014) for 0.25 mm solvent-cast films. These experimental observations were used to validate the computational modelling predictions of Shirazi et al. (J Mech Behav Biomed Mater 54: 48-59, 2016) on critical diffusion length scale and also to refine the model parameters. The specific material processing methods considered here did not have a significant effect on the degradation rate and the changes in mechanical properties during degradation; however, they influenced the initial molecular weight and they determined the stiffness and hardness of the poly(lactic-co-glycolic acid) material. The experimental observations strongly supported the computational modelling predictions that showed no significant difference in the degradation rate and the changes in the elastic modulus of poly(lactic-co-glycolic acid) films for thicknesses larger than 100 μm.

  10. Effects of material thickness and processing method on poly(lactic-co-glycolic acid) degradation and mechanical performance.

    PubMed

    Shirazi, Reyhaneh Neghabat; Aldabbagh, Fawaz; Ronan, William; Erxleben, Andrea; Rochev, Yury; McHugh, Peter

    2016-10-01

    In this study, the effects of material thickness and processing method on the degradation rate and the changes in the mechanical properties of poly(lactic-co-glycolic acid) material during simulated physiological degradation were investigated. Two types of poly(lactic-co-glycolic acid) materials were considered: 0.12 mm solvent-cast films and 1 mm compression-moulded plates. The experimental results presented in this study were compared to the experimental results of Shirazi et al. (Acta Biomaterialia 10(11):4695-703, 2014) for 0.25 mm solvent-cast films. These experimental observations were used to validate the computational modelling predictions of Shirazi et al. (J Mech Behav Biomed Mater 54: 48-59, 2016) on critical diffusion length scale and also to refine the model parameters. The specific material processing methods considered here did not have a significant effect on the degradation rate and the changes in mechanical properties during degradation; however, they influenced the initial molecular weight and they determined the stiffness and hardness of the poly(lactic-co-glycolic acid) material. The experimental observations strongly supported the computational modelling predictions that showed no significant difference in the degradation rate and the changes in the elastic modulus of poly(lactic-co-glycolic acid) films for thicknesses larger than 100 μm. PMID:27590824

  11. Time Dependence of Material Properties of Polyethylene Glycol Hydrogels Chain Extended with Short Hydroxy Acid Segments

    PubMed Central

    Barati, Danial; Moeinzadeh, Seyedsina; Karaman, Ozan; Jabbari, Esmaiel

    2014-01-01

    The objective of this work was to investigate the effect of chemical composition and segment number (n) on gelation, stiffness, and degradation of hydroxy acid-chain-extended star polyethylene glycol acrylate (SPEXA) gels. The hydroxy acids included glycolide (G,), L-lactide (L), p-dioxanone (D) and -caprolactone (C). Chain-extension generated water soluble macromers with faster gelation rates, lower sol fractions, higher compressive moduli, and a wide-ranging degradation times when crosslinked into a hydrogel. SPEGA gels with the highest fraction of inter-molecular crosslinks had the most increase in compressive modulus with n whereas SPELA and SPECA had the lowest increase in modulus. SPEXA gels exhibited a wide range of degradation times from a few days for SPEGA to a few weeks for SPELA, a few months for SPEDA, and many months for SPECA. Marrow stromal cells and endothelial progenitor cells had the highest expression of vasculogenic markers when co-encapsulated in the faster degrading SPELA gel. PMID:25267858

  12. pH-Triggered release from surface-modified poly(lactic-co-glycolic acid) nanoparticles

    PubMed Central

    Häuser, Manuel; Langer, Klaus

    2015-01-01

    Summary Nanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium chloride) (PDADMAC) as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative 1H NMR, yielding a pH-dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by 1H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH-sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative. PMID:26885463

  13. Novel microbial screen for detection of 1,4-butanediol, ethylene glycol, and adipic acid.

    PubMed

    Stieglitz, B; Weimer, P J

    1985-03-01

    A novel microbial-screening procedure was developed for separate detection of 1,4-butanediol, ethylene glycol, and adipic acid, three commercially important oxychemicals potentially derivable from bacterial omega-oxidation of n-butanol, ethanol, and hexanoic acid, respectively. The screening method involved postproduction addition of one of several specific Pseudomonas strains which produce a soluble fluorescent pigment during growth on the product of interest. A mutation and selection procedure was developed for isolation of specific strains with phenotypes for growth and pigment production on the desired product (e.g., 1,4-butanediol), but not on its bioconversion substrate (e.g., n-butanol), common by-products (e.g., n-butyrate), or product isomers. Pigment production was growth associated and required cultivation of the screening strains under limiting Fe3+ concentrations. The pigments resembled well-characterized, iron-chelating siderophores produced by other fluorescent pseudomonads. The sensitivity of the assay for product accumulation was enhanced by (i) conducting the screening in microtiter dishes to permit examination of individual isolates of putative producers and to control product diffusion, (ii) using a wavelength cutoff filter to reduce background source light, and (iii) using adapted screening strains which grew at lower (0.3 mM) concentrations of test compounds. The potential utility of the method for detecting a variety of oxidative catabolic products is discussed.

  14. Enhancement of osteoinduction by continual simvastatin release from poly(lactic-co-glycolic acid)-hydroxyapatite-simvastatin nano-fibrous scaffold.

    PubMed

    Jiang, Liming; Sun, Haizhu; Yuan, Anliang; Zhang, Kai; Li, Daowei; Li, Chen; Shi, Ce; Li, Xiangwei; Gao, Kai; Zheng, Changyu; Yang, Bai; Sun, Hongchen

    2013-11-01

    Simvastatin is considered as a stimulator for bone formation. However, the half-life for simvastatin is generally 2 hours, which means, it is difficult to maintain biologically active simvastatin in vivo. To overcome this limitation, we created a system to slowly release simvastatin in vitro and in vivo. We constructed a poly(lactic-co-glycolic acid)/hydroxyapatite nano-fibrous scaffold to carry simvastatin. Releasing assays showed that simvastatin was released from poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin quickly within - 15 days, and small amounts continued to be released through day 56 (experiments terminated). MTT assays demonstrated that both poly(lactic-co-glycolic acid)/hydroxyapatite and poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin promoted MC3T3-E1 cell proliferation. However, Alkaline phosphatase assays showed that only poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold significantly promoted the osteogenic differentiation of MC3T3-E1 cells in vitro on day 14. To further test in vivo, we created calvaria bone defect models and implanted either poly(lactic-co-glycolic acid)/hydroxyapatite or poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin. After 4 or 8 weeks post-implantation, the results indicated that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold induced bone formation more efficiently than poly(lactic-co-glycolic acid)/hydroxyapatite alone. Our data demonstrates that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin has the potential to aid in healing bone defects and promoting bone regeneration in the future although we still need to optimize this complex to efficiently promote bone regeneration.

  15. Clinical performance of a dermal filler containing natural glycolic Acid and a polylactic Acid polymer: results of a clinical trial in human immunodeficiency virus subjects with facial lipoatrophy.

    PubMed

    Tagle, Jorge M; Macchetto, Pedro Cervantes; Durán Páramo, Rosa Margarita

    2010-02-01

    Lipoatrophy is a condition that affects certain individuals, most commonly those who are infected with the human immunodeficiency virus.(1-3) Injectable fillers are used for the treatment of these dermal contour deformities to smooth dermal depressions formed by the loss of volume. These dermal fillers (also known as soft tissue augmentation devices) can correct contour deformities caused by lipoatrophy in patients who are human immunodeficiency virus positive or negative. The product used in this study is a patented, second-generation, injectable, dermal collagen stimulator that combines glycolic acid and polylactic acid. The glycolic acid used is not a polymer, but rather an acid derived from sugar cane. Its chemical structure corresponds to that of an alpha-hydroxy acid. Glycolic acid is a well-characterized agent that is present in a number of cosmetic products. Polylactic acid is a synthetic, biocompatible, biodegradable, inert, synthetic polymer from the poly a-hydroxy-acid family that is believed to stimulate fibroblasts to produce more collagen, thus increasing facial volume. Together, polylactic acid and glycolic acid act in concert to 1) stimulate collagen production and 2) hydrate the outer layers of the skin. A multicenter, clinical investigation authorized by the Mexican Secretariat of Health was conducted between September 20, 2002, and September 19, 2004. This clinical study was conducted in male patients between 32 and 60 years of age with lipoatrophy as a result of highly active antiretroviral therapy for human immunodeficiency virus infection. The study objective was to measure the improvement of contour deformities after the injection of a dermal collagen stimulator containing glycolic acid and polylactic acid. In addition to safety, this dermal filler was assessed when used to correct volume deformities caused by lipoatrophy in subjects who are human immunodeficiency virus positive. Thirty male subjects participated and were treated as follows

  16. Study of photorespiration in marine microalgae through the determination of glycolic acid using hydrophilic interaction liquid chromatography.

    PubMed

    Rigobello-Masini, Marilda; Penteado, José C P; Tiba, Maurício; Masini, Jorge C

    2012-01-01

    Determination of organic acids in intracellular extracts and in the cultivation media of marine microalgae aid investigations about metabolic routes related to assimilation of atmospheric carbon by these organisms, which are known by their role in the carbon dioxide sink. The separation of these acids was investigated by hydrophilic interaction liquid chromatography (HILIC) using isocratic elution with a mobile phase composed of 70:30 v/v acetonitrile/20 mmol/L ammonium acetate buffer (pH 6.8) and detection at 220 nm. HILIC allowed the determinations of glycolic acid, the most important metabolite for the evaluation of the photorespiration process in algae, to be made with better selectivity than that achieved by reversed phase liquid chromatography, but with less detectability. The concentration of glycolic acid was determined in the cultivation media and in intracellular extracts of the algae Tetraselmis gracilis and Phaeodactylum tricornutum submitted to different conditions of aeration: (i) without forced aeration, (ii) aeration with atmospheric air, and (iii) bubbling with N(2). The concentration of glycolic acid had a higher increase as the cultures were aerated with nitrogen, showing higher photorespiratory flux than that occurring in the cultures aerated with atmospheric air.

  17. Raman spectroscopic evidence of low temperature stability of D,L-glycolic and L-(+)-lactic acid crystals.

    PubMed

    Mohaček-Grošev, Vlasta; Šoštarić, Vladimir; Maksimović, Aleksandar

    2015-04-01

    Raman and infrared spectra of polycrystalline D,L-glycolic and L-(+) lactic acid are presented and assigned both by an ab initio calculation of normal modes of free conformers and by self-consistent-charge density-functional-theory computational program DFTB+. Temperature dependent Raman spectra from 295 K to 10 K reveal great stability of crystal lattices, since no soft modes and no band splittings that could be attributed to changes of the number of molecules per unit cell were observed. A semiempirical calculation with GULP program was used to estimate the strength of hydrogen bonds in crystals: in glycolic acid they have energies of -0.337 eV/mol, -0.329 eV/mol, -0.262 eV/mol and -0.242 eV/mol, while in lactic acid two hydrogen bonds have energies of -0.283 eV/mol and -0.202 eV/mol.

  18. Miscibility and in vitro osteocompatibility of biodegradable blends of poly[(ethyl alanato) (p-phenyl phenoxy) phosphazene] and poly(lactic acid-glycolic acid)

    PubMed Central

    Deng, Meng; Nair, Lakshmi S.; Nukavarapu, Syam P.; Kumbar, Sangamesh G.; Jiang, Tao; Krogman, Nicholas R.; Singh, Anurima; Allcock, Harry R.; Laurencin, Cato T.

    2007-01-01

    Previously we demonstrated the ability of ethyl glycinato substituted polyphosphazenes to neutralize the acidic degradation products and control the degradation rate of poly(lactic acid-glycolic acid) by blending. In this study, blends of high strength poly[(50% ethyl alanato) (50% p-phenyl phenoxy) phosphazene] (PNEA50PhPh50) and 85:15 poly(lactic acid-glycolic acid) (PLAGA) were prepared using a mutual solvent approach. Three different solvents, methylene chloride (MC), chloroform (CF) and tetrahydrofuran (THF) were studied to investigate solvent effects on blend miscibility. Three different blends were then fabricated at various weight ratios namely 25:75 (BLEND25), 50:50 (BLEND50), and 75:25 (BLEND75) using THF as the mutual solvent. The miscibility of the blends was evaluated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Among these, BLEND25 was miscible while BLEND50 and BLEND75 were partially miscible. Furthermore, BLEND25 formed apatite layers on its surface as evidenced in a biomimetic study performed. These novel blends showed cell adhesion and proliferation comparable to PLAGA. However, the PNEA50PhPh50 component in the blends was able to increase the phenotypic expression and mineralized matrix synthesis of the primary rat osteoblasts (PRO) in vitro. Blends of high strength poly[(50% ethyl alanato) (50% p-phenyl phenoxy) phosphazene] (PNEA50PhPh50) and 85:15 poly(lactic acid-glycolic acid) (PLAGA) are promising biomaterials for a variety of musculoskeletal applications. PMID:17942150

  19. Improving of bowel cleansing effect for polyethylene glycol with ascorbic acid using simethicone

    PubMed Central

    Yoo, In Kyung; Jeen, Yoon Tae; Kang, Seung Hun; Lee, Jae Hyung; Kim, Seung Han; Lee, Jae Min; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Chun, Hoon Jai; Lee, Hong Sik; Kim, Chang Duck

    2016-01-01

    Abstract Background and Aim: Low-volume polyethylene glycol with ascorbic acid (PEG-Asc) use is reported to be as safe and effective as traditional 4-L polyethylene glycol use. However, PEG-Asc produces bubbles, which cause problems during colonoscopy. Data on the effects of using antifoaming agents such as simethicone with PEG-Asc are lacking. The aim of this CONSORT-prospective, randomized, observer-blinded, controlled trial is to compare the quality of bowel preparation and compliance between PEG-Asc users and PEG-Asc plus simethicone users. Methods: Adult outpatients aged 18 to 80 years undergoing colonoscopy were recruited to the study. Two hundred sixty patients were randomly assigned to 1 of 2 treatment arms, PEG-Asc or PEG-Asc plus simethicone. The primary outcome measure was the bowel cleansing quality using Boston bowel preparation scale and bubble scores. The secondary outcome measures were patient tolerability and doctor tolerability. Results: The simethicone group showed superior cleansing results (6–9 Boston scale scores: 99% vs. 84%, <5% bubble scores: 96% vs. 49%, P < 0.001) and fewer gastrointestinal symptoms (abdominal fullness: 24% vs. 55%, colicky pain: 5% vs. 24%, P < 0.001) than the non-simethicone group. Moreover, endoscopist fatigue during colonoscopy was lower in the simethicone group than in the non-simethicone group (1.31 ± 0.75 vs. 2.97 ± 2.14, P < 0.001). Conclusion: PEG-Asc plus simethicone use was more effective and associated with better patient and endoscopist tolerance than PEG-Asc use. Therefore, this combination is recommended as one of the promising methods for bowel preparation before colonoscopy. PMID:27428209

  20. Lewis base activation of Lewis acids: catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes.

    PubMed

    Denmark, Scott E; Chung, Won-Jin

    2008-06-20

    A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diastereoselectivity could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the alpha-oxygen provide enantiomerically enriched alpha,beta-dihydroxy esters with high syn-diastereoselectivity, whereas the tert-butyldimethylsilyl ketene acetals derived from bulky esters of alpha-methoxyacetic acid provide enantiomerically enriched alpha,beta-dihydroxy esters with high anti-diastereoselecitvity.

  1. Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation.

    PubMed

    Wu, Junzi; Williams, Gareth R; Branford-White, Christopher; Li, Heyu; Li, Yan; Zhu, Li-Min

    2016-09-20

    In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections. Reduced blood sugar levels were seen in the microsphere treatment groups, with the results being similar to those obtained with conventional injections between 10 and 25days after the commencement of treatment. After 5 and 30days of treatment, the microspheres seem a little slower to act than the injections. The pathology of the rats' spleen, heart, kidney and lungs was probed after the 30-day treatment period, and the results indicated that the microspheres were safe and had beneficial effects on the liver, reducing the occurrence of fatty deposits seen in untreated diabetic rats. Moreover, in terms of liver, renal and cardiac functions, and blood lipid and antioxidant levels, the microspheres were as effective as the injections. The expression of several proteases linked to the metabolism of aliphatic acids and homocysteine was promoted by the microsphere formulations. Inflammatory markers in the microsphere treatment groups were somewhat higher than the injection group, however. The liraglutide/PLGA microspheres prepared in this work are overall shown to be efficacious in a rat model of diabetes, and we thus believe they have strong potential for clinical use.

  2. Antibacterial Effects and Biocompatibility of Titania Nanotubes with Octenidine Dihydrochloride/Poly(lactic-co-glycolic acid).

    PubMed

    Xu, Zhiqiang; Lai, Yingzhen; Wu, Dong; Huang, Wenxiu; Huang, Sijia; Zhou, Lin; Chen, Jiang

    2015-01-01

    Titanium (Ti) implants with long-term antibacterial ability and good biocompatibility are highly desirable materials that can be used to prevent implant-associated infections. In this study, titania nanotubes (TNTs) were synthesized on Ti surfaces through electrochemical anodization. Octenidine dihydrochloride (OCT)/poly(lactic-co-glycolic acid) (PLGA) was infiltrated into TNTs using a simple solvent-casting technique. OCT/PLGA-TNTs demonstrated sustained drug release and maintained the characteristic hollow structures of TNTs. TNTs (200 nm in diameter) alone exhibited slight antibacterial effect and good osteogenic activity but also evidently impaired adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). OCT/PLGA-TNTs (100 nm in diameter) supported BMSC adhesion and proliferation and showed good osteogenesis-inducing ability. OCT/PLGA-TNTs also exhibited good long-term antibacterial ability within the observation period of 7 d. The synthesized drug carrier with relatively long-term antibacterial ability and enhanced excellent biocompatibility demonstrated significant potential in bone implant applications. PMID:26090449

  3. Nanomolar CFTR inhibition by pore-occluding divalent polyethylene glycol-malonic acid hydrazides.

    PubMed

    Sonawane, N D; Zhao, Dan; Zegarra-Moran, Olga; Galietta, Luis J V; Verkman, A S

    2008-07-21

    Inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel have potential application as antisecretory therapy in cholera. We synthesized mono- and divalent CFTR inhibitors consisting of a malonic acid hydrazide (MalH) coupled via a disulfonic stilbene linker to polyethylene glycols (PEGs; 0.2-100 kDa). IC50 values for CFTR inhibition were 10-15 microM for the monovalent MalH-PEGs, but substantially lower for divalent MalH-PEG-MalH compounds, decreasing from 1.5 to 0.3 microM with increasing PEG size and showing positive cooperativity. Whole-cell patch-clamp showed voltage-dependent CFTR block with inward rectification. Outside-out patch-clamp showed shortened single-channel openings, indicating CFTR pore block from the extracellular side. Luminally added MalH-PEG-MalH blocked by >90% cholera toxin-induced fluid secretion in mouse intestinal loops (IC50 approximately 10 pmol/loop), and greatly reduced mortality in a suckling mouse cholera model. These conjugates may provide safe, inexpensive antisecretory therapy. PMID:18635008

  4. Poly(acrylic acid)/poly(ethylene glycol) adduct for attaining multifunctional cellulosic fabrics.

    PubMed

    Ibrahim, N A; Amr, A; Eid, B M; Mohamed, Z E; Fahmy, H M

    2012-06-20

    Aqueous polymerization of partially neutralized acrylic acid (AA) along with polyethylene glycol (PEG-600) at AA/PEG-600 mass ratio 3/1 using ammonium persulfate as initiator under proper conditions results in formation of PAA/PEG-600 adduct. The structure of the adduct was confirmed by FT-IR spectra. The potential applications of the prepared adduct in: sizing, durable hand building of cotton cellulose, as well as in functional finishing of cellulose containing fabrics, i.e. cotton, viscose and cotton/polyester, with Ag- or TiO2-nanoparticles were investigated. The modified substrates using the prepared adduct showed a remarkable improvement in their sizing, hand building and/or functional properties, i.e. antibacterial, anti-UV, and self cleaning, in addition to durability to wash. TEM images of the prepared nano-particles, SEM images of the untreated and treated substrates, as well as EDX spectra to analyze the surface elemental compositions were examined. The tentative mechanisms were also suggested. PMID:24750770

  5. Retinal pigment epithelium cell culture on thin biodegradable poly(DL-lactic-co-glycolic acid) films.

    PubMed

    Lu, L; Garcia, C A; Mikos, A G

    1998-01-01

    Thin films of 50:50 and 75:25 poly(DL-lactic-co-glycolic acid) (PLGA) were manufactured with a controlled thickness of less than 10 microm. The effect of PLGA copolymer ratio on in vitro cell attachment, proliferation, morphology, and tight junction formation was evaluated using a human D407 retinal pigment epithelium (RPE) cell line. Almost complete cell attachment was achieved on both PLGA films after 8 h of cell seeding, which was comparable to that on tissue culture polystyrene (TCPS) controls. The initial cell seeding density affected attachment, and the optimal value for 50:50 PLGA was 25000 cells cm(-2). After 7 days of in vitro culture, cell density on 50:50 and 75:25 PLGA films increased 45 and 40 folds, respectively, and a 34-fold increase was observed on TCPS. The RPE cells cultured on PLGA films at confluence had a characteristic cobblestone morphology. Confluent RPE cells also developed normal tight junctions in vitro which were concentrated mainly at the apical surfaces of cell-cell junctions. These results demonstrated that thin biodegradable PLGA films can provide suitable substrates for human RPE cell culture, and may serve as temporary carriers for subretinal implantation of organized sheets of RPE.

  6. Thermal property and assessment of biocompatibility of poly(lactic-co-glycolic) acid/graphene nanocomposites

    SciTech Connect

    Adhikari, Ananta R.; Rusakova, Irene; Chu, Wei-Kan; Haleh, Ardebili; Luisi, Jonathan; Panova, Neli I.; Laezza, Fernanda

    2014-02-07

    Polymer-matrix nanocomposites based on Poly(lactic-co-glycolic) acid (PLGA) and Graphene platelets (GNPs) were studied. GNPs, nanomaterials with a 2D flat surface, were chosen with or without chemical modification in PLGA/GNP nanocomposites and their microstructure, thermal property, and their compatibility as scaffolds for cell growth were investigated. PLGA/GNP nanocomposites (0, 1, and 5 wt. % of GNPs) were prepared using a solution based technique. Transmission electron microscopy, X-ray diffraction, Differential scanning calorimeter, and Thermogravimetric analyzer were used to analyze morphology and thermal properties. This work demonstrated the role of GNPs flat surface to provide a favorable platform resulting in an enhanced PLGA crystallization. Functionalized GNPs suppress both the thermal stability and the crystallization of PLGA. Finally, to determine the potential usefulness of these scaffolds for biomedical applications, mammalian cells were cultured on various PLGA/GNP nanocomposites (0, 1, and 5 wt. % GNPs). 1 wt. % PLGA/GNP nanocomposites showed better biocompatibility for cell growth with/without graphenes functionalization compared to pure PLGA and 5 wt. % PLGA/GNP. The function of GNPs in PLGA/GNPs (1 wt. %) composites is to provide a stage for PLGA crystallization where cell growth is favored. These results provide strong evidence for a new class of materials that could be important for biomedical applications.

  7. Modulating the Rigidity and Mineralization of Collagen Gels Using Poly(Lactic-Co-Glycolic Acid) Microparticles

    PubMed Central

    DeVolder, Ross J.; Kim, Il Won; Kim, Eun-Suk

    2012-01-01

    Extensive efforts have been made to prepare osteoconductive collagen gels for the regeneration of normal bone and the pathological examination of diseased bone; however, collagen gels are often plagued by limited controllability of their rigidity and mineral deposition. This study reports a simple but efficient strategy that tunes the mechanical properties of, and apatite formation in, collagen gels by incorporating hydrolyzable poly(lactic-co-glycolic acid) (PLGA) microparticles within the gels. The PLGA microparticles are associated with the collagen fibrils and increased both the gel's elasticity and rigidity while minimally influencing its permeability. As compared with pure collagen gels, the PLGA microparticle-filled collagen gels, termed PLGA-Col hydrogels, significantly enhanced the deposition of apatite-like minerals within the gels when incubated in simulated body fluid or encapsulated with mesenchymal stem cells (MSCs) undergoing osteogenic differentiation. Finally, PLGA-Col hydrogels mineralized by differentiated MSCs led to an enhanced formation of bone-like tissues within the hydrogels. Overall, the PLGA-Col hydrogel system developed in this study will serve to improve the quality of osteoconductive matrices for both fundamental and clinical studies that are relevant to bone repair, regeneration, and pathogenesis. PMID:22480235

  8. Poly(lactic-co-glycolic acid) matrix incorporated with nisin as a novel antimicrobial biomaterial.

    PubMed

    Correia, Rafaela Coelho; Jozala, Angela Faustino; Martins, Kelly Fernanda; Penna, Thereza Christina Vessoni; Duek, Eliana Aparecida de Rezende; Rangel-Yagui, Carlota de Oliveira; Lopes, André Moreni

    2015-04-01

    The use of poly(lactic-co-glycolic acid) (PLGA) matrix as a biomolecule carrier has been receiving great attention due to its potential therapeutic application. In this context, we investigated the PLGA matrix capacity to incorporate nisin, an antimicrobial peptide capable of inhibiting the growth of Gram-positive bacteria and bacterial spores germination. Nisin-incorporated PLGA matrices were evaluated based on the inhibitory effect against the nisin-bioindicator Lactobacillus sakei. Additionally, the PLGA-nisin matrix stability over an 8-months period was investigated, as well as the nisin release profile. For the incorporation conditions, we observed that a 5 h incorporation time, at 30 °C, with 250 μg/mL nisin solution in PBS buffer pH 4.5, resulted in the highest inhibitory activity of 2.70 logAU/mL. The PLGA-nisin matrix was found to be relatively stable and showed sustained drug delivery, with continuous release of nisin for 2 weeks. Therefore, PLGA-nisin matrix is could be used as a novel antimicrobial delivery system and an alternative to antibiotics incorporated into PLGA matrices.

  9. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations

    PubMed Central

    Makita-Chingombe, Faithful; Kutscher, Hilliard L.; DiTursi, Sara L.; Morse, Gene D.; Maponga, Charles C.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and −20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  10. Increased osteoblast functions on nanophase titania dispersed in poly-lactic-co-glycolic acid composites.

    PubMed

    Liu, Huinan; Slamovich, Elliott B; Webster, Thomas J

    2005-07-01

    The design of nanophase titania/poly-lactic-co-glycolic acid (PLGA) composites offers an exciting approach to combine the advantages of a degradable polymer with nano-size ceramic grains to optimize physical and biological properties for bone regeneration. Importantly, nanophase titania mimics the size scale of constituent components of bone since it is a nanostructured composite composed of nanometre dimensioned hydroxyapatite well dispersed in a mostly collagen matrix. For these reasons, the objective of the present in vitro study was to investigate osteoblast (bone-forming cell) adhesion and long-term functions on nanophase titania/PLGA composites. Since nanophase titania tended to significantly agglomerate when added to polymers, different sonication output powers were applied in this study to improve titania dispersion. Results demonstrated that the dispersion of titania in PLGA was enhanced by increasing the intensity of sonication and that greater osteoblast adhesion correlated with improved nanophase titania dispersion in PLGA. Moreover, results correlated better osteoblast long-term functions, such as alkaline phosphatase activity and calcium-containing mineral deposition, on nanophase titania/PLGA composites compared to plain PLGA. In fact, the greatest collagen production by osteoblasts occurred when cultured on nanophase titania sonicated in PLGA at the highest powers. In this manner, the present study demonstrates that PLGA composites with well dispersed nanophase titania can enhance osteoblast functions necessary for improved bone tissue engineering applications.

  11. Biodegradability of poly(lactic-co-glycolic acid) after femtosecond laser irradiation

    PubMed Central

    Shibata, Akimichi; Yada, Shuhei; Terakawa, Mitsuhiro

    2016-01-01

    Biodegradation is a key property for biodegradable polymer-based tissue scaffolds because it can provide suitable space for cell growth as well as tailored sustainability depending on their role. Ultrashort pulsed lasers have been widely used for the precise processing of optically transparent materials, including biodegradable polymers. Here, we demonstrated the change in the biodegradation of a poly(lactic-co-glycolic acid) (PLGA) following irradiation with femtosecond laser pulses at different wavelengths. Microscopic observation as well as water absorption and mass change measurement revealed that the biodegradation of the PLGA varied significantly depending on the laser wavelength. There was a significant acceleration of the degradation rate upon 400 nm-laser irradiation, whereas 800 nm-laser irradiation did not induce a comparable degree of change. The X-ray photoelectron spectroscopy analysis indicated that laser pulses at the shorter wavelength dissociated the chemical bonds effectively, resulting in a higher degradation rate at an early stage of degradation. PMID:27301578

  12. Dendrigraft polylysine coated-poly(glycolic acid) fibrous scaffolds for hippocampal neurons.

    PubMed

    Kojima, Chie; Fusaoka-Nishioka, Eri; Imai, Toshio; Nakahira, Atsushi; Onodera, Hiroshi

    2016-11-01

    Poly(glycolic acid) (PGA) fibers are a good candidate material for nerve cell scaffolds, which is applicable to the treatment of peripheral nerve injuries. Polylysine is widely used as a coating material for cell substrates to promote nerve cell adhesion. In this study, linear and dendrigraft polylysines were used to coat PGA fibers. The association of large dendrigraft polylysines with PGA fibers was lower and unstable, compared with linear polylysine. However, more hippocampal neurons adhered to PGA fibers coated with large dendrigraft polylysine than linear polylysine. Enhanced cell adhesion was observed, even when the dendrigraft polylysine was coated on the PGA fibers at a low concentration (0.05 μg/mL) or when it was coated in water instead of alkaline buffer. Differences in cell adhesion properties were seen between the dendrigraft polylysine coating and a laminin coating. Thus, large dendrigraft polylysines are a useful coating material for nerve cell scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2744-2750, 2016.

  13. Activated carbon fibers/poly(lactic-co-glycolic) acid composite scaffolds: preparation and characterizations.

    PubMed

    Shi, Yanni; Han, Hao; Quan, Haiyu; Zang, Yongju; Wang, Ning; Ren, Guizhi; Xing, Melcolm; Wu, Qilin

    2014-10-01

    The present work is a first trial to introduce activated carbon fibers (ACF) with high adsorption capacity into poly(lactic-co-glycolic) acid (PLGA), resulting in a novel kind of scaffolds for tissue engineering applications. ACF, prepared via high-temperature processing of carbon fibers, are considered to possess bioactivity and biocompatibility. The ACF/PLGA composite scaffolds are prepared by solvent casting/particulate leaching method. Increments in both pore quantity and quality over the surface of ACF as well as a robust combination between ACF and PLGA matrix are observed via scanning electron microscopy (SEM). The high adsorption capacity of ACF is confirmed by methylene blue solution absorbency test. The surfaces of ACF are affiliated with many hydrophilic groups and characterized by Fourier transform infrared spectroscopy. Furthermore, the SEM images show that cells possess a favorable spreading morphology on the ACF/PLGA scaffolds. Besides, vivo experiments are also carried out to evaluate the histocompatibility of the composite scaffolds. The results show that ACF have the potential to become one of the most promising materials in biological fields.

  14. Control of Alginate Core Size in Alginate-Poly (Lactic-Co-Glycolic) Acid Microparticles

    NASA Astrophysics Data System (ADS)

    Lio, Daniel; Yeo, David; Xu, Chenjie

    2016-01-01

    Core-shell alginate-poly (lactic-co-glycolic) acid (PLGA) microparticles are potential candidates to improve hydrophilic drug loading while facilitating controlled release. This report studies the influence of the alginate core size on the drug release profile of alginate-PLGA microparticles and its size. Microparticles are synthesized through double-emulsion fabrication via a concurrent ionotropic gelation and solvent extraction. The size of alginate core ranges from approximately 10, 50, to 100 μm when the emulsification method at the first step is homogenization, vortexing, or magnetic stirring, respectively. The second step emulsification for all three conditions is performed with magnetic stirring. Interestingly, although the alginate core has different sizes, alginate-PLGA microparticle diameter does not change. However, drug release profiles are dramatically different for microparticles comprising different-sized alginate cores. Specifically, taking calcein as a model drug, microparticles containing the smallest alginate core (10 μm) show the slowest release over a period of 26 days with burst release less than 1 %.

  15. Curcumin loaded poly (lactic-co-glycolic) acid nanofiber for the treatment of carcinoma.

    PubMed

    Sampath, Malathi; Lakra, Rachita; Korrapati, Purnasai; Sengottuvelan, Balasubramanian

    2014-05-01

    Poly (DL-lactic-co-glycolic) acid [PLGA] copolymers with different ratios (78/22, 68/32 and 61/39) and molecular weight (15,400, 11,000 and 10,000 Da) were synthesized and characterized by (1)H NMR, FTIR, GPC and TGA-DTA studies. Curcumin loaded PLGA with the size of 100-300 nm were obtained by electrospinning in which no visible aggregation observed on the surface. The diameter of CPNF (61/39) nanofiber obtained from the topographical imaging by AFM is 160±10 nm. The water contact angle measurements indicate that an increase in GA content results in increase in the hydrophilicity of the PLGA copolymer. The in vitro release profile and release kinetics from the CPNF demonstrated a sustained release of curcumin from CPNF. The release profile follows Korsmeyer-Peppas model suggesting a combination of surface drug dissolution and non-Fickian diffusion as a major drug release mechanism. The effect of CPNF on cell viability was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay to examine the cytotoxic effect of released curcumin on A431 cells in vitro. PMID:24646452

  16. Activated carbon fibers/poly(lactic-co-glycolic) acid composite scaffolds: preparation and characterizations.

    PubMed

    Shi, Yanni; Han, Hao; Quan, Haiyu; Zang, Yongju; Wang, Ning; Ren, Guizhi; Xing, Melcolm; Wu, Qilin

    2014-10-01

    The present work is a first trial to introduce activated carbon fibers (ACF) with high adsorption capacity into poly(lactic-co-glycolic) acid (PLGA), resulting in a novel kind of scaffolds for tissue engineering applications. ACF, prepared via high-temperature processing of carbon fibers, are considered to possess bioactivity and biocompatibility. The ACF/PLGA composite scaffolds are prepared by solvent casting/particulate leaching method. Increments in both pore quantity and quality over the surface of ACF as well as a robust combination between ACF and PLGA matrix are observed via scanning electron microscopy (SEM). The high adsorption capacity of ACF is confirmed by methylene blue solution absorbency test. The surfaces of ACF are affiliated with many hydrophilic groups and characterized by Fourier transform infrared spectroscopy. Furthermore, the SEM images show that cells possess a favorable spreading morphology on the ACF/PLGA scaffolds. Besides, vivo experiments are also carried out to evaluate the histocompatibility of the composite scaffolds. The results show that ACF have the potential to become one of the most promising materials in biological fields. PMID:25175194

  17. Antibacterial Effects and Biocompatibility of Titania Nanotubes with Octenidine Dihydrochloride/Poly(lactic-co-glycolic acid)

    PubMed Central

    Xu, Zhiqiang; Lai, Yingzhen; Wu, Dong; Huang, Wenxiu; Huang, Sijia; Zhou, Lin; Chen, Jiang

    2015-01-01

    Titanium (Ti) implants with long-term antibacterial ability and good biocompatibility are highly desirable materials that can be used to prevent implant-associated infections. In this study, titania nanotubes (TNTs) were synthesized on Ti surfaces through electrochemical anodization. Octenidine dihydrochloride (OCT)/poly(lactic-co-glycolic acid) (PLGA) was infiltrated into TNTs using a simple solvent-casting technique. OCT/PLGA-TNTs demonstrated sustained drug release and maintained the characteristic hollow structures of TNTs. TNTs (200 nm in diameter) alone exhibited slight antibacterial effect and good osteogenic activity but also evidently impaired adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). OCT/PLGA-TNTs (100 nm in diameter) supported BMSC adhesion and proliferation and showed good osteogenesis-inducing ability. OCT/PLGA-TNTs also exhibited good long-term antibacterial ability within the observation period of 7 d. The synthesized drug carrier with relatively long-term antibacterial ability and enhanced excellent biocompatibility demonstrated significant potential in bone implant applications. PMID:26090449

  18. Poly(lactic-co-glycolic) Acid/Solutol HS15-Based Nanoparticles for Docetaxel Delivery.

    PubMed

    Cho, Hyun-Jong; Park, Ju-Hwan; Kim, Dae-Duk; Yoon, In-Soo

    2016-02-01

    Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lactic- co-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method. PLGA/Solutol HS15/DCT NPs with about 169 nm of mean diameter, narrow size distribution, negative zeta potential, and spherical morphology were prepared. The results of solid-state studies revealed the successful dispersion of DCT in PLGA matrix and its amorphization during the preparation process of NPs. According to the result of in vitro release test, emulsifying property of Solutol HS15 seemed to contribute to the enhanced drug release from NPs at physiological pH. All these findings imply that developed PLGA/Solutol HS15-based NP can be a promising local anticancer drug delivery system for cancer therapy.

  19. Nanomechanical properties of poly(lactic-co-glycolic) acid film during degradation.

    PubMed

    Shirazi, Reyhaneh Neghabat; Aldabbagh, Fawaz; Erxleben, Andrea; Rochev, Yury; McHugh, Peter

    2014-11-01

    Despite the potential applications of poly(lactic-co-glycolic) acid (PLGA) coatings in medical devices, the mechanical properties of this material during degradation are poorly understood. In the present work, the nanomechanical properties and degradation of PLGA film were investigated. Hydrolysis of solvent-cast PLGA film was studied in buffer solution at 37 °C. The mass loss, water uptake, molecular weight, crystallinity and surface morphology of the film were tracked during degradation over 20 days. Characterization of the surface hardness and Young's modulus was performed using the nanoindentation technique for different indentation loads. The initially amorphous films were found to remain amorphous during degradation. The molecular weight of the film decreased quickly during the initial days of degradation. Diffusion of water into the film resulted in a reduction in surface hardness during the first few days, followed by an increase that was due to the surface roughness. There was a significant delay between the decrease in the mechanical properties of the film and the decrease in the molecular weight. A sudden decline in mechanical properties indicated that significant bulk degradation had occurred.

  20. Curcumin loaded poly (lactic-co-glycolic) acid nanofiber for the treatment of carcinoma.

    PubMed

    Sampath, Malathi; Lakra, Rachita; Korrapati, Purnasai; Sengottuvelan, Balasubramanian

    2014-05-01

    Poly (DL-lactic-co-glycolic) acid [PLGA] copolymers with different ratios (78/22, 68/32 and 61/39) and molecular weight (15,400, 11,000 and 10,000 Da) were synthesized and characterized by (1)H NMR, FTIR, GPC and TGA-DTA studies. Curcumin loaded PLGA with the size of 100-300 nm were obtained by electrospinning in which no visible aggregation observed on the surface. The diameter of CPNF (61/39) nanofiber obtained from the topographical imaging by AFM is 160±10 nm. The water contact angle measurements indicate that an increase in GA content results in increase in the hydrophilicity of the PLGA copolymer. The in vitro release profile and release kinetics from the CPNF demonstrated a sustained release of curcumin from CPNF. The release profile follows Korsmeyer-Peppas model suggesting a combination of surface drug dissolution and non-Fickian diffusion as a major drug release mechanism. The effect of CPNF on cell viability was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay to examine the cytotoxic effect of released curcumin on A431 cells in vitro.

  1. Efficacy of Poly-Lactic-Co-Glycolic Acid Micro- and Nanoparticles of Ciprofloxacin Against Bacterial Biofilms.

    PubMed

    Thomas, Nicky; Thorn, Chelsea; Richter, Katharina; Thierry, Benjamin; Prestidge, Clive

    2016-10-01

    Bacterial biofilms are associated with a number of recurring infectious diseases and are a major cause for antibiotic resistance. Despite the broad use of polymeric microparticles and nanoparticles in biomedical research, it is not clear which particle size is more effective against biofilms. The purpose of this study was to evaluate the efficacy of sustained release poly-lactic-co-glycolic acid (PLGA) micro- and nanoparticles containing ciprofloxacin against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. The PLGA particles were prepared by the double emulsion solvent evaporation method. The resulting microparticles (12 μm) and nanoparticles (300 nm) contained drug loads of 7.3% and 4.5% (wt/wt) ciprofloxacin, respectively. Drug release was complete within 1 week following comparable release profiles for both particle sizes. Micro- and nanoparticles demonstrated a similar in vitro antibiofilm performance against mature P aeruginosa and S aureus with marked differences between the 2 strains. The sustained release of ciprofloxacin from micro- and nanoparticles over 6 days was equally effective as the continuous treatment with ciprofloxacin solution over the same period resulting in the eradication of culturable S aureus suggesting that reformulation of ciprofloxacin as sustained release PLGA micro- and nanoparticles might be valuable formulation approaches for the treatment of biofilms. PMID:27519649

  2. Poly(lactic-co-glycolic) Acid/Solutol HS15-Based Nanoparticles for Docetaxel Delivery.

    PubMed

    Cho, Hyun-Jong; Park, Ju-Hwan; Kim, Dae-Duk; Yoon, In-Soo

    2016-02-01

    Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lactic- co-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method. PLGA/Solutol HS15/DCT NPs with about 169 nm of mean diameter, narrow size distribution, negative zeta potential, and spherical morphology were prepared. The results of solid-state studies revealed the successful dispersion of DCT in PLGA matrix and its amorphization during the preparation process of NPs. According to the result of in vitro release test, emulsifying property of Solutol HS15 seemed to contribute to the enhanced drug release from NPs at physiological pH. All these findings imply that developed PLGA/Solutol HS15-based NP can be a promising local anticancer drug delivery system for cancer therapy. PMID:27433600

  3. Dendrigraft polylysine coated-poly(glycolic acid) fibrous scaffolds for hippocampal neurons.

    PubMed

    Kojima, Chie; Fusaoka-Nishioka, Eri; Imai, Toshio; Nakahira, Atsushi; Onodera, Hiroshi

    2016-11-01

    Poly(glycolic acid) (PGA) fibers are a good candidate material for nerve cell scaffolds, which is applicable to the treatment of peripheral nerve injuries. Polylysine is widely used as a coating material for cell substrates to promote nerve cell adhesion. In this study, linear and dendrigraft polylysines were used to coat PGA fibers. The association of large dendrigraft polylysines with PGA fibers was lower and unstable, compared with linear polylysine. However, more hippocampal neurons adhered to PGA fibers coated with large dendrigraft polylysine than linear polylysine. Enhanced cell adhesion was observed, even when the dendrigraft polylysine was coated on the PGA fibers at a low concentration (0.05 μg/mL) or when it was coated in water instead of alkaline buffer. Differences in cell adhesion properties were seen between the dendrigraft polylysine coating and a laminin coating. Thus, large dendrigraft polylysines are a useful coating material for nerve cell scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2744-2750, 2016. PMID:27324925

  4. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations.

    PubMed

    Makita-Chingombe, Faithful; Kutscher, Hilliard L; DiTursi, Sara L; Morse, Gene D; Maponga, Charles C

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and -20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1.

  5. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations.

    PubMed

    Makita-Chingombe, Faithful; Kutscher, Hilliard L; DiTursi, Sara L; Morse, Gene D; Maponga, Charles C

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and -20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  6. Effect of l-lysine-assisted surface grafting for nano-hydroxyapatite on mechanical properties and in vitro bioactivity of poly(lactic acid-co-glycolic acid).

    PubMed

    Liuyun, Jiang; Lixin, Jiang; Chengdong, Xiong; Lijuan, Xu; Ye, Li

    2016-01-01

    It is promising and challenging to study surface modification for nano-hydroxyapatite to improve the dispersion and enhance the mechanical properties and bioactivity of poly(lactic acid-co-glycolic acid). In this paper, we designed an effective new surface grafting with the assist of l-lysine for nano-hydroxyapatite, and the nano-hydroxyapatite surface grafted with the assist of l-lysine (g-nano-hydroxyapatite) was incorporated into poly(lactic acid-co-glycolic acid) to develop a series of g-nano-hydroxyapatite/poly(lactic acid-co-glycolic acid) nano-composites. The surface modification reaction for nano-hydroxyapatite, the mechanical properties, and in vitro human osteoblast-like cell (MG-63) response were characterized and investigated by Fourier transformation infrared, thermal gravimetric analysis, dispersion test, electromechanical universal tester, differential scanning calorimeter measurements, and in vitro cells culture experiment. The results showed that the grafting amount on the surface of nano-hydroxyapatite was enhanced with the increase of l-lysine, and the dispersion of nano-hydroxyapatite was improved more, so that it brought about better promotion crystallization and more excellent mechanical enhancement effect for poly(lactic acid-co-glycolic acid), comparing with the unmodified nano-hydroxyapatite. Moreover, the cells' attachment and proliferation results confirmed that the incorporation of the g-nano-hydroxyapatite into poly(lactic acid-co-glycolic acid) exhibited better biocompatibility than poly(lactic acid-co-glycolic acid). The above results indicated that the new surface grafting with the assist of l-lysine for nano-hydroxyapatite was an ideal novel surface modification method, which brought about better mechanical enhancement effect and in vitro bioactivity for poly(lactic acid-co-glycolic acid) with adding higher g-nano-hydroxyapatite content, suggesting it had a great potential to be used as bone fracture internal fixation materials

  7. Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment.

    PubMed

    Sundara Rajan, Sujata; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L; Sinko, Patrick J

    2014-11-28

    Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH7.4) and acetate buffer (AB, pH4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%-14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV.

  8. Designing improved poly lactic-co-glycolic acid microspheres for a malarial vaccine: incorporation of alginate and polyinosinic-polycytidilic acid.

    PubMed

    Salvador, Aiala; Igartua, Manoli; Hernández, Rosa María; Pedraz, José Luis

    2014-01-01

    Vaccination using proteins and peptides is currently gaining importance. One of the major drawbacks of this approach is the lack of an efficient immune response when the antigens are administered without adjuvants. In this study, we have taken the advantage of a combined adjuvant system in order to improve the immunogenicity of the SPf66 malarial antigen. For that purpose, we have combined poly (lactic-co-glycolic) acid microspheres, alginate, and polyinosinic polycytidilic acid. Our results show that microspheres can enhance the IgG production obtained with Freund's complete adjuvant. We have attributed this improvement to the presence of polyinosinic polycytidilic acid, since formulations comprising this adjuvant overcame the immune response from the others. In addition, our microspheres produced both IgG1 and IgG2a, leading to mixed Th1/Th2 activation, optimal for malaria vaccination. In conclusion, we have designed a preliminary formulation with a high potential for the treatment of malaria.

  9. Poly-lactic-glycolic-acid surface nanotopographies selectively decrease breast adenocarcinoma cell functions

    NASA Astrophysics Data System (ADS)

    Zhang, Lijuan; Webster, Thomas J.

    2012-04-01

    The ability of poly(lactic-co-glycolic acid) (PLGA, 50:50 PLG/PGA, wt%) nanotopographies to decrease lung epithelial carcinoma cell functions (including adhesion, proliferation, apoptosis and vascular endothelial growth factor (VEGF) secretion) has been previously reported. Specifically, results demonstrated decreased lung epithelial carcinoma cell VEGF synthesis on 23 nm surface-featured PLGA compared to traditional nanosmooth PLGA. However, clearly, different cell lines could have different behaviors on similar biomaterials. Thus, to investigate the universality of nanopatterned PLGA substrates to inhibit numerous cancer cell functions, here, breast epithelial adenocarcinoma cell (MCF-7) adhesion, proliferation, apoptosis and VEGF secretion were determined on different PLGA nanometer surface topographies. To isolate surface nanotopographical effects from all other surface properties, PLGA surfaces with various nanotopographies but similar chemistry and hydrophobicity were fabricated here. Atomic force microscopy (AFM) verified the varied nanotopographies on the PLGA surfaces prepared in this study. Importantly, results demonstrated for the first time significantly decreased breast adenocarcinoma cell functions (including decreased proliferation rate, increased apoptosis and decreased VEGF synthesis) on 23 nm featured PLGA surfaces compared to all other PLGA surface topographies fabricated (specifically, nanosmooth, 300 and 400 nm surface-featured PLGA surfaces). In contrast, healthy breast epithelial cells proliferated more (24%) on the 23 nm featured PLGA surfaces compared to all other PLGA samples. In summary, these results provided further insights into understanding the role PLGA surface nanotopographies can have on cancer cell functions and, more importantly, open the possibility of using polymer nanotopographies for a wide range of anticancer regenerative medicine applications (without resorting to the use of chemotherapeutics).

  10. Mucoadhesive plasticized system of branched poly(lactic-co-glycolic acid) with aciclovir.

    PubMed

    Snejdrova, Eva; Drastik, Martin; Dittrich, Milan; Kastner, Petr; Nguyenova, Jana

    2016-10-01

    Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug-polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00 s(-1) at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at Tg depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters. PMID:26925606

  11. Mucoadhesive plasticized system of branched poly(lactic-co-glycolic acid) with aciclovir.

    PubMed

    Snejdrova, Eva; Drastik, Martin; Dittrich, Milan; Kastner, Petr; Nguyenova, Jana

    2016-10-01

    Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug-polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00 s(-1) at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at Tg depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.

  12. The effect of Centella asiatica, vitamins, glycolic acid and their mixtures preparations in stimulating collagen and fibronectin synthesis in cultured human skin fibroblast.

    PubMed

    Hashim, Puziah

    2014-03-01

    Centella asiatica (Linn.) Urban is well known in promoting wound healing and provides significant benefits in skin care and therapeutic products formulation. Glycolic acid and vitamins also play a role in the enhancement of collagen and fibronectin synthesis. Here, we evaluate the specific effect of Centella asiatica (CA), vitamins, glycolic acid and their mixture preparations to stimulate collagen and fibronectin synthesis in cultured human fibroblast cells. The fibroblast cells are incubated with CA, glycolic acid, vitamins and their mixture preparations for 48 h. The cell lysates were analyzed for protein content and collagen synthesis by direct binding enzyme immunoassay. The fibronectin of the cultured supernatant was measured by sandwich enzyme immunoassay. The results showed that CA, glycolic acid, vitamins A, E and C significantly stimulate collagen and fibronectin synthesis in the fibroblast. Addition of glycolic acid and vitamins to CA further increased the levels of collagen and fibronectin synthesis to 8.55 and 23.75 μg/100 μg, respectively. CA, glycolic acid, vitamins A, E, and C, and their mixtures demonstrated stimulatory effect on both extra-cellular matrix synthesis of collagen and fibronectin in in vitro studies on human foreskin fibroblasts, which is beneficial to skin care and therapeutic products formulation.

  13. Development Of Ion Chromatography Methods To Support Testing Of The Glycolic Acid Reductant Flowsheet In The Defense Waste Processing Facility

    SciTech Connect

    Wiedenman, B. J.; White, T. L.; Mahannah, R. N.; Best, D. R.; Stone, M. E.; Click, D. R.; Lambert, D. P.; Coleman, C. J.

    2013-10-01

    Ion Chromatography (IC) is the principal analytical method used to support studies of Sludge Reciept and Adjustment Tank (SRAT) chemistry at DWPF. A series of prior analytical ''Round Robin'' (RR) studies included both supernate and sludge samples from SRAT simulant, previously reported as memos, are tabulated in this report.2,3 From these studies it was determined to standardize IC column size to 4 mm diameter, eliminating the capillary column from use. As a follow on test, the DWPF laboratory, the PSAL laboratory, and the AD laboratory participated in the current analytical RR to determine a suite of anions in SRAT simulant by IC, results also are tabulated in this report. The particular goal was to confirm the laboratories ability to measure and quantitate glycolate ion. The target was + or - 20% inter-lab agreement of the analyte averages for the RR. Each of the three laboratories analyzed a batch of 12 samples. For each laboratory, the percent relative standard deviation (%RSD) of the averages on nitrate, glycolate, and oxalate, was 10% or less. The three laboratories all met the goal of 20% relative agreement for nitrate and glycolate. For oxalate, the PSAL laboratory reported an average value that was 20% higher than the average values reported by the DWPF laboratory and the AD laboratory. Because of this wider window of agreement, it was concluded to continue the practice of an additional acid digestion for total oxalate measurement. It should also be noted that large amounts of glycolate in the SRAT samples will have an impact on detection limits of near eluting peaks, namely Fluoride and Formate. A suite of scoping experiments are presented in the report to identify and isolate other potential interlaboratory disceprancies. Specific ion chromatography inter-laboratory method conditions and differences are tabulated. Most differences were minor but there are some temperature control equipment differences that are significant leading to a recommendation of

  14. From lignocellulosic biomass to lactic- and glycolic-acid oligomers: a gram-scale microwave-assisted protocol.

    PubMed

    Carnaroglio, Diego; Tabasso, Silvia; Kwasek, Beata; Bogdal, Dariusz; Gaudino, Emanuela Calcio; Cravotto, Giancarlo

    2015-04-24

    The conversion of lignocellulosic biomass into platform chemicals is the key step in the valorization of agricultural waste. Of the biomass-derived platform chemicals currently produced, lactic acid plays a particularly pivotal role in modern biorefineries as it is a versatile commodity chemical and building block for the synthesis of biodegradable polymers. Microwave-assisted processes that furnish lactic acid avoid harsh depolymerization conditions while cutting down reaction time and energy consumption. We herein report a flash catalytic conversion (2 min) of lignocellulosic biomass into lactic and glycolic acids under microwave irradiation. The batch procedure was successfully adapted to a microwave-assisted flow process (35 mL min(-1) ), with the aim of designing a scalable process with higher productivity. The C2 and C4 units recovered from the depolymerization were directly used as the starting material for a solvent and catalyst-free microwave-assisted polycondensation that afforded oligomers in good yields.

  15. New formulation of chemical peeling agent: 30% salicylic acid in polyethylene glycol. Absorption and distribution of 14C-salicylic acid in polyethylene glycol applied topically to skin of hairless mice.

    PubMed

    Ueda, Setsuko; Mitsugi, Koichi; Ichige, Kazumi; Yoshida, Kenji; Sakuma, Tomoko; Ninomiya, Shin-ichi; Sudou, Tetsuji

    2002-04-01

    Salicylic acid is used in chemical peeling procedures. However, they have caused many side effects, even salicylism. To achieve a salicylic acid peeling that would be safer for topical use, we recently developed a new formulation consisting of 30% salicylic acid in polyethylene glycol (PEG) vehicle. In an extension of our previous research, we studied the absorption of 30% salicylic acid labeled with 14C in PEG vehicle applied topically to the intact and damaged skin of male hairless mice. An ointment containing 3 mg salicylic acid in 10 mg vehicle was applied to both groups. In animals with intact skin, 1 h after application the plasma concentration of radioactivity was 1665.1 ng eq/ml, significantly lower than the 21437.6 ng eq/ml observed in mice with damaged skin. Microautoradiograms of intact skin showed that the level of radioactivity in the cornified cell layer was similar at 6 h after application. However, in damaged skin, the overall level of radioactivity showed a decrease by 3 h after application. In the carcasses remaining after the treated intact and damaged skin had been removed, 0.09 and 11.38% of the applied radioactivity remained, respectively. These findings confirm that 30% salicylic acid in PEG vehicle is little absorbed through the intact skin of hairless mice, and suggest that salicylism related to absorption through the skin of quantities of topically applied salicylic acid is not likely to occur in humans with intact skin during chemical peeling with this preparation. This new preparation of 30% salicylic acid in PEG vehicle is believed to be safe for application as a chemical peeling agent.

  16. Degradation behavior of hydroxyapatite/poly(lactic-co-glycolic) acid nanocomposite in simulated body fluid

    SciTech Connect

    Liuyun, Jiang; Chengdong, Xiong; Lixin, Jiang; Lijuan, Xu

    2013-10-15

    Graphical abstract: In this manuscript, we initiated a systematic study to investigate the effect of HA on thermal properties, inner structure, reduction of mechanical strength, surface morphology and the surface deposit of n-HA/PLGA composite with respect to the soaking time. The results showed that n-HA played an important role in improving the degradation behavior of n-HA/PLGA composite, which can accelerate the degradation of n-HA/PLGA composite and endow it with bioactivity, after n-HA was detached from PLGA during the degradation, so that n-HA/PLGA composite may have a more promising prospect of the clinical application than pure PLGA as bone fracture internal fixation materials, and the results would be of reference significance to predict the in vivo degradation and biological properties. - Highlights: • Effect of n-HA on degradation behavior of n-HA/PLGA composite was investigated. • Degradation behaviors of n-HA/PLGA and PLGA were carried out in SBF for 6 months. • Viscosity, thermal properties, inner structure and bending strength were tested. • n-HA can accelerate the degradation and endows it with bioactivity. - Abstract: To investigate the effect of hydroxyapatite(HA) on the degradation behavior of hydroxyapatite/poly(lactic-co-glycolic) acid (HA/PLGA) nanocomposite, the degradation experiment of n-HA/PLGA composite and pure PLGA were carried out by soaking in simulated body fluid(SBF) at 37 °C for 1, 2, 4 and 6 months. The change of intrinsic viscosity, thermal properties, inner structure, bending strength reduction, surface morphology and the surface deposit of n-HA/PLGA composite and pure PLGA with respect to the soaking time were investigated by means of UbbeloHde Viscometer, differential scanning calorimeter (DSC), scanning electron microscope(SEM), electromechanical universal tester, a conventional camera and X-ray diffraction (XRD). The results showed that n-HA played an important role in improving the degradation behavior of n

  17. Poly(ethylene glycol)-co-methacrylamide-co-acrylic acid based nanogels for delivery of doxorubicin.

    PubMed

    Kumar, Parveen; Behl, Gautam; Sikka, Manisha; Chhikara, Aruna; Chopra, Madhu

    2016-10-01

    Polymeric nanogels have been widely explored for their potential application as delivery carriers for cancer therapeutics. The ability of nanogels to encapsulate therapeutics by simple diffusion mechanism and the ease of their fabrication to impart target specificity in addition to their ability to get internalized into target cells make them good candidates for drug delivery. The present study aims to investigate the applicability of poly(ethylene glycol)-co-methacrylamide-co-acrylic acid (PMA)-based nanogels as a viable option for the delivery of doxorubicin (DOX). The nanogels were synthesized by free radical polymerization in an inverse mini-emulsion and characterized by nuclear magnetic resonance spectroscopy ((1)H NMR), Fourier transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy (TEM), X-ray diffraction and differential scanning calorimetry. DOX was physically incorporated into the nanogels (PMA-DOX) and the mechanism of its in vitro release was studied. TEM experiment revealed spherical morphology of nanogels and the hydrodynamic diameter of the neat nanogels was in the range of 160 ± 46.95 nm. The size of the nanogels increased from 235.1 ± 28.46 to 403.7 ± 89.89 nm with the increase in drug loading capacity from 4.68 ± 0.03 to 13.71 ± 0.01%. The sustained release of DOX was observed upto 80 h and the release rate decreased with increased loading capacity following anomalous release mechanism as indicated by the value of diffusion exponent (n = 0.64-0.75) obtained from Korsmeyer-Peppas equation. Further, cytotoxicity evaluation of PMA-DOX nanogels on HeLa cells resulted in relatively higher efficacy (IC50~5.88 μg/mL) as compared to free DOX (IC50~7.24 μg/mL) thus demonstrating that the preparation is potentially a promising drug delivery carrier.

  18. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

    PubMed Central

    Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

    2016-01-01

    Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve

  19. Biocompatibility Assessment of Polyethylene Glycol-Poly L-Lysine-Poly Lactic-Co-Glycolic Acid Nanoparticles In Vitro and In Vivo.

    PubMed

    Guo, Liting; Chen, Baoan; Liu, Ran; Xia, Guohua; Wang, Yonglu; Li, Xueming; Wei, Chen; Wang, Xuemei; Jiang, Hulin

    2015-05-01

    The present study was designed to evaluate the biocompatibility of nanoparticles polyethylene glycol (PEG)-poly L-lysine (PLL)-poly lactic-co-glycolic acid copolymer (PLGA) (PEG-PLL-PLGA) before clinical application. We applied some tests to assess the safety of PEG-PLL-PLGA nanoparticles (NPs). There was low cytotoxicity of PEG-PLL-PLGA NPs in vitro as detected by MTT assay. Cell apoptosis and intracellular accumulation of PEG-PLL-PLGA were determined by FCM assay. The apoptotic rate induced by nanoparticles and the fluorescence intensity of intracellular daunorubicin (DNR) demonstrated that DNR-PEG-PLL-PLGA could be taken up by the mouse fibroblast cells (L929 cells). Hemolysis test and micronucleus (MN) assay demonstrated that the nanoparticles have no obviously blood toxicity and genotoxicity. DNR-PEG-PLL-PLGA NPs were injected into mice through tail vein to calculate the median lethal dose (LD50), the results showed that they had a wide safe scale. Blood was taken by removing the eyeball of mice to study the influence of DNR-PEG-PLL-PLGA in hepatic and renal functions. The results revealed that there was no significant difference as compared with the control group. Interestingly, the pathologic changes of heart, liver, spleen, lung and kidney were observed in nanoparticles treated mice. Thus, this study demonstrates that PEG-PLL-PLGA NPs appear to be highly biocompatible and safe nanoparticles that can be suitable for further application in the treatment of tumor.

  20. Biodegradable Poly (Lactic-co-Glycolic Acid)-Polyethylene Glycol Nanocapsules: An Efficient Carrier for Improved Solubility, Bioavailability, and Anticancer Property of Lutein.

    PubMed

    Arunkumar, Ranganathan; Prashanth, Keelara Veerappa Harish; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya; Dharmesh, Shylaja Mallaiah; Baskaran, Vallikannan

    2015-06-01

    Lutein bioavailability is limited because of its poor aqueous solubility. In this study, lutein-poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) nanocapsules were prepared to improve the solubility, bioavailability, and anticancer property of lutein. The scanning electron microscopy and dynamic light scattering examination revealed that the nanocapsules are smooth and spherical with size ranging from 80 to 500 nm (mean = 200 nm). In vitro lutein release profile from nanocapsules showed controlled sustainable release (66%) up to 72 h. Aqueous solubility of lutein nanocapsules was much higher by 735-fold than the lutein. Fourier transform infrared spectroscopy analyses showed no chemical interaction among PLGA, PEG, and lutein, indicating possible weak intermolecular forces like hydrogen bonds. X-ray diffraction revealed lutein is distributed in a disordered amorphous state in nanocapsules. Postprandial plasma kinetics (area under the curve) of an oral dose of lutein from nanocapsules was higher by 5.4-fold compared with that of micellar lutein (control). The antiproliferative effect of lutein from nanocapsules (IC50 value, 10.9 μM) was higher (43.6%) than the lutein (IC50 value, 25 μM). Results suggest that PLGA-PEG nanocapsule is an efficient carrier for enhancing hydrophilicity, bioavailability, and anticancer property of lipophilic molecules such as lutein. PMID:25824524

  1. Biodegradable Poly (Lactic-co-Glycolic Acid)-Polyethylene Glycol Nanocapsules: An Efficient Carrier for Improved Solubility, Bioavailability, and Anticancer Property of Lutein.

    PubMed

    Arunkumar, Ranganathan; Prashanth, Keelara Veerappa Harish; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya; Dharmesh, Shylaja Mallaiah; Baskaran, Vallikannan

    2015-06-01

    Lutein bioavailability is limited because of its poor aqueous solubility. In this study, lutein-poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) nanocapsules were prepared to improve the solubility, bioavailability, and anticancer property of lutein. The scanning electron microscopy and dynamic light scattering examination revealed that the nanocapsules are smooth and spherical with size ranging from 80 to 500 nm (mean = 200 nm). In vitro lutein release profile from nanocapsules showed controlled sustainable release (66%) up to 72 h. Aqueous solubility of lutein nanocapsules was much higher by 735-fold than the lutein. Fourier transform infrared spectroscopy analyses showed no chemical interaction among PLGA, PEG, and lutein, indicating possible weak intermolecular forces like hydrogen bonds. X-ray diffraction revealed lutein is distributed in a disordered amorphous state in nanocapsules. Postprandial plasma kinetics (area under the curve) of an oral dose of lutein from nanocapsules was higher by 5.4-fold compared with that of micellar lutein (control). The antiproliferative effect of lutein from nanocapsules (IC50 value, 10.9 μM) was higher (43.6%) than the lutein (IC50 value, 25 μM). Results suggest that PLGA-PEG nanocapsule is an efficient carrier for enhancing hydrophilicity, bioavailability, and anticancer property of lipophilic molecules such as lutein.

  2. Solubility prediction of salicylic acid in water-ethanol-propylene glycol mixtures using the Jouyban-Acree model.

    PubMed

    Jouyban, A; Chew, N Y K; Chan, H K; Khoubnasabjafari, M; Acree, W E

    2006-04-01

    To show the applicability of a solution model, i.e. the Jouyban-Acree model, for predicting the solubility of a solute in ternary solvent systems based on model constants computed using solubility data of the solute in binary solvent systems, the solubility of salicylic acid in water-ethanol, water-propylene glycol, ethanol-propylene glycol mixtures was determined. A minimum number of three data points from each binary system was used to calculate the binary interaction parameters of the model. Then the solubility in other binary solvent compositions and also in a number of ternary solvents was predicted, and the mean percentage deviation (MPD) was calculated as an accuracy criterion. The overall MPD (+/-SD) was 7.3 (+/-7.3)% and those of a similar predictive model was 15.7 (+/-11.5)%. The mean difference between the proposed and a previous model was statistically significant (paired t-test, p < 0.004).

  3. Treating cutaneous squamous cell carcinoma using 5-aminolevulinic acid polylactic-co-glycolic acid nanoparticle-mediated photodynamic therapy in a mouse model

    PubMed Central

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Zhao, Feng; Luan, Hansen; Wang, Xiuli

    2015-01-01

    Background Squamous cell carcinoma (SCC) is a common skin cancer, and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted 5-aminolevulinic acid (ALA) delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Materials and methods Ultraviolet-induced cutaneous SCCs were established in hairless mice. ALA-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NP-induced protoporphyrin IX fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results PLGA NPs enhanced protoporphyrin IX production in SCC. ALA PLGA NP-mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC. PMID:25609949

  4. Effects of lactic acid and glycolic acid on human osteoblasts: a way to understand PLGA involvement in PLGA/calcium phosphate composite failure.

    PubMed

    Meyer, Florent; Wardale, John; Best, Serena; Cameron, Ruth; Rushton, Neil; Brooks, Roger

    2012-06-01

    The use of degradable composite materials in orthopedics remains a field of intense research due to their ability to support new bone formation and degrade in a controlled manner, broadening their use for orthopedic applications. Poly (lactide-co-glycolide) acid (PLGA), a degradable biopolymer, is now a popular material for different orthopedic applications and is proposed for use in tissue engineering scaffolds either alone or combined with bioactive ceramics. Interference screws composed of calcium phosphates and PLGA are readily available in the market. However, some reports highlight problems of screw migration or aseptic cyst formation following screw degradation. In order to understand these phenomena and to help to improve implant formulation, we have evaluated the effects of PLGA degradation products: lactic acid and glycolic acid on human osteoblasts in vitro. Cell proliferation, differentiation, and matrix mineralization, important for bone healing were studied. It was found that the toxicity of polymer degradation products under buffering conditions was limited to high concentrations. However, non-toxic concentrations led to a decrease in cell proliferation, rapid cell differentiation, and mineralization failure. Calcium, whilst stimulating cell proliferation was not able to overcome the negative effects of high concentrations of lactic and glycolic acids on osteoblasts. These effects help to explain recently reported clinical failures of calcium phosphate/PLGA composites, but further in vitro analyses are needed to mimic the dynamic situation which occurs in the body by, for example, culture of osteoblasts with materials that have been pre-degraded to different extents and thus be able to relate these findings to the degradation studies that have been performed previously.

  5. Synthesis, characterization, and evaluation of paclitaxel loaded in six-arm star-shaped poly(lactic-co-glycolic acid)

    PubMed Central

    Chen, Yongxia; Yang, Ziying; Liu, Chao; Wang, Cuiwei; Zhao, Shunxin; Yang, Jing; Sun, Hongfan; Zhang, Zhengpu; Kong, Deling; Song, Cunxian

    2013-01-01

    Background Star-shaped polymers provide more terminal groups, and are promising for application in drug-delivery systems. Methods A new series of six-arm star-shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles’ encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs). Results The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40°C–50°C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4±6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from

  6. Miscibility and degradability of poly(lactic acid)poly(ethylene oxide)/poly(ethylene glycol) blends

    SciTech Connect

    Yue, C.L.; Dave, V.; Gross, R.A.; McCarthy, S.P.

    1995-12-01

    Poly(lactic acid) [PLA] was melt blended with polyethylene(oxide) [PEG] and poly(ethylene glycol) [PEG] in different compositions to form blown films. It was determined that PLA was miscible with PEO in all compositions. Based on Gordon-Taylor equation, it was determined that the interactions between PLA and PEO is stronger than PEG. The addition of low molecular weight PEG improved the elongation and tear strength of the blends. Enzymatic degradation results shows that the weight loss of all the samples was more than 80% of the initial weight in 48 hours.

  7. Drug release behavior of poly (lactic-glycolic acid) grafting from sodium alginate (ALG-g-PLGA) prepared by direct polycondensation.

    PubMed

    Shi, Gang; Ding, Yuanyuan; Zhang, Xin; Wu, Luyan; He, Fei; Ni, Caihua

    2015-01-01

    Hydrophobically modified sodium alginate, poly (lactic-glycolic acid) grafting from sodium alginate (ALG-g-PLGA), was successfully synthesized through direct one-step polymerization of sodium alginate, glycolic acid, and lactic acid. ALG-g-PLGA self-assembled to colloidal nanoparticles and subsequently hydrogel microspheres were obtained by crosslinking ALG-g-PLGA nanoparticles in the solution of calcium chloride. The modified hydrogel microspheres could be used as the drug delivery vehicles for a hydrophobic ibuprofen. Compared with sodium alginate, ALG-g-PLGA demonstrated an improved drug loading rate, encapsulation efficiency, and prolonged release speed. The products, as novel and highly promising biomaterials, have potential applications.

  8. Novel hydrogels of chitosan and poly(vinyl alcohol)-g-glycolic acid copolymer with enhanced rheological properties.

    PubMed

    Lejardi, A; Hernández, R; Criado, M; Santos, Jose I; Etxeberria, A; Sarasua, J R; Mijangos, C

    2014-03-15

    Poly(vinyl alcohol) (PVA) has been grafted with glycolic acid (GL), a biodegradable hydroxyl acid to yield modified poly(vinyl alcohol) (PVAGL). The formation of hydrogels at pH = 6.8 and physiological temperature through blending chitosan (CS) and PVAGL at different concentrations has been investigated. FTIR, DOSY NMR and oscillatory rheology measurements have been carried out on CS/PVAGL hydrogels and the results have been compared to those obtained for CS/PVA hydrogels prepared under the same conditions. The experimental results point to an increase in the number of interactions between chitosan and PVAGL in polymer hydrogels prepared with modified PVA. The resulting materials with enhanced elastic properties and thixotropic behavior are potential candidates to be employed as injectable materials for biomedical applications.

  9. Importance of Poly(lactic-co-glycolic acid) in Scaffolds for Guided Bone Regeneration: A Focused Review.

    PubMed

    Castillo-Dalí, Gabriel; Velázquez-Cayón, Rocío; Serrera-Figallo, M Angeles; Rodríguez-González-Elipe, Agustín; Gutierrez-Pérez, José-Luis; Torres-Lagares, Daniel

    2015-08-01

    Total or partial tissue damage and loss of function in an organ are two of the most serious and costly issues in human health. Initially, these problems were approached through organ and allogenic tissue transplantation, but this option is limited by the scarce availability of donors. In this manner, new bone for restoring or replacing lost and damaged bone tissue is an important health and socioeconomic necessity. Tissue engineering has been used as a strategy during the 21st century for mitigating this need through the development of guided bone regeneration scaffold and composites. In this manner, compared with other traditional methods, bone tissue engineering offers a new and interesting approach to bone repair. The poly-α-hydroxy acids, which include the copolymers of lactic acid and glycolic acid, have been used commonly in the fabrication of these scaffolds. The objective of our article was to review the characteristics and functions of scaffold with biomedical applications, with special interest in scaffold construction using poly(lactic-co-glycolic acid) polymers, in order to update the current methods used for fabrication and to improve the quality of these scaffolds, integrating this information into the context of advancements made in tissue engineering based on these structures. In the future, research into bone regeneration should be oriented toward a fruitful exchange between disciplines involved in tissue engineering, which is coming very close to filling the gaps in our ability to provide implants and restoration of functionality in bone tissue. Overcoming this challenge will provide benefits to a major portion of the population and facilitate substantial improvements to quality of life.

  10. Propylene glycol-linked amino acid/dipeptide diester prodrugs of oleanolic acid for PepT1-mediated transport: synthesis, intestinal permeability, and pharmacokinetics.

    PubMed

    Cao, Feng; Gao, Yahan; Wang, Meng; Fang, Lei; Ping, Qineng

    2013-04-01

    In our previous studies, ethylene glycol-linked amino acid diester prodrugs of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug, designed to target peptide transporter 1 (PepT1) have been synthesized and evaluated. Unlike ethylene glycol, propylene glycol is of very low toxicity in vivo. In this study, propylene glycol was used as a linker to further compare the effect of the type of linker on the stability, permeability, affinity, and bioavailability of the prodrugs of OA. Seven diester prodrugs with amino acid/dipeptide promoieties containing L-Val ester (7a), L-Phe ester (7b), L-Ile ester (7c), D-Val-L-Val ester (9a), L-Val-L-Val ester (9b), L-Ala-L-Val ester (9c), and L-Ala-L-Ile ester (9d) were designed and successfully synthesized. In situ rat single-pass intestinal perfusion (SPIP) model was performed to screen the effective permeability (P(eff)) of the prodrugs. P(eff) of 7a, 7b, 7c, 9a, 9b, 9c, and 9d (6.7-fold, 2.4-fold, 1.24-fold, 1.22-fold, 4.15-fold, 2.2-fold, and 1.4-fold, respectively) in 2-(N-morpholino)ethanesulfonic acid buffer (MES) with pH 6.0 showed significant increase compared to that of OA (p < 0.01). In hydroxyethyl piperazine ethanesulfonic acid buffer (HEPES) of pH 7.4, except for 7c, 9a, and 9d, P(eff) of the other prodrugs containing 7a (5.2-fold), 7b (2.0-fold), 9b (3.1-fold), and 9c (1.7-fold) exhibited significantly higher values than that of OA (p < 0.01). In inhibition studies with glycyl-sarcosine (Gly-Sar, a typical substrate of PepT1), P(eff) of 7a (5.2-fold), 7b (2.0-fold), 9b (3.1-fold), and 9c (2.3-fold) had significantly reduced values (p < 0.01). Compared to the apparent permeability coefficient (P(app)) of OA with Caco-2 cell monolayer, significant enhancement of the P(app) of 7a (5.27-fold), 9b (3.31-fold), 9a (2.26-fold), 7b (2.10-fold), 7c (2.03-fold), 9c (1.87-fold), and 9d (1.39-fold) was also observed (p < 0.01). Inhibition studies with Gly-Sar (1 mM) showed that P(app) of 7a, 9b, and

  11. Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments

    PubMed Central

    Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

    2013-01-01

    Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression and resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent, for imaging the acidic tumor microenvironment. The preparation included conjugation of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water soluble glycol chitosan (GC) polymer, which contains pH titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate to polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM−1s−1. GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor bearing mice 2 h post-injection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment. PMID:24044414

  12. Synthesis and Characterization of Silicate Ester Prodrugs and Poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) Block Copolymers for Formulation into Prodrug-Loaded Nanoparticles

    NASA Astrophysics Data System (ADS)

    Wohl, Adam Richard

    Fine control of the physical and chemical properties of customized materials is a field that is rapidly advancing. This is especially critical in pursuits to develop and optimize novel nanoparticle drug delivery. Specifically, I aim to apply chemistry concepts to test the hypothesis "Silicate ester prodrugs of paclitaxel, customized to have the proper hydrophobicity and hydrolytic lability, can be formulated with well-defined, biocompatible, amphiphilic block copolymers into nanoparticles that are effective drugs." Chapter 1 briefly describes the context and motivation of the scientific pursuits described in this thesis. In Chapter 2, a family of model silicate esters is synthesized, the hydrolysis rate of each compound is benchmarked, and trends are established based upon the steric bulk and leaving group ability of the silicate substituents. These trends are then applied to the synthesis of labile silicate ester prodrugs in Chapter 3. The bulk of this chapter focuses on the synthesis, hydrolysis, and cytotoxicity of prodrugs based on paclitaxel, a widely used chemotherapeutic agent. In Chapter 4, a new methodology for the synthesis of narrowly dispersed, "random" poly(lactic-co-glycolic acid) polymers by a constant infusion of the glycolide monomer is detailed. Using poly(ethylene glycol) as a macroinitiator, amphiphilic block copolymers were synthesized. Co-formulating a paclitaxel silicate and an amphiphilic block copolymer via flash nanoprecipitation led to highly prodrug-loaded, kinetically trapped nanoparticles. Studies to determine the structure, morphology, behavior, and efficacy of these nanoparticles are described in Chapter 5. Efforts to develop a general strategy for the selective end-functionalization of the polyether block of these amphiphilic block copolymers are discussed in Chapter 6. Examples of this strategy include functionalization of the polyether with an azide or a maleimide. Finally, Chapter 7 provides an outlook for future development of

  13. A new formulation of curcumin using poly (lactic-co-glycolic acid)—polyethylene glycol diblock copolymer as carrier material

    NASA Astrophysics Data System (ADS)

    Phuong Tuyen Dao, Thi; Hoai Nguyen, To; To, Van Vinh; Ho, Thanh Ha; Nguyen, Tuan Anh; Chien Dang, Mau

    2014-09-01

    The aim of this study is to fabricate a nanoparticle formulation of curcumin using a relatively new vehicle as the matrix polymer: poly(lactic-co-glycolic acid) (PLGA)- polyethylene glycol (PEG) diblock copolymer, and to investigate the effects of the various processing parameters on the characteristics of nanoparticles (NPs). We successfully synthesized the matrix polymer of PLGA-PEG by conjugation of PLGA copolymer with a carboxylate end group to a heterobifunctional amine-PEG-methoxy using N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide as conjugation crosslinkers. The composition of the formed product (PLGA-PEG) was characterized with 500 MHz 1H nuclear magnetic resonance (NMR). The conjugation of PLGA-PEG was confirmed using Fourier transform infrared (FTIR) spectrum study. This diblock copolymer was then used to prepare the curcumin-loaded NPs through nanoprecipitation technique. With this method, we found that the size distribution depends on the type of solvent, the concentration of polymer and the concentration of surfactant. The particle size and size distribution were measured by dynamic light scattering (DLS). Transmission electron microscope (TEM) and scanning electron microscope (SEM) were used to confirm the size, structure and morphology of the successfully prepared NPs. All of our results showed that they are spherical and quite homologous with mean diameter around of 100-300 nm. Further, we evaluated encapsulation efficiency and some characteristics of NPs through high performance liquid chromatography (HPLC) analyses, zeta-potential measurements and x-ray diffraction studies. The HPLC analyses were performed to determine the amount of curcumin entrapped in NPs. The zeta-potential measurements confirmed the stability of NPs and the successful encapsulation of curcumin within NPs and the x-ray diffraction patterns showed the disordered-crystalline phase of curcumin inside the polymeric matrix.

  14. Dexamethasone-loaded poly(D, L-lactic acid) microspheres/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles composite for skin augmentation.

    PubMed

    Fan, Min; Liao, Jinfeng; Guo, Gang; Ding, Qiuxia; Yang, Yi; Luo, Feng; Qian, Zhiyong

    2014-04-01

    Soft tissue augmentation using various injectable fillers has gained popularity as more patients seek esthetic improvement through minimally invasive procedures requiring little or no recovery time. The currently available injectable skin fillers can be divided into three categories. With careful assessment, stimulatory fillers are the most ideal fillers. In this study, dexamethasone-loaded poly(D, L-lactic acid) (PLA) microspheres of approximately 90 micro m suspended in poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles were prepared as stimulatory filler for skin augmentation. The biodegradable PECE copolymer can form nano-sized micelles in water, which instantly turns into a non-flowing gel at body temperature due to micellar aggregation. The PECE micelles (making up 90% of composite) served as vehicle for subcutaneous injection were metabolized within 44 days. At the same time, the dexamethasone-loaded PLA microspheres (10% of composite) merely served as stimulus for connective tissue formation. Dexamethasone-loaded PLA microspheres/PECE micelles composite presented great hemocompatibility in vitro. It was demonstrated in the in vive study that the composite was biodegradable, biocompatible, nontoxic and nonmigratory. Histopathological studies indicated that the composite could stimulate collagen regeneration. Furthermore, granuloma, the main complication of the stimulatory fillers, did not appear when the composite was injected into the back of SD rats, because of the dexamethasone controlled release from the composite. All results suggested that dexamethasone-loaded PLA microspheres/PECE micelles composite may be an efficient and promising biomaterial for skin augmentation. PMID:24734511

  15. Dexamethasone-loaded poly(D, L-lactic acid) microspheres/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles composite for skin augmentation.

    PubMed

    Fan, Min; Liao, Jinfeng; Guo, Gang; Ding, Qiuxia; Yang, Yi; Luo, Feng; Qian, Zhiyong

    2014-04-01

    Soft tissue augmentation using various injectable fillers has gained popularity as more patients seek esthetic improvement through minimally invasive procedures requiring little or no recovery time. The currently available injectable skin fillers can be divided into three categories. With careful assessment, stimulatory fillers are the most ideal fillers. In this study, dexamethasone-loaded poly(D, L-lactic acid) (PLA) microspheres of approximately 90 micro m suspended in poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles were prepared as stimulatory filler for skin augmentation. The biodegradable PECE copolymer can form nano-sized micelles in water, which instantly turns into a non-flowing gel at body temperature due to micellar aggregation. The PECE micelles (making up 90% of composite) served as vehicle for subcutaneous injection were metabolized within 44 days. At the same time, the dexamethasone-loaded PLA microspheres (10% of composite) merely served as stimulus for connective tissue formation. Dexamethasone-loaded PLA microspheres/PECE micelles composite presented great hemocompatibility in vitro. It was demonstrated in the in vive study that the composite was biodegradable, biocompatible, nontoxic and nonmigratory. Histopathological studies indicated that the composite could stimulate collagen regeneration. Furthermore, granuloma, the main complication of the stimulatory fillers, did not appear when the composite was injected into the back of SD rats, because of the dexamethasone controlled release from the composite. All results suggested that dexamethasone-loaded PLA microspheres/PECE micelles composite may be an efficient and promising biomaterial for skin augmentation.

  16. Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

    PubMed Central

    Vasconcelos, Aimee; Vega, Estefania; Pérez, Yolanda; Gómara, María J; García, María Luisa; Haro, Isabel

    2015-01-01

    In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. PMID:25670897

  17. Urea, Glycolic Acid, and Glycerol in an Organic Residue Produced by Ultraviolet Irradiation of Interstellar/Pre-Cometary Ice Analogs

    NASA Astrophysics Data System (ADS)

    Nuevo, Michel; Bredehöft, Jan Hendrik; Meierhenrich, Uwe J.; d'Hendecourt, Louis; Thiemann, Wolfram H.-P.

    2010-03-01

    More than 50 stable organic molecules have been detected in the interstellar medium (ISM), from ground-based and onboard-satellite astronomical observations, in the gas and solid phases. Some of these organics may be prebiotic compounds that were delivered to early Earth by comets and meteorites and may have triggered the first chemical reactions involved in the origin of life. Ultraviolet irradiation of ices simulating photoprocesses of cold solid matter in astrophysical environments have shown that photochemistry can lead to the formation of amino acids and related compounds. In this work, we experimentally searched for other organic molecules of prebiotic interest, namely, oxidized acid labile compounds. In a setup that simulates conditions relevant to the ISM and Solar System icy bodies such as comets, a condensed CH3OH:NH3â = 1:1 ice mixture was UV irradiated at ˜80 K. The molecular constituents of the nonvolatile organic residue that remained at room temperature were separated by capillary gas chromatography and identified by mass spectrometry. Urea, glycolic acid, and glycerol were detected in this residue, as well as hydroxyacetamide, glycerolic acid, and glycerol amide. These organics are interesting target molecules to be searched for in space. Finally, tentative mechanisms of formation for these compounds under interstellar/pre-cometary conditions are proposed.

  18. Urea, glycolic acid, and glycerol in an organic residue produced by ultraviolet irradiation of interstellar/pre-cometary ice analogs.

    PubMed

    Nuevo, Michel; Bredehöft, Jan Hendrik; Meierhenrich, Uwe J; d'Hendecourt, Louis; Thiemann, Wolfram H-P

    2010-03-01

    More than 50 stable organic molecules have been detected in the interstellar medium (ISM), from ground-based and onboard-satellite astronomical observations, in the gas and solid phases. Some of these organics may be prebiotic compounds that were delivered to early Earth by comets and meteorites and may have triggered the first chemical reactions involved in the origin of life. Ultraviolet irradiation of ices simulating photoprocesses of cold solid matter in astrophysical environments have shown that photochemistry can lead to the formation of amino acids and related compounds. In this work, we experimentally searched for other organic molecules of prebiotic interest, namely, oxidized acid labile compounds. In a setup that simulates conditions relevant to the ISM and Solar System icy bodies such as comets, a condensed CH(3)OH:NH(3) = 1:1 ice mixture was UV irradiated at approximately 80 K. The molecular constituents of the nonvolatile organic residue that remained at room temperature were separated by capillary gas chromatography and identified by mass spectrometry. Urea, glycolic acid, and glycerol were detected in this residue, as well as hydroxyacetamide, glycerolic acid, and glycerol amide. These organics are interesting target molecules to be searched for in space. Finally, tentative mechanisms of formation for these compounds under interstellar/pre-cometary conditions are proposed.

  19. Urea, glycolic acid, and glycerol in an organic residue produced by ultraviolet irradiation of interstellar/pre-cometary ice analogs.

    PubMed

    Nuevo, Michel; Bredehöft, Jan Hendrik; Meierhenrich, Uwe J; d'Hendecourt, Louis; Thiemann, Wolfram H-P

    2010-03-01

    More than 50 stable organic molecules have been detected in the interstellar medium (ISM), from ground-based and onboard-satellite astronomical observations, in the gas and solid phases. Some of these organics may be prebiotic compounds that were delivered to early Earth by comets and meteorites and may have triggered the first chemical reactions involved in the origin of life. Ultraviolet irradiation of ices simulating photoprocesses of cold solid matter in astrophysical environments have shown that photochemistry can lead to the formation of amino acids and related compounds. In this work, we experimentally searched for other organic molecules of prebiotic interest, namely, oxidized acid labile compounds. In a setup that simulates conditions relevant to the ISM and Solar System icy bodies such as comets, a condensed CH(3)OH:NH(3) = 1:1 ice mixture was UV irradiated at approximately 80 K. The molecular constituents of the nonvolatile organic residue that remained at room temperature were separated by capillary gas chromatography and identified by mass spectrometry. Urea, glycolic acid, and glycerol were detected in this residue, as well as hydroxyacetamide, glycerolic acid, and glycerol amide. These organics are interesting target molecules to be searched for in space. Finally, tentative mechanisms of formation for these compounds under interstellar/pre-cometary conditions are proposed. PMID:20402585

  20. Production of glycolic acid by chemolithotrophic iron- and sulfur-oxidizing bacteria and its role in delineating and sustaining acidophilic sulfide mineral-oxidizing consortia.

    PubMed

    Nancucheo, Ivan; Johnson, D Barrie

    2010-01-01

    Glycolic acid was detected as an exudate in actively growing cultures of three chemolithotrophic acidophiles that are important in biomining operations, Leptospirillum ferriphilum, Acidithiobacillus (At.) ferrooxidans, and At. caldus. Although similar concentrations of glycolic acid were found in all cases, the concentrations corresponded to ca. 24% of the total dissolved organic carbon (DOC) in cultures of L. ferriphilum but only ca. 5% of the total DOC in cultures of the two Acidithiobacillus spp. Rapid acidification (to pH 1.0) of the culture medium of At. caldus resulted in a large increase in the level of DOC, although the concentration of glycolic acid did not change in proportion. The archaeon Ferroplasma acidiphilum grew in the cell-free spent medium of At. caldus; glycolic acid was not metabolized, although other unidentified compounds in the DOC pool were metabolized. Glycolic acid exhibited levels of toxicity with 21 strains of acidophiles screened similar to those of acetic acid. The most sensitive species were chemolithotrophs (L. ferriphilum and At. ferrivorans), while the most tolerant species were chemoorganotrophs (Acidocella, Acidobacterium, and Ferroplasma species), and the ability to metabolize glycolic acid appeared to be restricted (among acidophiles) to Firmicutes (chiefly Sulfobacillus spp.). Results of this study help explain why Sulfobacillus spp. rather than other acidophiles are the main organic carbon-degrading bacteria in continuously fed stirred tanks used to bioprocess sulfide mineral concentrates and also why temporary cessation of pH control in these systems, resulting in rapid acidification, often results in a plume of the archaeon Ferroplasma.

  1. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy.

    PubMed

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  2. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy.

    PubMed

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  3. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    PubMed Central

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  4. 21 CFR 172.856 - Propylene glycol mono- and diesters of fats and fatty acids.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.856 Propylene glycol mono- and... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Propylene glycol mono- and diesters of fats...

  5. Glycyrrhetinic acid-poly(ethylene glycol)-glycyrrhetinic acid tri-block conjugates based self-assembled micelles for hepatic targeted delivery of poorly water soluble drug.

    PubMed

    Wu, Fengbo; Xu, Ting; Liu, Chi; Chen, Can; Song, Xiangrong; Zheng, Yu; He, Gu

    2013-01-01

    The triblock 18β-glycyrrhetinic acid-poly(ethylene glycol)18β-glycyrrhetinic acid conjugates (GA-PEG-GA) based self-assembled micelles were synthesized and characterized by FTIR, NMR, transmission electron microscopy, and particle size analysis. The GA-PEG-GA conjugates having the critical micelle concentration of 6 × 10(-5) M were used to form nanosized micelles, with mean diameters of 159.21 ± 2.2 nm, and then paclitaxel (PTX) was incorporated into GA-PEG-GA micelles by self-assembly method. The physicochemical properties of the PTX loaded GA-PEG-GA micelles were evaluated including in vitro cellular uptake, cytotoxicity, drug release profile, and in vivo tissue distribution. The results demonstrate that the GA-PEG-GA micelles had low cytotoxicity and good ability of selectively delivering drug to hepatic cells in vitro and in vivo by the targeting moiety glycyrrhetinic acid. In conclusion, the GA-PEG-GA conjugates have potential medical applications for targeted delivery of poor soluble drug delivery.

  6. Guided bone regeneration by poly(lactic-co-glycolic acid) grafted hyaluronic acid bi-layer films for periodontal barrier applications.

    PubMed

    Park, Jung Kyu; Yeom, Junseok; Oh, Eun Ju; Reddy, Mallikarjuna; Kim, Jong Young; Cho, Dong-Woo; Lim, Hyun Pil; Kim, Nam Sook; Park, Sang Won; Shin, Hong-In; Yang, Dong Jun; Park, Kwang Bum; Hahn, Sei Kwang

    2009-11-01

    A novel protocol for the synthesis of biocompatible and degradation controlled poly(lactic-co-glycolic acid) grafted hyaluronic acid (HA-PLGA) was successfully developed for periodontal barrier applications. HA was chemically modified with adipic acid dihydrazide (ADH) in the mixed solvent of water and ethanol, which resulted in a high degree of HA modification up to 85 mol.%. The stability of HA-ADH to enzymatic degradation by hyaluronidase increased with ADH content in HA-ADH. When the ADH content in HA-ADH was higher than 80 mol.%, HA-ADH became soluble in dimethyl sulfoxide and could be grafted to the activated PLGA with N,N'-dicyclohexyl carbodiimide and N-hydroxysuccinimide. The resulting HA-PLGA was used for the preparation of biphasic periodontal barrier membranes in chloroform. According to in vitro hydrolytic degradation tests in phosphate buffered saline, HA-PLGA/PLGA blend film with a weight ratio of 1/2 degraded relatively slowly compared to PLGA film and HA coated PLGA film. Four different samples of a control, OSSIX(TM) membrane, PLGA film, and HA-PLGA/PLGA film were assessed as periodontal barrier membranes for the calvarial critical size bone defects in SD rats. Histological and histomorphometric analyses revealed that HA-PLGA/PLGA film resulted in the most effective bone regeneration compared to other samples with a regenerated bone area of 63.1% covering the bone defect area. PMID:19477304

  7. Modeling of hyaluronic acid containing anti-cancer drugs-loaded polylactic-co-glycolic acid bioconjugates for targeted delivery to cancer cells

    NASA Astrophysics Data System (ADS)

    Gul-e-Saba, Adulphakdee, A.; Madthing, A.; Zafar, M. N.; Abdullah, M. A.

    2012-09-01

    Molecular modeling of hyaluronan (HA), polylactic-co-glycolic acid (PLGA), polyethylene glycol-bis-amine (PEG-bis-amine), Curcumin, Cisplatin and the conjugate HA-PEG-PLGA containing Curcumin/Cisplatin were performed using Discovery Studio 2.5 to better understand issues and constraints related to targeted delivery of potent anticancer drugs to cancer cells. HA, a versatile biopolymer is a ligand of cancer cell receptor, CD44 that can be particularly useful in a receptor-mediated cellular uptake of drug-incorporated nanoparticles. Biocompatible and biodegradable polymers, PLGA and PEG, serve as polymeric micelles for controlled-release of drug. Curcumin as a natural anticancer agent has poor solubility that limits its use in drug therapeutics, while platinum-based Cisplatin exhibits systemic cytotoxicity. These can be overcome via drug delivery in polymeric biocompatible vehicles. The PLGA-PEG-HA conjugate shows the total measurement of 105 bond length with average bond length of 1.274163 Å. The conjugation between PEG and HA occurs at C8-O1 atoms and can be manipulated to improve properties.

  8. Health Hazard Evaluation Report HETA 83-166-1594, Witco Chemical Corporation, Perth Amboy, New Jersey. [Ethylene oxide, glycols, and adipic acid

    SciTech Connect

    Cummings, C.E.; Roseman, J.

    1985-05-01

    Area and personel air samples were analyzed for ethylene oxide, glycols, and adipic-acid at the Witco Chemical Corporation, Perth Amboy, New Jersey from November to December, 1983 and May, 1984. The evaluation was requested by the union to investigate possible health effects due to polychlorinated biphenyls (PCBs), glycols, and ethylene oxide. The evaluation was assigned to the New Jersey State Department of Health. The authors conclude that health hazards due to ethylene oxide and airborne fatty acid exposures exist. Recommendations include improving ventilation and work practices and implementing an OSHA approved respirator program.

  9. Hyaluronic acid/poly(lactic-co-glycolic acid) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate as skin tissue engineering scaffolds.

    PubMed

    Lee, Eun Ji; Lee, Jong Ho; Jin, Linhua; Jin, Oh Seong; Shin, Yong Cheol; Sang, Jin Oh; Lee, Jaebeom; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-11-01

    In this study, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) for application to tissue engineering scaffolds for skin regeneration were prepared via coaxial electrospinning. Physicochemical properties of HA/PLGA-E core/shell fiber meshes were characterized by SEM, Raman spectroscopy, contact angle, EGCG release profiling and in vitro degradation. Biomechanical properties of HA/PLGA-E meshes were also investigated by a tensile strength test. SEM images showed that HA/PLGA-E fiber meshes had a three-dimensional interconnected pore structure with an average fiber diameter of about 1270 nm. Raman spectra revealed that EGCG was uniformly dispersed in the PLGA shell of meshes. HA/PLGA-E meshes showed sustained EGCG release patterns by controlled diffusion and PLGA degradation over 4 weeks. EGCG loading did not adversely affect the tensile strength and elastic modulus of HA/PLGA meshes, while increased their hydrophilicity and surface energy. Attachment of human dermal fibroblasts on HA/PLGA-E meshes was appreciably increased and their proliferation was steadily retained during the culture period. These results suggest that HA/PLGA-E core/shell fiber meshes can be potentially used as scaffolds supporting skin regeneration. PMID:25958546

  10. High performance quasi-solid-state dye-sensitized solar cells based on poly(lactic acid-co-glycolic acid)

    NASA Astrophysics Data System (ADS)

    Kwon, Woosung; Rhee, Shi-Woo

    A stable quasi-solid-state dye-sensitized solar cell (DSC) with a novel amphiphilic polymer gel electrolyte (APGE) based on poly(lactic acid-co-glycolic acid) (PLGA) is fabricated. The APGE could be readily prepared by a simple method at low temperature of 50 °C and exhibits a quasi-solid property, high conductivity, and long-term stability. The 20 and 40 wt% APGE-based DSCs show high photovoltaic conversion efficiency of 7.5 and 7.4%, respectively, under AM 1.5 simulated sunlight, which is comparable to the liquid electrolyte-based DSC with the efficiency of 7.6%. The 40 wt% APGE-based DSC maintains 95% of the initial performance after 60 days in practical conditions. It is also noteworthy that the APGE endows with higher short-circuit current density than the liquid electrolyte. Different natures of the APGE from the typical polymer gel electrolytes have been elucidated by the I- V measurements, electrochemical impedance spectroscopy, electrophoretic measurements, and transmission electron microscopy.

  11. Shape Memory Performance of Thermoplastic Amphiphilic Triblock Copolymer poly(D,L-lactic acid-co-ethylene glycol-co-D,L-lactic acid) (PELA)/Hydroxyapatite Composites

    PubMed Central

    Kutikov, Artem B.; Reyer, Kevin A.

    2015-01-01

    Biodegradable polymer/hydroxyapatite (HA) composites are desired for skeletal tissue engineering. When engineered with thermal-responsive shape memory properties, they may be delivered in a minimally invasive temporary shape and subsequently triggered to conform to a tissue defect. Here we report the shape memory properties of thermoplastic amphiphilic poly(D,L-lactic acid-co-ethylene glycol-co-D,L-lactic acid) (PELA, 120 kDa) and HA-PELA composites. These materials can be cold-deformed and stably fixed into temporary shapes at room temperature and undergo rapid shape recovery (< 3 s) at 50 °C. Stable fixation (>99% fixing ratio) of large deformations is achieved at −20 °C. While the shape recovery from tensile deformations slows with higher HA contents, all composites (up to 20 wt% HA) achieve high shape recovery (>90%) upon 10-min equilibration at 50 °C. The permanent shapes of HA-PELA can be reprogramed at 50 °C, and macroporous shape memory scaffolds can be fabricated by rapid prototyping. PMID:26457046

  12. Preparation and evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) nanoparticles.

    PubMed

    Pradhan, Roshan; Poudel, Bijay Kumar; Choi, Ju Yeon; Choi, Im Soon; Shin, Beom Soo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2015-01-01

    In the present study, we developed the novel 17-allyamino-17-demethoxygeldanamycin (17-AAG)-loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate and poloxamer 407 as the anionic and non-ionic surfactant for stabilization. The PLGA NPs were prepared by emulsification/solvent evaporation method. Both the drug/polymer ratio and phase ratio were 1:10 (w/w). The optimized formulation of 17-AAG-loaded PLGA NPs had a particle size and polydispersity index of 151.6 ± 2.0 and 0.152 ± 0.010 nm, respectively, which was further supported by TEM image. The encapsulation efficiency and drug loading capacity were 69.9 and 7.0%, respectively. In vitro release study showed sustained release. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.468, which suggested that the drug was released by anomalous or non-Fickian diffusion. In addition, 17-AAG-loaded PLGA NPs in 72 h, displayed approximately 60% cell viability reduction at 10 µg/ml 17-AAG concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of 17-AAG into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

  13. Dimensionality reduction, and function approximation of poly(lactic-co-glycolic acid) micro- and nanoparticle dissolution rate.

    PubMed

    Ojha, Varun Kumar; Jackowski, Konrad; Abraham, Ajith; Snášel, Václav

    2015-01-01

    Prediction of poly(lactic-co-glycolic acid) (PLGA) micro- and nanoparticles' dissolution rates plays a significant role in pharmaceutical and medical industries. The prediction of PLGA dissolution rate is crucial for drug manufacturing. Therefore, a model that predicts the PLGA dissolution rate could be beneficial. PLGA dissolution is influenced by numerous factors (features), and counting the known features leads to a dataset with 300 features. This large number of features and high redundancy within the dataset makes the prediction task very difficult and inaccurate. In this study, dimensionality reduction techniques were applied in order to simplify the task and eliminate irrelevant and redundant features. A heterogeneous pool of several regression algorithms were independently tested and evaluated. In addition, several ensemble methods were tested in order to improve the accuracy of prediction. The empirical results revealed that the proposed evolutionary weighted ensemble method offered the lowest margin of error and significantly outperformed the individual algorithms and the other ensemble techniques.

  14. The influence of nanotexturing of poly(lactic-co-glycolic acid) films upon human ovarian cancer cell attachment

    NASA Astrophysics Data System (ADS)

    Yaşayan, Gökçen; Xue, Xuan; Collier, Pamela; Clarke, Philip; Alexander, Morgan R.; Marlow, Maria

    2016-06-01

    In this study, we have produced nanotextured poly(lactic-co-glycolic acid) (PLGA) films by using polystyrene (PS) particles as a template to make a polydimethylsiloxane mould against which PLGA is solvent cast. Biocompatible, biodegradable and nanotextured PLGA films were prepared with PS particles of diameter of 57, 99, 210, and 280 nm that produced domes of the same dimension in the PLGA surface. The effect of the particulate monolayer templating method was investigated to enable preparation of the films with uniformly ordered surface nanodomes. Cell attachment of a human ovarian cancer cell line (OVCAR3) alone and co-cultured with mesenchymal stem cells (MSCs) was evaluated on flat and topographically nano-patterned surfaces. Cell numbers were observed to increase on the nanotextured surfaces compared to non-textured surfaces both with OVCAR3 cultures and OVCAR3-MSC co-cultures at 24 and 48 h time points.

  15. An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

    PubMed Central

    Gentile, Piergiorgio; Chiono, Valeria; Carmagnola, Irene; Hatton, Paul V.

    2014-01-01

    Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function. PMID:24590126

  16. Photodynamic therapy of tumors with pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles

    PubMed Central

    Liu, Hui; Zhao, Mei; Wang, Jin; Pang, Mingpei; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan; Hong, Zhangyong

    2016-01-01

    Photodynamic therapy (PDT) has many advantages in treating cancers, but the lack of ideal photosensitizers continues to be a major limitation restricting the clinical utility of PDT. This study aimed to overcome this obstacle by generating pyropheophorbide-a-loaded polyethylene glycol–poly(lactic-co-glycolic acid) nanoparticles (NPs) for efficient tumor-targeted PDT. The fabricated NPs were efficiently internalized in the mitochondrion by cancer cells, and they efficiently killed cancer cells in a dose-dependent manner when activated with light. Systemically delivered NPs were highly enriched in tumor sites, and completely ablated the tumors in a xenograft KB tumor mouse model when illuminated with 680 nm light (156 mW/cm2, 10 minutes). The results suggested that this tumor-specific NP-delivery system for pyropheophorbide-a has the potential to be used in tumor-targeted PDT. PMID:27729788

  17. Alpha-tocopheryl polyethylene glycol succinate-emulsified poly(lactic-co-glycolic acid) nanoparticles for reversal of multidrug resistance in vitro

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Guo, Miao; Lu, Yu; Ding, Li-Ying; Ron, Wen-Ting; Liu, Ya-Qing; Song, Fei-Fei; Yu, Shu-Qin

    2012-12-01

    Multidrug resistance (MDR) is one of the factors in the failure of anticancer chemotherapy. In order to enhance the anticancer effect of P-glycoprotein (P-gp) substrates, inhibition of the P-gp efflux pump on MDR cells is a good tactic. We designed novel multifunctional drug-loaded alpha-tocopheryl polyethylene glycol succinate (TPGS)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPGS/PLGA/SN-38 NPs; SN-38 is 7-ethyl-10-hydroxy-camptothecin), with TPGS-emulsified PLGA NPs as the carrier and modulator of the P-gp efflux pump and SN-38 as the model drug. TPGS/PLGA/SN-38 NPs were prepared using a modified solvent extraction/evaporation method. Physicochemical characterizations of TPGS/PLGA/SN-38 NPs were in conformity with the principle of nano-drug delivery systems (nDDSs), including a diameter of about 200 nm, excellent spherical particles with a smooth surface, narrow size distribution, appropriate surface charge, and successful drug-loading into the NPs. The cytotoxicity of TPGS/PLGA/SN-38 NPs to MDR cells was increased by 3.56 times compared with that of free SN-38. Based on an intracellular accumulation study relative to the time-dependent uptake and efflux inhibition, we suggest novel mechanisms of MDR reversal of TPGS/PLGA NPs. Firstly, TPGS/PLGA/SN-38 NPs improved the uptake of the loaded drug by clathrin-mediated endocytosis in the form of unbroken NPs. Simultaneously, intracellular NPs escaped the recognition of P-gp by MDR cells. After SN-38 was released from TPGS/PLGA/SN-38 NPs in MDR cells, TPGS or/and PLGA may modulate the efflux microenvironment of the P-gp pump, such as mitochondria and the P-gp domain with an ATP-binding site. Finally, the controlled-release drug entered the nucleus of the MDR cell to induce cytotoxicity. The present study showed that TPGS-emulsified PLGA NPs could be functional carriers in nDDS for anticancer drugs that are also P-gp substrates. More importantly, to enhance the therapeutic effect of P-gp substrates, this work

  18. Controlled Dual Drug Release and In Vitro Cytotoxicity of Electrospun Poly(lactic-co-glycolic acid) Nanofibers Encapsulated with Micelles.

    PubMed

    Liu, Wanyun; Wei, Junchao; Wei, Yen; Chen, Yiwang

    2015-03-01

    In order to realize controlled dual release of two hydrophobic drugs with distinct rates in a vehicle, novel poly(lactic-co-glycolic acid) (PLGA) composite nanofibers encapsulated with micelles were successfully fabricated by "emulsion-electrospinning." Brefeldin A (BFA) was firstly embedded in monomethoxy-poly(ethylene glycol)-b-poly(L-lactide) (MePEG-PLLA) micelles. By means of "emulsion-electrospinning," paclitaxel (PTX) and polymeric micelles contained BFA were successfully loaded into the electrospun PLGA composite nanofibers. The in vitro release results demonstrated that the location of the drugs in the electrospun fibers determined their release profiles. BFA had a long-term and sustained release while PTX had a relatively rapid release in the dual drugs delivery system. In vitro cytotoxicity studies revealed that the composite nanofibers with two drugs restrained HepG-2 cells more efficiently. These results strongly suggested that the electrospun composite nanofibers containing polymeric micelles can be used as an effective controlled dual release of hydrophobic drugs and were suitable for postoperative chemotherapy of cancers. PMID:26307826

  19. Microporous Poly(L-Lactic Acid) Membranes Fabricated by Polyethylene Glycol Solvent-Cast/Particulate Leaching Technique

    PubMed Central

    Selvam, Shivaram; Chang, Wenji V.; Nakamura, Tamako; Samant, Deedar M.; Thomas, Padmaja B.; Trousdale, Melvin D.; Mircheff, Austin K.; Schechter, Joel E.

    2009-01-01

    With the eventual goal of developing a tissue-engineered tear secretory system, we found that primary lacrimal gland acinar cells grown on solid poly(L-lactic acid) (PLLA) supports expressed the best histiotypic morphology. However, to be able to perform vectorial transport functions, epithelia must be supported by a permeable substratum. In the present study, we describe the use of a solvent-cast/particulate leaching technique to fabricate microporous PLLA membranes (mpPLLAm) from PLLA/polyethylene glycol blends. Scanning electron microscopy revealed pores on both the air-cured (∼4 μm) and glass-cured sides (<2 μm) of the mpPLLAm. Diffusion studies were performed with mpPLLAm fabricated from 57.1% PLLA/42.9% polyethylene glycol blends to confirm the presence of channelized pores. The data reveal that glucose, L-tryptophan, and dextran (a high molecular weight glucose polymer) readily permeate mpPLLAm. Diffusion of the immunoglobulin G through the mpPLLAm decreased with time, suggesting the possible adsorption and occlusion of the pores. Cells cultured on the mpPLLAm (57.1/42.9 wt%) grew to subconfluent monolayers but retained histiotypic morphological and physiological characteristics of lacrimal acinar cells in vivo. Our results suggest that mpPLLAm fabricated using this technique may be useful as a scaffold for a bioartificial lacrimal gland device. PMID:19260769

  20. Biocompatibility and bone-repairing effects: comparison between porous poly-lactic-co-glycolic acid and nano-hydroxyapatite/poly(lactic acid) scaffolds.

    PubMed

    Zong, Chen; Qian, Xiaodan; Tang, Zihua; Hu, Qinghong; Chen, Jiarong; Gao, Changyou; Tang, Ruikang; Tong, Xiangmin; Wang, Jinfu

    2014-06-01

    Copolymer composite scaffolds and bioceramic/polymer composite scaffolds are two representative forms of composite scaffolds used for bone tissue engineering. Studies to compare biocompatibility and bone-repairing effects between these two scaffolds are significant for selecting or improving the scaffold for clinical application. We prepared two porous scaffolds comprising poly-lactic-acid/poly-glycolic-acid (PLGA) and poly-lactic-acid/nano-hydroxyapatite (nHAP/PLA) respectively, and examined their biocompatibility with human bone marrow-derived mesenchymal stem cells (hMSCs) through evaluating adhesion, proliferation and osteogenic differentiation potentials of hMSCs in the scaffold. Then, the PLGA scaffold with hMSCs (PM construct) and the nHAP/PLA scaffold with hMSCs (HPM construct) were transplanted into the rat calvarial defect areas to compare their effects on the bone reconstruction. The results showed that the nHAP/PLA scaffold was in favor of adhesion, matrix deposition and osteogenic differentiation of hMSCs. For in vivo transplantation, both HPM and PM constructs led to mineralization and osteogenesis in the defect area of rat. However, the area grafted with PM construct showed a better formation of mature bone than that with HPM construct. In addition, the evaluation of in vitro and in vivo degradation indicated that the degradation rate of nHAP/PLA scaffold was much lower than that of PLGA scaffold. It is inferred that the lower degradation of nHAP/PLA scaffold should result in its inferior bone reconstruction in rat calvaria. Therefore, the preparation of an ideal composite scaffold for bone tissue engineering should be taken into account of the balance between its biocompatibility, degradation rate, osteoconductivity and mechanical property.

  1. Rapid treatment of mild acne with a novel skin care system containing 1% salicylic acid, 10% buffered glycolic acid, and botanical ingredients.

    PubMed

    Bhatia, Ashish C; Jimenez, Felipe

    2014-06-01

    The biggest hurdle in the treatment of acne vulgaris is patient non-compliance that is due in large part to poor tolerability to common acne medications. As such, new acne treatments must be developed that balance good anti-acne efficacy with excellent tolerability in order to ensure patient adherence and by extension ensure good clinical outcomes. The goal of the present study was to determine the tolerability and efficacy of a novel skin care system, composed of a cleanser, containing 1% salicylic acid and botanical ingredients, and a treatment gel, containing 1% salicylic acid, 10% buffered glycolic acid and botanical ingredients for the treatment of mild acne. In this single-center, open-label clinical study, 25 male and female volunteers used the test cleanser and test gel twice daily over six weeks. Tolerability assessments showed that the skin care regimen was very well tolerated by all study volunteers. Acne severity was significantly reduced by two acne grades at six weeks. Inflammatory lesion counts were significantly reduced, on average, by 59.06% (P ≤ 0.0001), 91.62% (P ≤ 0.0001), 90.85% (P ≤ 0.0001) and by 98.55% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Non-inflammatory lesion counts were reduced, on average, by 13.54% (ns), 38.95% (P ≤ 0.0001), 44.48% (P ≤ 0.0001), and by 56.10% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Standardized photography also demonstrated a progressive reduction in acne lesions over time. In conclusion, results of the present study suggest that the tested skin care regimen offers rapid acne clearance and excellent tolerability that together may help to improve patient adherence as well as treatment outcome.

  2. New Insights into Poly(Lactic-co-glycolic acid) Microstructure: Using Repeating Sequence Copolymers to Decipher Complex NMR and Thermal Behavior

    PubMed Central

    Stayshich, Ryan M.; Meyer, Tara Y.

    2012-01-01

    Sequence, which Nature uses to spectacular advantage, has not been fully exploited in synthetic copolymers. To investigate the effect of sequence and stereosequence on the physical properties of copolymers a family of complex isotactic, syndiotactic and atactic repeating sequence poly(lactic-co-glycolic acid) copolymers (RSC PLGAs) were prepared and their NMR and thermal behavior was studied. The unique suitability of polymers prepared from the bioassimilable lactic and glycolic acid monomers for biomedical applications makes them ideal candidates for this type of sequence engineering. Polymers with repeating units of LG, GLG and LLG (L = lactic, G = glycolic) with controlled and varied tacticities were synthesized by assembly of sequence specific, stereopure dimeric, trimeric and hexameric segmer units. Specifically labeled deuterated lactic and glycolic acid segmers were likewise prepared and polymerized. Molecular weights for the copolymers ranged from Mn = 12-40 kDa by size exclusion chromatography in THF. Although the effects of sequence-influenced solution conformation were visible in all resonances of the 1H and 13C NMR spectra, the diastereotopic methylene resonances in the 1H NMR (CDCl3) for the glycolic units of the copolymers proved most sensitive. An octad level of resolution, which corresponds to an astounding 31-atom distance between the most separated stereocenters, was observed in some mixed sequence polymers. Importantly, the level of sensitivity of a particular NMR resonance to small differences in sequence was found to depend on the sequence itself. Thermal properties were also correlated with sequence. PMID:20681726

  3. Block and Random Copolymers Bearing Cholic Acid and Oligo(ethylene glycol) Pendant Groups: Aggregation, Thermosensitivity, and Drug Loading

    PubMed Central

    2015-01-01

    A series of block and random copolymers consisting of oligo(ethylene glycol) and cholic acid pendant groups were synthesized via ring-opening metathesis polymerization of their norbornene derivatives. These block and random copolymers were designed to have similar molecular weights and comonomer ratios; both types of copolymers showed thermosensitivity in aqueous solutions with similar cloud points. The copolymers self-assembled into micelles in water as shown by dynamic light scattering and transmission electron microscopy. The hydrodynamic diameter of the micelles formed by the block copolymer is much larger and exhibited a broad and gradual shrinkage from 20 to 54 °C below its cloud point, while the micelles formed by the random copolymers are smaller in size but exhibited some swelling in the same temperature range. Based on in vitro drug release studies, 78% and 24% paclitaxel (PTX) were released in 24 h from micelles self-assembled by the block and random copolymers, respectively. PTX-loaded micelles formed by the block and random copolymers exhibited apparent antitumor efficacy toward the ovarian cancer cells with a particularly low half-maximal inhibitory concentration (IC50) of 27.4 and 40.2 ng/mL, respectively. Cholic acid-based micelles show promise as a versatile and potent platform for cancer chemotherapy. PMID:24725005

  4. Block and random copolymers bearing cholic acid and oligo(ethylene glycol) pendant groups: aggregation, thermosensitivity, and drug loading.

    PubMed

    Shao, Yu; Jia, Yong-Guang; Shi, Changying; Luo, Juntao; Zhu, X X

    2014-05-12

    A series of block and random copolymers consisting of oligo(ethylene glycol) and cholic acid pendant groups were synthesized via ring-opening metathesis polymerization of their norbornene derivatives. These block and random copolymers were designed to have similar molecular weights and comonomer ratios; both types of copolymers showed thermosensitivity in aqueous solutions with similar cloud points. The copolymers self-assembled into micelles in water as shown by dynamic light scattering and transmission electron microscopy. The hydrodynamic diameter of the micelles formed by the block copolymer is much larger and exhibited a broad and gradual shrinkage from 20 to 54 °C below its cloud point, while the micelles formed by the random copolymers are smaller in size but exhibited some swelling in the same temperature range. Based on in vitro drug release studies, 78% and 24% paclitaxel (PTX) were released in 24 h from micelles self-assembled by the block and random copolymers, respectively. PTX-loaded micelles formed by the block and random copolymers exhibited apparent antitumor efficacy toward the ovarian cancer cells with a particularly low half-maximal inhibitory concentration (IC50) of 27.4 and 40.2 ng/mL, respectively. Cholic acid-based micelles show promise as a versatile and potent platform for cancer chemotherapy. PMID:24725005

  5. Complexes of Imidazole with Poly(ethylene glycol) as a Corrosion Inhibitor for Carbon Steel in Sulphuric Acid

    NASA Astrophysics Data System (ADS)

    Salimi, Saeed; Nasr-Esfahani, Mojtaba; Umoren, Saviour A.; Saebnoori, Ehsan

    2015-12-01

    The inhibiting action of polyethylene glycol and imidazole (PEG/IMZ)) complexes prepared by a simple deprotonation procedure on carbon steel corrosion in 0.5 mol/L sulphuric acid was evaluated using the weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy techniques complemented by surface analysis using scanning electron microscopy. The inhibiting effect of the PEG/IMZ complexes on carbon steel corrosion was compared with the non-complex forms. Results obtained show that PEG/IMZ complex is a very effective corrosion inhibitor of carbon steel in the acid environment. The inhibition efficiency increased with the increase in the temperature and also with increasing percentage of imidazole in the complex. Corrosion inhibition occurs by virtue of adsorption of PEG/IMZ complexes on the steel surface which was found to follow the Temkin adsorption isotherm model. The PEG/IMZ complexes function as a mixed-type inhibitor. Results from all the methods employed are in a reasonably good agreement.

  6. Tracheal reconstruction using chondrocytes seeded on a poly(L-lactic-co-glycolic acid)-fibrin/hyaluronan.

    PubMed

    Hong, Hyun Jun; Chang, Jae Won; Park, Ju-Kyeong; Choi, Jae Won; Kim, Yoo Suk; Shin, Yoo Seob; Kim, Chul-Ho; Choi, Eun Chang

    2014-11-01

    Reconstruction of trachea is still a clinical dilemma. Tissue engineering is a recent and promising concept to resolve this problem. This study evaluated the feasibility of allogeneic chondrocytes cultured with fibrin/hyaluronic acid (HA) hydrogel and degradable porous poly(L-lactic-co-glycolic acid) (PLGA) scaffold for partial tracheal reconstruction. Chondrocytes from rabbit articular cartilage were expanded and cultured with fibrin/HA hydrogel and injected into a 5 × 10 mm-sized, curved patch-shape PLGA scaffold. After 4 weeks in vitro culture, the scaffold was implanted on a tracheal defect in eight rabbits. Six and 10 weeks postoperatively, the implanted sites were evaluated by bronchoscope and radiologic and histologic analyses. Ciliary beat frequency (CBF) of regenerated epithelium was also evaluated. None of the eight rabbits showed any sign of respiratory distress. Bronchoscopic examination did not reveal stenosis of the reconstructed trachea and the defects were completely recovered with respiratory epithelium. Computed tomography scan showed good luminal contour of trachea. Histologic data showed that the implanted chondrocytes successfully formed neocartilage with minimal granulation tissue. CBF of regenerated epithelium was similar to that of normal epithelium. Partial tracheal defect was successfully reconstructed anatomically and functionally using allogeneic chondrocytes cultured with PLGA-fibrin/HA composite scaffold.

  7. Poly(acrylic acid)/polyethylene glycol hygrogel prepared by using gamma-ray irradiation for mucosa adhesion

    NASA Astrophysics Data System (ADS)

    Nho, Young-Chang; Park, Jong-Seok; Shin, Jung-Woong; Lim, Youn-Mook; Jeong, Sung-In; Shin, Young-Min; Gwon, Hui-Jeong; Khil, Myung-Seob; Lee, Deok-Won; Ahn, Sung-Jun

    2015-01-01

    A buccal delivery system provides a much milder environment for drug delivery compared to an oral delivery which presents a hostile environment for drugs, especially proteins and polypeptides, owing to acid hydrolysis. Local delivery in an oral cavity has particular applications in the treatment of toothaches, periodontal disease, and bacterial infections. Poly(acrylic acid) (PAA)-based hydrogels prepared using a chemical initiator have been attempted for a mucoadhesive system owing to their flexibility and excellent bioadhesion. In this experiment, PAA and polyethylene glycol (PEG) were selected to prepare using a radiation process a bioadhesive hydrogel for adhesion to mucosal surfaces. PAA and PEG were dissolved in purified water to prepare a homogeneous PAA/PEG solution, and the solution was then irradiated using an electron beam at dose up to 70 kGy to make the hydrogels. Their physical properties, such as gel percent, swelling percent, and adhesive strength to mucosal surfaces, were investigated. In this experiment, various amounts of PEG were incorporated into the PAA to enhance the mucoadhesive property of the hydrogels. The effect of the molecular weight of PEG on the mucoadhesion was also examined.

  8. Hydroxy acetone and lactic acid synthesis from aqueous propylene glycol/hydrogen peroxide catalysis on Pd-black

    SciTech Connect

    Disselkamp, Robert S.; Harris, Benjamin D.; Hart, Todd R.

    2008-07-20

    The production of polyol chemicals is of increasing interest as they are obtained from the catalytic processing of biological feedstock materials, which also is becoming more prevalent. A case in point is glycerol production, formed as a byproduct in biodiesel catalytic processing. Here we report the reaction of a simple 1,2-diol, propylene glycol, with hydrogen peroxide and a Pd-black catalyst under reflux conditions at 368 K. The experiments were performed by either co-addition of hydrogen peroxide with air sparging, or addition of hydrogen peroxide alone, each yielding hydroxy acetone (HA) and acetic acid (AA) products, with a lesser amount of lactic acid (LA) formed. Product conversion data at near neutral pH versus hydrogen peroxide equivalents added relative to substrate is presented. Hydrogen peroxide addition without air sparging at 5 equivalents resulted in 65% conversion with an HA:AA molar ratio of 2:1. Conversely, hydrogen peroxide addition with air sparging at only 0.75 equivalents resulted in 40% conversion with an HA:AA ratio of 3:1. From this it is concluded that although the product distribution in these chemistries is somewhat unchanged by air sparging, it is surprising that the amount of reactive oxygen is greatly enhanced with co-addition of O2/H2O2. Additional studies have revealed the amount of LA formed can be enhanced under acidic conditions (pH=1.5 compared to pH=8.5), such that 26% of total product formation is LA. Since hydrogen peroxide is an environmentally clean reagent and becoming more cost effective to use, this work may guide future applied investigations into polyol chemical syntheses.

  9. Improving enzymatic hydrolysis of corn stover pretreated by ethylene glycol-perchloric acid-water mixture.

    PubMed

    He, Yu-Cai; Liu, Feng; Gong, Lei; Lu, Ting; Ding, Yun; Zhang, Dan-Ping; Qing, Qing; Zhang, Yue

    2015-02-01

    To improve the enzymatic saccharification of lignocellulosic biomass, a mixture of ethylene glycol-HClO4-water (88.8:1.2:10, w/w/w) was used for pretreating corn stover in this study. After the optimization in oil-bath system, the optimum pretreatment temperature and time were 130 °C and 30 min, respectively. After the saccharification of 10 g/L pretreated corn stover for 48 h, the saccharification rate was obtained in the yield of 77.4 %. To decrease pretreatment temperature and shorten pretreatment time, ethylene glycol-HClO4-water (88.8:1.2:10, w/w/w) media under microwave irradiation was employed to pretreat corn stover effectively at 100 °C and 200 W for 5 min. Finally, the recovered hydrolyzates containing glucose obtained from the enzymatic hydrolysis of pretreated corn stovers could be fermented into ethanol efficiently. These results would be helpful for developing a cost-effective pretreatment combined with enzymatic saccharification of cellulosic materials for the production of lignocellulosic ethanol.

  10. Self-assembled poly(ethylene glycol)-co-acrylic acid microgels to inhibit bacterial colonization of synthetic surfaces.

    PubMed

    Wang, Qichen; Uzunoglu, Emel; Wu, Yong; Libera, Matthew

    2012-05-01

    We explored the use of self-assembled microgels to inhibit the bacterial colonization of synthetic surfaces both by modulating surface cell adhesiveness at length scales comparable to bacterial dimensions (∼1 μm) and by locally storing/releasing an antimicrobial. Poly(ethylene glycol) [PEG] and poly(ethylene glycol)-co-acrylic acid [PEG-AA] microgels were synthesized by suspension photopolymerization. Consistent with macroscopic gels, a pH dependence of both zeta potential and hydrodynamic diameter was observed in AA-containing microgels but not in pure PEG microgels. The microgels were electrostatically deposited onto poly(l-lysine) (PLL) primed silicon to form submonolayer surface coatings. The microgel surface density could be controlled via the deposition time and the microgel concentration in the parent suspension. In addition to their intrinsic antifouling properties, after deposition, the microgels could be loaded with a cationic antimicrobial peptide (L5) because of favorable electrostatic interactions. Loading was significantly higher in PEG-AA microgels than in pure PEG microgels. The modification of PLL-primed Si by unloaded PEG-AA microgels reduced the short-term (6 h) S. epidermidis surface colonization by a factor of 2, and the degree of inhibition increased when the average spacing between microgels was reduced. Postdeposition L5 peptide loading into microgels further reduced bacterial colonization to the extent that, after 10 h of S. epidermidis culture in tryptic soy broth, the colonization of L5-loaded PEG-AA microgel-modified Si was comparable to the very small level of colonization observed on macroscopic PEG gel controls. The fact that these microgels can be deposited by a nonline-of-sight self-assembly process and hinder bacterial colonization opens the possibility of modifying the surfaces of topographically complex biomedical devices and reduces the rate of biomaterial-associated infection.

  11. New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles

    PubMed Central

    Gossmann, Rebecca; Langer, Klaus; Mulac, Dennis

    2015-01-01

    Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower

  12. The pharmacokinetics and pharmacodynamics of lidocaine- loaded biodegradable poly(lactic-co-glycolic acid) microspheres.

    PubMed

    Liu, Jianming; Lv, Xin

    2014-01-01

    The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(D,L-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34±0.3 μm. The poly disperse index was 0.21±0.03, and the zeta potential was +0.34±0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5%±4.3% and 11.2%±1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02-2.06-fold that of lidocaine injection (p<0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency.

  13. In vitro evaluation of biodegradation of poly(lactic-co-glycolic acid) sponges.

    PubMed

    Yoshioka, Taiyo; Kawazoe, Naoki; Tateishi, Tetsuya; Chen, Guoping

    2008-01-01

    Evaluation of the degradability of porous scaffolds is very important for tissue engineering. A protocol in which the condition is close to the in vivo pH environment was established for in vitro evaluation of biodegradable porous scaffolds. Degradation of PLGA sponges in phosphate-buffered solution (PBS) was evaluated with the protocol. The PLGA sponges degraded with incubation time. For the first 12 weeks, the weight loss increased gradually and then remarkably after 12 weeks. In contrast, the number-average molecular weight (Mn) decreased dramatically for the first 12 weeks and then less markedly after 12 weeks. Thermal analysis showed that the glass transition temperatures (Tg) decreased rapidly for the first 12 weeks, and the change became less evident after 12 weeks. These results suggest that the degradation mechanism of PLGA sponges was dominated by autocatalyzed bulk degradation for the first 12 weeks and then by surface degradation after 12 weeks. Physical aging was observed during incubation at 37 degrees C. The heterogeneous structure caused by physical aging might be one of the driving forces that induced autocatalyzed bulk degradation. The degradation mechanism was further supported by the data of pH change and the morphology of the degraded PLGA sponges. The autocatalyzed acidic products flooded out after 8 weeks, the pH dropped, and the walls of the sponges became more porous. The increase of the pore surface area facilitated surface degradation after 12 weeks. The pH was in the range between 7.43 and 7.24 during the entire incubation time. The protocol suppressed extreme changes of the pH and will be useful in the biodegradation evaluation of porous scaffolds for tissue engineering.

  14. Glycolic acid inhibits enzymatic, hemorrhagic and edema-inducing activities of BaP1, a P-I metalloproteinase from Bothrops asper snake venom: insights from docking and molecular modeling.

    PubMed

    Pereañez, Jaime Andrés; Patiño, Arley Camilo; Rey-Suarez, Paola; Núñez, Vitelbina; Henao Castañeda, Isabel Cristina; Rucavado, Alexandra

    2013-09-01

    Glycolic acid (GA) (2-Hydroxyethanoic acid) is widely used as chemical peeling agent in Dermatology and, more recently, as a therapeutic and cosmetic compound in the field of skin care and disease treatment. In this work we tested the inhibitory ability of glycolic acid on the enzymatic, hemorrhagic and edema-inducing activities of BaP1, a P-I metalloproteinase from Bothrops asper venom, which induces a variety of toxic actions. Glycolic acid inhibited the proteolytic activity of BaP1 on azocasein, with an IC₅₀ of 1.67 mM. The compound was also effective at inhibiting the hemorrhagic activity of BaP1 in skin and muscle in experiments involving preincubation of enzyme and inhibitor prior to injection. When BaP1 was injected i.m. and then, at the same site, different concentrations of glycolic acid were administered at either 0 or 5 min, 7 mM solutions of the inhibitor partially abrogated hemorrhagic activity when administered at 0 min. Moreover, glycolic acid inhibited, in a concentration-dependent manner, edema-forming activity of BaP1 in the footpad. In order to have insights on the mode of action of glycolic acid, UV-vis and intrinsic fluorescence studies were performed. Results of these assays suggest that glycolic acid interacts directly with BaP1 and chelates the Zn²⁺ ion at the active site. These findings were supported by molecular docking results, which suggested that glycolic acid forms hydrogen bonds with residues Glu143, Arg110 and Ala111 of the enzyme. Additionally, molecular modeling results suggest that the inhibitor chelates Zn²⁺, with a distance of 3.58 Å, and may occupy part of substrate binding cleft of BaP1. Our results suggest that glycolic acid is a candidate for the development of inhibitors to be used in snakebite envenomation.

  15. Spontaneous Differentiation of Human Mesenchymal Stem Cells on Poly-Lactic-Co-Glycolic Acid Nano-Fiber Scaffold

    PubMed Central

    Sonomoto, Koshiro; Yamaoka, Kunihiro; Kaneko, Hiroaki; Yamagata, Kaoru; Sakata, Kei; Zhang, Xiangmei; Kondo, Masahiro; Zenke, Yukichi; Sabanai, Ken; Nakayamada, Shingo; Sakai, Akinori; Tanaka, Yoshiya

    2016-01-01

    Introduction Mesenchymal stem cells (MSCs) have immunosuppressive activity and can differentiate into bone and cartilage; and thus seem ideal for treatment of rheumatoid arthritis (RA). Here, we investigated the osteogenesis and chondrogenesis potentials of MSCs seeded onto nano-fiber scaffolds (NFs) in vitro and possible use for the repair of RA-affected joints. Methods MSCs derived from healthy donors and patients with RA or osteoarthritis (OA) were seeded on poly-lactic-glycolic acid (PLGA) electrospun NFs and cultured in vitro. Results Healthy donor-derived MSCs seeded onto NFs stained positive with von Kossa at Day 14 post-stimulation for osteoblast differentiation. Similarly, MSCs stained positive with Safranin O at Day 14 post-stimulation for chondrocyte differentiation. Surprisingly, even cultured without any stimulation, MSCs expressed RUNX2 and SOX9 (master regulators of bone and cartilage differentiation) at Day 7. Moreover, MSCs stained positive for osteocalcin, a bone marker, and simultaneously also with Safranin O at Day 14. On Day 28, the cell morphology changed from a spindle-like to an osteocyte-like appearance with processes, along with the expression of dentin matrix protein-1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE), suggesting possible differentiation of MSCs into osteocytes. Calcification was observed on Day 56. Expression of osteoblast and chondrocyte differentiation markers was also noted in MSCs derived from RA or OA patients seeded on NFs. Lactic acid present in NFs potentially induced MSC differentiation into osteoblasts. Conclusions Our PLGA scaffold NFs induced MSC differentiation into bone and cartilage. NFs induction process resembled the procedure of endochondral ossification. This finding indicates that the combination of MSCs and NFs is a promising therapeutic technique for the repair of RA or OA joints affected by bone and cartilage destruction. PMID:27055270

  16. Glycolic Acid Silences Inflammasome Complex Genes, NLRC4 and ASC, by Inducing DNA Methylation in HaCaT Cells.

    PubMed

    Tang, Sheau-Chung; Yeh, Jih-I; Hung, Sung-Jen; Hsiao, Yu-Ping; Liu, Fu-Tong; Yang, Jen-Hung

    2016-03-01

    AHAs (α-hydroxy acids), including glycolic acid (GA), have been widely used in cosmetic products and superficial chemical peels. Inflammasome complex has been shown to play critical roles in inflammatory pathways in human keratinocytes. However, the anti-inflammatory mechanism of GA is still unknown. The aim of this study is to investigate the relationship between the expression of the inflammasome complex and epigenetic modification to elucidate the molecular mechanism of the anti-inflammatory effect of GA in HaCaT cells. We evaluated NLRP3, NLRC4, AIM2, and ASC inflammasome complex gene expression on real-time polymerase chain reaction (PCR). Methylation changes were detected in these genes following treatment with DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-Aza) with or without the addition of GA using methylation-specific PCR (MSP). GA inhibited the expressions of these inflammasome complex genes, and the decreases in the expressions of mRNA were reversed by 5-Aza treatment. Methylation was detected in NLRC4 and ASC on MSP, but not in NLRP3 or AIM2. GA decreased NLRC4 and ASC gene expression by increasing not only DNA methyltransferase 3B (DNMT-3B) protein level, but also total DNMT activity. Furthermore, silencing of DNMT-3B (shDNMT-3B) increased the expressions of NLRC4 and ASC. Our data demonstrated that GA treatment induces hypermethylation of promoters of NLRC4 and ASC genes, which may subsequently lead to the hindering of the assembly of the inflammasome complex in HaCaT cells. These results highlight the anti-inflammatory potential of GA-containing cosmetic agents in human skin cells and demonstrate for the first time the role of aberrant hypermethylation in this process.

  17. Multi-ligand poly(L-lactic-co-glycolic acid) nanoparticles inhibit activation of endothelial cells.

    PubMed

    Xu, Hao; Kona, Soujanya; Su, Lee-Chun; Tsai, Yi-Ting; Dong, Jing-Fei; Brilakis, Emmanouil S; Tang, Liping; Banerjee, Subhash; Nguyen, Kytai T

    2013-08-01

    Endothelial cell (EC) activation and inflammation is a key step in the initiation and progression of many cardiovascular diseases. Targeted delivery of therapeutic reagents to inflamed EC using nanoparticles is challenging as nanoparticles do not arrest on EC efficiently under high shear stress. In this study, we developed a novel polymeric platelet-mimicking nanoparticle for strong particle adhesion onto ECs and enhanced particle internalization by ECs. This nanoparticle was encapsulated with dexamethasone as the anti-inflammatory drug, and conjugated with polyethylene glycol, glycoprotein 1b, and trans-activating transcriptional peptide. The multi-ligand nanoparticle showed significantly greater adhesion on P-selectin, von Willebrand Factor, than the unmodified particles, and activated EC in vitro under both static and flow conditions. Treatment of injured rat carotid arteries with these multi-ligand nanoparticles suppressed neointimal stenosis more than unconjugated nanoparticles did. These results indicate that this novel multi-ligand nanoparticle is efficient to target inflamed EC and inhibit inflammation and subsequent stenosis.

  18. Infrared and Raman studies on polylactide acid and polyethylene glycol-400 blend

    NASA Astrophysics Data System (ADS)

    Yuniarto, Kurniawan; Purwanto, Yohanes Aris; Purwanto, Setyo; Welt, Bruce A.; Purwadaria, Hadi Karia; Sunarti, Titi Candra

    2016-04-01

    As a biodegradableplastic, polylactideacid (PLA) can be blended with polyethylene glycol (PEG) to form a polymer blend because PEG has a good miscibility with PLA. Furthermore, this paper study the functional groups of PLA-PEG400 blend using direct casting to produce matrix film. Fourier Transform Infrared (FTIR) and Raman spectroscopy was used to identify alteration of functional group PLA-PEG400 blend. Absorbance and frequency wavenumber were used to observe any changing among functional group. In general, PLA-PEG blend did not produce a new configuration or chemical properties although some functional groups tended to decrease. PLA-PEG400 film spectra showed a similaritycompared to those of neat PLA because of each pristine polymer. However, FTIR and Raman investigated reducing carbonyl group of PLA with PEG400 addition and followed improving CH-COC bonding. Methyl group represented CH3symmetricchanged both the shift and absorbance.FTIR and Raman spectroscopy observed increasing hydrogen bonding with increasing PEG400 addition where a largest was found at PEG 10% and appeared at frequency range from 3400 cm-1 to 3600 cm-1. According to PEG400 addition, a FTIR measuredenhancing crystalline region.

  19. Influence of micro and submicro poly(lactic-glycolic acid) fibers on sensory neural cell locomotion and neurite growth.

    PubMed

    Binder, Carmen; Milleret, Vincent; Hall, Heike; Eberli, Daniel; Lühmann, Tessa

    2013-10-01

    For successful peripheral nerve regeneration, a complex interplay of growth factors, topographical guidance structure by cells and extracellular matrix proteins, are needed. Aligned fibrous biomaterials with a wide variety in fiber diameter have been used successfully to support neuronal guidance. To better understand the importance of size of the topographical features, we investigated the directionality of neuronal migration of sensory ND7/23 cells on aligned electrospun poly(lactic-glycolic acid) PLGA fibers in the range of micrometer and submicrometer diameters by time-lapse microscopy. Cell trajectories of single ND7/23 cells were found to significantly follow topographies of PLGA fibers with micrometer dimensions in contrast to PLGA fibers within the submicrometer range, where cell body movement was observed to be independent of fibrous structures. Moreover, neurite alignment of ND7/23 cells on various topographies was assessed. PLGA fibers with micrometer dimensions significantly aligned 83.3% of all neurites after 1 day of differentiation compared to similar submicrometer structures, which orientated 25.8% of all neurites. Interestingly, after 7 days of differentiation ND7/23 cells on submicrometer PLGA fibers increased their alignment of neurites to 52.5%. Together, aligned PLGA fibers with micrometer dimensions showed a superior influence on directionality of neuronal migration and neurite outgrowth of sensory ND7/23 cells, indicating that electrospun micro-PLGA fibers might represent a potential material to induce directionality of neuronal growth in engineering applications for sensory nerve regeneration.

  20. Synergistic Chemotherapeutic Activity of Curcumin Bearing Methoxypolyethylene Glycol-g-Linoleic Acid Based Micelles on Breast Cancer Cells.

    PubMed

    Guzzarlamudi, Sofia; Singh, Pankaj K; Pawar, Vivek K; Singh, Yuvraj; Sharma, Komal; Paliwal, S K; Chourasia, Manish K; Ramana, M V; Chaurasia, Mohini

    2016-04-01

    Although curcumin (Cur), has been poised to be an anticancer boon for quite some, its progress from bench to bed has been strained due to various pharmaceutical hurdles. Consequently curcumin has been entrapped in methoxy poly ethylene glycol and linoleic acid conjugated polymeric micelles (PMs) to not only tackle the routine issues but to also provide a synergetic effect against MCF-7 breast cancer cells. Optimized PMs of Cur had size 186.53 ± 12.10 nm with polydispersity index 0.143 ± 0.031 and zeta potential -30.1 ± 3.2 mV. Developed formulation (Mpeg-Cla-Cur PMs) was hemocompatible and had high cytotoxicity (IC50 55.80 ± 4.63 µ/mL) against MCF-7 cells in comparison to pure Cur suspension (IC50 75.05 ± 5.75 µg/mL). As postulated cell cycle arrest and apoptosis studies revealed synergetic effect of Mpeg-Cla-Cur PMs with higher cell population in G1 phase in addition to high apoptosis of MCF-7 cells as compared to pure Cur suspension and con- trol group. Pharmacokinetic studies also show PMs enhanced MRT and T1/2 of Cur indicating its longer retention time in body. Mpeg-Cla-Cur PMs might become as an excellent chemotherapeutic alternative candidate for treatment of breast cancer with higher commercial value. PMID:27451784

  1. Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers.

    PubMed

    Jeong, Ji Hoon; Park, Tae Gwan

    2002-07-18

    Poly(lactic-co-glycolic acid) (PLGA)-grafted poly(L-lysine) (PLL) (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/l. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200-300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Here, we demonstrated that biodegradable and cationic PLL-g-PLGA micelles could be used as an effective DNA condensation carrier for gene delivery system.

  2. Cytotoxic and genotoxic characterization of titanium dioxide, gadolinium oxide, and poly(lactic-co-glycolic acid) nanoparticles in human fibroblasts.

    PubMed

    Setyawati, Magdiel Inggrid; Khoo, Pheng Kian Stella; Eng, Bao Hui; Xiong, Sijing; Zhao, Xinxin; Das, Gautom Kumar; Tan, Timothy Thatt-Yang; Loo, Joachim Say Chye; Leong, David Tai; Ng, Kee Woei

    2013-03-01

    Engineered nanomaterials have become prevalent in our everyday life. While the popularity of using nanomaterials in consumer products continues to rise, increasing awareness of nanotoxicology has also fuelled efforts to accelerate our understanding of the ill effects that different nanomaterials can bring to biological systems. In this study, we investigated the potential cytotoxicity and genotoxicity of three nanoparticles: titanium dioxide (TiO(2)), terbium-doped gadolinium oxide (Tb-Gd(2)O(3)), and poly(lactic-co-glycolic acid) (PLGA). To evaluate nanoparticle-induced genotoxicity more realistically, a human skin fibroblast cell line (BJ) with less mutated genotype compared with cancer cell line was used. The nanoparticles were first characterized by size, morphology, and surface charge. Cytotoxicity effects of the nanoparticles were then evaluated by monitoring the proliferation of treated BJ cells. Genotoxic influence was ascertained by profiling DNA damage via detection of γH2AX expression. Our results suggested that both TiO(2) and Tb-Gd(2)O(3) nanoparticles induced cytotoxicity in a dose dependent way on BJ cells. These two nanomaterials also promoted genotoxicity via DNA damage. On the contrary, PLGA nanoparticles did not induce significant cytotoxic or genotoxic effects on BJ cells. PMID:22927021

  3. Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles.

    PubMed

    Xiong, Sijing; George, Saji; Yu, Haiyang; Damoiseaux, Robert; France, Bryan; Ng, Kee Woei; Loo, Joachim Say-Chye

    2013-06-01

    The aim of this study is to uncover the size influence of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO(2)) nanoparticles on their potential cytotoxicity. PLGA and TiO(2) nanoparticles of three different sizes were thoroughly characterized before in vitro cytotoxic tests which included viability, generation of reactive oxygen species (ROS), mitochondrial depolarization, integrity of plasma membrane, intracellular calcium influx and cytokine release. Size-dependent cytotoxic effect was observed in both RAW264.7 cells and BEAS-2B cells after cells were incubated with PLGA or TiO(2) nanoparticles for 24 h. Although PLGA nanoparticles did not trigger significantly lethal toxicity up to a concentration of 300 μg/ml, the TNF-α release after the stimulation of PLGA nanoparticles should not be ignored especially in clinical applications. Relatively more toxic TiO(2) nanoparticles triggered cell death, ROS generation, mitochondrial depolarization, plasma membrane damage, intracellular calcium concentration increase and size-dependent TNF-α release, especially at a concentration higher than 100 μg/ml. These cytotoxic effects could be due to the size-dependent interaction between nanoparticles and biomolecules, as smaller particles tend to adsorb more biomolecules. In summary, we demonstrated that the ability of protein adsorption could be an important paradigm to predict the in vitro cytotoxicity of nanoparticles, especially for low toxic nanomaterials such as PLGA and TiO(2) nanoparticles. PMID:22983807

  4. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury

    PubMed Central

    Wang, Ya-ling; Gu, Xiao-mei; Kong, Yan; Feng, Qi-lin; Yang, Yu-min

    2015-01-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  5. Protective effect of recombinant staphylococcal enterotoxin A entrapped in polylactic-co-glycolic acid microspheres against Staphylococcus aureus infection.

    PubMed

    Chen, Liben; Li, Shuang; Wang, Zhengfang; Chang, Ruilong; Su, Jingliang; Han, Bo

    2012-03-19

    Staphylococcus aureus is an important cause of nosocomial and community-acquired infections in humans and animals, as well as the cause of mastitis in dairy cattle. Vaccines aimed at preventing S. aureus infection in bovine mastitis have been studied for many years, but have so far been unsuccessful due to the complexity of the bacteria, and the lack of suitable vaccine delivery vehicles. The current study developed an Escherichia coli protein expression system that produced a recombinant staphylococcal enterotoxin A (rSEA) encapsulated into biodegradable microparticles generated by polylactic-co-glycolic acid (PLGA) dissolved in methylene chloride and stabilized with polyvinyl acetate. Antigen loading and surface properties of the microparticles were investigated to optimize particle preparation protocols. The prepared PLGA-rSEA microspheres had a diameter of approximately 5 μm with a smooth and regular surface. The immunogenicity of the PLGA-rSEA vaccine was assessed using mice as an animal model and showed that the vaccine induced a strong humoral immune response and increased the percent survival of challenged mice and bacterial clearance. Histological analysis showed moderate impairment caused by the pathogen upon challenge afforded by immunization with PLGA-rSEA microspheres. Antibody titer in the sera of mice immunized with PLGA-rSEA microparticles was higher than in vaccinated mice with rSEA. In conclusion, the PLGA-rSEA microparticle vaccine developed here could potentially be used as a vaccine against enterotoxigenic S. aureus.

  6. Effect of hydrion evolution by polylactic-co-glycolic acid coating on degradation rate of pure iron.

    PubMed

    Wu, Jingyao; Lu, Xi; Tan, Lili; Zhang, Bingchun; Yang, Ke

    2013-10-01

    For biodegradable iron coronary stents, the major problem is the low degradation rate in body environment. In this study, a new strategy was proposed to increase the degradation rate of iron in vitro. The hydrion evolution was intended to be introduced into the degradation system to increase the degradation rate. To realize this strategy, polylactic-co-glycolic acid (PLGA) was coated onto the surface of pure iron. The degradation process and mechanism of pure iron coated with PLGA were investigated. The results showed that iron coated with PLGA exhibited higher degradation rate in the static immersion test all along. With the degradation of PLGA, the oligomers of PLGA could release abundant H(+) which could dissolve the ferrous oxide to make the electrolyte and oxygen to reach the surface of iron again and simultaneity trigger the hydrion evolution at the middle stage of the degradation. The study also revealed that the solution ions failed to permeate the PLGA coating and the deposition of calcium and phosphorus in the degradation layer was inhibited which further enhanced the degradation.

  7. Cytotoxic and genotoxic characterization of titanium dioxide, gadolinium oxide, and poly(lactic-co-glycolic acid) nanoparticles in human fibroblasts.

    PubMed

    Setyawati, Magdiel Inggrid; Khoo, Pheng Kian Stella; Eng, Bao Hui; Xiong, Sijing; Zhao, Xinxin; Das, Gautom Kumar; Tan, Timothy Thatt-Yang; Loo, Joachim Say Chye; Leong, David Tai; Ng, Kee Woei

    2013-03-01

    Engineered nanomaterials have become prevalent in our everyday life. While the popularity of using nanomaterials in consumer products continues to rise, increasing awareness of nanotoxicology has also fuelled efforts to accelerate our understanding of the ill effects that different nanomaterials can bring to biological systems. In this study, we investigated the potential cytotoxicity and genotoxicity of three nanoparticles: titanium dioxide (TiO(2)), terbium-doped gadolinium oxide (Tb-Gd(2)O(3)), and poly(lactic-co-glycolic acid) (PLGA). To evaluate nanoparticle-induced genotoxicity more realistically, a human skin fibroblast cell line (BJ) with less mutated genotype compared with cancer cell line was used. The nanoparticles were first characterized by size, morphology, and surface charge. Cytotoxicity effects of the nanoparticles were then evaluated by monitoring the proliferation of treated BJ cells. Genotoxic influence was ascertained by profiling DNA damage via detection of γH2AX expression. Our results suggested that both TiO(2) and Tb-Gd(2)O(3) nanoparticles induced cytotoxicity in a dose dependent way on BJ cells. These two nanomaterials also promoted genotoxicity via DNA damage. On the contrary, PLGA nanoparticles did not induce significant cytotoxic or genotoxic effects on BJ cells.

  8. A mesoporous silicon/poly-(DL-lactic-co-glycolic) acid microsphere for long time anti-tuberculosis drug delivery.

    PubMed

    Xu, Weikang; Wei, Xinmiao; Wei, Kun; Cao, Xiaodong; Zhong, Shizhen

    2014-12-10

    In this study, drug delivery systems for controlling release of hydrophobic anti-tuberculosis (TB) drug-rifampicin (RIF) or hydrophilic anti-TB drug-isoniazid (INH) from mesoporous silica (MS) were fabricated. The drug was first filled into the mesopores of MS particles, and then the drug-laden MS constructs were incorporated into the bulk of poly-(DL-lactic-co-glycolic) acid (PLGA) microspheres. In comparison with mono-component construct (drug-laden MS and drug-laden PLGA), this multi-component system significantly improved the release time of RIF and INH. For drug-laden MS, about 100% INH was released after 15 h, and about 70% RIF was released after 50 h. For drug-laden PLGA, about 100% INH and RIF were released after 30 and 40 days, respectively. After 60 days, the total RIF and INH release from MS/PLGA had only reached around only 48% and 57%, respectively. This MS/PLGA system could significantly prolong RIF or INH release compared to MS and PLGA. CCK-8 assay demonstrated that this MS/PLGA system had no cytotoxicity. And there has not been study of documenting the controlled release of anti-TB drugs such as RIF or INH from MS/PLGA. Considering the long time release of RIF and INH from MS/PLGA, a new door to bone TB would be opened.

  9. In-vitro degradation characteristics of poly(e-caprolactone)/poly(glycolic acid) scaffolds fabricated via solid-state cryomilling.

    PubMed

    Jonnalagadda, John B; Rivero, Iris V; Warzywoda, Juliusz

    2015-10-01

    Poly(e-caprolactone) (PCL)/poly(glycolic acid) (PGA) scaffolds were fabricated via solid-state cryomilling along with compression molding and porogen leaching techniques. Four types of scaffolds were produced using four distinct cryomilling times. These scaffolds were evaluated for their in-vitro degradation behavior hydrolytically in phosphate buffer saline (PBS). The degradation profiles were investigated over a period of 60 days. The percentage of weight loss, percentage of water absorption, morphology, compressive, thermal, and material properties were studied as a function of degradation time. Weight loss and water absorption demonstrated a high correlation, which showed an increasing behavior with increase in cryomilling time and degradation time. Morphology of the scaffolds analyzed through scanning electron microscopy (SEM) revealed micro-cracks on the surface of the cylindrical struts due to hydrolytic attack and dissolution of hydrophilic PGA. Changes in compressive modulus and crystallinity over the degradation period and material properties were analyzed using X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. DSC and XRD results indicated that hydrolytic attack had taken place during degradation, resulting in moments of increased and decreased percent crystallinity. This study successfully brought forth the differences in resultant properties of the PCL/PGA scaffolds as a function of degradation time.

  10. Evaluation of Physical and Mechanical Properties of Porous Poly (Ethylene Glycol)-co-(L-Lactic Acid) Hydrogels during Degradation

    PubMed Central

    Chiu, Yu-Chieh; Kocagöz, Sevi; Larson, Jeffery C.; Brey, Eric M.

    2013-01-01

    Porous hydrogels of poly(ethylene glycol) (PEG) have been shown to facilitate vascularized tissue formation. However, PEG hydrogels exhibit limited degradation under physiological conditions which hinders their ultimate applicability for tissue engineering therapies. Introduction of poly(L-lactic acid) (PLLA) chains into the PEG backbone results in copolymers that exhibit degradation via hydrolysis that can be controlled, in part, by the copolymer conditions. In this study, porous, PEG-PLLA hydrogels were generated by solvent casting/particulate leaching and photopolymerization. The influence of polymer conditions on hydrogel architecture, degradation and mechanical properties was investigated. Autofluorescence exhibited by the hydrogels allowed for three-dimensional, non-destructive monitoring of hydrogel structure under fully swelled conditions. The initial pore size depended on particulate size but not polymer concentration, while degradation time was dependent on polymer concentration. Compressive modulus was a function of polymer concentration and decreased as the hydrogels degraded. Interestingly, pore size did not vary during degradation contrary to what has been observed in other polymer systems. These results provide a technique for generating porous, degradable PEG-PLLA hydrogels and insight into how the degradation, structure, and mechanical properties depend on synthesis conditions. PMID:23593296

  11. Anti-melanogenic effects of resveratryl triglycolate, a novel hybrid compound derived by esterification of resveratrol with glycolic acid.

    PubMed

    Park, Soojin; Seok, Jin Kyung; Kwak, Jun Yup; Choi, Yun-Hyeok; Hong, Seong Su; Suh, Hwa-Jin; Park, Woncheol; Boo, Yong Chool

    2016-07-01

    Resveratrol is known to inhibit cellular melanin synthesis by multiple mechanisms. Glycolic acid (GA) is used in skin care products for its excellent skin penetration. The purpose of this study was to examine the anti-melanogenic effects of resveratryl triglycolate (RTG), a novel hybrid compound of resveratrol and GA, in comparison with resveratrol, GA, resveratryl triacetate (RTA) and arbutin. Resveratrol, RTG, and RTA inhibited the catalytic activity human tyrosinase (TYR) more potently than arbutin or GA did. Their cytotoxic and anti-melanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEMs). The cytotoxicity of RTG was similar to that of resveratrol and RTA. RTG at 3-10 μM decreased melanin levels and cellular TYR activities in α-melanocyte-stimulating hormone-stimulated B16/F10 cells, and L-tyrosine-stimulated HEMs. RTG also suppressed mRNA and protein expression of TYR, tyrosinase-related protein 1, L-3,4-dihydroxyphenylalanine chrome tautomerase, and microphthalmia-associated transcription factor (MITF) in HEMs stimulated with L-tyrosine. This study suggests that, like resveratrol and RTA, RTG can attenuate cellular melanin synthesis effectively through the suppression of MITF-dependent expression of melanogenic enzymes and the inhibition of catalytic activity of TYR enzyme. RTG therefore has potential for use as a cosmeceutical ingredient for skin whitening.

  12. Highly Stable PEGylated Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for the Effective Delivery of Docetaxel in Prostate Cancers

    NASA Astrophysics Data System (ADS)

    Cao, Long-Bin; Zeng, Sha; Zhao, Wei

    2016-06-01

    In the present study, a highly stable luteinizing-hormone-releasing hormone (LHRH)-conjugated PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles were developed for the successful treatment of prostate cancers. We have demonstrated that a unique combination of targeted drug delivery and controlled drug release is effective against prostate cancer therapy. The docetaxel (DTX)/PLGA-LHRH micelles possessed a uniform spherical shape with an average diameter of ~170 nm. The micelles exhibited a controlled drug release for up to 96 h which can minimize the non-specific systemic spread of toxic drugs during circulation while maximizing the efficiency of tumor-targeted drug delivery. The LHRH-conjugated micelles showed enhanced cellular uptake and exhibited significantly higher cytotoxicity against LNCaP cancer cells. We have showed that PLGA-LHRH induced greater caspase-3 activity indicating its superior apoptosis potential. Consistently, LHRH-conjugated micelles induced threefold and twofold higher G2/M phase arrest than compared to free DTX or PLGA NP-treated groups. Overall, results indicate that use of LHRH-conjugated nanocarriers may potentially be an effective nanocarrier to effectively treat prostate cancer.

  13. Preparing Poly (Lactic-co-Glycolic Acid) (PLGA) Microspheres Containing Lysozyme-Zinc Precipitate Using a Modified Double Emulsion Method

    PubMed Central

    Nafissi Varcheh, Nastaran; Luginbuehl, Vera; Aboofazeli, Reza; Peter Merkle, Hans

    2011-01-01

    Lysozyme, as a model protein, was precipitated through the formation of protein-Zn complex to micronize for subsequent encapsulation within poly (lactic-co-glycolic acid) (PLGA) microspheres. Various parameters, including pH, type and concentration of added salts and protein concentration, were modified to optimize the yield of protein complexation and precipitation. The resulting protein particles (lysozyme-Zn complex as a freshly prepared suspension or a freeze-dried solid) were then loaded into PLGA (Resomer® 503H) microspheres, using a double emulsion technique and microspheres encapsulation efficiency and their sizes were determined. It was observed that salt type could significantly influence the magnitude of protein complexation. At the same conditions, zinc chloride was found to be more successful in producing pelletizable lysozyme. Generally, higher concentrations of protein solution led also to the higher yields of complexation and at the optimum conditions, the percentage of pelletizable lysozyme reached to 80%. Taking advantage of this procedure, a modified technique for preparation of protein-loaded PLGA microspheres was established, although it is also expected that this technique increases the protein drugs stabilization during the encapsulation process. PMID:24250344

  14. Liver-targeted cyclosporine A-encapsulated poly (lactic-co-glycolic) acid nanoparticles inhibit hepatitis C virus replication.

    PubMed

    Jyothi, K R; Beloor, Jagadish; Jo, Ara; Nguyen, Minh Nam; Choi, Tae Gyu; Kim, Jin-Hwan; Akter, Salima; Lee, Sang-Kyung; Maeng, Chi Hoon; Baik, Hyung Hwan; Kang, Insug; Ha, Joohun; Kim, Sung Soo

    2015-01-01

    Therapeutic options for hepatitis C virus (HCV) infection have been limited by drug resistance and adverse side effects. Targeting the host factor cyclophilin A (CypA), which is essential for HCV replication, offers a promising strategy for antiviral therapy. However, due to its immunosuppressive activity and severe side effects, clinical application of cyclosporine A (CsA) has been limited as an antiviral agent. To overcome these drawbacks, we have successfully developed a liver-specific, sustained drug delivery system by conjugating the liver-targeting peptide (LTP) to PEGylated CsA-encapsulated poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Furthermore, our delivery system exhibited high specificity to liver, thus contributing to the reduced immunosuppressive effect and toxicity profile of CsA. Finally, targeted nanoparticles were able to effectively inhibit viral replication in vitro and in an HCV mouse model. As a proof of principle, we herein show that our delivery system is able to negate the adverse effects of CsA and produce therapeutic effects in an HCV mouse model.

  15. Controlled release and antibacterial activity of antibiotic-loaded electrospun halloysite/poly(lactic-co-glycolic acid) composite nanofibers.

    PubMed

    Qi, Ruiling; Guo, Rui; Zheng, Fuyin; Liu, Hui; Yu, Jianyong; Shi, Xiangyang

    2013-10-01

    Fabrication of nanofiber-based drug delivery system with controlled release property is of general interest in biomedical sciences. In this study, we prepared an antibiotic drug tetracycline hydrochloride (TCH)-loaded halloysite nanotubes/poly(lactic-co-glycolic acid) composite nanofibers (TCH/HNTs/PLGA), and evaluated the drug release and antibacterial activity of this drug delivery system. The structure, morphology, and mechanical properties of the formed electrospun TCH/HNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. We show that the incorporation of TCH-loaded HNTs within the PLGA nanofibers is able to improve the tensile strength and maintain the three-dimensional structure of the nanofibrous mats. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the fibrous scaffolds demonstrate that the developed TCH/HNTs/PLGA composite nanofibers are cytocompatible. More importantly, the TCH/HNTs/PLGA composite nanofibers are able to release the antibacterial drug TCH in a sustained manner for 42 days and display antimicrobial activity solely associated with the encapsulated TCH drug. With the improved mechanical durability, sustained drug release profile, good cytocompatibility, and non-compromised therapeutic efficacy, the developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for tissue engineering and drug delivery applications.

  16. Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid) electrospun fibrous scaffold for bone regeneration

    PubMed Central

    Chen, Shijie; Jian, Zhiyuan; Huang, Linsheng; Xu, Wei; Liu, Shaohua; Song, Dajiang; Wan, Zongmiao; Vaughn, Amanda; Zhan, Ruisen; Zhang, Chaoyue; Wu, Song; Hu, Minghua; Li, Jinsong

    2015-01-01

    A mesoporous bioactive glass (MBG) surface modified with poly(lactic-co-glycolic acid) (PLGA) electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration. PMID:26082632

  17. Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid) electrospun fibrous scaffold for bone regeneration.

    PubMed

    Chen, Shijie; Jian, Zhiyuan; Huang, Linsheng; Xu, Wei; Liu, Shaohua; Song, Dajiang; Wan, Zongmiao; Vaughn, Amanda; Zhan, Ruisen; Zhang, Chaoyue; Wu, Song; Hu, Minghua; Li, Jinsong

    2015-01-01

    A mesoporous bioactive glass (MBG) surface modified with poly(lactic-co-glycolic acid) (PLGA) electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration. PMID:26082632

  18. Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating network hydrogel by intrastromal implantation in rabbit cornea

    PubMed Central

    Zheng, Luo Luo; Vanchinathan, Vijay; Dalal, Roopa; Noolandi, Jaan; Waters, Dale J.; Hartmann, Laura; Cochran, Jennifer R.; Frank, Curtis W.; Yu, Charles Q.; Ta, Christopher N.

    2015-01-01

    We evaluated the biocompatibility of a poly(ethylene glycol) and poly(acrylic acid) (PEG/PAA) interpenetrating network hydrogel designed for artificial cornea in a rabbit model. PEG/PAA hydrogel measuring 6 mm in diameter was implanted in the corneal stroma of twelve rabbits. Stromal flaps were created with a microkeratome. Randomly, six rabbits were assigned to bear the implant for 2 months, two rabbits for 6 months, two rabbits for 9 months, one rabbit for 12 months, and one rabbit for 16 months. Rabbits were evaluated monthly. After the assigned period, eyes were enucleated, and corneas were processed for histology and immunohistochemistry. There were clear corneas in three of six rabbits that had implantation of hydrogel for 2 months. In the six rabbits with implant for 6 months or longer, the corneas remained clear in four. There was a high rate of epithelial defect and corneal thinning in these six rabbits. One planned 9-month rabbit developed extrusion of implant at 4 months. The cornea remained clear in the 16-month rabbit but histology revealed epithelial in-growth. Intrastromal implantation of PEG/PAA resulted in a high rate of long-term complications. PMID:25778285

  19. Functionalized Poly(lactic-co-glycolic acid) Enhances Drug Delivery and Provides Chemical Moieties for Surface Engineering while Preserving Biocompatibility

    PubMed Central

    Bertram, James P.; Jay, Steven M.; Hynes, Sara R.; Robinson, Rebecca; Criscione, Jason M.; Lavik, Erin B.

    2009-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is one of the more widely used polymers for biomedical applications. Nonetheless, PLGA lacks chemical moieties that facilitate cellular interactions and surface chemistries. Furthermore, incorporation of hydrophilic molecules is often problematic. The integration of polymer functionalities would afford the opportunity to alter device characteristics, thereby enabling control over drug interactions, conjugations, and cellular phenomena. In an effort to introduce amine functionalities and improve polymer versatility, we synthesized two block copolymers (PLGA-PLL 502H and PLGA-PLL 503H) comprised of PLGA and Poly(ε-carbobenzoxy-L-lysine) utilizing dicyclohexyl carbodiimide (DCC) coupling. PLGA-PLL micropsheres encapsulated approximately six-fold (502H) and three-fold (503H) more vascular endothelial growth factor (VEGF), and 41% (503H) more ciliary neurotrophic factor (CNTF) than their PLGA counterparts. While the amine functionalities were amenable to the delivery of large molecules and surface conjugations, they did not comprise polymer biocompatibility. With the versatile combination of properties, biocompatibility, and ease of synthesis, these block copolymers have the potential for diverse utility in the fields of drug delivery and tissue engineering. PMID:19433141

  20. Anti-melanogenic effects of resveratryl triglycolate, a novel hybrid compound derived by esterification of resveratrol with glycolic acid.

    PubMed

    Park, Soojin; Seok, Jin Kyung; Kwak, Jun Yup; Choi, Yun-Hyeok; Hong, Seong Su; Suh, Hwa-Jin; Park, Woncheol; Boo, Yong Chool

    2016-07-01

    Resveratrol is known to inhibit cellular melanin synthesis by multiple mechanisms. Glycolic acid (GA) is used in skin care products for its excellent skin penetration. The purpose of this study was to examine the anti-melanogenic effects of resveratryl triglycolate (RTG), a novel hybrid compound of resveratrol and GA, in comparison with resveratrol, GA, resveratryl triacetate (RTA) and arbutin. Resveratrol, RTG, and RTA inhibited the catalytic activity human tyrosinase (TYR) more potently than arbutin or GA did. Their cytotoxic and anti-melanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEMs). The cytotoxicity of RTG was similar to that of resveratrol and RTA. RTG at 3-10 μM decreased melanin levels and cellular TYR activities in α-melanocyte-stimulating hormone-stimulated B16/F10 cells, and L-tyrosine-stimulated HEMs. RTG also suppressed mRNA and protein expression of TYR, tyrosinase-related protein 1, L-3,4-dihydroxyphenylalanine chrome tautomerase, and microphthalmia-associated transcription factor (MITF) in HEMs stimulated with L-tyrosine. This study suggests that, like resveratrol and RTA, RTG can attenuate cellular melanin synthesis effectively through the suppression of MITF-dependent expression of melanogenic enzymes and the inhibition of catalytic activity of TYR enzyme. RTG therefore has potential for use as a cosmeceutical ingredient for skin whitening. PMID:27059716

  1. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release.

    PubMed

    Hao, Shilei; Wang, Yazhou; Wang, Bochu; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-06-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery.

  2. Antitumor Activity of Doxorubicin-Loaded Carbon Nanotubes Incorporated Poly(Lactic-Co-Glycolic Acid) Electrospun Composite Nanofibers

    NASA Astrophysics Data System (ADS)

    Yu, Yuan; Kong, Lijun; Li, Lan; Li, Naie; Yan, Peng

    2015-08-01

    The drug-loaded composite electrospun nanofiber has attracted more attention in biomedical field, especially in cancer therapy. In this study, a composite nanofiber was fabricated by electrospinning for cancer treatment. Firstly, the carbon nanotubes (CNTs) were selected as carriers to load the anticancer drug—doxorubicin (DOX) hydrochloride. Secondly, the DOX-loaded CNTs (DOX@CNTs) were incorporated into the poly(lactic-co-glycolic acid) (PLGA) nanofibers via electrospinning. Finally, a new drug-loaded nanofibrous scaffold (PLGA/DOX@CNTs) was formed. The properties of the prepared composite nanofibrous mats were characterized by various techniques. The release profiles of the different DOX-loaded nanofibers were measured, and the in vitro antitumor efficacy against HeLa cells was also evaluated. The results showed that DOX-loaded CNTs can be readily incorporated into the nanofibers with relatively uniform distribution within the nanofibers. More importantly, the drug from the composite nanofibers can be released in a sustained and prolonged manner, and thereby, a significant antitumor efficacy in vitro is obtained. Thus, the prepared composite nanofibrous mats are a promising alternative for cancer treatment.

  3. Highly Stable PEGylated Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for the Effective Delivery of Docetaxel in Prostate Cancers.

    PubMed

    Cao, Long-Bin; Zeng, Sha; Zhao, Wei

    2016-12-01

    In the present study, a highly stable luteinizing-hormone-releasing hormone (LHRH)-conjugated PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles were developed for the successful treatment of prostate cancers. We have demonstrated that a unique combination of targeted drug delivery and controlled drug release is effective against prostate cancer therapy. The docetaxel (DTX)/PLGA-LHRH micelles possessed a uniform spherical shape with an average diameter of ~170 nm. The micelles exhibited a controlled drug release for up to 96 h which can minimize the non-specific systemic spread of toxic drugs during circulation while maximizing the efficiency of tumor-targeted drug delivery. The LHRH-conjugated micelles showed enhanced cellular uptake and exhibited significantly higher cytotoxicity against LNCaP cancer cells. We have showed that PLGA-LHRH induced greater caspase-3 activity indicating its superior apoptosis potential. Consistently, LHRH-conjugated micelles induced threefold and twofold higher G2/M phase arrest than compared to free DTX or PLGA NP-treated groups. Overall, results indicate that use of LHRH-conjugated nanocarriers may potentially be an effective nanocarrier to effectively treat prostate cancer.

  4. Neuroprotective effect of estradiol-loaded poly(lactic-co-glycolic acid) nanoparticles on glutamate-induced excitotoxic neuronal death.

    PubMed

    Kim, Jeong Hwan; Kim, Gyu Hyun; Jeong, Ji Heun; Lee, In Ho; Lee, Ye Ji; Lee, Nam Seob; Jeong, Young Gil; Lee, Je Hun; Yu, Kwang Sik; Lee, Shin Hye; Hong, Seul Ki; Kang, Seong Hee; Kang, Bo Sun; Kim, Do Kyung; Han, Seung Yun

    2014-11-01

    Different concentrations of estradiol (E2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (E2-PLGA-NPs) were synthesized using the emulsion-diffusion method. Transmission electron microscopy results showed that the average particle size of E2-PLGA-NPs was 98 ± 1.9 nm when stabilized with polyvinyl alcohol and 103 ± 4.9 nm when stabilized with Tween-80. Fourier transform-infrared spectroscopy with diamond attenuated total reflectance was used to identify the presence or absence of E2 molecules in PLGA nanocapsules. Cell proliferation was assessed after treating SH-SY5Y neuroblastoma cells with 1 nM-1 μM of E2 and E2-PLGA-NPs. The neuroprotective efficacy against glutamate-induced excitotoxicity was also investigated in SH-SY5Y neuroblastoma cells. Neuroprotection was greater in E2-PLGA-NP-treated cells than in cells treated with the same concentration of E2. Furthermore, E2- and E2-PLGA-NP-treated cells expressed more p-ERK1/2 and p-CREB than cells treated with glutamate only. Moreover, the expression of p-ERK1/2 was higher than that of p-CREB. In this study, p-ERK1/2 had a greater influence on the neuroprotective effect of E2 and E2-PLGA-NPs than p-CREB. PMID:25958534

  5. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release.

    PubMed

    Hao, Shilei; Wang, Yazhou; Wang, Bochu; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-06-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. PMID:24863206

  6. Fabrication of poly(lactic-co-glycolic acid) scaffolds containing silk fibroin scaffolds for tissue engineering applications.

    PubMed

    Ju, Hyung Woo; Sheikh, Faheem A; Moon, Bo Mi; Park, Hyun Jung; Lee, Ok Joo; Kim, Jung Ho; Eun, Jang Ji; Khang, Gilson; Park, Chan Hum

    2014-08-01

    The present study deals with the fabrication of poly(lactic-co-glycolic acid) (PLGA) scaffolds modified with silk fibroin for biomedical application. The PLGA solutions were added with salt particles and pressed with high pressures; which were further subjected to salt leaching resulting in the creation of large sized pores in the PLGA scaffolds. To fill up these pores, 2%, 4%, and 8% of silk solutions were added, however, the addition created extra small sized pores. The scaffolds were characterized by various state of techniques; the scanning electronic microscopy revealed the large sized pores in the pristine scaffold can be tailored into smaller architecture by the addition of silk fibroin. The contact angle measurements confirmed the introduction of silk helped to change the hydrophobic nature of PLGA into hydrophilic, which is the main constrain for PLGA. The mechanical properties of scaffold can be easily improved by applying the higher amounts of silk into the scaffolds. The thermal gravimetric analyses and fourier transform infrared spectroscopy confirmed the presence of silk fibroin in scaffolds. The cell viability and cell attachment was checked by culturing the scaffolds with NIH 3T3 fibroblasts and chondrocytes. Furthermore, these results revealed that the introduction of silk had significant impact on the viability of fibroblast also had a good affinity for cell attachment and infiltration of human chondrocytes in scaffolds after culturing the cells for 2 and 5 weeks of time. PMID:24026912

  7. Effect of agitation regimen on the in vitro release of leuprolide from poly(lactic-co-glycolic) acid microparticles.

    PubMed

    Schoubben, Aurélie; Blasi, Paolo; Deluca, Patrick P

    2012-03-01

    Because of the importance of in vitro release tests in establishing batch-to-batch reproducibility and in vitro-in vivo correlation, this study investigated the influence of agitation regimen on the in vitro release behavior of leuprolide from poly(lactic-co-glycolic) acid microparticles. Leuprolide-loaded microspheres were prepared using Resomer(®) RG502H and RG503H as polymers. Leuprolide in vitro release was performed in phosphate buffer solution under continuous or once-a-week agitation. At predetermined intervals, leuprolide release, polymer mass loss, and degree of hydration were investigated. Leuprolide release and polymer mass loss were higher under continuous agitation with respect to that under intermittent agitation. Using a modified version of Koizumi equation, it was possible to fit leuprolide release profiles. Similarity factor comparison showed a high level of similarity between experimental and modeled data in the case of once-a-week agitation regimen. This work highlights the importance of the in vitro release conditions on peptide release behavior from polyester microparticles.

  8. Coating of ß-tricalcium phosphate scaffolds-a comparison between graphene oxide and poly-lactic-co-glycolic acid.

    PubMed

    Ardjomandi, N; Henrich, A; Huth, J; Klein, C; Schweizer, E; Scheideler, L; Rupp, F; Reinert, S; Alexander, D

    2015-08-04

    Bone regeneration in critical size defects is a major challenge in oral and maxillofacial surgery, and the gold standard for bone reconstruction still requires the use of autologous tissue. To overcome the need for a second intervention and to minimize morbidity, the development of new biomaterials with osteoinductive features is the focus of current research. As a scaffolding material, ß-tricalcium phosphate (ß-TCP) is suitable for bone regeneration purposes, although it does not carry any functional groups for the covalent immobilization of molecules. The aim of the present study was to establish effective coating variants for ß-TCP constructs to enable the biofunctionalization of anorganic blocks with different osteogenic molecules in future studies. We established working protocols for thin surface coatings consisting of polylactic-co-glycolic acid (PLGA) and graphene oxide (GO) by varying parameters. Surface properties such as the angularity and topography of the developed scaffolds were analyzed. To examine biological functionality, the adhesion and proliferation behavior of jaw periosteal cells (JPCs) were tested on the coated constructs. Our results suggest that PLGA is the superior material for surface coating of ß-TCP matrices, leading to higher JPC proliferation rates and providing a more suitable basis for further biofunctionalization in the field of bone tissue engineering.

  9. Porous calcium phosphate-poly (lactic-co-glycolic) acid composite bone cement: A viable tunable drug delivery system.

    PubMed

    Roy, Abhijit; Jhunjhunwala, Siddharth; Bayer, Emily; Fedorchak, Morgan; Little, Steve R; Kumta, Prashant N

    2016-02-01

    Calcium phosphate based cements (CPCs) are frequently used as bone void fillers for non-load bearing segmental bone defects due to their clinically relevant handling characteristics and ability to promote natural bone growth. Macroporous CPC scaffolds with interconnected pores are preferred for their ability to degrade faster and enable accelerated bone regeneration. Herein, a composite CPC scaffold is developed using newly developed resorbable calcium phosphate cement (ReCaPP) formulation containing degradable microspheres of bio-compatible poly (lactic-co-glycolic acid) (PLGA) serving as porogen. The present study is aimed at characterizing the effect of in-vitro degradation of PLGA microspheres on the physical, chemical and structural characteristics of the composite cements. The porosity measurements results reveal the formation of highly interconnected macroporous scaffolds after degradation of PLGA microspheres. The in-vitro characterizations also suggest that the degradation by products of PLGA reduces the pH of the local environment thereby increasing the dissolution rate of the cement. In addition, the in-vitro vancomycin release from the composite CPC scaffold suggests that the drug association with the composite scaffolds can be tuned to achieve control release kinetics. Further, the study demonstrates control release lasting for longer than 10weeks from the composite cements in which vancomycin is encapsulated in PLGA microspheres.

  10. Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

    PubMed

    García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

    2015-03-30

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes.

  11. Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid) electrospun fibrous scaffold for bone regeneration.

    PubMed

    Chen, Shijie; Jian, Zhiyuan; Huang, Linsheng; Xu, Wei; Liu, Shaohua; Song, Dajiang; Wan, Zongmiao; Vaughn, Amanda; Zhan, Ruisen; Zhang, Chaoyue; Wu, Song; Hu, Minghua; Li, Jinsong

    2015-01-01

    A mesoporous bioactive glass (MBG) surface modified with poly(lactic-co-glycolic acid) (PLGA) electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration.

  12. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury.

    PubMed

    Wang, Ya-Ling; Gu, Xiao-Mei; Kong, Yan; Feng, Qi-Lin; Yang, Yu-Min

    2015-10-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  13. Gelatin-poly(lactic-co-glycolic acid) scaffolds with oriented pore channel architecture - From in vitro to in vivo testing.

    PubMed

    Thiem, A; Bagheri, M; Große-Siestrup, C; Zehbe, R

    2016-05-01

    A gelatin-poly(lactic-co-glycolic acid), PLGA, composite scaffold, featuring a highly oriented pore channel structure, was developed as a template for articular cartilage regeneration. As a design principle the composite scaffold was optimized to contain only medical grade educts and accordingly no chemical cross linking agents or other toxicological relevant substances or methods were used. Scaffolds were synthesized using a freeze structuring method combined with an electrochemical process followed by freeze-drying. Finally, cross linking was performed using dehydrothermal treatment, which was simultaneously used for sterilization purposes. These composite scaffolds were analyzed in regard to structural and biomechanical properties, and to their degradation behavior. Furthermore, cell culture performance was tested using chondrocytes originated from joint articular cartilage tissue from 6 to 10 months old domestic pigs. Finally, the scaffolds were tested for tissue biocompatibility and their ability for tissue integration in a rat model. The scaffolds showed both excellent functional performance and high biocompatibility in vitro and in vivo. We expect that these gelatin-PLGA scaffolds can effectively support chondrogenesis in vivo demonstrating great potential for the use in cartilage defect treatment. PMID:26952462

  14. Effect of alumina on triethylene glycol diacetate-2-propenoic acid butyl ester composite polymer electrolytes for flexible lithium ion batteries

    NASA Astrophysics Data System (ADS)

    Wang, Qiujun; Song, Wei-Li; Fan, Li-Zhen; Shi, Qiao

    2015-04-01

    Triethylene glycol diacetate-2-propenoic acid butyl ester (TEGDA-BA) based composite polymer electrolytes (CPE) are fabricated by incorporating alumina (Al2O3) nanoparticles (average particle size 10-20 nm) as inorganic filler via in situ polymerization. Effects of Al2O3 concentration on ionic conductivities, Li+ transfer numbers and charge/discharge properties are studied in details. Due to the uniformly dispersed Al2O3 nanoparticles, significant improvements in the mechanical flexibility and bendability are presented in the resulting polymer electrolytes. The CPE with 5 wt% Al2O3 nanoparticles exhibits the highest ionic conductivity up to 6.02 × 10-3 S cm-1 at 25 °C and the highest Li+ transference number (0.675), coupled with the most stable electrochemical window (>4.5 V vs. Li/Li+). With the presence of Al2O3, the growth of interface resistance is retarded, which increases the interface stability. The Li|CPE|Li4Ti5O12 and Li|CPE|LiFePO4 cells demonstrate remarkably stable charge/discharge performance and excellent capacity retention during cycling test. The results suggest that the CPE holds great application potential in flexible lithium ion batteries.

  15. Kinetics of the esterification of active pharmaceutical ingredients containing carboxylic acid functionality in polyethylene glycol: formulation implications.

    PubMed

    Schou-Pedersen, Anne Marie V; Hansen, Steen Honoré; Moesgaard, Birthe; Østergaard, Jesper

    2014-08-01

    Polyethylene glycols (PEGs) are attractive as excipients in the manufacture of drug products because they are water soluble and poorly immunogenic. They are used in various pharmaceutical preparations. However, because of their terminal hydroxyl groups, PEGs can participate in esterification reactions. In this study, kinetics of two active pharmaceutical ingredients, cetirizine and indomethacin possessing carboxylic acid functionality, has been studied in PEG 400 and PEG 1000 at 50 °C, 60 °C, 70 °C, and 80 °C. HPLC-UV was applied for the determination of concentrations in the kinetic studies, whereas HPLC-MS was used to identify reaction products. The esterification reactions were observed to be reversible. A second-order reversible kinetic model was applied and rate constants were determined. The rate constants demonstrated that cetirizine was esterified about 240 times faster than indomethacin at 80 °C. The shelf-life for cetirizine in a PEG 400 formulation at 25 °C expressed as t(95%) was predicted to be only 30 h. Further, rate constants for esterification of cetirizine in PEG 1000 in relation to PEG 400 decreased by a factor of 10, probably related to increased viscosity. However, it is important to be aware of this drug-excipient interaction, as it can reduce the shelf-life of a low-average molecular weight PEG formulation considerably.

  16. Structure and DNA Hybridization Properties of Mixed Nucleic Acid/Maleimide-Ethylene Glycol Monolayers

    SciTech Connect

    Lee,C.; Nguyen, P.; Grainger, D.; Gamble, L.; Castner, D.

    2007-01-01

    The surface structure and DNA hybridization performance of thiolated single-strand DNA (HS-ssDNA) covalently attached to a maleimide-ethylene glycol disulfide (MEG) monolayer on gold have been investigated. Monolayer immobilization chemistry and surface coverage of reactive ssDNA probes were studied by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. Orientation of the ssDNA probes was determined by near-edge X-ray absorption fine structure (NEXAFS). Target DNA hybridization on the DNA-MEG probe surfaces was measured by surface plasmon resonance (SPR) to demonstrate the utility of these probe surfaces for detection of DNA targets from both purified target DNA samples and complex biological mixtures such as blood serum. Data from complementary techniques showed that immobilized ssDNA density is strongly dependent on the spotted bulk DNA concentration and buffer ionic strength. Variation of the immobilized ssDNA density had a profound influence on the DNA probe orientation at the surface and subsequent target hybridization efficiency. With increasing surface probe density, NEXAFS polarization dependence results (followed by monitoring the N 1s {yields} {pi}* transition) indicate that the immobilized ssDNA molecules reorient toward a more upright position on the MEG monolayer. SPR assays of DNA targets from buffer and serum showed that DNA hybridization efficiency increased with decreasing surface probe density. However, target detection in serum was better on the 'high-density' probe surface than on the 'high-efficiency' probe surface. The amounts of target detected for both ssDNA surfaces were several orders of magnitude poorer in serum than in purified DNA samples due to nonspecific serum protein adsorption onto the sensing surface.

  17. Bioinspired insights into silicic acid stabilization mechanisms: the dominant role of polyethylene glycol-induced hydrogen bonding.

    PubMed

    Preari, Melina; Spinde, Katrin; Lazic, Joëlle; Brunner, Eike; Demadis, Konstantinos D

    2014-03-19

    Mono- and disilicic acids were stabilized by uncharged polyethylene glycols (PEGs) in silica-supersaturated solutions (the starting solution contained 500 ppm/8.3 mM sodium orthosilicate, Na2SiO3·5H2O, expressed as SiO2) at pH = 7, most likely by hydrogen bonding between the silanol groups and -CH2-CH2-O-ether moieties. The stabilization was monitored by measuring molybdate-reactive silica and also by a combination of liquid- and solid-state (29)Si NMR spectroscopy. It depends on PEG concentration (20-100 ppm) and molecular weight (1550-20,000 Da). Two narrow (29)Si NMR signals characteristic for monosilicic acid (Q(0)) and disilicic acid (Q(1)) can be observed in (29)Si NMR spectra of solutions containing PEG 10000 with intensities distinctly higher than the control, that is, in the absence of PEG. Silica-containing precipitates are observed in the presence of PEG, in contrast to the gel formed in the absence of PEG. These precipitates exhibit similar degrees of silica polycondensation as found in the gel as can be seen from the (29)Si MAS NMR spectra. However, the (2)D HETCOR spectra show different (1)H NMR signal shifts: The signal due to H-bonded SiOH/H2O, which is found at 6 ppm in the control, is shifted to ~7 ppm in the PEG-containing precipitate. This indicates the formation of slightly stronger H-bonds than in the control sample, most likely between PEG and the silica species. The presence of PEG in these precipitates is unequivocally proven by (13)C CP MAS NMR spectroscopy. The (13)C signal of PEG significantly shifts and is much narrower in the precipitates as compared to the pristine PEG, indicating that PEG is embedded into the silica or at least bound to its surface (or both), and not phase separated. FT-IR spectra corroborate the above arguments. The H-bonding between silanol and ethereal O perturbs the band positions attributed to vibrations involving the O atom. This work may invoke an alternative way to envision silica species stabilization

  18. Humidity-dependent compression-induced glass transition of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA).

    PubMed

    Kim, Hyun Chang; Lee, Hoyoung; Jung, Hyunjung; Choi, Yun Hwa; Meron, Mati; Lin, Binhua; Bang, Joona; Won, You-Yeon

    2015-07-28

    Constant rate compression isotherms of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA) show a distinct feature of an exponential increase in surface pressure in the high surface polymer concentration regime. We have previously demonstrated that this abrupt increase in surface pressure is linked to the glass transition of the polymer film, but the detailed mechanism of this process is not fully understood. In order to obtain a molecular-level understanding of this behavior, we performed extensive characterizations of the surface mechanical, structural and rheological properties of Langmuir PLGA films at the air-water interface, using combined experimental techniques including the Langmuir film balance, X-ray reflectivity and double-wall-ring interfacial rheometry methods. We observed that the mechanical and structural responses of the Langmuir PLGA films are significantly dependent on the rate of film compression; the glass transition was induced in the PLGA film only at fast compression rates. Surprisingly, we found that this deformation rate dependence is also dependent on the humidity of the environment. With water acting as a plasticizer for the PLGA material, the diffusion of water molecules through the PLGA film seems to be the key factor in the determination of the glass transformation properties and thus the mechanical response of the PLGA film against lateral compression. Based on our combined results, we hypothesize the following mechanism for the compression-induced glass transformation of the Langmuir PLGA film; (1) initially, a humidified/non-glassy PLGA film is formed in the full surface-coverage region (where the surface pressure shows a plateau) during compression; (2) further compression leads to the collapse of the PLGA chains and the formation of new surfaces on the air side of the film, and this newly formed top layer of the PLGA film is transiently glassy in character because the water evaporation rate

  19. Humidity-dependent compression-induced glass transition of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA).

    PubMed

    Kim, Hyun Chang; Lee, Hoyoung; Jung, Hyunjung; Choi, Yun Hwa; Meron, Mati; Lin, Binhua; Bang, Joona; Won, You-Yeon

    2015-07-28

    Constant rate compression isotherms of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA) show a distinct feature of an exponential increase in surface pressure in the high surface polymer concentration regime. We have previously demonstrated that this abrupt increase in surface pressure is linked to the glass transition of the polymer film, but the detailed mechanism of this process is not fully understood. In order to obtain a molecular-level understanding of this behavior, we performed extensive characterizations of the surface mechanical, structural and rheological properties of Langmuir PLGA films at the air-water interface, using combined experimental techniques including the Langmuir film balance, X-ray reflectivity and double-wall-ring interfacial rheometry methods. We observed that the mechanical and structural responses of the Langmuir PLGA films are significantly dependent on the rate of film compression; the glass transition was induced in the PLGA film only at fast compression rates. Surprisingly, we found that this deformation rate dependence is also dependent on the humidity of the environment. With water acting as a plasticizer for the PLGA material, the diffusion of water molecules through the PLGA film seems to be the key factor in the determination of the glass transformation properties and thus the mechanical response of the PLGA film against lateral compression. Based on our combined results, we hypothesize the following mechanism for the compression-induced glass transformation of the Langmuir PLGA film; (1) initially, a humidified/non-glassy PLGA film is formed in the full surface-coverage region (where the surface pressure shows a plateau) during compression; (2) further compression leads to the collapse of the PLGA chains and the formation of new surfaces on the air side of the film, and this newly formed top layer of the PLGA film is transiently glassy in character because the water evaporation rate

  20. Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic acid blended with nanoparticulate amorphous calcium phosphate in vascular stent applications.

    PubMed

    Zheng, Xiaoxin; Wang, Yujue; Lan, Zhiyuan; Lyu, Yongnan; Feng, Gaoke; Zhang, Yipei; Tagusari, Shizu; Kislauskis, Edward; Robich, Michael P; McCarthy, Stephen; Sellke, Frank W; Laham, Roger; Jiang, Xuejun; Gu, Wei Wang; Wu, Tim

    2014-06-01

    Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.

  1. Reactive Poly(Amic Acid)/ Poly(Glycidyl Methacrylate-r-Poly(ethylene Glycol) Methyl Ether Methacrylate) Blends as Gas Permeation Membranes

    NASA Astrophysics Data System (ADS)

    Beaulieu, Michael; Watkins, James

    2012-02-01

    Polymers containing polar moieties, such as ether groups show an affinity for acidic gases, such as CO2 due to dipole-quadrapole interactions. Polymer blends in which one of the components is poly(ethylene glycol) (PEG) have been studied extensively in literature as a CO2/light gas permeation membrane, but due to the crystallization and poor mechanical properties have been difficult to incorporate PEG above 60wt%. In this study, a series of random copolymers containing both glycidyl methacrylate and poly(ethylene glycol) methyl ether methacrylate in different ratios are blended with a poly(amic acid) prepolymer made from 4, 4'-oxydianiline and pyromellitic dianhydride to create gas permeation membranes. By using a reactive blend PEG loadings above 70% have been realized with sufficient mechanical properties, and since the side chain on the PEGMA is short these blends do not suffer from crystallization.

  2. Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)-tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide.

    PubMed

    Shao, Weili; He, Jianxin; Sang, Feng; Wang, Qian; Chen, Li; Cui, Shizhong; Ding, Bin

    2016-05-01

    To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering. PMID:26952489

  3. Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)-tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide.

    PubMed

    Shao, Weili; He, Jianxin; Sang, Feng; Wang, Qian; Chen, Li; Cui, Shizhong; Ding, Bin

    2016-05-01

    To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering.

  4. Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury.

    PubMed

    Wang, Dong; Fan, Yuhong; Zhang, Jianjun

    2013-03-15

    Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly(D,L-lactide-co-glycolic acid) has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly(D,L-lactide-co-glycolic acid) into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced cells plus the poly(D,L-lactide-co-glycolic acid) scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly(D,L-lactide-co-glycolic acid) scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.

  5. Accuracy of Motor Axon Regeneration Across Autograft, Single Lumen, and Multichannel Poly(lactic-co-glycolic Acid) (PLGA) Nerve Tubes

    PubMed Central

    de Ruiter, Godard C.; Spinner, Robert J.; Malessy, Martijn J. A.; Moore, Michael J.; Sorenson, Eric J.; Currier, Bradford L.; Yaszemski, Michael J.; Windebank, Anthony J.

    2012-01-01

    Objective Accuracy of motor axon regeneration becomes an important issue in the development of a nerve tube for motor nerve repair. Dispersion of regeneration across the nerve tube may lead to misdirection and polyinnervation. In this study, we present a series of methods to investigate the accuracy of regeneration, which we used to compare regeneration across autografts and single lumen poly(lactic-co-glycolic acid) (PLGA) nerve tubes. We also present the concept of the multichannel nerve tube that may limit dispersion by separately guiding groups of regenerating axons. Methods Simultaneous tracing of the tibial and peroneal nerves with fast blue (FB) and diamidino yellow (DY), 8 weeks after repair of a 1-cm nerve gap in the rat sciatic nerve, was performed to determine the percentage of double-projecting motoneurons. Sequential tracing of the peroneal nerve with DY 1 week before and FB 8 weeks after repair was performed to determine the percentage of correctly directed peroneal motoneurons. Results In the cases in which there was successful regeneration across single lumen nerve tubes, more motoneurons had double projections to both the tibial and peroneal nerve branches after single lumen nerve tube repair (21.4%) than after autograft repair (5.9%). After multichannel nerve tube repair, this percentage was slightly reduced (16.9%), although not significantly. The direction of regeneration was nonspecific after all types of repair. Conclusion Retrograde tracing techniques provide new insights into the process of regeneration across nerve tubes. The methods and data presented in this study can be used as a basis in the development of a nerve tube for motor nerve repair. PMID:18728579

  6. Comparative studies on chitosan and polylactic-co-glycolic acid incorporated nanoparticles of low molecular weight heparin.

    PubMed

    Yang, Tianzhi; Nyiawung, Divine; Silber, Alexandra; Hao, Jiukuan; Lai, Leanne; Bai, Shuhua

    2012-12-01

    This study was performed to test the feasibility of chitosan and polylactic-co-glycolic acid (PLGA) incorporated nanoparticles as sustained-release carriers for the delivery of negatively charged low molecular weight heparin (LMWH). Fourier transform infrared (FTIR) spectrometry was used to evaluate the interactions between chitosan and LMWH. The shifts, intensity, and broadening of the characteristic peaks for the functional groups in the FTIR spectra indicated that strong interactions occur between the positively charged chitosans and the negatively charged LMWHs. Three types of LMWH nanoparticles (NP-1, NP-2, and NP-3) were prepared using chitosan with or without PLGA: NP-1 nanoparticles were formed by polyelectrolyte complexation after single mixing, NP-2 nanoparticles were prepared by polyelectrolyte complexation after single emulsion-diffusion-evaporation, and NP-3 nanoparticles were optimized by double emulsion-diffusion-evaporation. NP-3 nanoparticles of LMWH prepared by the emulsion-diffusion-evaporation method showed significant differences in particle morphology, size, zeta potential, and drug release profile compared to NP-1 nanoparticles formed by polyelectrolyte complexation. Another ionic complex of LMWH with chitosan-incorporated PLGA nanoparticles (NP-2) showed lower drug entrapment efficiency than that of NP-1 and NP-3. The drug release rate of NP-3 was slower than the release rates of NP-1 and NP-2, although particle morphology of NP-3 was similar to that of NP-2. Cell viability was not adversely affected when cells were treated with all three types of nanoparticles. The data presented in this study demonstrate that nanoparticles formulated with chitosan-PLGA could be a safe sustained-release carrier for the delivery of LMWH.

  7. Preparation of Porous Core-Shell Poly L-Lactic Acid/Polyethylene Glycol Superfine Fibres Containing Drug.

    PubMed

    Yang, Wenjing; He, Nongyue; Fu, Juan; Li, Zhiyang; Ji, Xuyuan

    2015-12-01

    In this paper, poly L-lactic acid (PLLA) blended with polyethylene glycol (PEG) was dissolved in methylene dichloride solution as the shell solution, and rapamycin (RAPA), was encapsulated inside the core of PLLA micro/nano fibres as a model drug. The effects of the blending ratio of PLLA to PEG, the concentration of the electrospinning solution, the voltage, the flow rate, and the encapsulation efficiency were studied. Uniform and porous RAPA-Loading PLLA fibres were obtained when the ratio of PLLA to PEG was 7/3, the concentration of PLLA was 3%, the applied voltage was 7.5 kV, and the pump speed was V(core) = 0.1 mL/h, V(shell) = 1 mL/h, repectively. The average diameter of PLLA fibres increased with the gradual increase in PLLA concentration. FTIR results showed that RAPA was successfully encapsulated into the core-co-shell PLLA fibres. Meanwhile, the RAPA-loading of coaxial electrospun PLLA fibres was significantly higher than that of the blending electrospun fibres. It was also found that the porous core-shell PLLA/PEG blending superfine fibres could regulate the appearance of pore on the surface of superfine fibres by adjusting the electrospinning parameters. The porous PLLA/PEG blending fibres can be used as drug carriers and, to improve the single way of drug release depending on the degradation of shell material to meet different need. It will be a remarkable breakthrough in the area for sustained and controlled release drug delivery system. PMID:26682434

  8. Epigallocatechin-3-O-Gallate-Loaded Poly(lactic-co-glycolic acid) Fibrous Sheets as Anti-Adhesion Barriers.

    PubMed

    Lee, Jong Ho; Shin, Yong Cheol; Yang, Won Jun; Park, Jong-chul; Hyon, Suong-hyu; Han, Dong-wook

    2015-08-01

    Epigallocatechin-3-O-gallate (EGCG), the main polyphenolic component of green tea, has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, and anti-fibrotic effects. In this study, EGCG-loaded poly(lactic-co-glycolic acid) (PLGA) sheets were prepared by electrospinning nanofibers and evaluating their potential as tissue-adhesion barriers. EGCG-loaded PLGA (E-PLGA) fibrous sheets were electrospun from a PLGA solution containing 8% (w/v) EGCG. The average diameter of E-PLGA fibers was 397 ± 159 nm, which was comparable to that of pure PLGA fibers (459 ± 154 nm). EGCG was uniformly dispersed in E-PLGA sheets without direct chemical interactions. E-PLGA fibrous sheets showed sustained release of EGCG by controlled diffusion and PLGA degradation. The attachment and proliferation of L-929 fibroblastic cells were significantly (p < 0.05) suppressed in E-PLGA sheets. Furthermore, E-PLGA fibrous sheets did not induce any inflammatory response to J774A.1 macrophages. The anti-adhesion efficacy of E-PLGA fibrous sheets was evaluated in the intraperitoneal adhesion model in rats. Two weeks after surgical treatment, macroscopic adhesion (extent and severity) scores and histopathological tissue responses of E-PLGA fibrous sheets were significantly lower than those of non-treated controls and pure PLGA sheets. The results suggest that the scores are comparable, and in some cases superior, to those of other commercialized tissue-adhesion barriers. In conclusion, our study findings suggest that E-PLGA fibrous sheets may be exploited as potential tissue-adhesion barriers for the prevention of post-surgical adhesion formation. PMID:26295146

  9. Potential of Hydrogels Based on Poly(Ethylene Glycol) and Sebacic Acid as Orthopedic Tissue Engineering Scaffolds

    PubMed Central

    Kim, Jinku; Hefferan, Theresa E.; Yaszemski, Michael J.

    2009-01-01

    In this study, the bioactive effects of poly(ethylene glycol) (PEG) sebacic acid diacrylate (PEGSDA) hydrogels with or without RGD peptide modification on osteogenic differentiation and mineralization of marrow stromal cells (MSCs) were examined. In a separate experiment, the ability of PEGSDA hydrogel to serve as a delivery vehicle for bone morphogenetic protein 2 (BMP-2) was also investigated. As a scaffold, the attachment and proliferation of MSCs on PEGSDA hydrogel scaffolds with and without RGD peptide modification was similar to the control, tissue culture polystyrene. In contrast, cells were barely seen on unmodified PEG diacrylate (PEGDA) hydrogel throughout the culture period for up to 21 days. Osteogenic phenotypic expression such as alkaline phosphatase (ALP) of MSCs as well as mineralized calcium content were significantly higher on PEGSDA-based hydrogels than those on the control or PEGDA hydrogels. Potential use of PEGSDA scaffold as a delivery vehicle of osteogenic molecules such as BMP-2 was also evaluated. Initial burst release of BMP-2 from PEGSDA hydrogel scaffold (14.7%) was significantly reduced compared to PEGDA hydrogel scaffold (84.2%) during the first 3 days of a 21-day release period. ALP activity of an osteoblast was significantly higher in the presence of BMP-2 released from PEGSDA hydrogel scaffolds compared to that in the presence of BMP-2 released from PEGDA scaffolds, especially after 6 days of release. Overall, PEGSDA hydrogel scaffolds without further modification may be useful as orthopedic tissue engineering scaffolds as well as local drug carriers for prolonged sustained release of osteoinductive molecules. PMID:19292677

  10. Preparation of Porous Core-Shell Poly L-Lactic Acid/Polyethylene Glycol Superfine Fibres Containing Drug.

    PubMed

    Yang, Wenjing; He, Nongyue; Fu, Juan; Li, Zhiyang; Ji, Xuyuan

    2015-12-01

    In this paper, poly L-lactic acid (PLLA) blended with polyethylene glycol (PEG) was dissolved in methylene dichloride solution as the shell solution, and rapamycin (RAPA), was encapsulated inside the core of PLLA micro/nano fibres as a model drug. The effects of the blending ratio of PLLA to PEG, the concentration of the electrospinning solution, the voltage, the flow rate, and the encapsulation efficiency were studied. Uniform and porous RAPA-Loading PLLA fibres were obtained when the ratio of PLLA to PEG was 7/3, the concentration of PLLA was 3%, the applied voltage was 7.5 kV, and the pump speed was V(core) = 0.1 mL/h, V(shell) = 1 mL/h, repectively. The average diameter of PLLA fibres increased with the gradual increase in PLLA concentration. FTIR results showed that RAPA was successfully encapsulated into the core-co-shell PLLA fibres. Meanwhile, the RAPA-loading of coaxial electrospun PLLA fibres was significantly higher than that of the blending electrospun fibres. It was also found that the porous core-shell PLLA/PEG blending superfine fibres could regulate the appearance of pore on the surface of superfine fibres by adjusting the electrospinning parameters. The porous PLLA/PEG blending fibres can be used as drug carriers and, to improve the single way of drug release depending on the degradation of shell material to meet different need. It will be a remarkable breakthrough in the area for sustained and controlled release drug delivery system.

  11. Effect of osteoblastic culture conditions on the structure of poly(DL-lactic-co-glycolic acid) foam scaffolds

    NASA Technical Reports Server (NTRS)

    Goldstein, A. S.; Zhu, G.; Morris, G. E.; Meszlenyi, R. K.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1999-01-01

    Poly(DL-lactic-co-glycolic acid) (PLGA) foams are an osteoconductive support that holds promise for the development of bone tissue in vitro and implantation into orthopedic defects. Because it is desirable that foams maintain their shape and size, we examined a variety of foams cultured in vitro with osteoblastic cells. Foams were prepared with different porosities and pore sizes by the method of solvent casting/porogen leaching using 80, 85, and 90 wt% NaCl sieved with particle sizes of 150-300 and 300-500 microm and characterized by mercury intrusion porosimetry. Foams seeded with cells were found to have volumes after 7 days in static culture that decreased with increasing porosity: the least porous exhibited no change in volume while the most porous foams decreased by 39 +/- 10%. In addition, a correlation was observed between decreasing foam volume after 7 days in culture and decreasing internal surface area of the foams prior to seeding. Furthermore, foams prepared with the 300-500 microm porogen had lower porosities, greater mean wall thicknesses between adjacent pores, and larger volumes after 7 days in culture than those prepared with the smaller porogen. Two culture conditions for maintaining cells, static and agitated (in a rotary vessel), were found to have similar influences on foam size, cell density, and osteoblastic function for 7 and 14 days in culture. Finally, we examined unseeded foams in aqueous solutions of pH 3.0, 5.0, and 7.4 and found no significant decrease in foam size with degradation. This study demonstrates that adherent osteoblastic cells may collapse very porous PLGA foams prepared by solvent casting/particulate leaching: a potentially undesirable property for repair of orthopedic defects.

  12. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections.

    PubMed

    Flores, Claudia; Degoutin, Stephanie; Chai, Feng; Raoul, Gwenael; Hornez, Jean-Chritophe; Martel, Bernard; Siepmann, Juergen; Ferri, Joel; Blanchemain, Nicolas

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60μm, allowing for incorporation inside the macropores (100μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25-30days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions.

  13. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections.

    PubMed

    Flores, Claudia; Degoutin, Stephanie; Chai, Feng; Raoul, Gwenael; Hornez, Jean-Chritophe; Martel, Bernard; Siepmann, Juergen; Ferri, Joel; Blanchemain, Nicolas

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60μm, allowing for incorporation inside the macropores (100μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25-30days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions. PMID:27127034

  14. Protective Effects of Indole-3-Carbinol-Loaded Poly(lactic-co-glycolic acid) Nanoparticles Against Glutamate-Induced Neurotoxicity.

    PubMed

    Jeong, Ji Heun; Kim, Jwa-Jin; Bak, Dong Ho; Yu, Kwang Sik; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Do Kyung; Kim, Dong-Kwan; Han, Seung-Yun

    2015-10-01

    Indole-3-carbinol (I3C) has anti-oxidant and anti-inflammatory properties. Nonetheless, the potential of I3C to treat neurodegenerative diseases remains unclear because of its poor ability to penetrate the blood-brain barrier (BBB). Because polymer-based drug delivery systems stabilized by surfactants have been intensively utilized as a strategy to cross the blood-brain barrier, we prepared I3C-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that were stabilized by Tween 80 (T80) (I3C-PLGA-T80-NPs) and examined their neuroprotective potential in vitro. We prepared I3C-PLGA-T80-NPs with an oil-in-water (o/w) emulsion solvent evaporation technique and confirmed their successful synthesis with both transmission electron microscopy and Fourier transform-infrared spectroscopy. I3C-PLGA-T80-NPs were then used to treat PC12 neuronal cells injured by glutamate excitotoxicity (GE) and examined the resulting survival rates compared with PC12 cells treated with I3C only. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay revealed higher survival rates in I3C-PLGA-T80-NPs-treated cells after GE injury compared with those treated with I3C only. Furthermore, I3C-PLGA-T80-NPs decreased the levels of reactive oxygen species (ROS) and apoptosis-related enzymes (Caspase-3 and -8) in GE-damaged neuronal cells. Taken together, I3C-PLGA-T80-NPs might possess neuroprotective effects against GE through ROS scavenging and subsequent apoptosis blockage. PMID:26726441

  15. Increased norfloxacin skin permeability for fatty alcohol propylene glycol (FAPG) ointment by optimized process of preparation: behavior of stearic acid in stratum corneum lipids.

    PubMed

    Lin, H H; Hsu, L R; Wu, P C; Tsai, Y H

    1995-11-01

    Preparation of the fatty alcohol propylene glycol (FAPG) ointment base plays an important role in controlling the physicochemical properties of ointments. These essay investigates the effects of preparative conditions such as cooling rate and stirring rate on the percutaneous absorption of norfloxacin from FAPG ointment. The influence of process-induced variation in enhancing effect of stearic acid which was incorporated into FAPG base was evaluated in vitro on rat skin. In the permeation experiment, norfloxacin penetration significantly increased with faster cooling rate. This result directly related to the increasing norfloxacin skin--vehicle partition coefficient. Histological analysis results showed no appreciable exfoliation of the stratum corneum. The differential scanning calorimetry (DSC) results show that stearic acid enriched lipid in the stratum corneum resulting from treatment with supercooling products may result in more crystalline structure and, hence preferential partitioning of the norfloxacin into the more crystalline regions of the membrane can be observed. A much greater enhancing effect can be achieved when we use stearic acid together with norfloxacin in propylene glycol (PG); but such effect cannot be found if 5 wt% stearic acid/PG suspension is used to pretreat skin before the application of norfloxacin PG solution.

  16. Biocompatibility and enhanced osteogenic differentiation of human mesenchymal stem cells in response to surface engineered poly(D,L-lactic-co-glycolic acid) microparticles.

    PubMed

    Rogers, Catherine M; Deehan, David J; Knuth, Callie A; Rose, Felicity R A J; Shakesheff, Kevin M; Oldershaw, Rachel A

    2014-11-01

    Tissue engineering strategies can be applied to enhancing osseous integration of soft tissue grafts during ligament reconstruction. Ligament rupture results in a hemarthrosis, an acute intra-articular bleed rich in osteogenic human mesenchymal stem cells (hMSCs). With the aim of identifying an appropriate biomaterial with which to combine hemarthrosis fluid-derived hMSCs (HF-hMSCs) for therapeutic application, this work has investigated the biocompatibility of microparticles manufactured from two forms of poly(D,L-lactic-co-glycolic acid) (PLGA), one synthesized with equal monomeric ratios of lactic acid to glycolic acid (PLGA 50:50) and the other with a higher proportion of lactic acid (PLGA 85:15) which confers a longer biodegradation time. The surfaces of both types of microparticles were functionalized by plasma polymerization with allylamine to increase hydrophilicity and promote cell attachment. HF-hMSCs attached to and spread along the surface of both forms of PLGA microparticle. The osteogenic response of HF-hMSCs was enhanced when cultured with PLGA compared with control cultures differentiated on tissue culture plastic and this was independent of the type of polymer used. We have demonstrated that surface engineered PLGA microparticles are an appropriate biomaterial for combining with HF-hMSCs and the selection of PLGA is relevant only when considering the biodegradation time for each biomedical application.

  17. pH-Responsive Polyethylene Glycol Monomethyl Ether-ε-Polylysine-G-Poly (Lactic Acid)-Based Nanoparticles as Protein Delivery Systems

    PubMed Central

    Liu, Huiqin; Li, Yijia; Yang, Rui; Gao, Xiujun; Ying, Guoguang

    2016-01-01

    The application of poly(lactic acid) for sustained protein delivery is restricted by the harsh pH inside carriers. In this study, we synthesized a pH-responsive comb-shaped block copolymer, polyethylene glycol monomethyl ether-ε-polylysine-g-poly (lactic acid) (PEP)to deliver protein (bovine serum albumin (BSA)). The PEP nanoparticles could automatically adjust the internal pH to a milder level, as shown by the quantitative ratio metric results. The circular dichroism spectra showed that proteins from the PEP nanoparticles were more stable than those from poly(lactic acid) nanoparticles. PEP nanoparticles could achieve sustained BSA release in both in vitro and in vivo experiments. Cytotoxicity results in HL-7702 cells suggested good cell compatibility of PEP carriers. Acute toxicity results showed that the PEP nanoparticles induced no toxic response in Kunming mice. Thus, PEP nanoparticles hold potential as efficient carriers for sustained protein release. PMID:27467072

  18. Poly(lactic acid)-poly(ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA.

    PubMed

    Perez, C; Sanchez, A; Putnam, D; Ting, D; Langer, R; Alonso, M J

    2001-07-10

    The purpose of the present work was to produce and characterize poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nanoparticles (size lower than 300 nm) containing a high loading of plasmid DNA in a free form or co-encapsulated with either poly(vinyl alcohol) (PVA) or poly(vinylpyrrolidone) (PVP). The plasmid alone or with PVA or PVP was encapsulated by two different techniques: an optimized w/o/w emulsion-solvent evaporation technique as well as by a new w/o emulsion-solvent diffusion technique. Particle size, zeta potential, plasmid DNA loading and in vitro release were determined for the three plasmid-loaded formulations. The influence of the initial plasmid loadings (5, 10, 20 microg plasmid DNA/mg PLA-PEG) on those parameters was also investigated. The plasmid loaded into the nanoparticles and released in vitro was quantified by fluorimetry and the different molecular forms were identified by gel electrophoresis. PLA-PEG nanoparticles containing plasmid DNA in a free form or co-encapsulated with PVA or PVP were obtained in the range size of 150-300 nm and with a negative zeta potential, both parameters being affected by the preparation technique. Encapsulation efficiencies were high irrespective of the presence of PVA or PVP (60-90%) and were slightly affected by the preparation technique and by the initial loading. The final plasmid DNA loading in the nanoparticles was up to 10-12 microg plasmid DNA/mg polymer. Plasmid DNA release kinetics varied depending on the plasmid incorporation technique: nanoparticles prepared by the w/o diffusion technique released their content rapidly whereas those obtained by the w/o/w showed an initial burst followed by a slow release for at least 28 days. No significant influence of the plasmid DNA loading and of the co-encapsulation of PVP or PVA on the in vitro release rate was observed. In all cases the conversion of the supercoiled form to the open circular and linear forms was detected. In conclusion, plasmid DNA can be

  19. Synthesis of amphiphilic poly(ether-amide) dendrimer endcapped with poly(ethylene glycol) grafts and its solubilization to salicylic acid.

    PubMed

    Yang, Zhu; Zhang, Wenquan; Liu, Jianhua; Shi, Wenfang

    2007-04-01

    An amphiphilic dendrimer (DPEA-PEG) grafting polyethylene glycol at the terminals was prepared by endcapping of dendritic poly(ether-amide) (DPEA) with isocyanate terminated linear polyethylene glycol (PEG-NCO). The molecular structure was verified by gel permeation chromatography (GPC), (1)H NMR and FT-IR. The micelle characteristic of DPEA-PEG in water was investigated. The critical micelle concentration (CMC) was determined by a fluorescence technique to be 55.5 mg/L. The hydrodynamic radius of micelles was measured by dynamic light scattering (DLS) to be 76.2 nm. The UV-vis spectrum showed that the solubility of salicylic acid increased from 1.91 to 2.78 mg/L when the concentration of DPEA-PEG attained 5 mg/mL in an aqueous solution.

  20. Sustained release of hydrophobic drugs by the microfluidic assembly of multistage microgel/poly (lactic-co-glycolic acid) nanoparticle composites

    PubMed Central

    Hsu, Myat Noe; Luo, Rongcong; Kwek, Kerwin Zeming; Por, Yong Chen; Zhang, Yong; Chen, Chia-Hung

    2015-01-01

    The poor solubility of many newly discovered drugs has resulted in numerous challenges for the time-controlled release of therapeutics. In this study, an advanced drug delivery platform to encapsulate and deliver hydrophobic drugs, consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporated within poly (ethylene glycol) (PEG) microgels, was developed. PLGA nanoparticles were used as the hydrophobic drug carrier, while the PEG matrix functioned to slow down the drug release. Encapsulation of the hydrophobic agents was characterized by fluorescence detection of the hydrophobic dye Nile Red within the microgels. In addition, the microcomposites prepared via the droplet-based microfluidic technology showed size tunability and a monodisperse size distribution, along with improved release kinetics of the loaded cargo compared with bare PLGA nanoparticles. This composite system has potential as a universal delivery platform for a variety of hydrophobic molecules. PMID:25825623

  1. Simultaneous determination of allantoin and glycolic acid in snail mucus and cosmetic creams with high performance liquid chromatography and ultraviolet detection.

    PubMed

    El Mubarak, Mohamed Ahmed S; Lamari, Fotini N; Kontoyannis, Christos

    2013-12-27

    A new methodology for simultaneous quantitative analysis of allantoin and glycolic acid in snail mucus and cosmetic creams was developed. HPLC separation was achieved a Synergi-Hydro RP column within 7min using isocratic elution with potassium phosphate (pH 2.7; 10mM) at a flow rate of 0.7mL/min at 30°C. Sample pretreatment was performed by dilution of mucus or cosmetic cream in the elution buffer, heating at 60°C for 20min, adjusting the pH to 2.9 and purification with hexane extraction. Linearity was determined with spiked samples and the LLOQ values of 0.0125 and 0.2500mg/mL were determined for allantoin and glycolic acid, respectively. Accuracy and intra- and inter-day repeatability were studied at three levels of concentrations (0.04, 0.08 and 0.16mg/mL for allantoin and 0.1, 1.5 and 4.0mg/mL for glycolic acid) using spiked mucus and cream base samples; mean values of recovery were in the range of 96.81-102.42% in all matrices tested, whereas the respective RSDs (%Relative Standard Deviation) were less than 3.04% in all cases. Spiked mucus and cream samples were stable (RSD<4.16 and relative error<4.34%) at room temperature and at 4°C for 1 week and at -18°C for 6 months; samples were also stable after three freeze-thaw cycles. The method was applied to the analysis of different lots of snail mucus, and of three commercial creams containing snail mucus.

  2. Tetraethylene glycol promoted two-step, one-pot rapid synthesis of indole-3-[1-11C]acetic acid

    DOE PAGES

    Lee, Sojeong; Qu, Wenchao; Alexoff, David L.; Shea, Colleen; Kim, Dohyun; Schueller, Michael; Fowler, Joanna S.

    2014-12-12

    An operationally friendly, two-step, one-pot process has been developed for the rapid synthesis of carbon-11 labeled indole-3-acetic acid ([11]IAA or [11]auxin). By replacing an aprotic polar solvent with tetraethylene glycol, nucleophilic [11]cyanation and alkaline hydrolysis reactions were performed consecutively in a single pot without a time-consuming intermediate purification step. The entire production time for this updated procedure is 55 min, which dramatically simplifies the entire synthesis and reduces the starting radioactivity required for a whole plant imaging study.

  3. Tetraethylene glycol promoted two-step, one-pot rapid synthesis of indole-3-[1-11C]acetic acid

    SciTech Connect

    Lee, Sojeong; Qu, Wenchao; Alexoff, David L.; Shea, Colleen; Kim, Dohyun; Schueller, Michael; Fowler, Joanna S.

    2014-12-12

    An operationally friendly, two-step, one-pot process has been developed for the rapid synthesis of carbon-11 labeled indole-3-acetic acid ([11]IAA or [11]auxin). By replacing an aprotic polar solvent with tetraethylene glycol, nucleophilic [11]cyanation and alkaline hydrolysis reactions were performed consecutively in a single pot without a time-consuming intermediate purification step. The entire production time for this updated procedure is 55 min, which dramatically simplifies the entire synthesis and reduces the starting radioactivity required for a whole plant imaging study.

  4. Resveratrol-Loaded Nanoparticles Based on Poly(epsilon-caprolactone) and Poly(d,l-lactic-co-glycolic acid)–Poly(ethylene glycol) Blend for Prostate Cancer Treatment

    PubMed Central

    Sanna, Vanna; Siddiqui, Imtiaz Ahmad; Sechi, Mario; Mukhtar, Hasan

    2014-01-01

    Nanoencapsulation of antiproliferative and chemopreventive phytoalexin trans-resveratrol (RSV) is likely to provide protection against degradation, enhancement of bioavailability, improvement in intracellular penetration and control delivery. In this study, polymeric nanoparticles (NPs) encapsulating RSV (nano-RSV) as novel prototypes for prostate cancer (PCa) treatment were designed, characterized and evaluated using human PCa cells. Nanosystems, composed of a biocompatible blend of poly(epsilon-caprolactone) (PCL) and poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) conjugate (PLGA-PEG-COOH), were prepared by a nanoprecipitation method, and characterized in terms of morphology, particle size and zeta potential, encapsulation efficiency, thermal analyses, and in vitro release studies. Cellular uptake of NPs was then evaluated in PCa cell lines DU-145, PC-3, and LNCaP using confocal fluorescence microscopy, and antiproliferative efficacy was assessed using MTT assay. With encapsulation efficiencies ranging from 74% to 98%, RSV was successfully loaded in PCL:PLGA-PEG-COOH NPs, which showed an average diameter of 150 nm. NPs were able to control the RSV release at pH 6.5 and 7.4, mimicking the acidic tumoral microenvironment and physiological conditions, respectively, with only 55% of RSV released within 7 h. In gastrointestinal simulated fluids, NPs released about 55% of RSV in the first 2 h in acidic medium, and their total RSV content within the subsequent 5 h at pH 7.4. Confocal fluorescence microscopy observations revealed that NPs were efficiently taken up by PCa cell lines. Furthermore, nano-RSV significantly improved the cytotoxicity compared to that of free RSV toward all three cell lines, at all tested concentrations (from 10 µM to 40 µM), proving a consistent sensitivity toward both the androgen-independent DU-145 and hormone-sensitive LNCaP cells. Our findings support the potential use of developed nanoprototypes for the controlled delivery of

  5. Impact of a Glycolic Acid-Containing pH 4 Water-in-Oil Emulsion on Skin pH.

    PubMed

    Behm, Barbara; Kemper, Michael; Babilas, Philipp; Abels, Christoph; Schreml, Stephan

    2015-01-01

    The skin pH is crucial for physiological skin functions. A decline in stratum corneum acidity, as observed in aged or diseased skin, may negatively affect physiological skin functions. Therefore, glycolic acid-containing water-in-oil (W/O) emulsions adjusted to pH 4 were investigated regarding their effect on normal or increased skin pH. A pH 4 W/O emulsion was applied on three areas with pathologically increased skin surface pH in diabetics (n = 10). Further, a 28-day half-side trial (n = 30) was performed to test the long-term efficacy and safety of a pH 4 W/O emulsion (n = 30). In summary, the application of a pH 4 W/O emulsion reduced the skin pH in healthy, elderly and diabetic subjects, which may improve epidermal barrier functions.

  6. Electrospraying and Electrospinning of Polymers for Biomedical Applications. Poly(Lactic-Co-Glycolic Acid) and Poly(Ethylene-Co-Vinylacetate). Appendix 2

    NASA Technical Reports Server (NTRS)

    Stitzel, Joel D.; Bowlin, Gary L.; Mansfield, Kevin; Wnek, Gary E.; Simpson, David G.

    2000-01-01

    Significant opportunities exist for the processing of polymers (homopolymers and blends) using electric fields. Specific attention is given here to electrospinning, but we note that electroaerosol formation and field-modulated film casting represent additional processing options. Of particular interest is the ability to generate polymer fibers of sub-micron dimensions using electrospinning, down to about 0.05 microns (50 nm), a size range that has been traditionally difficult to access. In our work, poly(lactic-co-glycolic acid), PLA/PGA, poly(lactic acid) PLA, and poly(ethylene-co-vinylacetate) (PEVA) have been deposited from solutions in methylene chloride or chloroform by electrospraying or electrospinning to afford morphologically tailored materials for tissue engineering and related applications. Low solution concentrations tend to favor electrostatic spraying ('electro-aerosolization') while higher concentrations lead to spinning on fibrous mats. Preliminary observations of muscle cell growth on PLA electrospun mats are reported.

  7. Tuning the degradation rate of calcium phosphate cements by incorporating mixtures of polylactic-co-glycolic acid microspheres and glucono-delta-lactone microparticles.

    PubMed

    Sariibrahimoglu, Kemal; An, Jie; van Oirschot, Bart A J A; Nijhuis, Arnold W G; Eman, Rhandy M; Alblas, Jacqueline; Wolke, Joop G C; van den Beucken, Jeroen J J P; Leeuwenburgh, Sander C G; Jansen, John A

    2014-11-01

    Calcium phosphate cements (CPCs) are frequently used as synthetic bone graft materials in view of their excellent osteocompatibility and clinical handling behavior. Hydroxyapatite-forming CPCs, however, degrade at very low rates, thereby limiting complete bone regeneration. The current study has investigated whether degradation of apatite-forming cements can be tuned by incorporating acid-producing slow-resorbing poly(D,L-lactic-co-glycolic) acid (PLGA) porogens, fast-resorbing glucono-delta-lactone (GDL) porogens, or mixtures thereof. The physicochemical, mechanical, and degradation characteristics of these CPC formulations were systematically analyzed upon soaking in phosphate-buffered saline (PBS). In parallel, various CPC formulations were implanted intramuscularly and orthotopically on top of the transverse process of goats followed by analysis of the soft tissue response and bone ingrowth after 12 weeks. In vitro degradation of GDL was almost completed after 2 weeks, as evidenced by characterization of the release of gluconic acid, while PLGA-containing CPCs released glycolic acid throughout the entire study (12 weeks), resulting in a decrease in compression strength of CPC. Extensive in vitro degradation of the CPC matrix was observed upon simultaneous incorporation of 30% PLGA-10% GDL. Histomorphometrical evaluation of the intramuscularly implanted samples revealed that all CPCs exhibited degradation, accompanied by an increase in capsule thickness. In the in vivo goat transverse process model, incorporation of 43% PLGA, 30% PLGA-5% GDL, and 30% PLGA-10% GDL in CPC significantly increased bone formation and resulted in higher bone height compared with both 10% GDL and 20% GDL-containing CPC samples.

  8. Self-aggregated nanoparticles of linoleic acid-modified glycol chitosan conjugate as delivery vehicles for paclitaxel: preparation, characterization and evaluation.

    PubMed

    Yu, Jingmou; Liu, Yonghua; Zhang, Lei; Zhao, Jianguo; Ren, Jin; Zhang, Lifang; Jin, Yi

    2015-01-01

    A series of linoleic acid-modified glycol chitosan (LAGC) conjugates were synthesized and characterized by FTIR and (1)H NMR. The effect of the amount of linoleic acid (LA) on the physicochemical properties of LAGC conjugates was investigated. The mean diameters of three LAGC nanoparticles determined by dynamic light scattering ranged from 204 to 289 nm. The critical aggregation concentration values of LAGC conjugates in aqueous solution were 0.0148, 0.0348, and 0.0807 mg/ml, respectively. Paclitaxel (PTX) was physically loaded into the LAGC nanoparticles by a dialysis method. The drug loading content and encapsulation efficiency of PTX-loaded LAGC (PTX-LAGC) nanoparticles increased with an increasing ratio of the hydrophobic LA to hydrophilic glycol chitosan in the conjugates. PTX-LAGC nanoparticles were almost spherical in shape observed by transmission electron microscopy. In vitro release revealed that PTX release from the nanoparticles was reduced as the LA substitution degree of LAGC conjugates increased. Compared with the commercial formulation Taxol, PTX-LAGC-1 nanoparticles exhibited comparable cellular uptake and cytotoxicity against HepG2 cells in vitro. Importantly, PTX-LAGC-1 nanoparticles demonstrated the stronger antitumor efficacy against hepatic H22 tumor-bearing mice than Taxol (p < 0.05). Therefore, glycolipid-like LAGC nanoparticles had a potential as delivery vehicles for tumor therapy.

  9. Short communication: Efficacy of glycolic acid-based and iodine-based postmilking barrier teat disinfectants for prevention of new intramammary infections in dairy cattle.

    PubMed

    Lago, A; Bruno, D R; Lopez-Benavides, M; Leibowitz, S

    2016-09-01

    A positive-control, natural exposure noninferiority field study was conducted to test the efficacy of a novel glycolic acid-based postmilking barrier teat disinfectant compared with a commercial iodine-based postmilking barrier teat disinfectant (positive control). Cows from 2 pens from a California Central Valley dairy farm were dipped after milking either with the positive-control product (PC) or the experimental product (EX) over 12 wk. New intramammary infections (NIMI) were determined by biweekly sampling of all quarters of study cows and classified as a NIMI based on somatic cell count and milk bacteriological culture results. The mean quarter-level incidence risks during a 2 wk study period were 3.50% (EX) and 4.28% (PC). The majority of NIMI were caused by coagulase-negative staphylococci, followed by non-agalactiae streptococci. The study results indicated that EX was noninferior to PC, with a 17% relative efficacy (improvement) in reducing NIMI compared with the PC group. Also, quarter somatic cell count was not affected by the postmilking teat disinfectant used. Finally, the EX product was safe in terms of teat conditioning: teat condition scores were not different between study groups. The study concluded that the glycolic acid-based experimental post-dip barrier was noninferior to the control, and could be considered a safe and effective postmilking teat disinfectant. PMID:27320665

  10. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.

    PubMed

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections.

  11. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

    PubMed Central

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  12. Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity.

    PubMed

    Nurhasni, Hasan; Cao, Jiafu; Choi, Moonjeong; Kim, Il; Lee, Bok Luel; Jung, Yunjin; Yoo, Jin-Wook

    2015-01-01

    Nitric oxide (NO)-releasing nanoparticles (NPs) have emerged as a wound healing enhancer and a novel antibacterial agent that can circumvent antibiotic resistance. However, the NO release from NPs over extended periods of time is still inadequate for clinical application. In this study, we developed NO-releasing poly(lactic-co-glycolic acid)-polyethylenimine (PEI) NPs (NO/PPNPs) composed of poly(lactic-co-glycolic acid) and PEI/diazeniumdiolate (PEI/NONOate) for prolonged NO release, antibacterial efficacy, and wound healing activity. Successful preparation of PEI/NONOate was confirmed by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet/visible spectrophotometry. NO/PPNPs were characterized by particle size, surface charge, and NO loading. The NO/PPNPs showed a prolonged NO release profile over 6 days without any burst release. The NO/PPNPs exhibited potent bactericidal efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa concentration-dependently and showed the ability to bind on the surface of the bacteria. We also found that the NO released from the NO/PPNPs mediates bactericidal efficacy and is not toxic to healthy fibroblast cells. Furthermore, NO/PPNPs accelerated wound healing and epithelialization in a mouse model of a MRSA-infected wound. Therefore, our results suggest that the NO/PPNPs presented in this study could be a suitable approach for treating wounds and various skin infections. PMID:25960648

  13. Dorsal root ganglion-derived Schwann cells combined with poly(lactic-co-glycolic acid)/chitosan conduits for the repair of sciatic nerve defects in rats.

    PubMed

    Zhao, Li; Qu, Wei; Wu, Yuxuan; Ma, Hao; Jiang, Huajun

    2014-11-15

    Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and purification of Schwann cells are complicated by contamination with fibroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly purified Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells (> 95%) using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly(lactic-co-glycolic acid)/chitosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were significantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental findings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly(lactic-co-glycolic acid)/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.

  14. Surface characterization of poly(L-lactic acid)-methoxy poly(ethylene glycol) diblock copolymers by static and dynamic contact angle measurements, FTIR, and ATR-FTIR.

    PubMed

    Mert, O; Doganci, E; Erbil, H Y; Demir, A S

    2008-02-01

    The surface composition and surface free energy properties of two types of amphiphilic and semicrystalline diblock copolymers consisting of poly(L-lactic acid) coupled to (methoxy poly(ethylene glycol) (PLLA-MePEG) having differing block lengths of PEG were investigated by using static and dynamic contact angle measurements, transmission Fourier infrared spectroscopy (FTIR), and attenuated total reflection spectroscopy (ATR-FTIR) and compared with results obtained from PLLA and MePEG homopolymers. The contact angle results were evaluated by using the van Oss-Good method (acid-base method), and it was determined that the Lewis base surface tension coefficient (gamma-) of the copolymers increased with an increase of the PEG molar content at the copolymer surface. This result is in good agreement with the transmission FTIR and ATR-FTIR results but not proportional to them, indicating that the surfaces of the copolymers are highly mobile and that the molecular rearrangement takes place upon contact with a polar liquid drop. The dynamic contact angle measurements showed that the strong acid-base interaction between the oxygen atoms in the copolymer backbone of the relatively more hydrophilic PEG segments with the Lewis acidic groups of the polar and hydrogen-bonding water molecules enabled the surface molecules to restructure (conformational change) at the contact area, so that the PEG segments moved upward, whereas the apolar methyl pendant groups of PLLA segments buried downward.

  15. Humidity-dependent compression-induced glass transition of the air–water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA)

    SciTech Connect

    Kim, Hyun Chang; Lee, Hoyoung; Jung, Hyunjung; Choi, Yun -Hwa; Meron, Mati; Lin, Binhua; Bang, Joona; Won, You -Yeon

    2015-08-26

    Constant rate compression isotherms of the air–water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA)show a distinct feature of an exponential increase in surface pressure in the high surface polymer concentration regime. We have previously demonstrated that this abrupt increase in surface pressure is linked to the glass transition of the polymer film, but the detailed mechanism of this process is not understood. In order to obtain a molecular-level understanding of this behavior, we performed extensive characterizations of the surface mechanical, structural and rheological properties of Langmuir PLGA films at the air–water interface, using combined experimental techniques including the Langmuir film balance, X-ray reflectivity and double-wall-ring interfacial rheometry methods.

  16. Haloperidol-loaded intranasally administered lectin functionalized poly(ethylene glycol)-block-poly(D,L)-lactic-co-glycolic acid (PEG-PLGA) nanoparticles for the treatment of schizophrenia.

    PubMed

    Piazza, Justin; Hoare, Todd; Molinaro, Luke; Terpstra, Kristen; Bhandari, Jayant; Selvaganapathy, P Ravi; Gupta, Bhagwati; Mishra, Ram K

    2014-05-01

    Lectin-functionalized, polyethylene glycol-block-poly-(D,L)-lactic-co-glycolic acid nanoparticles loaded with haloperidol were prepared with narrow size distributions and sizes <135nm. The nanoparticles exhibited high Solanum tuberosum lectin (STL) conjugation efficiencies, encapsulation efficiencies, and drug loading capacities. The in vitro release of haloperidol was 6-8% of the loaded amount in endo-lysosomal conditions over 96h, demonstrating minimal drug leakage and the potential for the efficient drug transport to the targeted brain tissue. The haloperidol released upon erosion was successful in displacing [(3)H] N-propylnorapomorphine and binding to bovine striatal dopamine D2 receptors. Both haloperidol-loaded nanoparticle formulations were found to be highly effective at inducing catalepsy. Intranasal administration of STL-functionalized nanoparticles increased the brain tissue haloperidol concentrations by 1.5-3-fold compared to non-STL-functionalized particles and other routes of administration. This formulation demonstrates promise in the reduction of the drug dose necessary to produce a therapeutic effect with antipsychotic drugs for the treatment of schizophrenia.

  17. Effect of forage conservation method, concentrate level and propylene glycol on the fatty acid composition and vitamin content of cows' milk.

    PubMed

    Shingfield, Kevin J; Salo-Väänänen, Pirjo; Pahkala, Eero; Toivonen, Vesa; Jaakkola, Seija; Piironen, Vieno; Huhtanen, Pekka

    2005-08-01

    Based on potential health benefits, there is a need to develop effective strategies for enhancing milk fat concentrations of cis-9 18:1, 18:3 n-3 and conjugated linoleic (CLA) content in milk without compromising the sensory or storage characteristics of processed milk or dairy products. Sixteen Finnish Ayrshire dairy cows were used in a cyclic change-over experiment with four 21-d experimental periods and a 4 x 2 x 2 factorial arrangement of treatments to evaluate the effects of forage conservation method, concentrate level and supplements of propylene glycol (PG), and their interactions on milk fatty acid composition and vitamin content. Experimental treatments consisted of four conserved forages offered ad libitum, supplemented with two levels of a standard concentrate (7 or 10 kg/d) and PG (0 and 210 g/d) fed as three equal meals. Primary growths of timothy and meadow fescue sward were conserved by ensiling with none (NA), an inoculant enzyme preparation (IE) or a formic acid based (FORM) additive or as hay 1 week later. Conservation of grass by drying rather than ensiling resulted in lower forage 18:2n-6, 18:3n-3, total fatty acid and fat-soluble vitamin concentrations. In spite of lower intakes, milk fat 18:2n-6 and 18:3n-3 content was higher (P < 0.05) for hay than for silage diets (12.1, 9.6, 9.6 and 9.3 and 5.00, 3.51, 4.27 and 2.93 g/kg total fatty acids, for hay, NA, IE and FORM silages, respectively). Forage conservation method had no clear effects on milk trans 18:1 or CLA content. Compared with silage, hay diets resulted in milk containing lower (P < 0.001) riboflavin, alpha-tocopherol and beta-carotene concentrations, but had no effect on ascorbic acid, thiamine, pyridoxine or retinol content. Feeding more concentrates had no effect on milk fatty acid composition or milk vitamin content, other than lowering (P < 0.001) 16:0 concentrations from 348 to 338 g/kg fatty acids. Supplements of PG led to small (P < 0.05) increases in milk 13:0 anteiso and 15

  18. Study of O/W micro- and nano-emulsions based on propylene glycol diester as a vehicle for geranic acid.

    PubMed

    Jaworska, Małgorzata; Sikora, Elżbieta; Ogonowski, Jan; Konieczna, Monika

    2015-01-01

    Nano- and microemulsions containing as the oil phase caprylic/capric propylene glycol diesters (Crodamol PC) were investigated as potential vehicle for controlled release of geranic acid. The influence of emulsifiers and co-surfactants on stability of the emulsions was investigated. Different kind of polysorbates (ethoxylated esters of sorbitan and fatty acids) were applied as the emulsifiers. The short-chain alcohols (ethanol, 1-propanol, 1-butanol) were used as co-surfactants. The emulsions were prepared at ambient temperature (25°C), by the phase inversion composition method (PIC). The stable O/W high dispersed emulsion systems based on Crodamol PC, of mean droplets size less than 200 nm, were prepared. Microemulsions stabilized by the mixture of Polisorbat 80 and 1-butanol were characterized by the largest degree of dispersion (137 nm) and the lowest PDI value (0.094), at surfactant/co-surfactant: oil weight ratio 90:10. The stable nano-emulsion (mean droplet size of 33 nm) was obtained for surfactant: oil (S:O) weight ratio 90:10, without co-surfactant addition. This nano-emulsion was chosen to release studies. The obtained results showed that the prepared stable nano-emulsion can be used as a carrier for controlled release of geranic acid. The active substance release from the nano-emulsion and the oil solution, after 24 hours was 22%.

  19. Preparation of Hemocompatible Poly(lactic-co-glycolic acid)-F127 Nanospheres and Their Application to Biosensor for Analysis of Whole Blood.

    PubMed

    Sun, Chong; Niu, Yanlian; Yang, Xujie; Liu, Min; Yang, Xiaodi; Huang, Xiaohua; Zhao, Wenbo

    2015-01-01

    In this paper, the novel poly(lactic-co-glycolic acid)-F127 nanospheres (PLGA-F127 NSs) were synthesized and used to establish an amperometric glucose biosensor that can be applied in whole blood directly. This property of glucose biosensor was based on the antibiofouling property of PLGA-F127 NSs. More details of preparing PLGA-F127 NSs and immobilizing glucose oxidase (GOx) on (PLGA-F127)/glass carbon electrode (GCE) were presented. Then, the electrochemical behaviors of the biosensor in whole blood were studied. The cyclic voltammetric results indicated that GOx immobilized on PLGA-F127 NSs exhibited direct electron transfer reaction, which led to stable amperometric biosensing for glucose with a detection limit of 5.57 x 10(-6) M (S/N = 3). The glucose biosensor did not respond to ascorbic acid (AA) and uric.acid (UA) at their concentration normally encountered in blood. The development of materials science will bring significant input to high-performance biosensors relevant to diagnostics and therapy of interest for human health. PMID:26328311

  20. Cellular behaviour of hepatocyte-like cells from nude mouse bone marrow-derived mesenchymal stem cells on galactosylated poly(D,L-lactic-co-glycolic acid).

    PubMed

    Roh, Hyun; Yang, Dae Hyeok; Chun, Heung Jae; Khang, Gilson

    2015-07-01

    Previously, the galactosylation of poly(d,l-lactic-co-glycolic acid) (PLGA) surface was accomplished by grafting allylamine (AA), using inductively coupled plasma-assisted chemical vapour deposition (ICP-CVD) and conjugating lactobionic acid (LA) with AA via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) activation for hepatic tissue-engineering purposes. As a continuation study, the cellular behaviour of hepatocyte-like cells (HLCs) on the surface of the galactosylated PLGA were investigated. Nude mouse bone marrow-derived mesenchymal stem cells (MSCs) were cultured under hepatogenic conditions and the differentiated cells were characterized by reverse-transcription polymerase chain reaction (RT-PCR), immunofluorescence and periodic acid-Schiff (PAS) staining. Galactosylated PLGA enhanced the proliferation rate of HLCs compared to the control; HLCs on the surface of the sample became aggregated and formed spheroids after 3 days of culture. A large number of cells on the surface of the sample exhibited increased liver-specific functional activities, such as albumin and urea secretions. In addition, multicellular spheroids in the sample strongly expressed phospholyated focal adhesion kinase (pFAK) (cell-matrix interactions), E-cadherin (cell-cell interactions) and connexin 32 (Cox32; gap junction).

  1. Radiosensitization of TPGS-emulsified docetaxel-loaded poly(lactic-co-glycolic acid) nanoparticles in CNE-1 and A549 cells.

    PubMed

    Shi, Wei; Yuan, Yin; Chu, Min; Zhao, Shuang; Song, Qingle; Mu, Xiaoqian; Xu, Shuangbing; Zhang, Zhiping; Yang, Kunyu

    2016-03-01

    Docetaxel is among the most effective radiosensitizers. It is widely used as radiosensitizer in many tumors, including head and neck carcinoma. Nevertheless, poor solubility and severe hypersensitivity limit its clinical use and its therapeutic effect remains to be improved. In this study, docetaxel-loaded polymeric nanoparticles were prepared by nanoprecipitation method to be new radiosensitizer with lower side effects and higher efficacy. The physiochemical characteristics of the nanoparticles were studied. Two human tumor cell lines which are resistant to radiotherapy were used in this research. We have compared the radioenhancement efficacy of docetaxel-loaded nanoparticles with docetaxel in A549 and CNE-1 cells. Compared with docetaxel, radiosensitization of docetaxel-loaded nanoparticles was improved significantly (sensitization enhancement ratio in A549 increased 1.24-fold to 1.68-fold when the radiation was applied 2 h after the drug, p < 0.01, sensitization enhancement ratio in CNE-1 increased 1.32-fold to 1.61-fold, p < 0.05). We explored the mechanisms for the radiosensitization efficiency and the difference between docetaxel and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, promoted apoptosis and the role of D-alpha-tocopheryl polyethylene glycol 1000 succinate which will enhance the cell uptake and inhibit the multiple drug resistance. Moreover, the radiosensitization efficacy of docetaxel-loaded nanoparticles was more prominent than docetaxel. In conclusion, tocopheryl polyethylene glycol 1000 succinate-emulsified docetaxel-loaded PLGA nanoparticles were more efficacious and fewer adverse effects were observed than with the commercial docetaxel formulation. Thus, PLGA nanoparticles hold promise as a radiosensitizing agent. PMID:26608458

  2. Synthesis and Characterization of Poly(lactic-co-glycolic) Acid Nanoparticles-Loaded Chitosan/Bioactive Glass Scaffolds as a Localized Delivery System in the Bone Defects

    PubMed Central

    Nazemi, K.; Moztarzadeh, F.; Jalali, N.; Asgari, S.; Mozafari, M.

    2014-01-01

    The functionality of tissue engineering scaffolds can be enhanced by localized delivery of appropriate biological macromolecules incorporated within biodegradable nanoparticles. In this research, chitosan/58S-bioactive glass (58S-BG) containing poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been prepared and then characterized. The effects of further addition of 58S-BG on the structure of scaffolds have been investigated to optimize the characteristics of the scaffolds for bone tissue engineering applications. The results showed that the scaffolds had high porosity with open pores. It was also shown that the porosity decreased with increasing 58S-BG content. Furthermore, the PLGA nanoparticles were homogenously distributed within the scaffolds. According to the obtained results, the nanocomposites could be considered as highly bioactive bone tissue engineering scaffolds with the potential of localized delivery of biological macromolecules. PMID:24949477

  3. Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.

    PubMed

    Chen, Zhanfei; Lian, Fen; Wang, Xiaoqian; Chen, Yanling; Tang, Nanhong

    2016-01-01

    The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine-glycine-aspartic acid (RGD) peptide. Our studies demonstrate that RGD-polyethylene glycol (PEG)-PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT-MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system. PMID:27621619

  4. Structural and cyclic volta metric investigations on BIPBVOX solid electrolyte synthesized by ethylene glycol-citric acid sol-gel route

    NASA Astrophysics Data System (ADS)

    Naqvi, Faria K.; Beg, Saba; Al-Areqi, Niyazi A. S.

    2016-05-01

    Samples of BIPBVOX.x (Bi2V1-xPbxO5.5-x/2) in the composition range 0.05 ≤ x ≤ 0.20 were prepared by ethylene glycol- citric acid sol-gel synthesis route. Structural investigations were carried out by X-ray diffraction, DTA. The highly conducting γ'- phase was effectively stabilized at room temperature for compositions with x ≥ 0.17. Cyclic voltammetric measurements showed reversible redox reactions of vanadium and irreversible redox reaction of Bi3+ in the BIPBVOX system during the first cathodic and anodic sweep. However, a higher stability against the reduction of Bi3+ to metallic bismuth was seen for x=0.20.

  5. Preparation and electrochemical properties of gel polymer electrolytes using triethylene glycol diacetate-2-propenoic acid butyl ester copolymer for high energy density lithium-ion batteries

    NASA Astrophysics Data System (ADS)

    Fan, Huanhuan; Li, Hongxiao; Fan, Li-Zhen; Shi, Qiao

    2014-03-01

    Gel polymer electrolytes (GPE) composed of triethylene glycol diacetate (TEGDA)-2-propenoic acid butyl ester (BA) copolymer and commercial used liquid organic electrolyte are prepared via in situ polymerization. The ionic conductivity of the as-prepared GPE can reach 5.5 × 10-3 S cm-1 with 6 wt% monomers and 94 wt% liquid electrolyte at 25 °C. Additionally, the temperature dependence of the ionic conductivity is consistent with an Arrhenius temperature behavior in a temperature range of 20-90 °C. Furthermore, the electrochemical stability window of the GPE is 5 V at 25 °C. A Li|GPE|(Li[Li1/6Ni1/4Mn7/12]O2) cell has been fabricated, which shows good charge-discharge properties and stable cycle performance compared to liquid electrolyte under the same test conditions.

  6. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

    PubMed

    Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

    2005-08-01

    Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.

  7. Radiolabeling of Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles with Biotinylated F-18 Prosthetic Groups and Imaging of Their Delivery to the Brain with Positron Emission Tomography

    PubMed Central

    2015-01-01

    The avidin–biotin interaction permits rapid and nearly irreversible noncovalent linkage between biotinylated molecules and avidin-modified substrates. We designed a biotinylated radioligand intended for use in the detection of avidin-modified polymer nanoparticles in tissue with positron emission tomography (PET). Using an F-18 labeled prosthetic group, [18F]4-fluorobenzylamine, and a commercially available biotin derivate, NHS-PEG4-biotin, [18F]-fluorobenzylamide-poly(ethylene glycol)4-biotin ([18F]NPB4) was prepared with high purity and specific activity. The attachment of the [18F]NPB4 radioligand to avidin-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles was tested by using PET imaging to measure the kinetics of convection-enhanced delivery (CED) of nanoparticles of varying size to the rat brain. PET imaging enabled the direct observation of nanoparticle delivery by measurement of the spatial volume of distribution of radiolabeled nanoparticles as a function of time, both during and after the infusion. This work thus validates new methods for radiolabeling PEG-biotin derivatives and also provides insight into the fate of nanoparticles that have been infused directly into the brain. PMID:25322194

  8. In vivo/in vitro pharmacokinetic and pharmacodynamic study of spray-dried poly-(dl-lactic-co-glycolic) acid nanoparticles encapsulating rifampicin and isoniazid.

    PubMed

    Booysen, L L I J; Kalombo, L; Brooks, E; Hansen, R; Gilliland, J; Gruppo, V; Lungenhofer, P; Semete-Makokotlela, B; Swai, H S; Kotze, A F; Lenaerts, A; du Plessis, L H

    2013-02-28

    Poly-(dl-lactic-co-glycolic) acid (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation spray-drying technique and coated with polyethylene glycol (PEG 1% v/v). The PLGA nanoparticles had a small size (229±7.6 to 382±23.9nm), uniform size distribution and positive zeta potential (+12.45±4.53mV). In vitro/in vivo assays were performed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) performance of these nanoparticles following nanoencapsulation of the anti-tuberculosis drugs rifampicin (RIF) and isoniazid (INH). The results demonstrated the potential for the reduction in protein binding of these drugs by protection in the polymer core. Furthermore, in vitro efficacy was demonstrated using Mycobacterium tuberculosis (M. tb.) (strain H37Rv). Sustained drug release over seven days were observed for these drugs following once-off oral administration in mice with subsequent drug distribution of up to 10 days in the liver and lungs for RIF and INH, respectively. It was concluded by these studies combined with our previous reports that spray-dried PLGA nanoparticles demonstrate potential for the improvement of tuberculosis chemotherapy by nanoencapsulation of anti-tuberculosis drugs.

  9. Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages.

    PubMed

    Bitencourt, Claudia da Silva; Silva, Letícia Bueno da; Pereira, Priscilla Aparecida Tartari; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-12-01

    Microencapsulation of bioactive molecules for modulating the immune response during infectious or inflammatory events is a promising approach, since microspheres (MS) protect these labile biomolecules against fast degradation, prolong the delivery over longer periods of time and, in many situations, target their delivery to site of action, avoiding toxic side effects. Little is known, however, about the influence of different polymers used to prepare MS on macrophages. This paper aims to address this issue by evaluating in vitro cytotoxicity, phagocytosis profile and cytokines release from alveolar macrophages (J-774.1) treated with MS prepared with chitosan, and four different co-polymers of PLGA [poly (lactic-co-glycolic acid)]. The five MS prepared presented similar diameter and zeta potential each other. Chitosan-MS showed to be cytotoxic to J-774.1 cells, in contrast to PLGA-MS, which were all innocuous to this cell linage. PLGA 5000-MS was more efficiently phagocytized by macrophages compared to the other MS tested. PLGA 5000-MS and 5002-MS induced significant production of TNF-α, while 5000-MS, 5004-MS and 7502-MS decreased spontaneous IL-6 release. Nevertheless, only PLGA 5002-MS induced significant NFkB/SEAP activation. These findings together show that MS prepared with distinct PLGA co-polymers are differently recognized by macrophages, depending on proportion of lactic and glycolic acid in polymeric chain, and on molecular weight of the co-polymer used. Selection of the most adequate polymer to prepare a microparticulate drug delivery system to modulate immunologic system may take into account, therefore, which kind of immunomodulatory response is more adequate for the required treatment.

  10. Comparison of removal of endodontic smear layer using ethylene glycol bis (beta-amino ethyl ether)-N, N, N', N'-tetraacetic acid and citric acid in primary teeth: A scanning electron microscopic study

    PubMed Central

    Hegde, Rahul J.; Bapna, Kavita

    2016-01-01

    Background: Root canal irrigants are considered momentous in their tissue dissolving property, eliminating microorganisms, and removing smear layer. The present study was aimed to compare the removal of endodontic smear layer using ethylene glycol bis (beta-amino ethyl ether)-N, N, N', N'-tetraacetic acid (EGTA) and citric acid solutions with saline as a control in primary anterior teeth. Materials and Methods: Thirty primary anterior teeth were chosen for the study. The teeth were distributed into three groups having ten teeth each. Following instrumentation, root canals of the first group were treated with 17% EGTA and the second group with 6% citric acid. Only saline was used as an irrigant for the control group. Then, the teeth were subjected to scanning electron microscopy (SEM) study. The scale given by Rome et al. for the smear layer removal was used in the present study. Results: The pictures from the SEM showed that among the tested irrigants, 17% EGTA + 5% sodium hypochlorite (NaOCl) group showed the best results when compared to other groups. Conclusion: The results advocate that the sequential irrigation of the pulp canal walls with 17% EGTA followed by 5% NaOCl produced efficacious and smear-free root canal walls. PMID:27307670

  11. Development of poly(lactic-co-glycolic) acid nanoparticles-embedded hyaluronic acid-ceramide-based nanostructure for tumor-targeted drug delivery.

    PubMed

    Park, Ju-Hwan; Lee, Jae-Young; Termsarasab, Ubonvan; Yoon, In-Soo; Ko, Seung-Hak; Shim, Jae-Seong; Cho, Hyun-Jong; Kim, Dae-Duk

    2014-10-01

    A hyaluronic acid-ceramide (HACE) nanostructure embedded with docetaxel (DCT)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) was fabricated for tumor-targeted drug delivery. NPs with a narrow size distribution and negative zeta potential were prepared by embedding DCT-loaded PLGA NPs into a HACE nanostructure (DCT/PLGA/HACE). DCT-loaded PLGA and DCT/PLGA/HACE NPs were characterized by solid-state techniques, including Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). A sustained drug release pattern from the NPs developed was observed and negligible cytotoxicity was seen in NIH3T3 cells (normal fibroblast, CD44 receptor negative) and MDA-MB-231 cells (breast cancer cells, CD44 receptor positive). PLGA/HACE NPs containing coumarin 6, used as a fluorescent dye, exhibited improved cellular uptake efficiency, based on the HA-CD44 receptor interaction, compared to plain PLGA NPs. Cyanine 5.5 (Cy5.5)-labeled PLGA/HACE NPs were injected intravenously into a MDA-MB-231 tumor xenograft mouse model and demonstrated enhanced tumor targetability, compared with Cy5.5-PLGA NPs, according to a near-infrared fluorescence (NIRF) imaging study. Considering these experimental results, the DCT/PLGA/HACE NPs developed may be useful as a tumor-targeted drug delivery system.

  12. Development of poly(lactic-co-glycolic) acid nanoparticles-embedded hyaluronic acid-ceramide-based nanostructure for tumor-targeted drug delivery.

    PubMed

    Park, Ju-Hwan; Lee, Jae-Young; Termsarasab, Ubonvan; Yoon, In-Soo; Ko, Seung-Hak; Shim, Jae-Seong; Cho, Hyun-Jong; Kim, Dae-Duk

    2014-10-01

    A hyaluronic acid-ceramide (HACE) nanostructure embedded with docetaxel (DCT)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) was fabricated for tumor-targeted drug delivery. NPs with a narrow size distribution and negative zeta potential were prepared by embedding DCT-loaded PLGA NPs into a HACE nanostructure (DCT/PLGA/HACE). DCT-loaded PLGA and DCT/PLGA/HACE NPs were characterized by solid-state techniques, including Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). A sustained drug release pattern from the NPs developed was observed and negligible cytotoxicity was seen in NIH3T3 cells (normal fibroblast, CD44 receptor negative) and MDA-MB-231 cells (breast cancer cells, CD44 receptor positive). PLGA/HACE NPs containing coumarin 6, used as a fluorescent dye, exhibited improved cellular uptake efficiency, based on the HA-CD44 receptor interaction, compared to plain PLGA NPs. Cyanine 5.5 (Cy5.5)-labeled PLGA/HACE NPs were injected intravenously into a MDA-MB-231 tumor xenograft mouse model and demonstrated enhanced tumor targetability, compared with Cy5.5-PLGA NPs, according to a near-infrared fluorescence (NIRF) imaging study. Considering these experimental results, the DCT/PLGA/HACE NPs developed may be useful as a tumor-targeted drug delivery system. PMID:25079433

  13. In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain

    SciTech Connect

    Liu Qingfeng; Shao Xiayan; Chen Jie; Shen Yehong; Feng Chengcheng; Gao Xiaoling; Zhao Yue; Li Jingwei; Zhang Qizhi Jiang, Xinguo

    2011-02-15

    Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-{alpha} level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.

  14. Chitosan-coated poly(lactic-co-glycolic) acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine

    PubMed Central

    Zhao, Kai; Zhang, Yang; Zhang, Xiaoyan; Shi, Ci; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Cui, Shangjin

    2014-01-01

    We determined the efficacy and safety of chitosan (CS)-coated poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) as a delivery system for a vaccine to protect chickens against Newcastle disease virus (NDV). The newly constructed vaccine contained DNA (the F gene) of NDV. The Newcastle disease virus (NDV) F gene deoxyribonucleic acid (DNA) plasmid (pFDNA)-CS/PLGA-NPs were spherical (diameter =699.1±5.21 nm [mean ± standard deviation]) and smooth, with an encapsulation efficiency of 98.1% and a Zeta potential of +6.35 mV. An in vitro release assay indicated that CS controlled the burst release of plasmid DNA, such that up to 67.4% of the entire quantity of plasmid DNA was steadily released from the pFDNA-CS/PLGA-NPs. An in vitro expression assay indicated that the expression of nanoparticles (NPs) was maintained in the NPs. In an immunization test with specific pathogen-free chickens, the pFDNA-CS/PLGA-NPs induced stronger cellular, humoral, and mucosal immune responses than the plasmid DNA vaccine alone. The pFDNA-CS/PLGA-NPs did not harm 293T cells in an in vitro assay and did not harm chickens in an in vivo assay. Overall, the results indicated that CS-coated PLGA NPs can serve as an efficient and safe mucosal immune delivery system for NDV DNA vaccine. PMID:25356070

  15. Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.

    PubMed

    Love, Ryan J; Jones, Kim S

    2013-12-01

    Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo.

  16. Magnetic nanocarriers of doxorubicin coated with poly(ethylene glycol) and folic acid: relation between coating structure, surface properties, colloidal stability, and cancer cell targeting.

    PubMed

    Kaaki, Karine; Hervé-Aubert, Katel; Chiper, Manuela; Shkilnyy, Andriy; Soucé, Martin; Benoit, Roland; Paillard, Archibald; Dubois, Pierre; Saboungi, Marie-Louise; Chourpa, Igor

    2012-01-17

    We report the efficient one-step synthesis and detailed physicochemical evaluation of novel biocompatible nanosystems useful for cancer therapeutics and diagnostics (theranostics). These systems are the superparamagnetic iron oxide nanoparticles (SPIONs) carrying the anticancer drug doxorubicin and coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG), native and modified with the biological cancer targeting ligand folic acid (PEG-FA). These multifunctional nanoparticles (SPION-DOX-PEG-FA) are designed to rationally combine multilevel mechanisms of cancer cell targeting (magnetic and biological), bimodal cancer cell imaging (by means of MRI and fluorescence), and bimodal cancer treatment (by targeted drug delivery and by hyperthermia effect). Nevertheless, for these concepts to work together, the choice of ingredients and particle structure are critically important. Therefore, in the present work, a detailed physicochemical characterization of the organic coating of the hybrid nanoparticles is performed by several surface-specific instrumental methods, including surface-enhanced Raman scattering (SERS) spectroscopy, X-ray photoelectron spectrometry (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). We demonstrate that the anticancer drug doxorubicin is attached to the iron oxide surface and buried under the polymer layers, while folic acid is located on the extreme surface of the organic coating. Interestingly, the moderate presence of folic acid on the particle surface does not increase the particle surface potential, while it is sufficient to increase the particle uptake by MCF-7 cancer cells. All of these original results contribute to the better understanding of the structure-activity relationship for hybrid biocompatible nanosystems and are encouraging for the applications in cancer theranostics.

  17. Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres.

    PubMed

    Ruiz, J M; Busnel, J P; Benoît, J P

    1990-09-01

    The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes. PMID:2235892

  18. Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres.

    PubMed

    Ruiz, J M; Busnel, J P; Benoît, J P

    1990-09-01

    The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes.

  19. Fabrication and surface modification of macroporous poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds for human skin fibroblast cell culture.

    PubMed

    Yang, Jian; Shi, Guixin; Bei, Jianzhong; Wang, Shenguo; Cao, Yilin; Shang, Qingxin; Yang, Guanghui; Wang, Wenjing

    2002-12-01

    The fabrication and surface modification of a porous cell scaffold are very important in tissue engineering. Of most concern are high-density cell seeding, nutrient and oxygen supply, and cell affinity. In the present study, poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds with different pore structures were fabricated. An improved method based on Archimedes' Principle for measuring the porosity of scaffolds, using a density bottle, was developed. Anhydrous ammonia plasma treatment was used to modify surface properties to improve the cell affinity of the scaffolds. The results show that hydrophilicity and surface energy were improved. The polar N-containing groups and positive charged groups also were incorporated into the sample surface. A low-temperature treatment was used to maintain the plasma-modified surface properties effectively. It would do help to the further application of plasma treatment technique. Cell culture results showed that pores smaller than 160 microm are suitable for human skin fibroblast cell growth. Cell seeding efficiency was maintained at above 99%, which is better than the efficiency achieved with the common method of prewetting by ethanol. The plasma-treatment method also helped to resolve the problem of cell loss during cell seeding, and the negative effects of the ethanol trace on cell culture were avoided. The results suggest that anhydrous ammonia plasma treatment enhances the cell affinity of porous scaffolds. Mass transport issues also have been considered. PMID:12209930

  20. Folic Acid

    MedlinePlus

    Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

  1. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  2. Tacticity-induced changes in the micellization and degradation properties of poly(lactic acid)-block-poly(ethylene glycol) copolymers.

    PubMed

    Agatemor, Christian; Shaver, Michael P

    2013-03-11

    Poly(lactic acid)-block-poly(ethylene glycol) copolymers (PLA-b-PEG) featuring varying tacticities (atactic, heterotactic, isotactic) in the PLA block were synthesized and investigated for their micellar stability, degradation, and thermal properties. Utilizing tin(II) bis(2-ethylhexanoate), aluminum salan, and aluminum salen catalysts, the copolymers were synthesized through the ring-opening polymerization of d-, l-, rac-, or a blend of l- and rac-lactide using monomethoxy-poly(ethylene glycol) as a macroinitiator. The critical micelle concentration, which reflects the micellar stability, was probed using a fluorescence spectroscopic method with pyrene as the probe. The copolymers were degraded in a methanolic solution of 1,5,7-triaza-bicyclo[4.4.0]dec-5-ene and the degradation was measured by (1)H NMR spectroscopic and gel permeation chromatographic analyses. Differential scanning calorimetry and thermogravimetric analysis provided information on the thermal properties of the copolymers. Atactic and heterotactic microstructures in the PLA block resulted in lower micellar stability, as well as faster degradation and shorter erosion time compared to polymers with high isotactic enchainment (Pm). By modification of the Pm, micellar stability, degradation, and erosion rates of the copolymers can be tuned to specific biomedical applications. Interestingly, while tin(II) bis(2-ethylhexanoate) and aluminum salan-catalyzed PLA-b-PEG copolymers exhibited similar micellization behavior, the aluminum salen-catalyzed PLA-b-PEG exhibited unique behavior at high micelle concentration in the presence of the pyrene probe. This unique behavior can be attributed to the disintegration of the micelles through the interactions of long isotactic stereoblock segments. PMID:23402292

  3. Amino acids

    MedlinePlus

    ... amino acids are: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan , and valine. Nonessential amino acids "Nonessential" means that our bodies produce an amino ...

  4. Characterization of pH-Responsive Hydrogels of Poly(Itaconic acid-g-Ethylene Glycol) Prepared by UV-Initiated Free Radical Polymerization as Biomaterials for Oral Delivery of Bioactive Agents

    PubMed Central

    Betancourt, Tania; Pardo, Juan; Soo, Ken; Peppas, Nicholas A.

    2009-01-01

    Effective oral delivery of proteins is impeded by steep pH gradients and proteolytic enzymes in the gastrointestinal tract, as well as low absorption of the proteins into the bloodstream due to their size, charge or solubility. In the present work, pH-responsive complexation hydrogels of poly(itaconic acid) with poly(ethylene glycol) grafts were synthesized for applications in oral drug delivery. These hydrogels were expected to be in collapsed configuration at low pH due to hydrogen bonding between poly(itaconic acid) carboxyl groups and poly(ethylene glycol), and to swell with increasing pH because of charge repulsion between deprotonated carboxylic acid groups. Hydrogels were prepared by UV-initiated free radical polymerization using tetraethylene glycol as the crosslinking agent and Irgacure® 2959 as the initiator. The effect of monomer ratios, crosslinking ratio and solvent amount on the properties of the hydrogels were investigated. The composition of the hydrogels was confirmed by FTIR. Equilibrium swelling studies in the pH range of 1.2 to 7 revealed that the extent of swelling increased with increasing pH up to a pH of about 6, when no further carboxylic acid deprotonation occurred. Studies in Caco-2 colorectal carcinoma cells confirmed the cytocompatibility of these materials at concentrations of up to 5 mg/ml. PMID:19536838

  5. Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs

    PubMed Central

    Binjawadagi, Basavaraj; Dwivedi, Varun; Manickam, Cordelia; Ouyang, Kang; Wu, Yun; Lee, Ly James; Torrelles, Jordi B; Renukaradhya, Gourapura J

    2014-01-01

    Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic-co-glycolic) acid (PLGA) nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg) induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate. In vaccinated virulent heterologous PRRSV-challenged pigs, the immune correlates in the blood were as follows: 1) enhanced PRRSV-specific antibody response with enhanced avidity of both immunoglobulin (Ig)-G and IgA isotypes, associated with augmented virus-neutralizing antibody titers; 2) comparable and increased levels of virus-specific IgG1 and IgG2 antibody subtypes and production of high levels of both T-helper (Th)-1 and Th2 cytokines, indicative of a balanced Th1–Th2 response; 3) suppressed immunosuppressive cytokine response; 4) increased frequency of interferon-γ+ lymphocyte subsets and expanded population of antigen-presenting cells; and most importantly 5) complete clearance of detectable replicating challenged heterologous PRRSV and close to threefold reduction in viral ribonucleic acid load detected in the blood. In conclusion, intranasal delivery of adjuvanted NP-KAg vaccine formulation to growing pigs elicited a broadly cross-protective immune response, showing the potential of this innovative vaccination strategy to prevent PRRS outbreaks in pigs. A similar approach to control other respiratory diseases in food animals and humans appears to be feasible. PMID:24493925

  6. Doxorubicin-loaded poly(lactic-co-glycolic acid) microspheres prepared using the solid-in-oil-in-water method for the transarterial chemoembolization of a liver tumor.

    PubMed

    Choi, Jin Woo; Park, Ju-Hwan; Baek, Song Yi; Kim, Dae-Duk; Kim, Hyo-Cheol; Cho, Hyun-Jong

    2015-08-01

    Doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were fabricated using the solid-in-oil-in-water (S/O/W) emulsification method for transarterial chemoembolization (TACE) of a liver tumor. DOX-loaded PLGA MSs with a mean diameter of 26 μm and a spherical shape were prepared. The biodegradation of PLGA MSs was observed in serum using a scanning electron microscope (SEM). Drug release from the PLGA MSs was accelerated at an acidic pH (pH 5.5) compared to a normal physiological pH (pH 7.4). According to the results of a pharmacokinetic study in rats, the area under the curve (AUC) value of a drug, which indicates the systemic exposure extent of the drug, of the PLGA MSs group was 29.9% of that of a hepatic arterial injection (HAI) group. The DOX concentration ratio for liver tumors compared to normal livers was significantly higher in the PLGA MSs group than that of the HAI group (p<0.05). After the TACE procedure was performed with DOX-PLGA MSs in a rat hepatoma model, the mean size increment of tumor in DOX-PLGA MSs group was found to be lower than that of the HAI group, and the viable portion of the DOX-PLGA MSs group was less than the other groups (p<0.05). All these findings suggested that the developed DOX-loaded PLGA MSs fabricated with the S/O/W method can be used as a promising drug delivery system in TACE for liver tumors.

  7. Tuning of thermally induced sol-to-gel transitions of moderately concentrated aqueous solutions of doubly thermosensitive hydrophilic diblock copolymers poly(methoxytri(ethylene glycol) acrylate)-b-poly(ethoxydi(ethylene glycol) acrylate-co-acrylic acid).

    PubMed

    Jin, Naixiong; Zhang, Hao; Jin, Shi; Dadmun, Mark D; Zhao, Bin

    2012-03-15

    We report in this article a method to tune the sol-to-gel transitions of moderately concentrated aqueous solutions of doubly thermosensitive hydrophilic diblock copolymers that consist of two blocks exhibiting distinct lower critical solution temperatures (LCSTs) in water. A small amount of weak acid groups is statistically incorporated into the lower LCST block so that its LCST can be tuned by varying solution pH. Well-defined diblock copolymers, poly(methoxytri(ethylene glycol) acrylate)-b-poly(ethoxydi(ethylene glycol) acrylate-co-acrylic acid) (PTEGMA-b-P(DEGEA-co-AA)), were prepared by reversible addition-fragmentation chain transfer polymerization and postpolymerization modification. PTEGMA and PDEGEA are thermosensitive water-soluble polymers with LCSTs of 58 and 9 °C, respectively, in water. A 25 wt % aqueous solution of PTEGMA-b-P(DEGEA-co-AA) with a molar ratio of DEGEA to AA units of 100:5.2 at pH = 3.24 underwent multiple phase transitions upon heating, from a clear, free-flowing liquid (<15 °C) to a clear, free-standing gel (15-46 °C) to a clear, free-flowing hot liquid (47-56 °C), and a cloudy mixture (≥57 °C). With the increase of pH, the sol-to-gel transition temperature (T(sol-gel)) shifted to higher values, while the gel-to-sol transition (T(gel-sol)) and the clouding temperature (T(clouding)) of the sample remained essentially the same. These transitions and the tunability of T(sol-gel) originated from the thermosensitive properties of two blocks of the diblock copolymer and the pH dependence of the LCST of P(DEGEA-co-AA), which were confirmed by dynamic light scattering and differential scanning calorimetry studies. Using the vial inversion test method, we mapped out the C-shaped sol-gel phase diagrams of the diblock copolymer in aqueous buffers in the moderate concentration range at three different pH values (3.24, 5.58, and 5.82, all measured at ~0 °C). While the upper temperature boundaries overlapped, the lower temperature boundary

  8. Acid Rain.

    ERIC Educational Resources Information Center

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  9. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects.

    PubMed

    He, Shu; Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang; Bi, Long; Liu, Jian

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration.

  10. VITRIFICATION OF THAI NATIVE CATTLE OOCYTES: EFFECTS OF ETHYLENE GLYCOL CONCENTRATIONS AND EXPOSURE TIME, LINOLEIC ACID ALBUMIN AND CHOLESTEROL-LOADED METHYL-B-CYCLODEXTRIN.

    PubMed

    Chasombat, Jakkhaphan; Vongpralub, Thevin; Sirisathien, Saksiri; Phasuk, Yupin; Sonseeda, Pronjit

    2015-01-01

    The present study aimed to improve the oocyte vitrification procedure for preservation of Thai native cattle genetic resources. In Experiment I, oocytes were exposed to various doses (2%, 4% and 6%) of ethylene glycol (EG) in vitrification solution I (VS-I) for different equilibration times (10 or 20 min) before being exposed to VS-II and then subjected to vitrification. Experiment II was divided into two parts: (a) oocytes were matured in medium supplemented with linoleic acid albumin (LAA) (1% or 2%) and then vitrified; (b) matured oocytes were preincubated with cholesterol-loaded methyl-β-cyclodextrin (CLC) (1% or 2%) and then vitrified. Equilibration of oocytes by exposure to 6% EG in VS-I for 10 min (Experiment I), and in vitro maturation of immature oocytes in medium supplementation with 2% LAA (Experiment II) were the most effective methods; vitrified/thawed oocytes showed higher rates of survival and subsequent embryonic development compared with the other experimental groups. PMID:26510334

  11. Modelling the degradation and elastic properties of poly(lactic-co-glycolic acid) films and regular open-cell tissue engineering scaffolds.

    PubMed

    Shirazi, Reyhaneh Neghabat; Ronan, William; Rochev, Yury; McHugh, Peter

    2016-02-01

    Scaffolding plays a critical rule in tissue engineering and an appropriate degradation rate and sufficient mechanical integrity are required during degradation and healing of tissue. This paper presents a computational investigation of the molecular weight degradation and the mechanical performance of poly(lactic-co-glycolic acid) (PLGA) films and tissue engineering scaffolds. A reaction-diffusion model which predicts the degradation behaviour is coupled with an entropy-based mechanical model which relates Young׳s modulus and the molecular weight. The model parameters are determined based on experimental data for in-vitro degradation of a PLGA film. Microstructural models of three different scaffold architectures are used to investigate the degradation and mechanical behaviour of each scaffold. Although the architecture of the scaffold does not have a significant influence on the degradation rate, it determines the initial stiffness of the scaffold. It is revealed that the size of the scaffold strut controls the degradation rate and the mechanical collapse. A critical length scale due to competition between diffusion of degradation products and autocatalytic degradation is determined to be in the range 2-100μm. Below this range, slower homogenous degradation occurs; however, for larger samples monomers are trapped inside the sample and faster autocatalytic degradation occurs.

  12. Tantalum oxide and barium sulfate as radiopacifiers in injectable calcium phosphate-poly(lactic-co-glycolic acid) cements for monitoring in vivo degradation.

    PubMed

    Hoekstra, Jan Willem M; van den Beucken, Jeroen J J P; Leeuwenburgh, Sander C G; Bronkhorst, Ewald M; Meijer, Gert J; Jansen, John A

    2014-01-01

    Monitoring the degradation of calcium phosphate-based bone substitute materials in vivo by means of noninvasive techniques (e.g., radiography) is often a problem due to the chemical resemblance of those substitutes with the mineral phase of bone. In the view of that, the present study aimed at enhancing the radiopacity of calcium phosphate cement enriched with poly(lactic-co-glycolic acid) (CPC-PLGA) microspheres, by adding tantalum oxide (Ta2O5) or the more traditional radiopacifier barium sulfate (BaSO4). The radiopacifying capacity of these radiopacifiers was first evaluated in vitro by microcomputed tomography (μCT). Thereafter, both radiopacifiers were tested in vivo using a distal femoral condyle model in rabbits, with subsequent ex vivo μCT analysis in parallel with histomorphometry. Addition of either one of the radiopacifiers proved to enhance radiopacity of CPC-PLGA in vitro. The in vivo experiment showed that both radiopacifiers did not induce alterations in biological performance compared to plain CPC-PLGA, hence both radiopacifiers can be considered safe and biocompatible. The histomorphometrical assessment of cement degradation and bone formation showed similar values for the three experimental groups. Interestingly, μCT analysis showed that monitoring cement degradation becomes feasible upon incorporation of either type of radiopacifier, albeit that BaSO4 showed more accuracy compared to Ta2O5.

  13. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres enhance large-wound healing by delivering growth factors in platelet-rich plasma.

    PubMed

    La, Wan-Geun; Yang, Hee Seok

    2015-04-01

    Platelet-rich plasma (PRP) contains many growth factors that are involved in tissue regeneration processes. For successful tissue regeneration, protein growth factors require a delivery vehicle for long-term and sustained release to a defect site in order to maintain their bioactivity. Previously, we showed that heparin-conjugated poly(lactic-co-glycolic acid) nanospheres (HCPNs) can provide long-term delivery of growth factors with affinity for heparin. In this study, we hypothesize that treatment of a skin wound with a mixture of PRP and HCPNs would provide long-term delivery of several growth factors contained in PRP to promote the skin wound healing process with preservation of bioactivity. The release of platelet-derived growth factor-BB (PDGF-BB), contained in PRP, from HCPN with fibrin gel (FG) showed a prolonged release period versus a PRP mixture with FG alone (FG-PRP). Also, growth factors released from PRP with HCPN and FG showed sustained human dermal fibroblast growth for 12 days. Full-thickness skin wound treatment in mice with FG-HCPN-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 9 compared with treatment with FG-HCPN or FG-PRP. The enhanced wound healing using FG-HCPN-PRP may be due to the prolonged release not only of PDGF-BB but also of other growth factors in the PRP. The delivered growth factors accelerated angiogenesis at the wound site. PMID:25284020

  14. Promotion of full-thickness wound healing using epigallocatechin-3-O-gallate/poly (lactic-co-glycolic acid) membrane as temporary wound dressing.

    PubMed

    Kim, Hye-Lee; Lee, Jeong-Hyun; Kwon, Byeong Ju; Lee, Mi Hee; Han, Dong-Wook; Hyon, Suong-Hyu; Park, Jong-Chul

    2014-05-01

    Epigallocatechin-3-O-gallate (EGCG) is a major polyphenolic compound in green tea. It has been known that EGCG regulates the secretion of cytokines and the activation of skin cells during wound healing. In this study, various concentrations of EGCG were added to the electrospun membranes composed of poly (lactic-co-glycolic acid) (PLGA), and its healing effects on full-thickness wounds created in nude mice were investigated. The electrospun membranes containing 5 wt% EGCG (5EGCG/PLGA membrane) exhibited cytotoxicity in human dermal fibroblasts (HDFs) as HDF morphologies were transformed on them. In the animal study, cell infiltration of mice treated with electrospun membranes containing 1 wt% EGCG (1EGCG/PLGA membrane) significantly increased after 2 weeks. The immunoreactivity of Ki-67 (re-epithelialization at the wound site) and CD 31 (formation of blood vessels) also increased in the mice treated with 1EGCG/PLGA membranes in comparison with the mice treated with PLGA membranes. These results suggest that 1EGCG/PLGA can enhance wound healing in full thickness by accelerating cell infiltration, re-epithelialization, and angiogenesis. PMID:24571533

  15. Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Wang, Lei; Hao, Yongwei; Li, Haixia; Zhao, Yalin; Meng, Dehui; Li, Dong; Shi, Jinjin; Zhang, Hongling; Zhang, Zhenzhong; Zhang, Yun

    2015-01-01

    It is very challenging to treat brain cancer because of the blood-brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.

  16. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis.

    PubMed

    Li, Wenchang; He, Bing; Dai, Wenbing; Zhang, Qiang; Liu, Yuling

    2014-06-01

    Conventional treatments of uveitis are not ideal because of the short period of therapeutic efficacy. In the present study, biodegradable polylactic-glycolic acid microspheres loaded with triamcinolone acetonide (TA) were prepared to achieve sustained drug release and their therapeutic efficacy was investigated on a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the solvent evaporation method and characterized for encapsulation efficiency, particle size, morphology and in vitro release. The therapeutic efficacy was studied on the rabbit experimental uveitis model based on scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination and histological examination. The TA-MS exhibited smooth and intact surfaces with an average diameter of 50.87 μm. The drug-loading coefficient and encapsulation efficiency were 15.2 ± 0.6 % and 91.24 ± 3.77 %, respectively. The drug release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The change in surface morphology also showed sustained drug release from TA-MS. TA-MS exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis compared to TA suspension, especially in regard to the inhibition of inflammation. The TA-MS had a longer-term therapeutic effect on intraocular inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The results suggested that TA-MS can be developed as a potential sustained-release system for the treatment of uveitis.

  17. Nanosized Mesoporous Bioactive Glass/Poly(lactic-co-glycolic Acid) Composite-Coated CaSiO3 Scaffolds with Multifunctional Properties for Bone Tissue Engineering

    PubMed Central

    Zhai, Dong; Zhao, Lang

    2014-01-01

    It is of great importance to prepare multifunctional scaffolds combining good mechanical strength, bioactivity, and drug delivery ability for bone tissue engineering. In this study, nanosized mesoporous bioglass/poly(lactic-co-glycolic acid) composite-coated calcium silicate scaffolds, named NMBG-PLGA/CS, were successfully prepared. The morphology and structure of the prepared scaffolds were characterized by scanning electron microscopy and X-ray diffraction. The effects of NMBG on the apatite mineralization activity and mechanical strength of the scaffolds and the attachment, proliferation, and alkaline phosphatase activity of MC3T3 cells as well as drug ibuprofen delivery properties were systematically studied. Compared to pure CS scaffolds and PLGA/CS scaffolds, the prepared NMBG-PLGA/CS scaffolds had greatly improved apatite mineralization activity in simulated body fluids, much higher mechanical property, and supported the attachment of MC3T3 cells and enhanced the cell proliferation and ALP activity. Furthermore, the prepared NMBG-PLGA/CS scaffolds could be used for delivering ibuprofen with a sustained release profile. Our study suggests that the prepared NMBG-PLGA/CS scaffolds have improved physicochemical, biological, and drug-delivery property as compared to conventional CS scaffolds, indicating that the multifunctional property of the prepared scaffolds for the potential application of bone tissue engineering. PMID:24724080

  18. The effect of bioactive glass content on synthesis and bioactivity of composite poly (lactic-co-glycolic acid)/bioactive glass substrate for tissue engineering.

    PubMed

    Yao, Jun; Radin, Shula; S Leboy, Phoebe; Ducheyne, Paul

    2005-05-01

    Tissue engineering offers a promising new approach to bone tissue grafting. One material that has received attention in this regard is the polymer poly (lactic-co-glycolic acid) (PLGA). It has the advantage of controllable bioresorption and ease of processing. Another material of interest is bioactive glass (BG), which shows the ability to stimulate osteoblastic differentiation of osteoprogenitor cells. In this study, we reported on the optimal synthesis parameters and the kinetics of formation of calcium phosphate (Ca-P) phase at the surface of PLGA/BG composites. The formation of calcium phosphate layer was confirmed using scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDXA). PLGA-30%BG microspheres based porous scaffolds for bone tissue engineering were examined for their ability to promote osteogenesis of marrow stromal cells (MSC). This porous scaffold supported both MSC proliferation and promoted MSC differentiation into cells expressing the osteoblast phenotype. It therefore demonstrates significant potential as a bone replacement material. PMID:15576167

  19. Surface characterization of poly(vinyl chloride) urinary catheters functionalized with acrylic acid and poly(ethylene glycol) methacrylate using gamma-radiation

    NASA Astrophysics Data System (ADS)

    Islas, Luisa; Ruiz, Juan-Carlos; Muñoz-Muñoz, Franklin; Isoshima, Takashi; Burillo, Guillermina

    2016-10-01

    Poly(vinyl chloride) (PVC) urinary catheters were modified with either a single or binary graft of acrylic acid (AAc) and/or poly(ethylene glycol) methacrylate (PEGMA) using gamma-radiation from 60Co to obtain PVC-g-AAc, PVC-g-PEGMA, [PVC-g-AAc]-g-PEGMA, and [PVC-g-PEGMA]-g-AAc copolymers. The outer and inner surfaces of the modified catheters were characterized using scanning electron microscopy (SEM), confocal laser microscopy (CLM) and X-ray photoelectron spectroscopy (XPS). The XPS analyses, by examining the correlation between the variation of the C1s and O1s content at the catheter's surface, revealed that the catheter's surfaces were successfully grafted with the chosen compounds, with those that were binary grafted showing a slightly more covered surface as was evidenced by the disappearance of PVC's Cl peak. The SEM and CLM analyses revealed that catheters that had been grafted with PEGMA had a rougher outer surface as compared to those that had only been grafted with AAc. In addition, these imaging techniques showed that the inner surface of the singly grafted catheters, whether they had been grafted with AAc or PEGMA, retained some smoothness at the analyzed grafting percentages, while the binary grafted catheters showed many protuberances and greater roughness on both outer and inner surfaces.

  20. Controlling the degradation kinetics of porous iron by poly(lactic-co-glycolic acid) infiltration for use as temporary medical implants

    PubMed Central

    Yusop, Abdul Hakim Md; Daud, Nurizzati Mohd; Nur, Hadi; Kadir, Mohammed Rafiq Abdul; Hermawan, Hendra

    2015-01-01

    Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron. PMID:26057073

  1. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects

    PubMed Central

    Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration. PMID:27652269

  2. Plant and animal glycolate oxidases have a common eukaryotic ancestor and convergently duplicated to evolve long-chain 2-hydroxy acid oxidases.

    PubMed

    Esser, Christian; Kuhn, Anke; Groth, Georg; Lercher, Martin J; Maurino, Veronica G

    2014-05-01

    Glycolate oxidase (GOX) is a crucial enzyme of plant photorespiration. The encoding gene is thought to have originated from endosymbiotic gene transfer between the eukaryotic host and the cyanobacterial endosymbiont at the base of plantae. However, animals also possess GOX activities. Plant and animal GOX belong to the gene family of (L)-2-hydroxyacid-oxidases ((L)-2-HAOX). We find that all (L)-2-HAOX proteins in animals and archaeplastida go back to one ancestral eukaryotic sequence; the sole exceptions are green algae of the chlorophyta lineage. Chlorophyta replaced the ancestral eukaryotic (L)-2-HAOX with a bacterial ortholog, a lactate oxidase that may have been obtained through the primary endosymbiosis at the base of plantae; independent losses of this gene may explain its absence in other algal lineages (glaucophyta, rhodophyta, and charophyta). We also show that in addition to GOX, plants possess (L)-2-HAOX proteins with different specificities for medium- and long-chain hydroxyacids (lHAOX), likely involved in fatty acid and protein catabolism. Vertebrates possess lHAOX proteins acting on similar substrates as plant lHAOX; however, the existence of GOX and lHAOX subfamilies in both plants and animals is not due to shared ancestry but is the result of convergent evolution in the two most complex eukaryotic lineages. On the basis of targeting sequences and predicted substrate specificities, we conclude that the biological role of plantae (L)-2-HAOX in photorespiration evolved by co-opting an existing peroxisomal protein. PMID:24408912

  3. Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma.

    PubMed

    Liu, Ping; Sun, Liang; Zhou, Dong-sheng; Zhang, Peng; Wang, Yong-hui; Li, Dong; Li, Qing-hu; Feng, Rong-Jie

    2015-01-01

    In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma. PMID:26619950

  4. Exovascular application of epigallocatechin-3-O-gallate-releasing electrospun poly(L-lactide glycolic acid) fiber sheets to reduce intimal hyperplasia in injured abdominal aorta.

    PubMed

    Lee, Mi Hee; Kwon, Byeong-ju; Koo, Min-Ah; Jang, Eui Hwa; Seon, Gyeung Mi; Park, Jong-Chul

    2015-09-01

    Intimal hyperplasia is an excessive ingrowth of tissue resulting in chronic structural lesions commonly found at sites of atherosclerotic lesions, arterial angioplasty, vascular graft anastomoses, and other vascular abnormalities. Epigallocatechin-3-O-gallate (EGCG) was shown to elicit antioxidant, anti-proliferative, and anti-thrombogenic effects. In this study, we used an electrospinning technique to synthesize EGCG-eluting biodegradable poly(L-lactide glycolic acid) (PLGA) fiber sheets for local delivery of EGCG and investigated the effect of their exovascular application on intimal hyperplasia following balloon-induced abdominal aorta injury in a rabbit experimental model. The morphology of the composite sheets was characterized using scanning electron microscopy and Fourier transform-infrared spectroscopy. EGCG was loaded and dispersed into the PLGA-based electrospun fibers. The EGCG-loaded PLGA sheets exhibited sustained EGCG release following the initial 24 h of burst release in phosphate-buffered saline. In vivo studies demonstrated significant inhibition of intimal hyperplasia following the application of the EGCG-eluting electrospun PLGA fiber sheets, compared with vehicle PLGA controls. In conclusion, our results show that exovascular application of EGCG-eluting PLGA electrospun fiber sheets may provide a useful system for the effective local delivery of drugs for the prevention of intimal hyperplasia. PMID:26391656

  5. Fabrication of honeycomb-structured poly(ethylene glycol)-block-poly(lactic acid) porous films and biomedical applications for cell growth

    NASA Astrophysics Data System (ADS)

    Yao, Bingjian; Zhu, Qingzeng; Yao, Linli; Hao, Jingcheng

    2015-03-01

    A series of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) copolymers with a hydrophobic PLA block of different molecular weights and a fixed length hydrophilic PEG were synthesized successfully and characterized. These amphiphilic block copolymers were used to fabricate honeycomb-structured porous films using the breath figure (BF) templating technique. The surface topology and composition of the highly ordered pattern film were further characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and fluorescence microscopy. The results indicated that the PEG-to-PLA block molecular weight ratio influenced the BF film surface topology. The film with the best ordered pores was obtained with a PEG-to-PLA ratio of 2.0 × 103:3.0 × 104. The self-organization of the hydrophilic PEG chains within the pores was confirmed by XPS and fluorescence labeled PEG. A model is proposed to elucidate the stabilization process of the amphiphilic PEG-PLA aggregated architecture on the water droplet-based templates. In addition, GFP-U87 cell viability has been investigated by MTS test and the cell morphology on the honeycomb-structured PEG-PLA porous film has been evaluated using phase-contrast microscope. This porous film is shown to be suitable as a matrix for cell growth.

  6. Efficient anti-tumor effect of photodynamic treatment with polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer encapsulating hydrophobic porphyrin derivative.

    PubMed

    Ogawara, Ken-ichi; Shiraishi, Taro; Araki, Tomoya; Watanabe, Taka-ichi; Ono, Tsutomu; Higaki, Kazutaka

    2016-01-20

    To develop potent and safer formulation of photosensitizer for cancer photodynamic therapy (PDT), we tried to formulate hydrophobic porphyrin derivative, photoprotoporphyrin IX dimethyl ester (PppIX-DME), into polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer (PN-Por). The mean particle size of PN-Por prepared was around 80nm and the zeta potential was determined to be weakly negative. In vitro phototoxicity study for PN-Por clearly indicated the significant phototoxicity of PN-Por for three types of tumor cells tested (Colon-26 carcinoma (C26), B16BL6 melanoma and Lewis lung cancer cells) in the PppIX-DME concentration-dependent fashion. Furthermore, it was suggested that the release of PppIX-DME from PN-Por would gradually occur to provide the sustained release of PppIX-DME. In vivo pharmacokinetics of PN-Por after intravenous administration was evaluated in C26 tumor-bearing mice, and PN-Por exhibited low affinity to the liver and spleen and was therefore retained in the blood circulation for a long time, leading to the efficient tumor disposition of PN-Por. Furthermore, significant and highly effective anti-tumor effect was confirmed in C26 tumor-bearing mice with the local light irradiation onto C26 tumor tissues after PN-Por injection. These findings indicate the potency of PN-Por for the development of more efficient PDT-based cancer treatments.

  7. Reduction of inflammatory responses and enhancement of extracellular matrix formation by vanillin-incorporated poly(lactic-co-glycolic acid) scaffolds.

    PubMed

    Lee, Yujung; Kwon, Jeongil; Khang, Gilson; Lee, Dongwon

    2012-10-01

    Vanillin is one of the major components of vanilla, a commonly used flavoring agent and preservative and is known to exert potent antioxidant and anti-inflammatory activities. In this work, vanillin-incorporated poly(lactic-co-glycolic acid) (PLGA) films and scaffolds were fabricated to evaluate the effects of vanillin on the inflammatory responses and extracellular matrix (ECM) formation in vitro and in vivo. The incorporation of vanillin to PLGA films induced hydrophilic nature, resulting in the higher cell attachment and proliferation than the pure PLGA film. Vanillin also reduced the generation of reactive oxygen species (ROS) in cells cultured on the pure PLGA film and significantly inhibited the PLGA-induced inflammatory responses in vivo, evidenced by the reduced accumulation of inflammatory cells and thinner fibrous capsules. The effects of vanillin on the ECM formation were evaluated using annulus fibrous (AF) cell-seeded porous PLGA/vanillin scaffolds. PLGA/vanillin scaffolds elicited the more production of glycosaminoglycan and collagen than the pure PLGA scaffold, in a concentration-dependent manner. Based on the low level of inflammatory responses and enhanced ECM formation, vanillin-incorporated PLGA constructs make them promising candidates in the future biomedical applications.

  8. Biocompatible cephalosporin-hydroxyapatite-poly(lactic-co-glycolic acid)-coatings fabricated by MAPLE technique for the prevention of bone implant associated infections

    NASA Astrophysics Data System (ADS)

    Rădulescu, Dragoş; Grumezescu, Valentina; Andronescu, Ecaterina; Holban, Alina Maria; Grumezescu, Alexandru Mihai; Socol, Gabriel; Oprea, Alexandra Elena; Rădulescu, Marius; Surdu, Adrian; Trusca, Roxana; Rădulescu, Radu; Chifiriuc, Mariana Carmen; Stan, Miruna S.; Constanda, Sabrina; Dinischiotu, Anca

    2016-06-01

    In this study we aimed to obtain functionalized thin films based on hydroxyapatite/poly(lactic-co-glycolic acid) (HAp/PLGA) containing ceftriaxone/cefuroxime antibiotics (ATBs) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The prepared thin films were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-Ray diffraction (XRD), selected area electron diffraction (SAED), and infra red (IR) analysis. HAp/PLGA/ATBs thin films sustained the growth of human osteoblasts, proving their good biocompatibility. The microscopic evaluation and the culture-based quantitative assay of the E. coli biofilm development showed that the thin films inhibited the initial step of microbial attachment as well as the subsequent colonization and biofilm development on the respective surfaces. This study demonstrates that MAPLE technique could represent an appealing technique for the fabrication of antibiotics-containing polymeric implant coatings. The bioevaluation results recommend this type of surfaces for the prevention of bone implant microbial contamination and for the enhanced stimulation of the implant osseointegration process.

  9. Formulation and evaluation of poly(lactic-co-glycolic acid) microspheres loaded with an altered collagen type II peptide for the treatment of rheumatoid arthritis.

    PubMed

    He, Jintian; Li, Huiqi; Liu, Chao; Wang, Gaizhen; Ge, Lan; Ma, Shufen; Huang, Lijing; Yan, Shaofeng; Xu, Xiaohong

    2015-01-01

    The aim of this research was to evaluate the potential of water-in-oil-in-water (w/o/w) and solid-in-oil-in-water (s/o/w) emulsification techniques to prepare the altered collagen type II peptide AP268-270 (ACTP)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres to make ACTP more convenient as an rheumatoid arthritis treatment. Microspheres produced by the s/o/w method had higher drug encapsulation efficiency (69.7-79.8%) than those prepared by the w/o/w method (21.8-39.3%). In vitro drug release was influenced by the microencapsulation technique, molecular weight, and composition of the polymer. After intramuscular injection of the optimal formulation to Lewis rats, the concentration of ACTP peptide in serum reached its maximum level on day 3 and then remained nearly stable for approximately 4 weeks. In a collagen-induced arthritis rat model, a single intramuscular injection of ACTP-loaded PLGA microspheres had comparable efficacy to the intravenous injection of ACTP peptide solution once every other day.

  10. CO2-free power generation on an iron group nanoalloy catalyst via selective oxidation of ethylene glycol to oxalic acid in alkaline media.

    PubMed

    Matsumoto, Takeshi; Sadakiyo, Masaaki; Ooi, Mei Lee; Kitano, Sho; Yamamoto, Tomokazu; Matsumura, Syo; Kato, Kenichi; Takeguchi, Tatsuya; Yamauchi, Miho

    2014-07-08

    An Fe group ternary nanoalloy (NA) catalyst enabled selective electrocatalysis towards CO2-free power generation from highly deliverable ethylene glycol (EG). A solid-solution-type FeCoNi NA catalyst supported on carbon was prepared by a two-step reduction method. High-resolution electron microscopy techniques identified atomic-level mixing of constituent elements in the nanoalloy. We examined the distribution of oxidised species, including CO2, produced on the FeCoNi nanoalloy catalyst in the EG electrooxidation under alkaline conditions. The FeCoNi nanoalloy catalyst exhibited the highest selectivities toward the formation of C2 products and to oxalic acid, i.e., 99 and 60%, respectively, at 0.4 V vs. the reversible hydrogen electrode (RHE), without CO2 generation. We successfully generated power by a direct EG alkaline fuel cell employing the FeCoNi nanoalloy catalyst and a solid-oxide electrolyte with oxygen reduction ability, i.e., a completely precious-metal-free system.

  11. On-resin synthesis of an acylated and fluorescence-labeled cyclic integrin ligand for modification of poly(lactic-co-glycolic acid).

    PubMed

    Hassert, Rayk; Hoffmeister, Peter-Georg; Pagel, Mareen; Hacker, Michael; Schulz-Siegmund, Michaela; Beck-Sickinger, Annette G

    2012-11-01

    Cyclic Arg-Gly-Asp (RGD) peptides show remarkable affinity and specificity to integrin receptors and mediate important physiological effects in tumor angiogenesis. Additionally, they are one of the keyplayers in improving the biocompatibility of biomaterials. The fully biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) is frequently used for biomedical implants and can be applied as nanoparticles for drug delivery. The aim of this work was the generation of a lipidated c[RGDfK] peptide including a second functionality for coating of hydrophobic PLGA. Therefore, we established a general and straightforward strategy for the introduction of two different modifications into the same c[RGDfK] peptide. This allowed the generation of a palmitoylated integrin-binding lipopeptide that shows high affinity to PLGA. Additionally, we coupled 5(6)-carboxyfluorescein to the second site for modification to enable sensitive quantification of the immobilized lipopeptide on PLGA. In conclusion, we present a synthesis protocol that enables the preparation of c[RGDfK] lipopeptides with a strong affinity to PLGA and an additional site for modifications. This will provide the opportunity to introduce a variety of effector molecules site-specifically to the c[RGDfK] lipopeptide, which will enable the introduction of multifunctionality into c[RGDfK]-coated PLGA devices or nanoparticles. PMID:23161641

  12. Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma

    NASA Astrophysics Data System (ADS)

    Liu, Ping; Sun, Liang; Zhou, Dong-Sheng; Zhang, Peng; Wang, Yong-Hui; Li, Dong; Li, Qing-Hu; Feng, Rong-Jie

    2015-12-01

    In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma.

  13. Nanosized mesoporous bioactive glass/poly(lactic-co-glycolic acid) composite-coated CaSiO3 scaffolds with multifunctional properties for bone tissue engineering.

    PubMed

    Shi, Mengchao; Zhai, Dong; Zhao, Lang; Wu, Chengtie; Chang, Jiang

    2014-01-01

    It is of great importance to prepare multifunctional scaffolds combining good mechanical strength, bioactivity, and drug delivery ability for bone tissue engineering. In this study, nanosized mesoporous bioglass/poly(lactic-co-glycolic acid) composite-coated calcium silicate scaffolds, named NMBG-PLGA/CS, were successfully prepared. The morphology and structure of the prepared scaffolds were characterized by scanning electron microscopy and X-ray diffraction. The effects of NMBG on the apatite mineralization activity and mechanical strength of the scaffolds and the attachment, proliferation, and alkaline phosphatase activity of MC3T3 cells as well as drug ibuprofen delivery properties were systematically studied. Compared to pure CS scaffolds and PLGA/CS scaffolds, the prepared NMBG-PLGA/CS scaffolds had greatly improved apatite mineralization activity in simulated body fluids, much higher mechanical property, and supported the attachment of MC3T3 cells and enhanced the cell proliferation and ALP activity. Furthermore, the prepared NMBG-PLGA/CS scaffolds could be used for delivering ibuprofen with a sustained release profile. Our study suggests that the prepared NMBG-PLGA/CS scaffolds have improved physicochemical, biological, and drug-delivery property as compared to conventional CS scaffolds, indicating that the multifunctional property of the prepared scaffolds for the potential application of bone tissue engineering.

  14. New platform for controlled and sustained delivery of the EGF receptor tyrosine kinase inhibitor AG1478 using poly(lactic-co-glycolic acid) microspheres

    PubMed Central

    Robinson, Rebecca; Bertram, James P.; Reiter, Jill L.; Lavik, Erin B.

    2015-01-01

    Inhibition of the epidermal growth factor receptor (EGFR) has been shown to reduce tumor growth and metastases and promote axon regeneration in the central nervous system. Current strategies for inhibiting EGFR include the administration of reversible or irreversible small-molecule tyrosine kinase inhibitors (TKIs). However, to be effective in vivo constant and sustained delivery is required. This study explored the feasibility of encapsulating the tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) in poly(lactic-co-glycolic acid) (PLGA) microspheres to achieve sustained delivery of the TKI. We characterized microspheres prepared using three different emulsion methods: solid-in-oil-in-water, oil-in-water, and oil-in-water with co-solvent. Addition of a co-solvent increased the loading and release of AG1478, and significantly (P<0.001) decreased the size of the microspheres which facilitates administration of the spheres. On average, sustained delivery of AG1478 from microspheres was achieved for six months. However, the addition of a co-solvent prolonged release for over nine months (266 days). In addition, AG1478 retained its bioactivity upon delivery, and inhibited EGFR in both immortalized rat fibroblasts and in EGFR-amplified human carcinoma cells. These results demonstrate that AG1478 can be encapsulated in PLGA and retain bioactivity; thereby providing a new platform for controlled administration of EGFR TKIs. PMID:20055747

  15. Effects of hesperidin loaded poly(lactic-co-glycolic acid) scaffolds on growth behavior of costal cartilage cells in vitro and in vivo.

    PubMed

    Cho, Sun Ah; Cha, Se Rom; Park, Sang Mi; Kim, Kyoung Hee; Lee, Hyun Gu; Kim, Eun Young; Lee, Dongwon; Khang, Gilson

    2014-01-01

    It has been widely accepted that costal cartilage cells (CCs) have more excellent initial proliferation capacity than articular cartilage cells. Biodegradable synthetic polymer poly(lactic-co-glycolic acid) (PLGA) was approved by Food and Drug Administration. Hesperidin has antifungal, antiviral, antioxidant, anti-inflammatory, and anticarcinogenic properties. Hesperidin loaded (0, 3, 5, and 10 wt.%) PLGA scaffolds were prepared and in vitro and in vivo properties were characterized. Scaffolds were seeded with CCs isolated from rabbit, which were kept in culture to harvest for histological analysis. Hesperidin/PLGA scaffolds were also implanted in nude mice for 7 and 28 days. Assays of 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfo-phenyl)-2H-tetrazolium, monosodium salt (WST), and scanning electron microscope were carried out to evaluate attachment and proliferation of CCs in hesperidin/PLGA scaffolds. Glycosaminoglycan assay was performed to confirm the effects of hesperidin on extracellular matrix formation. Reverse-transcriptase polymerase chain reaction was carried out to confirm the expression of the specific genes for CCs. In these results, we demonstrated that cell attachment and proliferation on hesperidin/PLGA scaffolds were more excellent compared with on PLGA scaffold. Specially, 5 wt.% hesperidin/PLGA scaffold represented the best results among other scaffolds. Thus, 5 wt.% hesperidin/PLGA scaffold will be applicable to tissue engineering cartilage. PMID:24588773

  16. Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma

    PubMed Central

    Liu, Ping; Sun, Liang; Zhou, Dong-sheng; Zhang, Peng; Wang, Yong-hui; Li, Dong; Li, Qing-hu; Feng, Rong-jie

    2015-01-01

    In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma. PMID:26619950

  17. Effect of cryomilling times on the resultant properties of porous biodegradable poly(e-caprolactone)/poly(glycolic acid) scaffolds for articular cartilage tissue engineering.

    PubMed

    Jonnalagadda, John B; Rivero, Iris V

    2014-12-01

    The aim of this research is to develop a parametric investigation of the fabrication of poly(e-caprolactone) (PCL)/poly(glycolic acid) (PGA) scaffolds to decipher the influence of cryomilling time on the scaffolds' resultant physical, morphological and mechanical characteristics. Scaffolds were fabricated via solid-state cryomilling to prepare a homogeneous blend along with conventional compression molding and porogen leaching yielding interconnected porous scaffolds. PCL/PGA scaffolds fabricated through this technique demonstrated high porosity at all cryomilling times. Morphological analysis revealed a co-continuous interconnected pore network. While mean pore size decreased, water uptake and compressive properties increased with increasing cryomilling times. Porous scaffolds cryomilled for 12min exhibited a mean pore size within the optimal range for tissue engineering and chondrocyte ingrowth. And the compressive modulus of scaffolds cryomilled for 12, 30 and 60min matched the compressive modulus of human articular cartilage. In addition, scaffolds exhibited water uptake, a key requirement in tissue engineering. A 60 day in vitro degradation study revealed mass loss starting from day 10 and increasing through day 60, while notable reduction in compressive properties was observed. The results indicated that cryomilling times affected the resultant properties of PCL/PGA scaffolds and will be interesting candidates for articular cartilage tissue engineering.

  18. Hindered Diffusion of Oligosaccharides in High Strength Poly(ethylene glycol)/Poly(acrylic acid) Interpenetrating Network Hydrogels: Hydrodynamic Versus Obstruction Models

    PubMed Central

    Waters, Dale J.; Frank, Curtis W.

    2010-01-01

    Diffusion coefficients of small oligosaccharides within high strength poly(ethylene glycol)/poly(acrylic acid) interpenetrating network (PEG/PAA IPN) hydrogels were measured by diffusion through hydrogel slabs. The ability of hindered diffusion models previously presented in the literature to fit the experimental data is examined. A model based solely on effects due to hydrodynamics is compared to a model based solely on solute obstruction. To examine the effect of polymer volume fraction on the observed diffusion coefficients, the equilibrium volume fraction of polymer in PEG/PAA IPNs was systematically varied by changing the initial PEG polymer concentration in hydrogel precursor solutions from 20 to 50 wt./wt.%. To examine the effect of solute radius on the observed diffusion coefficients, solute radii were varied from 3.3 to 5.1 Å by measuring diffusion coefficients of glucose, a monosaccharide; maltose, a disaccharide; and maltotriose, a trisaccharide. Both the hydrodynamic and obstruction models rely on scaling relationships to predict diffusion coefficients. The proper scaling relationship for each of the hindered diffusion models is evaluated based on fits to experimental data. The scaling relationship employed is found to have a greater significance for the hydrodynamic model than the obstruction model. Regardless of the scaling relationship employed, the obstruction model provides a better fit to our experimental data than the hydrodynamic model. PMID:20514136

  19. Subchronic toxicity and immunotoxicity of MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer nanoparticles delivered intravenously into rats

    NASA Astrophysics Data System (ADS)

    Liao, Longfei; Zhang, Mengtian; Liu, Huan; Zhang, Xuanmiao; Xie, Zhaolu; Zhang, Zhirong; Gong, Tao; Sun, Xun

    2014-06-01

    Although monomethoxy(polyethyleneglycol)-poly (D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) nanoparticles have been widely studied as a drug delivery system, little is known about their toxicity in vivo. Here we examined the subchronic toxicity and immunotoxicity of different doses of PELGE nanoparticles with diameters of 50 and 200 nm (PELGE50 and PELGE200) in rats. Neither size of PELGE nanoparticles showed obvious subchronic toxic effects during 28 d of continuous intravenous administration based on clinical observation, body weight, hematology parameters and histopathology analysis. PELGE200 nanoparticles showed no overt signs of immunotoxicity based on organ coefficients, histopathology analysis, immunoglobulin levels, blood lymphocyte subpopulations and splenocyte cytokines. Conversely, PELGE50 nanoparticles were associated with an increased organ coefficient and histopathological changes in the spleen, increased serum IgM and IgG levels, alterations in blood lymphocyte subpopulations and enhanced expression of spleen interferon-γ. Taken together, these results suggest that PELGE nanoparticles show low subchronic toxicity but substantial immunotoxicity, which depends strongly on particle size. These findings will be useful for safe application of PELGE nanoparticles in drug delivery systems.

  20. Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma

    PubMed Central

    Hrynyk, Michael; Ellis, Jordon P; Haxho, Fiona; Allison, Stephanie; Steele, Joseph AM; Abdulkhalek, Samar; Neufeld, Ronald J; Szewczuk, Myron R

    2015-01-01

    Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Here, the controlled release of OP from a biodegradable PLGA cylinder (PLGA-OP) implanted at tumor site was investigated for its role in limiting tumor neovascularization, growth, and metastasis. PLGA-OP cylinders over 30 days in vitro indicated 20%–25% release profiles within 48 hours followed by a continuous metronomic low dose release of 30%–50% OP for an additional 16 days. All OP was released by day 30. Surgically implanted PLGA-OP containing 20 mg OP and blank PLGA cylinders at the tumor site of heterotopic xenografts of human pancreatic PANC1 tumors in RAGxCγ double mutant mice impeded tumor neovascularization, growth rate, and spread to the liver and lungs compared with the untreated cohort. Xenograft tumors from PLGA and PLGA-OP-treated cohorts expressed significant higher levels of human E-cadherin with concomitant reduced N-cadherin and host CD31+ endothelial cells compared with the untreated cohort. These results clearly indicate that OP delivered from PLGA cylinders surgically implanted at the site of the solid tumor show promise as an effective treatment therapy for cancer. PMID:26309402

  1. Cooperation of Amphiphilicity and Crystallization for Regulating the Self-Assembly of Poly(ethylene glycol)-block-poly(lactic acid) Copolymers.

    PubMed

    Wang, Zhen; Cao, Yuanyuan; Song, Jiaqi; Xie, Zhigang; Wang, Yapei

    2016-09-20

    Tuning the amphiphilicity of block copolymers has been extensively exploited to manipulate the morphological transition of aggregates. The introduction of crystallizable moieties into the amphiphilic copolymers also offers increasing possibilities for regulating self-assembled structures. In this work, we demonstrate a detailed investigation of the self-assembly behavior of amphiphilic poly(ethylene glycol)-block-poly(l-lactic acid) (PEG-b-PLLA) diblock copolymers with the assistance of a common solvent in aqueous solution. With a given length of the PEG block, the molecular weight of the PLA block has great effect on the morphologies of self-assembled nanoaggregates as a result of varying molecular amphiphilicity and polymer crystallization. Common solvents including N,N-dimethylformamide, dioxane, and tetrahydrofuran involved in the early stage of self-assembly led to the change in chain configuration, which further influences the self-assembly of block copolymers. This study expanded the scope of PLA-based copolymers and proposed a possible mechanism of the sphere-to-lozenge and platelet-to-cylinder morphological transitions. PMID:27496056

  2. Comparative studies on exenatide-loaded poly (D,L-lactic-co-glycolic acid) microparticles prepared by a novel ultra-fine particle processing system and spray drying.

    PubMed

    Zhu, Chune; Huang, Ying; Zhang, Xiaoying; Mei, Liling; Pan, Xin; Li, Ge; Wu, Chuanbin

    2015-08-01

    The purpose of this study was to compare the properties of exenatide-loaded poly (D,L-lactic-co-glycolic acid) microparticles (Ex-PLGA-MPs) prepared by a novel ultra-fine particle processing system (UPPS) and spray drying. UPPS is a proprietary technology developed by our group based on the disk rotation principle. Characteristics of the MPs including morphology, particle size distribution, drug content, encapsulation efficiency and in vitro release were comparatively studied. Cytotoxicity of the MPs was examined on A549 cells and the pharmacodynamics was investigated in vivo in type 2 diabetes Sprague-Dawley (SD) rats. Ex-PLGA-MPs prepared by UPPS showed larger particle size, denser surface, greater encapsulation efficiency, less initial burst release, and stable sustained release for more than one month in vitro as compared with the spray drying MPs. Meanwhile, the UPPS MPs effectively controlled the body growth rate and blood glucose in diabetes rats for at least three weeks after a single injection, while the spray drying MPs showed effective control period of about two weeks. UPPS technology was demonstrated to manufacture Ex-PLGA-MPs as a potential sustained release protein/polypeptide delivery system, which is an alternative method for the most commonly used spray drying. This comparative research provides a new guidance for microparticle preparation technology. PMID:26037698

  3. Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice.

    PubMed

    Salari, Farhad; Varasteh, Abdol-Reza; Vahedi, Fatemeh; Hashemi, Maryam; Sankian, Mojtaba

    2015-12-01

    The goal of this study was to investigate whether poly (lactic-co-glycolic) acid (PLGA) nanoparticles could enhance sublingual immunotherapy (SLIT) efficacy. BALB/c mice sensitized to rChe a 3 were treated sublingually either with soluble rChe a 3 (100μg/dose) or PLGA-encapsulated rChe a 3 (5, 25, or 50μg/dose). SLIT with PLGA-encapsulated rChe a 3 (equivalent to 25 and 50μg rChe a 3 per dose) led to significantly increased antigen-specific IgG2a, along with no effect on allergen-specific IgE and IgG1 antibody levels. In addition, interleukin 4 (IL-4) levels in restimulated splenocytes were significantly less, while interferon-γ (IFN-γ), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) levels, as well as Foxp3 expression, were significantly greater than in the control groups. Our findings suggest that PLGA nanoparticle-based vaccination may help rational development of sublingual immunotherapy through reduction of the needed allergen doses and also significantly enhanced systemic T regulatory (Treg) and T helper 1 (Th1) immune responses.

  4. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres enhance large-wound healing by delivering growth factors in platelet-rich plasma.

    PubMed

    La, Wan-Geun; Yang, Hee Seok

    2015-04-01

    Platelet-rich plasma (PRP) contains many growth factors that are involved in tissue regeneration processes. For successful tissue regeneration, protein growth factors require a delivery vehicle for long-term and sustained release to a defect site in order to maintain their bioactivity. Previously, we showed that heparin-conjugated poly(lactic-co-glycolic acid) nanospheres (HCPNs) can provide long-term delivery of growth factors with affinity for heparin. In this study, we hypothesize that treatment of a skin wound with a mixture of PRP and HCPNs would provide long-term delivery of several growth factors contained in PRP to promote the skin wound healing process with preservation of bioactivity. The release of platelet-derived growth factor-BB (PDGF-BB), contained in PRP, from HCPN with fibrin gel (FG) showed a prolonged release period versus a PRP mixture with FG alone (FG-PRP). Also, growth factors released from PRP with HCPN and FG showed sustained human dermal fibroblast growth for 12 days. Full-thickness skin wound treatment in mice with FG-HCPN-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 9 compared with treatment with FG-HCPN or FG-PRP. The enhanced wound healing using FG-HCPN-PRP may be due to the prolonged release not only of PDGF-BB but also of other growth factors in the PRP. The delivered growth factors accelerated angiogenesis at the wound site.

  5. A controlled release of antibiotics from calcium phosphate-coated poly(lactic-co-glycolic acid) particles and their in vitro efficacy against Staphylococcus aureus biofilm.

    PubMed

    Bastari, Kelsen; Arshath, Mohamed; Ng, Zhi Hui Melissa; Chia, Jia Hua; Yow, Zhi Xian Daniel; Sana, Barindra; Tan, Meng Fong Cherine; Lim, Sierin; Loo, Say Chye Joachim

    2014-03-01

    Ceramic-polymer hybrid particles, intended for osteomyelitis treatment, were fabricated by preparing poly(lactic-co-glycolic acid) particles through an emulsion solvent evaporation technique, followed by calcium phosphate (CaP) coating via a surface adsorption-nucleation method. The presence of CaP coating on the surface of the particles was confirmed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Subsequently, two antibiotics for treating bone infection, nafcillin (hydrophilic) and levofloxacin (amphiphilic), were loaded into these hybrid particles and their in vitro drug release studies were investigated. The CaP coating was shown to reduce burst release, while providing sustained release of the antibiotics for up to 4 weeks. In vitro bacterial study against Staphylococcus aureus demonstrated the capability of these antibiotic-loaded hybrid particles to inhibit biofilm formation as well as deteriorate established biofilm, making this hybrid system a potential candidate for further investigation for osteomyelitis treatment.

  6. Stabilization and immune response of HBsAg encapsulated within poly(lactic-co-glycolic acid) microspheres using HSA as a stabilizer.

    PubMed

    Xu, Wenjuan; He, Jintian; Wu, Guanghao; Xiong, Fangfang; Du, Huijuan; Wang, Gaizhen

    2015-12-30

    The aim of this study was to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing hepatitis B virus surface antigen (HBsAg) using human serum albumin (HSA) as a stabilizer. Lyophilization and emulsification of HBsAg solution with dichloromethane caused a considerable loss of HBsAg antigenicity. Thus, the effects of HSA and trehalose on HBsAg recovery during lyophilization and emulsification were investigated. Adding HSA to HBsAg solutions significantly improved antigen recovery to >90% during lyophilization and emulsification. The effects of co-encapsulated HSA on the characteristics of the PLGA microspheres and stability of HBsAg released from the microspheres were also investigated. The in vitro release test showed that HBsAg was released from the PLGA microspheres continuously over seventy days. A large amount of released HBsAg was inactive without co-encapsulation of HSA. On the contrary, with HSA co-encapsulation, the released HBsAg retained approximately 90% of its antigenicity. The single injection of the HBsAg-HSA-loaded PLGA microspheres in rats resulted in higher anti-HBsAg IgG and Th1 cytokine levels than the single injection of the HBsAg-loaded microspheres or two injections of the conventional aluminum-adjuvanted HBsAg vaccine. Based on these findings, the HBsAg-HSA-loaded PLGA microspheres could be an effective carrier for HBsAg and form a promising depot system.

  7. Plant and animal glycolate oxidases have a common eukaryotic ancestor and convergently duplicated to evolve long-chain 2-hydroxy acid oxidases.

    PubMed

    Esser, Christian; Kuhn, Anke; Groth, Georg; Lercher, Martin J; Maurino, Veronica G

    2014-05-01

    Glycolate oxidase (GOX) is a crucial enzyme of plant photorespiration. The encoding gene is thought to have originated from endosymbiotic gene transfer between the eukaryotic host and the cyanobacterial endosymbiont at the base of plantae. However, animals also possess GOX activities. Plant and animal GOX belong to the gene family of (L)-2-hydroxyacid-oxidases ((L)-2-HAOX). We find that all (L)-2-HAOX proteins in animals and archaeplastida go back to one ancestral eukaryotic sequence; the sole exceptions are green algae of the chlorophyta lineage. Chlorophyta replaced the ancestral eukaryotic (L)-2-HAOX with a bacterial ortholog, a lactate oxidase that may have been obtained through the primary endosymbiosis at the base of plantae; independent losses of this gene may explain its absence in other algal lineages (glaucophyta, rhodophyta, and charophyta). We also show that in addition to GOX, plants possess (L)-2-HAOX proteins with different specificities for medium- and long-chain hydroxyacids (lHAOX), likely involved in fatty acid and protein catabolism. Vertebrates possess lHAOX proteins acting on similar substrates as plant lHAOX; however, the existence of GOX and lHAOX subfamilies in both plants and animals is not due to shared ancestry but is the result of convergent evolution in the two most complex eukaryotic lineages. On the basis of targeting sequences and predicted substrate specificities, we conclude that the biological role of plantae (L)-2-HAOX in photorespiration evolved by co-opting an existing peroxisomal protein.

  8. Facile and controllable preparation of mesoporous TiO2 using poly(ethylene glycol) as structure-directing agent and peroxotitanic acid as precursor

    NASA Astrophysics Data System (ADS)

    Nguyen, Dongthanh; Wang, Wei; Long, Haibo; Ru, Hongqiang

    2016-09-01

    This work demonstrated that mesoporous TiO2 (meso-TiO2) with controllable mesoporous and crystalline structures can be facilely prepared by using poly (ethylene glycol) (PEG) as structure-directing (SD) agent and peroxotitanic acid (PTA) as precursor. Meso-TiO2 with high specific surface area (157 m2•g-1), pore volume (0.45 cm3•g-1) and large mesopore size of 13.9 nm can be obtained after calcination at 450°C. Such meso-TiO2 also shows relatively high thermal stability. BET surface area still reaches 114 m2•g-1 after calcination at 550°C. In the synthesis and calcination process, PEG that plays multiple and important roles in delivering thermally stable and tunable mesoporous and crystalline structures shows to be a suitable low-cost SD agent for the controllable preparation of nanocrystalline meso-TiO2. The photocatalytic activity tests show that both high surface area and bi-crystallinity of obtained meso-TiO2 are important in enhancing the performance in photo-decomposing Rhodamine B in water.

  9. Therapeutic efficacy of poly (lactic-co-glycolic acid) nanoparticles encapsulated ivermectin (nano-ivermectin) against brugian filariasis in experimental rodent model.

    PubMed

    Ali, Mohammad; Afzal, Mohammad; Verma, Meenakshi; Bhattacharya, Shailja Misra; Ahmad, F J; Samim, Mohammad; Abidin, M Z; Dinda, A K

    2014-02-01

    The present study reports on the antifilarial activity of poly (lactic-co-glycolic acid) nanoparticles encapsulated ivermectin (nano-IVM) against human lymphatic filariid Brugia malayi in rodent host Mastomys coucha. Nano-IVM was prepared and optimized by nanoprecipitation method. The selected nano-IVM (F5) showed a uniform spherical shape with 96 nm diameter and 74.12 % entrapment efficiency, and when used at a suboptimal dose of 100 μg/kg body weight, completely eliminated filarial parasites from systemic circulation on 60 days post-infection in animals inflicted with B. malayi. In contrast, the coadministration of nano-IVM (F5) along with standard filaricide diethylcarbamazine (DEC) was found to be competent enough to suppress microfilarial stage of parasites and successfully eliminated microfilaria at 45 days posttreatment. However, the free form of both the drugs alone or in combination was unable to impart such suppression and followed by recurrence of the infection. Interestingly, nano-IVM (F5) was also found to be effective against adult stage parasites causing 36.67 % worm mortality and 75.89 % in combination with DEC; however, female sterilization remain almost similar. Thus, the combination of entrapped IVM with DEC exhibited enhanced microfilaricidal and marginally better macrofilaricidal efficacy than any of the single formulation or drugs combination.

  10. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects.

    PubMed

    He, Shu; Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang; Bi, Long; Liu, Jian

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration. PMID:27652269

  11. Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-co-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method.

    PubMed

    Pathak, Shiva; Gupta, Biki; Poudel, Bijay Kumar; Tran, Tuan Hiep; Regmi, Shobha; Pham, Tung Thanh; Thapa, Raj Kumar; Kim, Min-Soo; Yong, Chul Soon; Kim, Jong Oh; Jeong, Jee-Heon

    2016-01-01

    Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres (TAC-PLGA-M) can be administered for the long-term survival of transplanted organs due to their immunosuppressive activity. The purpose of our study was to optimize the parameters of the electrospray method, and to prepare TAC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. In vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Drug-loading efficiency was greater than 80% in all formulations with a maximum loading capacity of 16.81±0.37%. XRD and DSC studies suggested that the drug was incorporated in an amorphous state or was molecularly dispersed in the microspheres. The in vitro release study showed prolonged release patterns. TAC-PLGA-M with enhanced drug loading and prolonged-release patterns were successfully prepared using the electrospray method. PMID:26833445

  12. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects

    PubMed Central

    Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration.

  13. Effect of polyacrylonitrile on triethylene glycol diacetate-2-propenoic acid butyl ester gel polymer electrolytes with interpenetrating crosslinked network for flexible lithium ion batteries

    NASA Astrophysics Data System (ADS)

    Wang, Qiujun; Song, Wei-Li; Fan, Li-Zhen; Shi, Qiao

    2015-11-01

    A new flexible gel polymer electrolytes (GPE) with interpenetrating cross-linked network is fabricated by blending long-chain polyacrylonitrile (PAN) polymer matrix and short-chain triethylene glycol diacetate-2-propenoic acid butyl ester (TEGDA-BA) framework, with the purpose of enhancing the mechanical stability of the GPE frameworks via synergistic effects of the linear polymers and crosslinked monomers. The as fabricated frameworks enable the liquid electrolytes to be firmly entrapped in the polymeric matrices, which significantly improves the mechanical bendability and interface stability of the resultant GPE. The GPE with 5 wt% PAN exhibits high ionic conductivity up to 5.9 × 10-3 S cm-1 at 25 °C with a stable electrochemical window observed (>5.0 V vs. Li/Li+). The Li|GPE|LiFePO4 half cells demonstrate remarkably stable capacity retention and rate ability during cycling tests. As expected, the LiFePO4|GPE|Li4Ti5O12 full cells also exhibit discharge capacity of 125.2 mAh g-1 coupled with high columbic efficiency greater than 98% after 100 cycles. The excellent mechanical flexibility and charge/discharge performance suggest that the GPE holds great application potential in flexible LIBs.

  14. Acid rain

    SciTech Connect

    Not Available

    1985-01-01

    This report has four parts: they discuss acid rain in relation to acid soils, agriculture, forests, and aquatic ecosystems. Among findings: modern sources of acid deposition from the atmosphere for all the acid soils in the world, nor even chiefly responsible for those of northern U.S. Agriculture has its problems, but acid precipitation is probably not one of them. More research is needed to determine to what extent acid precipitation is responsible for forest declines and for smaller detrimental effects on forest growth where no damage to the foliage is evident. Many lakes and streams are extremely sensitive to added acids.

  15. Photoinduced Mild Hyperthermia and Synergistic Chemotherapy by One-Pot-Synthesized Docetaxel-Loaded Poly(lactic-co-glycolic acid)/Polypyrrole Nanocomposites.

    PubMed

    Yuan, Jie; Liu, Jialu; Song, Qi; Wang, Dan; Xie, Wensheng; Yan, Hao; Zhou, Junfeng; Wei, Yen; Sun, Xiaodan; Zhao, Lingyun

    2016-09-21

    Mild hyperthermia has shown great advantages when combined with chemotherapy. The development of a multifunctional platform for the integration of mild hyperthermia capability into a drug-loading system is a key issue for cancer multimodality treatment application. Herein, a facile one-pot in situ fabrication protocol of docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA)/polypyrrole (PPy) nanocomposites was developed. While the PLGA nanoparticles (NPs) allow efficient drug loading, the PPy nanobulges embedded within the surface of the PLGA NPs, formed by in situ pyrrole polymerization without the introduction of other template agents, can act as ideal mediators for photoinduced mild hyperthermia. Physiochemical characterizations of the as-prepared nanocomposites, including structure, morphology, photothermal effects, and an in vitro drug release profile, were systematically investigated. Further, 2-deoxyglucose-terminated poly(ethylene glycol) (PEG) was anchored onto the surface of the nanocomposites to endow the nanoplatform with targeting ability to tumor cells, which resulted in a 17-fold increase of NP internalization within human breast cancer cells (MCF-7) as competed with PEG-modified nanocomposites. Mild hyperthermia can be successfully mediated by the nanoplatform, and the temperature can be conveniently controlled by careful modulation of the PPy contents within the nanocomposites or the laser power density. Importantly, we have demonstrated that MCF-7 cells, which are markedly resistant to heat treatment of traditional water-bath hyperthermia, became sensitive to the PLGA/PPy nanocomposite-mediated photothermal therapy under the same mild-temperature hyperthermia. Moreover, DTX-loaded PLGA/PPy-nanocomposite-induced mild hyperthermia can strongly enhance drug cytotoxicity to MCF-7 cells. Under the same thermal dose, photoinduced hyperthermia can convert the interaction between hyperthermia and drug treatment from interference to synergism. This

  16. Photoinduced Mild Hyperthermia and Synergistic Chemotherapy by One-Pot-Synthesized Docetaxel-Loaded Poly(lactic-co-glycolic acid)/Polypyrrole Nanocomposites.

    PubMed

    Yuan, Jie; Liu, Jialu; Song, Qi; Wang, Dan; Xie, Wensheng; Yan, Hao; Zhou, Junfeng; Wei, Yen; Sun, Xiaodan; Zhao, Lingyun

    2016-09-21

    Mild hyperthermia has shown great advantages when combined with chemotherapy. The development of a multifunctional platform for the integration of mild hyperthermia capability into a drug-loading system is a key issue for cancer multimodality treatment application. Herein, a facile one-pot in situ fabrication protocol of docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA)/polypyrrole (PPy) nanocomposites was developed. While the PLGA nanoparticles (NPs) allow efficient drug loading, the PPy nanobulges embedded within the surface of the PLGA NPs, formed by in situ pyrrole polymerization without the introduction of other template agents, can act as ideal mediators for photoinduced mild hyperthermia. Physiochemical characterizations of the as-prepared nanocomposites, including structure, morphology, photothermal effects, and an in vitro drug release profile, were systematically investigated. Further, 2-deoxyglucose-terminated poly(ethylene glycol) (PEG) was anchored onto the surface of the nanocomposites to endow the nanoplatform with targeting ability to tumor cells, which resulted in a 17-fold increase of NP internalization within human breast cancer cells (MCF-7) as competed with PEG-modified nanocomposites. Mild hyperthermia can be successfully mediated by the nanoplatform, and the temperature can be conveniently controlled by careful modulation of the PPy contents within the nanocomposites or the laser power density. Importantly, we have demonstrated that MCF-7 cells, which are markedly resistant to heat treatment of traditional water-bath hyperthermia, became sensitive to the PLGA/PPy nanocomposite-mediated photothermal therapy under the same mild-temperature hyperthermia. Moreover, DTX-loaded PLGA/PPy-nanocomposite-induced mild hyperthermia can strongly enhance drug cytotoxicity to MCF-7 cells. Under the same thermal dose, photoinduced hyperthermia can convert the interaction between hyperthermia and drug treatment from interference to synergism. This

  17. Differential degradation rates in vivo and in vitro of biocompatible poly(lactic acid) and poly(glycolic acid) homo- and co-polymers for a polymeric drug-delivery microchip.

    PubMed

    Grayson, Amy C R; Voskerician, Gabriela; Lynn, Aaron; Anderson, James M; Cima, Michael J; Langer, Robert

    2004-01-01

    The biocompatibility and biodegradation rate of component materials are critical when designing a drug-delivery device. The degradation products and rate of degradation may play important roles in determining the local cellular response to the implanted material. In this study, we investigated the biocompatibility and relative biodegradation rates of PLA, PGA and two poly(lactic-co-glycolic acid) (PLGA) polymers of 50:50 mol ratio, thin-film component materials of a drug-delivery microchip developed in our laboratory. The in vivo biocompatibility and both in vivo and in vitro degradation of these materials were characterized using several techniques. Total leukocyte concentration measurements showed normal acute and chronic inflammatory responses to the PGA and low-molecular-weight PLGA that resolved by 21 days, while the normal inflammatory responses to the PLA and high-molecular-weight PLGA were resolved but at slower rates up to 21 days. These results were paralleled by thickness measurements of fibrous capsules surrounding the implants, which showed greater maturation of the capsules for the more rapidly degrading materials after 21 days, but less mature capsules of sustained thicknesses for the PLA and high-molecular-weight PLGA up to 49 days. Gel-permeation chromatography of residual polymer samples confirmed classification of the materials as rapidly or slowly degrading. These materials showed thinner fibrous capsules than have been reported for other materials by our laboratory and have suitable biocompatibility and biodegradation rates for an implantable drug-delivery device.

  18. Aminocaproic Acid

    MedlinePlus

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...

  19. Ethacrynic Acid

    MedlinePlus

    Ethacrynic acid, a 'water pill,' is used to treat swelling and fluid retention caused by various medical problems. It ... Ethacrynic acid comes as a tablet to take by mouth. It is usually taken once or twice a day ...

  20. Aristolochic Acids

    MedlinePlus

    ... Sciences NIH-HHS www.niehs.nih.gov Aristolochic Acids Key Points Report on Carcinogens Status Known to be human carcinogens Aristolochia Clematitis Aristolochic Acids n Known human carcinogens n Found in certain ...

  1. Obeticholic Acid

    MedlinePlus

    Obeticholic acid is used alone or in combination with ursodiol (Actigall, Urso) to treat primary biliary cholangitis (PBC; a ... were not treated successfully with ursodiol alone. Obeticholic acid is in a class of medications called farnesoid ...

  2. Acid mucopolysaccharides

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003368.htm Acid mucopolysaccharides To use the sharing features on this page, please enable JavaScript. Acid mucopolysaccharides is a test that measures the amount ...

  3. High strength of physical hydrogels based on poly(acrylic acid)-g-poly(ethylene glycol) methyl ether: role of chain architecture on hydrogel properties.

    PubMed

    Yang, Jun; Gong, Cheng; Shi, Fu-Kuan; Xie, Xu-Ming

    2012-10-01

    This investigation was to study the connections between polymer branch architecture of physical hydrogels and their properties. The bottle-brush-like polymer chains of poly(acrylic acid)-g-poly(ethylene glycol) methyl ether (PAA-g-mPEG) with PAA as backbones and mPEG as branch architecture were synthesized and in situ grafted from silica nanoparticles (SNs) to construct hydrogels cross-linked networks in aqueous solutions. The structural variables to be discussed included molecular weight and molar ratio of branch chains, and new aspects of the formation mechanism of physical hydrogels with branch structure in the absence of organic cross-links were present. The results indicated that the differences of polymer chain architecture could be distinguished via their different interactions that are present by gelation process and mature gel properties, such as gel strength and swelling ratio. The gelation occurred at the critical polymer concentration and molecular weight, respectively, and the inorganic/organic (SNs/PAA-g-mPEG) nanoparticles began to entangle and construct the cross-linking networks afterward. The gel-to-sol transition temperature (T(g-s)) and radii of SNs that were encapsulated by polymer chains as a function of time for chains' disentanglement were monitored according to the observation of the dissolution process, and the molecular weight between two consecutive entanglements (M(e)) was calculated thereafter. This study showed that the introduction of branch chain onto the linear backbone significantly promoted the chain interactions and increased entanglement density, which contributed to the hydrogels' network integrity and rigidity, thus illustrating greater elongation at break and tensile strength than the hydrogels formulated with linear polymer chains.

  4. Poly-(lactic-co-glycolic-acid)-based particulate vaccines: particle uptake by dendritic cells is a key parameter for immune activation.

    PubMed

    Silva, A L; Rosalia, R A; Varypataki, E; Sibuea, S; Ossendorp, F; Jiskoot, W

    2015-02-11

    Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects the type and magnitude of the immune response in comparison to sustained release from a local depot. PLGA microparticles (MP, volume mean diameter≈112 μm) and nanoparticles (NP, Z-average diameter≈350 nm) co-encapsulating ovalbumin (OVA) and poly(I:C), with comparable antigen (Ag) release characteristics, were prepared and characterized. The immunogenicity of these two distinct particulate vaccines was evaluated in vitro and in vivo. NP were efficiently taken up by DC and greatly facilitated MHC I Ag presentation in vitro, whereas DC cultured in the presence of MP failed to internalize significant amounts of Ag and hardly showed MHC I Ag presentation. Vaccination of mice with NP resulted in significantly better priming of Ag-specific CD8(+) T cells compared to MP and OVA emulsified with incomplete Freund's adjuvant (IFA). Moreover, NP induced a balanced TH1/TH2-type antibody response, compared to vaccinations with IFA which stimulated a predominant TH2-type response, whereas MP failed to increase antibody titers. In conclusion, we postulate that particle internalization is of crucial importance and therefore particulate vaccines should be formulated in the nano- but not micro-size range to achieve efficient uptake, significant MHC class I cross-presentation and effective T and B cell responses.

  5. Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co-Glycolic Acid) Microparticles Drives NFκB and Autophagy Dependent Bacillary Killing.

    PubMed

    Lawlor, Ciaran; O'Connor, Gemma; O'Leary, Seonadh; Gallagher, Paul J; Cryan, Sally-Ann; Keane, Joseph; O'Sullivan, Mary P

    2016-01-01

    The emergence of multiple-drug-resistant tuberculosis (MDR-TB) has pushed our available repertoire of anti-TB therapies to the limit of effectiveness. This has increased the urgency to develop novel treatment modalities, and inhalable microparticle (MP) formulations are a promising option to target the site of infection. We have engineered poly(lactic-co-glycolic acid) (PLGA) MPs which can carry a payload of anti-TB agents, and are successfully taken up by human alveolar macrophages. Even without a drug cargo, MPs can be potent immunogens; yet little is known about how they influence macrophage function in the setting of Mycobacterium tuberculosis (Mtb) infection. To address this issue we infected THP-1 macrophages with Mtb H37Ra or H37Rv and treated with MPs. In controlled experiments we saw a reproducible reduction in bacillary viability when THP-1 macrophages were treated with drug-free MPs. NFκB activity was increased in MP-treated macrophages, although cytokine secretion was unaltered. Confocal microscopy of immortalized murine bone marrow-derived macrophages expressing GFP-tagged LC3 demonstrated induction of autophagy. Inhibition of caspases did not influence the MP-induced restriction of bacillary growth, however, blockade of NFκB or autophagy with pharmacological inhibitors reversed this MP effect on macrophage function. These data support harnessing inhaled PLGA MP-drug delivery systems as an immunotherapeutic in addition to serving as a vehicle for targeted drug delivery. Such "added value" could be exploited in the generation of inhaled vaccines as well as inhaled MDR-TB therapeutics when used as an adjunct to existing treatments. PMID:26894562

  6. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.

    PubMed

    Sun, Changling; Wang, Xueling; Zheng, Zhaozhu; Chen, Dongye; Wang, Xiaoqin; Shi, Fuxin; Yu, Dehong; Wu, Hao

    2015-01-01

    This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.

  7. The effect of AZD2171- or sTRAIL/Apo2L-loaded polylactic-co-glycolic acid microspheres on a subcutaneous glioblastoma model.

    PubMed

    Shivinsky, Anna; Bronshtein, Tomer; Haber, Tom; Machluf, Marcelle

    2015-08-01

    Studies with AZD2171-a new anti-angiogenic inhibitor of tyrosine kinases associated with VEGF signaling-have shown great promise for treating glioblastoma. Unfortunately, AZD2171 success is limited by low permeability through the blood-brain barrier. Due to AZD2171's short half-life and high toxicity, its local administration will require multiple intracranial procedures, making this approach clinically unfeasible. In this study, we investigated the potential of the highly hydrophobic AZD2171, released from modified polylactic-co-glycolic acid microspheres (PLGA-MS), to treat glioblastoma. To further demonstrate the versatile loading capacity of this system, the same PLGA formulation, which was found optimal for the loading and release of AZD2171, was tested with sTRAIL/Apo2L-a biologic drug that is very different than AZD2171 in its molecular weight, solubility, and charge. AZD2171 released from PLGA-MS was at least effective as the free drug in inhibiting endothelial growth and proliferation (in vitro), and, surprisingly, had a profound cytotoxic effect also towards in vitro cultured glioblastoma cell-lines (U87 and A172). Complete tumor inhibition was achieved following a single treatment with AZD2171-loaded PLGA-MS (6 (mg)/kg) administered locally adjacent to human U87 glioma tumors inoculated subcutaneously in nude mice. This improved effect, compared to other therapeutic approaches involving AZD2171, was shown to affect both tumor vasculature and the glioma cells. sTRAIL-loaded microspheres, administered at very low doses (0.3 (mg)/kg), led to 35 % inhibition of tumor growth in 2 weeks. Collectively, our results provide pre-clinical evidence for the potential of PLGA formulations of AZD2171 and sTRAIL to serve as an effective treatment for glioblastoma.

  8. Polyacrylic acid attenuates ethylene glycol induced hyperoxaluric damage and prevents crystal aggregation in vitro and in vivo.

    PubMed

    Sridharan, Badrinathan; Ganesh, Rajesh Nachiappa; Viswanathan, Pragasam

    2016-05-25

    The study explores calcium oxalate crystal inhibiting characteristic of polyacrylic acid (pAA), an anionic polymer in in vitro and in vivo. Animals were divided into 5 groups where group 1 served as control, group 2 were made hyperoxaluric by supplementing with Ethylene glycol (EG) 0.75% (v/v) for 30 days. Group 3, 4 & 5 were also given with EG and treated simultaneously with 2.5, 5 & 10 mg of pAA/kg of body weight, respectively. Urine, serum and tissue analyses along with histological studies were performed at the end of the 30 days study. In vitro crystallization was significantly inhibited by pAA and further it was supported by particle size analyses, XRD and FT-IR studies. Toxicological analyses showed that pAA was safe to use in animals at concentrations below 100 mg/kg BW. In vivo anti-urolithic study showed significant improvement in urinary lithogenic factors (calcium, oxalate, phosphate, citrate & magnesium) and renal function parameters (creatinine, urea and protein). Tissue analyses on anti-oxidant enzyme activity and lipid peroxides showed maintenance of tissue antioxidant status in the pAA supplemented rats and histological studies demonstrated the nephroprotection offered by pAA and were concurrent to the biochemical analyses. Supplementation of pAA not only reduces the crystal aggregation but also regulates the expression and localization of crystal inhibiting proteins and gene expression of inflammatory cytokines in experimental animals. In summary, pAA is a potent anti-urolithic agent in rats and we can propose that 10 mg/kg body weight is the effective dosage of pAA and this concentration can be used for further studies.

  9. Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co-Glycolic Acid) Microparticles Drives NFκB and Autophagy Dependent Bacillary Killing

    PubMed Central

    Lawlor, Ciaran; O’Connor, Gemma; O’Leary, Seonadh; Gallagher, Paul J.

    2016-01-01

    The emergence of multiple-drug-resistant tuberculosis (MDR-TB) has pushed our available repertoire of anti-TB therapies to the limit of effectiveness. This has increased the urgency to develop novel treatment modalities, and inhalable microparticle (MP) formulations are a promising option to target the site of infection. We have engineered poly(lactic-co-glycolic acid) (PLGA) MPs which can carry a payload of anti-TB agents, and are successfully taken up by human alveolar macrophages. Even without a drug cargo, MPs can be potent immunogens; yet little is known about how they influence macrophage function in the setting of Mycobacterium tuberculosis (Mtb) infection. To address this issue we infected THP-1 macrophages with Mtb H37Ra or H37Rv and treated with MPs. In controlled experiments we saw a reproducible reduction in bacillary viability when THP-1 macrophages were treated with drug-free MPs. NFκB activity was increased in MP-treated macrophages, although cytokine secretion was unaltered. Confocal microscopy of immortalized murine bone marrow-derived macrophages expressing GFP-tagged LC3 demonstrated induction of autophagy. Inhibition of caspases did not influence the MP-induced restriction of bacillary growth, however, blockade of NFκB or autophagy with pharmacological inhibitors reversed this MP effect on macrophage function. These data support harnessing inhaled PLGA MP-drug delivery systems as an immunotherapeutic in addition to serving as a vehicle for targeted drug delivery. Such “added value” could be exploited in the generation of inhaled vaccines as well as inhaled MDR-TB therapeutics when used as an adjunct to existing treatments. PMID:26894562

  10. In vitro release characteristics and cellular uptake of poly(D,L-lactic-co-glycolic acid) nanoparticles for topical delivery of antisense oligodeoxynucleotides.

    PubMed

    Chen, Ying-Shan; Alany, Raid G; Young, Simon A; Green, Colin R; Rupenthal, Ilva D

    2011-01-01

    The efficacy of antisense oligodeoxynucleotides (AsODNs) is compromised by their poor stability in biological fluids and the inefficient cellular uptake due to their size and negative charge. Since chemical modifications of these molecules have resulted in a number of non-antisense activities, incorporation into particulate delivery systems has offered a promising alternative. The aim of this study was to evaluate various poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles for AsODN entrapment and delivery. PLGA nanoparticles were prepared using the double emulsion solvent evaporation method. The influence of formulation parameters such as PLGA concentration and volume ratio of internal aqueous phase volume (Va1) to organic phase volume (Vo) to external aqueous phase volume (Va2) on particle size, polydispersity index (PDI) and zeta potential (ZP) was investigated using a full factorial study. The particle size increased with increasing PLGA concentrations and volume ratios, with an interaction detectable between the two factors. AsODN entrapment efficiencies ranged between 49.97% and 54.95% with no significant difference between various formulations. By fitting the in vitro release profiles to a dual first order release model it was shown that the AsODN release occurred via two processes: a diffusion controlled process in the early phase (25 to 32% within one day) and a PLGA degradation process in the latter (39 to 70% after 14 days). Cellular uptake studies using primary corneal epithelial cells suggested active transport of nanoparticles via endocytosis. PLGA nanoparticles therefore show potential to successfully entrap AsODNs, transport them into cells and release them over time due to polymer erosion.

  11. Improved hemocompatibility and endothelialization of vascular grafts by covalent immobilization of sulfated silk fibroin on poly(lactic-co-glycolic acid) scaffolds.

    PubMed

    Liu, Haifeng; Li, Xiaoming; Niu, Xufeng; Zhou, Gang; Li, Ping; Fan, Yubo

    2011-08-01

    Endothelialization of vascular grafts prior to implantation has been investigated widely to enhance biocompatibility and antithrombogenicity. Thrombosis of artificial vessels is typically caused by platelet adhesion and agglomeration following endothelial cells detachment when exposed to the shear stress of blood circulation. The present study thus aimed at preventing platelet adhesion and aggregation onto biomaterials before the endothelial confluence is fully achieved. We report this modification of poly(lactic-co-glycolic acid) (PLGA) scaffolds, both to impart hemocompatibility to prevent platelet adhesion and aggregation before the endothelial confluence is fully achieved and to support EC growth to accelerate endothelialization. The modification was achieved by covalent immobilization of sulfated silk fibroin on PLGA scaffolds using γ irradiation. Using phosphate-buffered saline (PBS) as an aging medium, it was demonstrated that the scaffolds prepared by γ irradiation had a good retention of sulfated silk fibroin. The systematic in vitro hemocompatibility evaluation revealed that sulfated silk fibroin covalently immobilized PLGA (S-PLGA) scaffolds-reduced platelet adhesion and activation, prolonged whole blood clotting time, activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). To evaluate further in vitro cytocompatibility of the scaffolds, we seeded vascular ECs on the scaffolds and cultured them for 2 weeks. The ECs were seen to attach and proliferate well on S-PLGA scaffolds, forming cell aggregates that gradually increased in size and fused with adjacent cell aggregates to form a monolayer covering the scaffold surface. Moreover, it was demonstrated through the gene transcript levels and the protein expressions of EC-specific markers that the cell functions of ECs on S-PLGA scaffolds were better preserved than those on PLGA scaffolds. Therefore, this study has described the generation of a vascular graft that

  12. Activated Schwann Cell-Like Cells on Aligned Fibrin-Poly(Lactic-Co-Glycolic Acid) Structures: A Novel Construct for Application in Peripheral Nerve Regeneration.

    PubMed

    Schuh, Christina M A P; Morton, Tatjana J; Banerjee, Asmita; Grasl, Christian; Schima, Heinrich; Schmidhammer, Robert; Redl, Heinz; Ruenzler, Dominik

    2015-01-01

    Tissue engineering approaches in nerve regeneration search for ways to support gold standard therapy (autologous nerve grafts) and to improve results by bridging nerve defects with different kinds of conduits. In this study, we describe electrospinning of aligned fibrin-poly(lactic-co-glycolic acid) (PLGA) fibers in an attempt to create a biomimicking tissue-like material seeded with Schwann cell-like cells (SCLs) in vitro for potential use as an in vivo scaffold. Rat adipose-derived stem cells (rASCs) were differentiated into SCLs and evaluated with flow cytometry concerning their differentiation and activation status [S100b, P75, myelin-associated glycoprotein (MAG), and protein 0 (P0)]. After receiving the proliferation stimulus forskolin, SCLs expressed S100b and P75; comparable to native, activated Schwann cells, while cultured without forskolin, cells switched to a promyelinating phenotype and expressed S100b, MAG, and P0. Human fibrinogen and thrombin, blended with PLGA, were electrospun and the alignment and homogeneity of the fibers were proven by scanning electron microscopy. Electrospun scaffolds were seeded with SCLs and the formation of Büngner-like structures in SCLs was evaluated with phalloidin/propidium iodide staining. Carrier fibrin gels containing rASCs acted as a self-shaping matrix to form a tubular structure. In this study, we could show that rASCs can be differentiated into activated, proliferating SCLs and that these cells react to minimal changes in stimulus, switching to a promyelinating phenotype. Aligned electrospun fibrin-PLGA fibers promoted the formation of Büngner-like structures in SCLs, which also rolled the fibrin-PLGA matrix into a tubular scaffold. These in vitro findings favor further in vivo testing. PMID:26372904

  13. The surface grafting of graphene oxide with poly(ethylene glycol) as a reinforcement for poly(lactic acid) nanocomposite scaffolds for potential tissue engineering applications.

    PubMed

    Zhang, Chunmei; Wang, Liwei; Zhai, Tianliang; Wang, Xinchao; Dan, Yi; Turng, Lih-Sheng

    2016-01-01

    Graphene oxide (GO) was incorporated into poly(lactic acid) (PLA) as a reinforcing nanofiller to produce composite nanofibrous scaffolds using the electrospinning technique. To improve the dispersion of GO in PLA and the interfacial adhesion between the filler and matrix, GO was surface-grafted with poly(ethylene glycol) (PEG). Morphological, thermal, mechanical, and wettability properties, as well as preliminary cytocompatibility with Swiss mouse NIH 3T3 cells of PLA, PLA/GO, and PLA/GO-g-PEG electrospun nanofibers, were characterized. Results showed that the average diameter of PLA/GO-g-PEG electrospun nanofibers decreased with filler content. Both GO and GO-g-PEG improved the thermal stability of PLA, but GO-g-PEG was more effective. The water contact angle test of the nanofiber mats showed that the addition of GO in PLA did not change the surface wettability of the materials, but PLA/GO-g-PEG samples exhibited improved wettability with lower water contact angles. The tensile strength of the composite nanofiber mats was improved with the addition of GO, and it was further enhanced when GO was surface grafted with PEG. This suggested that improved interfacial adhesion between GO and PLA was achieved by grafting PEG onto the GO. The cell viability and proliferation results showed that the cytocompatibility of PLA was not compromised with the addition of GO and GO-g-PEG. With enhanced mechanical properties as well as good wettability and cytocompatibility, PLA/GO-g-PEG composite nanofibers have the potential to be used as scaffolds in tissue engineering. PMID:26409231

  14. Cisplatin Loaded Poly(L-glutamic acid)-g-Methoxy Poly(ethylene glycol) Complex Nanoparticles for Potential Cancer Therapy: Preparation, In Vitro and In Vivo Evaluation.

    PubMed

    Yu, Haiyang; Tang, Zhaohui; Li, Mingqiang; Song, Wantong; Zhang, Dawei; Zhang, Ying; Yang, Yan; Sun, Hai; Deng, Mingxiao; Chen, Xuesi

    2016-01-01

    A series of novel polypeptide-based graft copolymer poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) was synthesized through a Steglich esterification reaction of PLG with mPEG. The structure of the copolymers was confirmed by nuclear magnetic resonance spectra (NMR) and gel permeation chromatography (GPC). MTT assay demonstrated that the PLG-g-mPEGs had good cell compatibility. The unreacted carboxyl groups of the PLG-g-mPEGs were used to complex cisplatin to form polymer-metal complex nanoparticles (CDDP/PLG-g-mPEG) for cancer therapy. The average hydrodynamic radius of the CDDP/PLG-g-mPEG nanoparticles was inr the range of 14-25 nm, which was beneficial for solid tumor targeting delivery. A sustained release without initial burst was achieved for the CDDP/PLG-g-mPEG nanoparticles, indicating that the CDDP-loaded nanoparticles had great potential to suppress the drug release in blood circulation before the nanoparticles had arrived at targeting tumors. The CDDP/PLG-g-mPEG nanoparticles showed a much longer blood retention profile as compared with the free CDDP. This indicated that the CDDP-loaded nanoparticles had much more opportunity to accumulate in tumor tissue by exerting the EPR effect. In vitro tests demonstrated that the CDDP/PLG-g-mPEG nanoparticles could inhibit the proliferation of HeLa, MCF-7 and A549 cancer cells. At equal dose (4 mg kg(-1)), the CDDP/PLG-g-mPEG nanoparticles showed comparable in vivo antitumor efficacy and significantly lower systemic toxicity as compared with free cis-Diaminedichloroplatinum (cisplatin, CDDP) in MCF-7 tumor bearing mice. These suggested that the CDDP/PLG-g-mPEG nanoparticle drug delivery system had a great potential to be used for cancer therapy.

  15. Mechanisms of chitosan-coated poly(lactic-co-glycolic acid) nanoparticles for improving oral absorption of 7-ethyl-10-hydroxycamptothecin

    NASA Astrophysics Data System (ADS)

    Guo, Miao; Rong, Wen-Ting; Hou, Jie; Wang, Dong-Fang; Lu, Yu; Wang, Ying; Yu, Shu-Qin; Xu, Qian

    2013-06-01

    Chitosan-modified poly(lactic-co-glycolic acid) nanoparticles (CHI/PLGA NPs) loaded with 7-ethyl-10-hydroxycamptothecin (SN-38), named CHI/PLGA/SN-38 NPs, were successfully prepared using an oil-in-water (O/W) solvent evaporation method. The physicochemical properties of the novel NPs were characterized by DLS, Zeta potential, SEM, DSC, XRD, and FTIR. The encapsulation efficiency and drug loading content were 71.83 (±2.77)% and 6.79 (±0.26)%, respectively. In vitro drug release in the simulated gastric juice was lower than that in the intestinal juice. In situ single-pass intestinal perfusion (SPIP) studies indicated a dramatic improvement of drug absorption as a result of the synergistic effect between CHI and PLGA on P-glycoprotein (Pgp) inhibition. CHI/PLGA NPs showed high cellular uptake and low efflux for drugs in Caco-2 cells. The cytotoxicity studies revealed that CHI/PLGA NPs had a transient effect on the membrane integrity, but did not have an influence on cell viability. Based on the in vitro release studies, SPIP, and intracellular drug accumulation and transport investigations, we speculate rationally that CHI/PLGA NPs were mainly internalized in the form of intact NPs, thus escaping the recognition of enterocyte Pgp and avoiding efflux into the apical part of the enterocytes. After partial release of drugs inside the enterocytes, CHI/PLGA interfered with the microenvironment of Pgp and further weakened the Pgp-mediated efflux. Then, the drug-loaded NPs exited via the exocytose effect from the basal part of the enterocytes and entered the blood circulation. These results showed that CHI/PLGA NPs would be smart oral delivery carriers for antineoplastic agents that are also Pgp substrates.

  16. Superparamagnetic iron oxide--loaded poly(lactic acid)-D-alpha-tocopherol polyethylene glycol 1000 succinate copolymer nanoparticles as MRI contrast agent.

    PubMed

    Prashant, Chandrasekharan; Dipak, Maity; Yang, Chang-Tong; Chuang, Kai-Hsiang; Jun, Ding; Feng, Si-Shen

    2010-07-01

    We developed a strategy to formulate supraparamagnetic iron oxides (SPIOs) in nanoparticles (NPs) of biodegradable copolymer made up of poly(lactic acid) (PLA) and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) for medical imaging by magnetic resonance imaging (MRI) of high contrast and low side effects. The IOs-loaded PLA-TPGS NPs (IOs-PNPs) were prepared by the single emulsion method and the nanoprecipitation method. Effects of the process parameters such as the emulsifier concentration, IOs loading in the nanoparticles, and the solvent to non-solvent ratio on the IOs distribution within the polymeric matrix were investigated and the formulation was then optimized. The transmission electron microscopy (TEM) showed direct visual evidence for the well dispersed distribution of the IOs within the NPs. We further investigated the biocompatibility and cellular uptake of the IOs-PNPs in vitro with MCF-7 breast cancer cells and NIH-3T3 mouse fibroblast in close comparison with the commercial IOs imaging agent Resovist. MRI imaging was further carried out to investigate the biodistribution of the IOs formulated in the IOs-PNPs, especially in the liver to understand the liver clearance process, which was also made in close comparison with Resovist. We found that the PLA-TPGS NPs formulation at the clinically approved dose of 0.8 mg Fe/kg could be cleared within 24 h in comparison with several weeks for Resovist. Xenograft tumor model MRI confirmed the advantages of the IOs-PNPs formulation versus Resovist through the enhanced permeation and retention (EPR) effect of the tumor vasculature. PMID:20434210

  17. Cisplatin Loaded Poly(L-glutamic acid)-g-Methoxy Poly(ethylene glycol) Complex Nanoparticles for Potential Cancer Therapy: Preparation, In Vitro and In Vivo Evaluation.

    PubMed

    Yu, Haiyang; Tang, Zhaohui; Li, Mingqiang; Song, Wantong; Zhang, Dawei; Zhang, Ying; Yang, Yan; Sun, Hai; Deng, Mingxiao; Chen, Xuesi

    2016-01-01

    A series of novel polypeptide-based graft copolymer poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) was synthesized through a Steglich esterification reaction of PLG with mPEG. The structure of the copolymers was confirmed by nuclear magnetic resonance spectra (NMR) and gel permeation chromatography (GPC). MTT assay demonstrated that the PLG-g-mPEGs had good cell compatibility. The unreacted carboxyl groups of the PLG-g-mPEGs were used to complex cisplatin to form polymer-metal complex nanoparticles (CDDP/PLG-g-mPEG) for cancer therapy. The average hydrodynamic radius of the CDDP/PLG-g-mPEG nanoparticles was inr the range of 14-25 nm, which was beneficial for solid tumor targeting delivery. A sustained release without initial burst was achieved for the CDDP/PLG-g-mPEG nanoparticles, indicating that the CDDP-loaded nanoparticles had great potential to suppress the drug release in blood circulation before the nanoparticles had arrived at targeting tumors. The CDDP/PLG-g-mPEG nanoparticles showed a much longer blood retention profile as compared with the free CDDP. This indicated that the CDDP-loaded nanoparticles had much more opportunity to accumulate in tumor tissue by exerting the EPR effect. In vitro tests demonstrated that the CDDP/PLG-g-mPEG nanoparticles could inhibit the proliferation of HeLa, MCF-7 and A549 cancer cells. At equal dose (4 mg kg(-1)), the CDDP/PLG-g-mPEG nanoparticles showed comparable in vivo antitumor efficacy and significantly lower systemic toxicity as compared with free cis-Diaminedichloroplatinum (cisplatin, CDDP) in MCF-7 tumor bearing mice. These suggested that the CDDP/PLG-g-mPEG nanoparticle drug delivery system had a great potential to be used for cancer therapy. PMID:27301173

  18. Synthesis and self-assembly of biodegradable polyethylene glycol-poly (lactic acid) diblock copolymers as polymersomes for preparation of sustained release system of doxorubicin

    PubMed Central

    Alibolandi, Mona; Sadeghi, Fatemeh; Sazmand, Seyed Hossein; Shahrokhi, Seyed Mohammad; Seifi, Mahmoud; Hadizadeh, Farzin

    2015-01-01

    Introduction: The copolymer of polyethylene glycol (PEG) and polyesters has many interesting properties, such as amphiphilicity, biocompatibility, biodegradability, and self-assembly in an aqueous environment. Diblock copolymers of PEG-polyester can form different structures such as micelles, polymersome, capsules or micro-container in an aqueous environment according to the length of their blocks. Materials and Methods: Herein, a series of poly (lactic acid) (PLA) and PEG diblock copolymers were synthesized through the ring-opening polymerization. The polymerization reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The corresponding copolymers were implemented for the formation of polymersome structures using film rehydration method. Impact of methoxy PEG chain length and hydrophobic weight fraction on particle size of polymersomes were studied, and the proper ones were selected for loading of doxorubicin (DOX) via pH gradient method. Results and Discussion: Results obtained from 1HNMR and GPC revealed that microwave irradiation is a simple and reliable method for the synthesis of PEG-PLA copolymers. Further analysis indicated the copolymer with relative molecular weight of PLA to PEG ratios of 3 or fEo ~ 25% produced the smallest size polymersomes. Polymersomes prepared from PEG5000 to PLA15000 were more capable in loading and sustained release of DOX than those prepared from PEG2000 to PLA6000. Conclusion: In conclusion copolymers of PEG/PLA with fOE ~25% and relatively higher molecular weight are more suitable for encapsulation and providing sustained release of DOX. PMID:26258054

  19. Prospective, randomized comparison of same-day dose of 2 different bowel cleanser for afternoon colonoscopy: picosulfate, magnesium oxide, and citric acid versus polyethylene glycol.

    PubMed

    Gweon, Tae-Geun; Kim, Sang Woo; Noh, Yong-Sun; Hwang, Seawon; Kim, Na-Young; Lee, Yoonbum; Lee, Soon-Wook; Lee, Sung Won; Lee, Jong Yul; Lim, Chul-Hyun; Hun Kim, Hyung; Kim, Jin Su; Kyung Cho, Yu; Myung Park, Jae; Seok Lee, In; Myung-Gyu Choi

    2015-04-01

    For afternoon colonoscopy, same-day administration of sodium picosulfate, magnesium oxide, and citric acid (PM/Ca) is recommended. However, few studies have evaluated the bowel-cleansing efficacy and safety of this regimen. The aim of this study was to compare the bowel-cleansing efficacy, side effects, and patient's tolerability of a same-day split administration of PM/Ca with polyethylene glycol (PEG) for afternoon colonoscopy. Patients were randomly assigned to a PM/Ca group or a PEG group. The PM/Ca group consumed 1 sachet of PM/Ca at 06:00 and 1 sachet of PM/Ca 4 hours before the colonoscopy. They also took 2 tablets of bisacodyl before sleep on the night before. The PEG group consumed 2 L of PEG at 06:00 and 2 L of PEG 4 hours before the colonoscopy. All subjects were instructed to finish the bowel cleanser or fluid at least 2 hours before colonoscopy. All colonoscopic examinations were performed in the afternoon on the same day. The bowel-cleansing efficacy was scored using 2 scales: the Ottawa Bowel Preparation Scale (OBPS) and the Aronchick scale. Ease of using the bowel cleanser was rated from 1 (very easy) to 5 (very difficult). Two hundred nine patients underwent colonoscopy. The bowel-cleansing scores by OBPS did not differ between groups (5.0 vs 4.9, P = 0.63). Ease of using the bowel cleanser was superior in the PM/Ca group (P < 0.01). The cleansing efficacy of PM/Ca administered on the day of colonoscopy is comparable to that of PEG. Patients prefer PM/Ca.

  20. Screening of Hyaluronic Acid-Poly(ethylene glycol) Composite Hydrogels to Support Intervertebral Disc Cell Biosynthesis using Artificial Neural Network Analysis

    PubMed Central

    Jeong, Claire G.; Francisco, Aubrey T.; Niu, Zhenbin; Mancino, Robert L; Craig, Stephen L.; Setton, Lori A.

    2014-01-01

    Hyaluronic acid (HA) poly(ethylene glycol) (PEG) composite hydrogels have been widely studied for both cell delivery and soft tissue regeneration applications. A very broad range of physical and biological properties have been engineered into HA-PEG hydrogels that may differentially affect cellular “outcomes” of survival, synthesis and metabolism. The objective of this study was to rapidly screen multiple HA-PEG composite hydrogel formulations for an effect on matrix synthesis and behaviors of nucleus pulposus (NP) and anulus fibrosus (AF) cells of the intervertebral disc (IVD). A secondary objective was to apply artificial neural network (ANN) analysis to identify relationships between HA-PEG composite hydrogel formulation parameters and biological outcome measures for each cell type of the IVD. Eight different hydrogels were developed from preparations of thiolated HA (HA-SH) and PEG vinylsulfone (PEG-VS) macromers, and used as substrates for NP and AF cell culture in vitro. Hydrogel mechanical properties ranged from 70-489 kPa depending on HA molecular weight, and measures of matrix synthesis, metabolite consumption and production, and cell morphology were obtained to study relationships to hydrogel parameters. Results showed that NP and AF cell numbers were highest upon the HA-PEG hydrogels formed from the lower molecular weight HA, with evidence of higher sGAG production also upon lower HA molecular weight composite gels. All cells formed more multi-cell clusters upon any HA-PEG composite hydrogel as compared to gelatin substrates. Formulations were clustered into neurons based largely on their HA molecular weight, with few effects of PEG molecular weight observed on any measured parameters. PMID:24859415

  1. Release and pharmacokinetics of near-infrared labeled albumin from monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) microspheres after subcapsular renal injection.

    PubMed

    Kazazi-Hyseni, F; van Vuuren, S H; van der Giezen, D M; Pieters, E H; Ramazani, F; Rodriguez, S; Veldhuis, G J; Goldschmeding, R; van Nostrum, C F; Hennink, W E; Kok, R J

    2015-08-01

    Subcapsular renal injection is a novel administration method for local delivery of therapeutics for the treatment of kidney related diseases. The aim of this study was to investigate the feasibility of polymeric microspheres for sustained release of protein therapeutics in the kidney and study the subsequent redistribution of the released protein. For this purpose, monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres (40 μm in diameter) loaded with near-infrared dye-labeled bovine serum albumin (NIR-BSA) were prepared by a membrane emulsification method. Rats were injected with either free NIR-BSA or with NIR-BSA loaded microspheres (NIR-BSA-ms) and the pharmacokinetics of the released NIR-BSA was studied for 3 weeks by ex vivo imaging of organs and blood. Quantitative release data were obtained from kidney homogenates and possible metabolism of the protein was investigated by SDS-PAGE analysis of the samples. The ex vivo images showed a rapid decrease of the NIR signal within 24h in kidneys injected with free NIR-BSA, while, importantly, the signal of the labeled protein was still visible at day 21 in kidneys injected with NIR-BSA-ms. SDS-PAGE analysis of the kidney homogenates showed that intact NIR-BSA was released from the microspheres. The locally released NIR-BSA drained to the systemic circulation and subsequently accumulated in the liver, where it was degraded and excreted renally. The in vivo release of NIR-BSA was calculated after extracting the protein from the remaining microspheres in kidney homogenates. The in vivo release rate was faster (89 ± 4% of the loading in 2 weeks) compared to the in vitro release of NIR-BSA (38 ± 1% in 2 weeks). In conclusion, PLHMGA microspheres injected under the kidney capsule provide a local depot from which a formulated protein is released over a prolonged time-period.

  2. Effect of solvent on drug release and a spray-coated matrix of a sirolimus-eluting stent coated with poly(lactic-co-glycolic acid).

    PubMed

    Choi, Jiyeon; Jang, Bu Nam; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

    2014-08-26

    Sirolimus (SRL) release from the biodegradable poly(l-lactic-co-glycolic acid) (PLGA) matrix was investigated for the application of drug-eluting stents (DES). In particular, this study focused on whether various organic solvents affect the interaction between SRL and PLGA and the formation of microstructures during ultrasonic coating. The SRL-loaded PLGA coated by tetrahydrofuran or acetone showed a significant initial burst, whereas that from acetonitrile was constantly released during a period of 21 days. On the basis of these results, the interactions at the molecular level of SRL with the polymer matrix were estimated according to various organic solvents. Although the topographies of the coated surface were obviously different, the correlation between surface roughness and SRL release was very poor. Irrespective of organic solvents, FT-IR data showed significantly weak SRL-PLGA interactions. From the result of wide-angle X-ray diffraction, it was confirmed that SRL was dispersed in an amorphous state in the polymer matrix after ultrasonic coating. The glass-transition temperature was also influenced by organic solvents, resulting in a plasticizing effect. The particle size of SRL appeared to determine the release profile from the PLGA matrix, which was the combination of diffusion and polymer degradation at an SRL size of more than 800 nm and the Fickian release at that of less than 300 nm. Therefore, organic solvents can lead to a heterogeneous microstructure in the SRL-loaded PLGA matrix, which is at or near the surface, consisting of aggregated drug- and polymer-rich regions. It is expected that the drug release can be controlled by physicochemical properties of organic solvents, and this study can be used effectively for localized drug release in biomedical devices such as drug-eluting stents. PMID:25090045

  3. Bioabsorbable bone fixation plates for X-ray imaging diagnosis by a radiopaque layer of barium sulfate and poly(lactic-co-glycolic acid).

    PubMed

    Choi, Sung Yoon; Hur, Woojune; Kim, Byeung Kyu; Shasteen, Catherine; Kim, Myung Hun; Choi, La Mee; Lee, Seung Ho; Park, Chun Gwon; Park, Min; Min, Hye Sook; Kim, Sukwha; Choi, Tae Hyun; Choy, Young Bin

    2015-04-01

    Bone fixation systems made of biodegradable polymers are radiolucent, making post-operative diagnosis with X-ray imaging a challenge. In this study, to allow X-ray visibility, we separately prepared a radiopaque layer and attached it to a bioabsorbable bone plate approved for clinical use (Inion, Finland). We employed barium sulfate as a radiopaque material due to the high X-ray attenuation coefficient of barium (2.196 cm(2) /g). The radiopaque layer was composed of a fine powder of barium sulfate bound to a biodegradable material, poly(lactic-co-glycolic acid) (PLGA), to allow layer degradation similar to the original Inion bone plate. In this study, we varied the mass ratio of barium sulfate and PLGA in the layer between 3:1 w/w and 10:1 w/w to modulate the degree and longevity of X-ray visibility. All radiopaque plates herein were visible via X-ray, both in vitro and in vivo, for up to 40 days. For all layer types, the radio-opacity decreased with time due to the swelling and degradation of PLGA, and the change in the layer shape was more apparent for layers with a higher PLGA content. The radiopaque plates released, at most, 0.5 mg of barium sulfate every 2 days in a simulated in vitro environment, which did not appear to affect the cytotoxicity. The radiopaque plates also exhibited good biocompatibility, similar to that of the Inion plate. Therefore, we concluded that the barium sulfate-based, biodegradable plate prepared in this work has the potential to be used as a fixation device with both X-ray visibility and biocompatibility. PMID:24964903

  4. The surface grafting of graphene oxide with poly(ethylene glycol) as a reinforcement for poly(lactic acid) nanocomposite scaffolds for potential tissue engineering applications.

    PubMed

    Zhang, Chunmei; Wang, Liwei; Zhai, Tianliang; Wang, Xinchao; Dan, Yi; Turng, Lih-Sheng

    2016-01-01

    Graphene oxide (GO) was incorporated into poly(lactic acid) (PLA) as a reinforcing nanofiller to produce composite nanofibrous scaffolds using the electrospinning technique. To improve the dispersion of GO in PLA and the interfacial adhesion between the filler and matrix, GO was surface-grafted with poly(ethylene glycol) (PEG). Morphological, thermal, mechanical, and wettability properties, as well as preliminary cytocompatibility with Swiss mouse NIH 3T3 cells of PLA, PLA/GO, and PLA/GO-g-PEG electrospun nanofibers, were characterized. Results showed that the average diameter of PLA/GO-g-PEG electrospun nanofibers decreased with filler content. Both GO and GO-g-PEG improved the thermal stability of PLA, but GO-g-PEG was more effective. The water contact angle test of the nanofiber mats showed that the addition of GO in PLA did not change the surface wettability of the materials, but PLA/GO-g-PEG samples exhibited improved wettability with lower water contact angles. The tensile strength of the composite nanofiber mats was improved with the addition of GO, and it was further enhanced when GO was surface grafted with PEG. This suggested that improved interfacial adhesion between GO and PLA was achieved by grafting PEG onto the GO. The cell viability and proliferation results showed that the cytocompatibility of PLA was not compromised with the addition of GO and GO-g-PEG. With enhanced mechanical properties as well as good wettability and cytocompatibility, PLA/GO-g-PEG composite nanofibers have the potential to be used as scaffolds in tissue engineering.

  5. Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co-Glycolic Acid) Microparticles Drives NFκB and Autophagy Dependent Bacillary Killing.

    PubMed

    Lawlor, Ciaran; O'Connor, Gemma; O'Leary, Seonadh; Gallagher, Paul J; Cryan, Sally-Ann; Keane, Joseph; O'Sullivan, Mary P

    2016-01-01

    The emergence of multiple-drug-resistant tuberculosis (MDR-TB) has pushed our available repertoire of anti-TB therapies to the limit of effectiveness. This has increased the urgency to develop novel treatment modalities, and inhalable microparticle (MP) formulations are a promising option to target the site of infection. We have engineered poly(lactic-co-glycolic acid) (PLGA) MPs which can carry a payload of anti-TB agents, and are successfully taken up by human alveolar macrophages. Even without a drug cargo, MPs can be potent immunogens; yet little is known about how they influence macrophage function in the setting of Mycobacterium tuberculosis (Mtb) infection. To address this issue we infected THP-1 macrophages with Mtb H37Ra or H37Rv and treated with MPs. In controlled experiments we saw a reproducible reduction in bacillary viability when THP-1 macrophages were treated with drug-free MPs. NFκB activity was increased in MP-treated macrophages, although cytokine secretion was unaltered. Confocal microscopy of immortalized murine bone marrow-derived macrophages expressing GFP-tagged LC3 demonstrated induction of autophagy. Inhibition of caspases did not influence the MP-induced restriction of bacillary growth, however, blockade of NFκB or autophagy with pharmacological inhibitors reversed this MP effect on macrophage function. These data support harnessing inhaled PLGA MP-drug delivery systems as an immunotherapeutic in addition to serving as a vehicle for targeted drug delivery. Such "added value" could be exploited in the generation of inhaled vaccines as well as inhaled MDR-TB therapeutics when used as an adjunct to existing treatments.

  6. Nanoscale surface characterization and miscibility study of a spray-dried injectable polymeric matrix consisting of poly(lactic-co-glycolic acid) and polyvinylpyrrolidone.

    PubMed

    Meeus, Joke; Chen, Xinyong; Scurr, David J; Ciarnelli, Valeria; Amssoms, Katie; Roberts, Clive J; Davies, Martyn C; van Den Mooter, Guy

    2012-09-01

    Injectable controlled-release formulations are of increasing interest for the treatment of chronic diseases. This study aims to develop and characterize a polymeric matrix for intramuscular or subcutaneous injection, consisting of two biocompatible polymers, particularly suitable for formulating poorly soluble drugs. For this matrix, the water-insoluble polymer poly(lactic-co-glycolic acid) (PLGA) is combined with the water-soluble polymer polyvinylpyrrolidone (PVP). Microparticles of these two polymers were prepared by spray drying. The phase behavior of the samples was studied by means of modulated differential scanning calorimetry and the results showed that phase separation occurred in the bulk sample through evidence of two mixed amorphous phases, namely, a PLGA-rich phase and a PVP-rich phase. Characterization of the samples by scanning electron microscopy demonstrated that the spray-dried particles were hollow with a thin shell. Because of the importance in relation to stability and drug release, information about the surface of the microparticles was collected by different complementary surface analysis techniques. Atomic force microscopy gathered information about the morphology and phase behavior of the microparticle surface. Time-of-flight secondary ion mass spectrometry analysis of the particles revealed that the surface consisted mainly of the PLGA-rich phase. This was confirmed by X-ray photoelectron spectroscopy at an increased sampling depth (≈ 10 nm). Nanothermal analysis proved to be an innovative way to thermally detect the presence of the PLGA-dominated surface layer and the underlying PVP phase. Taken together, this information provides a rational basis for predicting the likely drug release behavior this formulation will display.

  7. Nanostructure formation and transition from surface to bulk degradation in polyethylene glycol gels chain-extended with short hydroxy acid segments.

    PubMed

    Moeinzadeh, Seyedsina; Barati, Danial; Sarvestani, Samaneh K; Karaman, Ozan; Jabbari, Esmaiel

    2013-08-12

    Degradable, in situ gelling, inert hydrogels with tunable properties are very attractive as a matrix for cell encapsulation and delivery to the site of regeneration. Cell delivery is generally limited by the toxicity of gelation and degradation reactions. The objective of this work was to investigate by simulation and experimental measurement gelation kinetics and degradation rate of star acrylated polyethylene glycol (PEG) macromonomers chain-extended with short hydroxy acid (HA) segments (SPEXA) as a function of HA monomer type and number of HA repeat units. HA monomers included least hydrophobic glycolide (G), lactide (L), p-dioxanone (D), and most hydrophobic ε-caprolactone (C). Chain extension of PEG with short HA segments resulted in micelle formation for all HA types. There was a significant decrease in gelation time of SPEXA precursor solutions with HA chain-extension for all HA types due to micelle formation, consistent with the simulated increase in acrylate-acrylate (Ac-Ac) and Ac-initiator integration numbers. The hydrolysis rate of SPEXA hydrogels was strongly dependent on HA type and number of HA repeat units. SPEXA gels chain-extended with the least hydrophobic glycolide completely degraded within days, lactide within weeks, and p-dioxanone and ε-caprolactone degraded within months. The wide range of degradation rates observed for SPEXA gels can be explained by large differences in equilibrium water content of the micelles for different HA monomer types. A biphasic relationship between HA segment length and gel degradation rate was observed for all HA monomers, which was related to the transition from surface (controlled by HA segment length) to bulk (controlled by micelle equilibrium water content) hydrolysis within the micelle phase. To our knowledge, this is the first report on transition from surface to bulk degradation at the nanoscale in hydrogels. PMID:23859006

  8. Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.

    PubMed

    Liu, James; Boonkaew, Benjawan; Arora, Jaspreet; Mandava, Sree Harsha; Maddox, Michael M; Chava, Srinivas; Callaghan, Cameron; He, Jibao; Dash, Srikanta; John, Vijay T; Lee, Benjamin R

    2015-03-01

    The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.

  9. Bioabsorbable bone fixation plates for X-ray imaging diagnosis by a radiopaque layer of barium sulfate and poly(lactic-co-glycolic acid).

    PubMed

    Choi, Sung Yoon; Hur, Woojune; Kim, Byeung Kyu; Shasteen, Catherine; Kim, Myung Hun; Choi, La Mee; Lee, Seung Ho; Park, Chun Gwon; Park, Min; Min, Hye Sook; Kim, Sukwha; Choi, Tae Hyun; Choy, Young Bin

    2015-04-01

    Bone fixation systems made of biodegradable polymers are radiolucent, making post-operative diagnosis with X-ray imaging a challenge. In this study, to allow X-ray visibility, we separately prepared a radiopaque layer and attached it to a bioabsorbable bone plate approved for clinical use (Inion, Finland). We employed barium sulfate as a radiopaque material due to the high X-ray attenuation coefficient of barium (2.196 cm(2) /g). The radiopaque layer was composed of a fine powder of barium sulfate bound to a biodegradable material, poly(lactic-co-glycolic acid) (PLGA), to allow layer degradation similar to the original Inion bone plate. In this study, we varied the mass ratio of barium sulfate and PLGA in the layer between 3:1 w/w and 10:1 w/w to modulate the degree and longevity of X-ray visibility. All radiopaque plates herein were visible via X-ray, both in vitro and in vivo, for up to 40 days. For all layer types, the radio-opacity decreased with time due to the swelling and degradation of PLGA, and the change in the layer shape was more apparent for layers with a higher PLGA content. The radiopaque plates released, at most, 0.5 mg of barium sulfate every 2 days in a simulated in vitro environment, which did not appear to affect the cytotoxicity. The radiopaque plates also exhibited good biocompatibility, similar to that of the Inion plate. Therefore, we concluded that the barium sulfate-based, biodegradable plate prepared in this work has the potential to be used as a fixation device with both X-ray visibility and biocompatibility.

  10. Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery

    NASA Technical Reports Server (NTRS)

    Ishaug-Riley, S. L.; Crane, G. M.; Gurlek, A.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.

  11. Comparison of cellular effects of starch-coated SPIONs and poly(lactic-co-glycolic acid) matrix nanoparticles on human monocytes

    PubMed Central

    Gonnissen, Dominik; Qu, Ying; Langer, Klaus; Öztürk, Cengiz; Zhao, Yuliang; Chen, Chunying; Seebohm, Guiscard; Düfer, Martina; Fuchs, Harald; Galla, Hans-Joachim; Riehemann, Kristina

    2016-01-01

    Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further

  12. IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL-1β-mediated degradation of nucleus pulposus in vitro

    PubMed Central

    2012-01-01

    Introduction Inflammation plays a key role in the progression of intervertebral disc degeneration, a condition strongly implicated as a cause of lower back pain. The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1 receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL-1β) mediated degradative changes in the nucleus pulposus (NP), using an in vitro model. Methods IL-1ra was encapsulated in PLGA microspheres and release kinetics were determined over 35 days. NP agarose constructs were cultured to functional maturity and treated with combinations of IL-1β and media conditioned with IL-1ra released from microspheres at intervals for up to 20 days. Construct mechanical properties, glycosaminoglycan content, nitrite production and mRNA expression of catabolic mediators were compared to properties for untreated constructs using unpaired Student's t-tests. Results IL-1ra release kinetics were characterized by an initial burst release reducing to a linear release over the first 10 days. IL-1ra released from microspheres attenuated the degradative effects of IL-1β as defined by mechanical properties, glycosaminoglycans (GAG) content, nitric oxide production and mRNA expression of inflammatory mediators for 7 days, and continued to limit functional degradation for up to 20 days. Conclusions In this study, we successfully demonstrated that IL-1ra microspheres can attenuate the degradative effects of IL-1β on the NP for extended periods. This therapeutic strategy may be appropriate for treating early-stage, cytokine-mediated disc degeneration. Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model of disc degeneration, as a prelude to clinical translation. PMID:22863285

  13. Transient aggregation of chitosan-modified poly(d,l-lactic-co-glycolic) acid nanoparticles in the blood stream and improved lung targeting efficiency.

    PubMed

    Lee, Song Yi; Jung, Eunjae; Park, Ju-Hwan; Park, Jin Woo; Shim, Chang-Koo; Kim, Dae-Duk; Yoon, In-Soo; Cho, Hyun-Jong

    2016-10-15

    Chitosan (CS)-modified poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were prepared and their lung targetability after intravenous administration was elucidated. PLGA NPs (mean diameter: 225nm; polydispersity index: 0.11; zeta potential: -15mV), 0.2% (w/v) CS-coated PLGA NPs (CS02-PLGA NPs, mean diameter: 264nm; polydispersity index: 0.17; zeta potential: -7mV), and 0.5% (w/v) CS-coated PLGA NPs (CS05-PLGA NPs, mean diameter: 338nm; polydispersity index: 0.23; zeta potential: 12mV) were fabricated by a modified solvent evaporation method. PLGA NPs maintained their initial particle size in different media, such as human serum albumin (HSA) solution, rat plasma, and distilled water (DW), while CS05-PLGA NPs exhibited the formation of aggregates in early incubation time and disassembly of those into the NPs in late incubation time (at 24h). According to the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the binding affinity of CS05-PLGA NPs with HSA and rat plasma was higher than that of PLGA NPs. By a near-infrared fluorescence (NIRF) imaging test in the mouse, the selective accumulation of CS05-PLGA NPs, rather than PLGA NPs, in lung tissue was demonstrated. These findings suggest that CS05-PLGA NPs can form transient aggregates in the blood stream after intravenous administration and markedly improve lung targeting efficiency, compared with PLGA NPs. PMID:27421112

  14. Cell-Adhesive Matrices Composed of RGD Peptide-Displaying M13 Bacteriophage/Poly(lactic-co-glycolic acid) Nanofibers Beneficial to Myoblast Differentiation.

    PubMed

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Kim, Chuntae; Hong, Suck Won; Oh, Jin Woo; Han, Dong-Wook

    2015-10-01

    Recently, there has been considerable effort to develop suitable scaffolds for tissue engineering applications. Cell adhesion is a prerequisite for cells to survive. In nature, the extracellular matrix (ECM) plays this role. Therefore, an ideal scaffold should be structurally similar to the natural ECM and have biocompatibility and biodegradability. In addition, the scaffold should have biofunctionality, which provides the potent ability to enhance the cellular behaviors, such as adhesion, proliferation and differentiation. This study concentrates on fabricating cell-adhesive matrices composed of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) nanofibers. Long rod-shaped M13 bacteriophages are non-toxic and can express many desired proteins on their surface. A genetically engineered M13 phage was constructed to display RGD peptides on its surface. PLGA is a biodegradable polymer with excellent biocompatibility and suitable physicochemical property for adhesive matrices. In this study, RGD-M13 phage/PLGA hybrid nanofiber matrices were fabricated by electrospinning. The physicochemical properties of these matrices were characterized by scanning electron microscopy, atomic force microscopy, Raman spectroscopy, and contact angle measurement. In addition, the cellular behaviors, such as the initial attachment, proliferation and differentiation, were analyzed by a CCK-8 assay and immunofluorescence staining to evaluate the potential application of these matrices to tissue engineering scaffolds. The RGD-M13 phage/PLGA nanofiber matrices could enhance the cellular behaviors and promote the differentiation of C2C12 myoblasts. These results suggest that the RGD-M13 phage/PLGA nanofiber matrices are beneficial to myoblast differentiation and can serve as effective tissue engineering scaffolds. PMID:26726438

  15. Fatty acids - trans fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  16. Evaluation of effectiveness of hyaluronic acid in combination with bioresorbable membrane (poly lactic acid-poly glycolic acid) for the treatment of infrabony defects in humans: A clinical and radiographic study

    PubMed Central

    Sehdev, Bhumika; Bhongade, Manohar Laxmanrao; Ganji, Kiran Kumar

    2016-01-01

    Background: The combination of biomaterials, bone graft substitutes along with guided tissue regeneration (GTR) has been shown to be an effective modality of periodontal regenerative therapy for infrabony defects. Therefore, the present randomized controlled clinical study was undertaken to evaluate the effectiveness of hyaluronic acid (HA) in combination with bioresorbable membrane for the treatment of human infrabony defects. Materials and Methods: Twenty four infrabony defects in 20 systemically healthy patients were randomly assigned to test (HA in combination with bioresorbable membrane) and control (bioresorbable membrane alone) treatment groups. Probing pocket depth (PPD), relative attachment level, and relative gingival margin level were measured with a computerized Florida disc probe at baseline and at 6 months follow-up. Radiographic measurements were also evaluated at baseline and at 6 months of postsurgery. Results: At 6 months, the mean reduction in PPD in test group and control group was 4.52 mm and 2.97 mm, respectively. Significantly higher clinical attachment level with a gain of 2.20 mm was found in the test group as compared to control group. In addition, statistically significant greater reduction of radiographic defect depth was observed in the test group. Conclusion: Regenerative approach using hyaloss in combination with GTR for the treatment of human infrabony defects resulted in a significant added benefit in terms of CAL gains, PPD reductions and radiographic defect fill, as well as LBG, compared to the GTR alone. PMID:27041838

  17. The delivery of poly(lactic acid)-poly(ethylene glycol) nanoparticles loaded with non-toxic drug to overcome drug resistance for the treatment of neuroblastoma

    NASA Astrophysics Data System (ADS)

    Dhulekar, Jhilmil

    Neuroblastoma is a rare cancer of the sympathetic nervous system. A neuroblastoma tumor develops in the nerve tissue and is diagnosed in infants and children. Approximately 10.2 per million children under the age of 15 are affected in the United States and is slightly more common in boys. Neuroblastoma constitutes 6% of all childhood cancers and has a long-term survival rate of only 15%. There are approximately 700 new cases of neuroblastoma each year in the United States. With such a low rate of survival, the development of more effective treatment methods is necessary. A number of therapies are available for the treatment of these tumors; however, clinicians and their patients face the challenges of systemic side effects and drug resistance of the tumor cells. The application of nanoparticles has the potential to provide a safer and more effective method of delivery drugs to tumors. The advantage of using nanoparticles for drug delivery is the ability to specifically or passively target tumors while reducing the harmful side effects of chemotherapeutics. Drug delivery via nanoparticles can also allow for lower dosage requirements with controlled release of the drugs, which can further reduce systemic toxicity. The aim of this research was to develop a polymeric nanoparticle drug delivery system for the treatment of high-risk neuroblastoma. Nanoparticles composed of a poly(lactic acid)-poly(ethylene glycol) block copolymer were formulated to deliver a non-toxic drug in combination with Temozolomide, a commonly used chemotherapeutic drug for the treatment of neuroblastoma. The non-toxic drug acts as an inhibitor to the DNA-repair protein present in neuroblastoma cells that is responsible for inducing drug resistance in the cells, which would potentially allow for enhanced temozolomide activity. A variety of studies were completed to prove the nanoparticles' low toxicity, loading abilities, and uptake into cells. Additionally, studies were performed to determine the

  18. Aspartic acid

    MedlinePlus

    ... Hormone production and release Normal nervous system function Plant sources of aspartic acid include: Legumes such as soybeans, garbanzo beans, and lentils Peanuts, almonds, walnuts, and flaxseeds Animal ...

  19. Usnic acid.

    PubMed

    Ingólfsdóttir, K

    2002-12-01

    Since its first isolation in 1844, usnic acid [2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione] has become the most extensively studied lichen metabolite and one of the few that is commercially available. Usnic acid is uniquely found in lichens, and is especially abundant in genera such as Alectoria, Cladonia, Usnea, Lecanora, Ramalina and Evernia. Many lichens and extracts containing usnic acid have been utilized for medicinal, perfumery, cosmetic as well as ecological applications. Usnic acid as a pure substance has been formulated in creams, toothpaste, mouthwash, deodorants and sunscreen products, in some cases as an active principle, in others as a preservative. In addition to antimicrobial activity against human and plant pathogens, usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti-inflammatory and analgesic activity. Ecological effects, such as antigrowth, antiherbivore and anti-insect properties, have also been demonstrated. A difference in biological activity has in some cases been observed between the two enantiomeric forms of usnic acid. Recently health food supplements containing usnic acid have been promoted for use in weight reduction, with little scientific support. The emphasis of the current review is on the chemistry and biological activity of usnic acid and its derivatives in addition to rational and ecologically acceptable methods for provision of this natural compound on a large scale.

  20. Acid rain

    SciTech Connect

    Elsworth, S.

    1985-01-01

    This book was written in a concise and readable style for the lay public. It's purpose was to make the public aware of the damage caused by acid rain and to mobilize public opinion to favor the elimination of the causes of acid rain.

  1. Acid rain

    SciTech Connect

    White, J.C. )

    1988-01-01

    This book presents the proceedings of the third annual conference sponsored by the Acid Rain Information Clearinghouse (ARIC). Topics covered include: Legal aspects of the source-receptor relationship: an energy perspective; Scientific uncertainty, agency inaction, and the courts; and Acid rain: the emerging legal framework.

  2. How Acidic Is Carbonic Acid?

    PubMed

    Pines, Dina; Ditkovich, Julia; Mukra, Tzach; Miller, Yifat; Kiefer, Philip M; Daschakraborty, Snehasis; Hynes, James T; Pines, Ehud

    2016-03-10

    Carbonic, lactic, and pyruvic acids have been generated in aqueous solution by the transient protonation of their corresponding conjugate bases by a tailor-made photoacid, the 6-hydroxy-1-sulfonate pyrene sodium salt molecule. A particular goal is to establish the pK(a) of carbonic acid H2CO3. The on-contact proton transfer (PT) reaction rate from the optically excited photoacid to the carboxylic bases was derived, with unprecedented precision, from time-correlated single-photon-counting measurements of the fluorescence lifetime of the photoacid in the presence of the proton acceptors. The time-dependent diffusion-assisted PT rate was analyzed using the Szabo-Collins-Kimball equation with a radiation boundary condition. The on-contact PT rates were found to follow the acidity order of the carboxylic acids: the stronger was the acid, the slower was the PT reaction to its conjugate base. The pK(a) of carbonic acid was found to be 3.49 ± 0.05 using both the Marcus and Kiefer-Hynes free energy correlations. This establishes H2CO3 as being 0.37 pK(a) units stronger and about 1 pK(a) unit weaker, respectively, than the physiologically important lactic and pyruvic acids. The considerable acid strength of intact carbonic acid indicates that it is an important protonation agent under physiological conditions. PMID:26862781

  3. Acid rain

    SciTech Connect

    Sweet, W.

    1980-06-20

    Acid precipitation includes not only rain but also acidified snow, hail and frost, as well as sulfur and nitrogen dust. The principal source of acid precipitation is pollution emitted by power plants and smelters. Sulfur and nitrogen compounds contained in the emissions combine with moisture to form droplets with a high acid content - sometimes as acidic as vinegar. When sufficiently concentrated, these acids can kill fish and damage material structures. Under certain circumstances they may reduce crop and forest yields and cause or aggravate respiratory diseases in humans. During the summer, especially, pollutants tend to collect over the Great Lakes in high pressure systems. Since winds typically are westerly and rotate clockwise around high pressure systems, the pollutants gradually are dispersed throughout the eastern part of the continent.

  4. Asparagusic acid.

    PubMed

    Mitchell, Stephen C; Waring, Rosemary H

    2014-01-01

    Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is a simple sulphur-containing 5-membered heterocyclic compound that appears unique to asparagus, though other dithiolane derivatives have been identified in non-food species. This molecule, apparently innocuous toxicologically to man, is the most probable culprit responsible for the curious excretion of odorous urine following asparagus ingestion. The presence of the two adjacent sulphur atoms leads to an enhanced chemical reactivity, endowing it with biological properties including the ability to substitute potentially for α-lipoic acid in α-keto-acid oxidation systems. This brief review collects the scattered data available in the literature concerning asparagusic acid and highlights its properties, intermediary metabolism and exploratory applications.

  5. Acid rain

    SciTech Connect

    Bess, F.D.

    1980-01-01

    The acid rain problem in the northeastern U.S. has been growing in severity and geographical areas affected. Acid rain has damaged, or will result in damage to visibility, physical structures and materials, aquatic life, timber, crops, and soils. The principal causes of acid rain in the northeastern U.S. are sulfur oxide and nitrogen oxide emissions from large power plants and smelters in the Ohio River Valley. Immediate corrective action and appropriate research are needed to reduce acid precipitation. Short-term programs that will define the rate of environmental deterioration, remaining environmental capacity to resist sudden deterioration, mechanisms of acid rain formation, and costs of various control options must be developed. (3 maps, 13 references, 1 table)

  6. Asparagusic acid.

    PubMed

    Mitchell, Stephen C; Waring, Rosemary H

    2014-01-01

    Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is a simple sulphur-containing 5-membered heterocyclic compound that appears unique to asparagus, though other dithiolane derivatives have been identified in non-food species. This molecule, apparently innocuous toxicologically to man, is the most probable culprit responsible for the curious excretion of odorous urine following asparagus ingestion. The presence of the two adjacent sulphur atoms leads to an enhanced chemical reactivity, endowing it with biological properties including the ability to substitute potentially for α-lipoic acid in α-keto-acid oxidation systems. This brief review collects the scattered data available in the literature concerning asparagusic acid and highlights its properties, intermediary metabolism and exploratory applications. PMID:24099657

  7. Acid fog

    SciTech Connect

    Hileman, B.

    1983-03-01

    Fog in areas of southern California previously thought to be pollution-free has been shown to have a pH as low as 1.69. It has been found to be most acidic after smoggy days, suggesting that it forms on the aerosol associated with the previously exiting smog. Studies on Whiteface Mountain in the Adirondacks show that fog water is often 10 times as acidic as rainwater. As a result of their studies, California plans to spend $4 million on acid deposition research in the coming year. (JMT)

  8. Tranexamic Acid

    MedlinePlus

    ... is used to treat heavy bleeding during the menstrual cycle (monthly periods) in women. Tranexamic acid is in ... tablets for more than 5 days in a menstrual cycle or take more than 6 tablets in a ...

  9. Mefenamic Acid

    MedlinePlus

    ... as mefenamic acid may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may ... like coffee grounds, blood in the stool, or black and tarry stools.Keep all appointments with your ...

  10. Acid Precipitation

    ERIC Educational Resources Information Center

    Likens, Gene E.

    1976-01-01

    Discusses the fact that the acidity of rain and snow falling on parts of the U.S. and Europe has been rising. The reasons are still not entirely clear and the consequences have yet to be well evaluated. (MLH)

  11. Open-label evaluation of a novel skin brightening system containing 0.01% decapeptide-12 in combination with 20% buffered glycolic acid for the treatment of mild to moderate facial melasma.

    PubMed

    Ramírez, Sandra P; Carvajal, Alfonso C; Salazar, Juan C; Arroyave, Gladys; Flórez, Ana M; Echeverry, Hector F

    2013-06-01

    Melasma is a cutaneous disorder that primarily affects females of Hispanic and Asian descent. Previous studies have shown that use of a brightening system comprised of 0.01% decapeptide-12 cream, an antioxidant cleanser, a 20% buffered glycolic acid lotion, and a broad spectrum SPF 30 sunscreen yields good clearance of mild-to-moderate melasma in Caucasian and Asian volunteers. The present open-label, prospective, and multicenter study sought to determine the tolerability and efficacy of the above-mentioned brightening system on mild-to-moderate melasma in 33 Hispanic females over 16 weeks. Clinical measures included self-assessment of tolerability, clinical grading, determination of Melasma Area and Severity Index (MASI) scores, and standardized clinical photography. Results showed that the system was well tolerated with no adverse events reported. Mean decreases of 36%, 46%, 54%, and 60% in MASI scores were observed at weeks 4, 8, 12, and 16, respectively, which were further corroborated by standardized photography showing visible reduction in the appearance of melasma. Results suggest that the brightening system consisting of 0.01% decapeptide-12 cream, an antioxidant cleanser, 20% buffered glycolic acid lotion, and broad spectrum SPF 30 sunscreen is safe and efficacious for the treatment of mild-to-moderate melasma in Hispanic females.

  12. Optimization and validation of liquid chromatography and headspace-gas chromatography based methods for the quantitative determination of capsaicinoids, salicylic acid, glycol monosalicylate, methyl salicylate, ethyl salicylate, camphor and l-menthol in a topical formulation.

    PubMed

    Pauwels, Jochen; D'Autry, Ward; Van den Bossche, Larissa; Dewever, Cédric; Forier, Michel; Vandenwaeyenberg, Stephanie; Wolfs, Kris; Hoogmartens, Jos; Van Schepdael, Ann; Adams, Erwin

    2012-02-23

    Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace-gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R² values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks). PMID:22094014

  13. Acidic precipitation

    SciTech Connect

    Martin, H.C.

    1987-01-01

    At the International Symposium on Acidic Precipitation, over 400 papers were presented, and nearly 200 of them are included here. They provide an overview of the present state of the art of acid rain research. The Conference focused on atmospheric science (monitoring, source-receptor relationships), aquatic effects (marine eutrophication, lake acidification, impacts on plant and fish populations), and terrestrial effects (forest decline, soil acidification, etc.).

  14. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  15. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  16. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  17. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  18. 40 CFR 180.1250 - C8, C10, and C12 fatty acid monoesters of glycerol and propylene glycol; exemption from the...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1250 C8... a tolerance. The C8, C10, and C12 straight-chain fatty acid monoesters of glycerol (glycerol... of a tolerance in or on all food commodities when used in accordance with approved label rates...

  19. Selective delivery of rifampicin incorporated into poly(DL-lactic-co-glycolic) acid microspheres after phagocytotic uptake by alveolar macrophages, and the killing effect against intracellular Mycobacterium bovis Calmette-Guérin.

    PubMed

    Yoshida, Aya; Matumoto, Makoto; Hshizume, Hiroyuki; Oba, Yoshiro; Tomishige, Tatuo; Inagawa, Hiroyuki; Kohchi, Chie; Hino, Mami; Ito, Fuminori; Tomoda, Keishiro; Nakajima, Takehisa; Makino, Kimiko; Terada, Hiroshi; Hori, Hitoshi; Soma, Gen-Ichiro

    2006-08-01

    Macrophages and their phagocytotic abilities play a dominant role for defense against infected organisms. However, Mycobacterium tuberculosis can survive in the phagosomes of macrophages. In this study, the effective delivery of a drug and the killing effect of tubercle bacilli within macrophages were investigated utilizing the phagocytotic uptake of rifampicin (RFP) that had been incorporated into poly(DL-lactic-co-glycolic) acid (PLGA) microspheres. The microspheres were composed of PLGA that had a monomer ratio (lactic acid/glycolic acid) of either 50/50 or 75/25. They had molecular weights from 5000 to 20,000, and diameters of 1.5, 3.5, 6.2 and 8.9 microm. The most significant factor for phagocytotic activity of macrophages was the diameter of the microspheres. By contrast, molecular weight and monomer ratio of PLGA did not influence phagocytosis. The amount of RFP delivered into cells was also investigated. RFP-PLGA microspheres composed of PLGA with a molecular weight of 20,000 and monomer ratio of 75/25 showed the highest amount of delivery (4 microg/1 x 10(6) cells). Fourteen days after infection, the survival rate of treated intracellular bacilli was 1% when compared with untreated cells. There was almost no killing effect of free RFP (4 or 15 microg/ml) on intracellular bacilli. In vivo efficacy of RFP-PLGA was also examined in rats infected with M. tuberculosis Kurono. Intratracheal administration of RFP-PLGA microspheres was shown to be superior to free RFP for killing of intracellular bacilli and preventing granuloma formation in some lobes. These results suggest that phagocytotic activity could be part of a new drug delivery system that selectively targeted macrophages.

  20. Salicylic acids

    PubMed Central

    Hayat, Shamsul; Irfan, Mohd; Wani, Arif; Nasser, Alyemeni; Ahmad, Aqil

    2012-01-01

    Salicylic acid is well known phytohormone, emerging recently as a new paradigm of an array of manifestations of growth regulators. The area unleashed yet encompassed the applied agriculture sector to find the roles to strengthen the crops against plethora of abiotic and biotic stresses. The skipped part of integrated picture, however, was the evolutionary insight of salicylic acid to either allow or discard the microbial invasion depending upon various internal factors of two interactants under the prevailing external conditions. The metabolic status that allows the host invasion either as pathogenesis or symbiosis with possible intermediary stages in close systems has been tried to underpin here. PMID:22301975

  1. Stearic Acid

    ERIC Educational Resources Information Center

    Young, Jay A.

    2004-01-01

    A chemical laboratory information profile (CLIP) is presented for the chemical, stearic acid. The profile lists the chemical's physical and harmful characteristics, exposure limits, and symptoms of major exposure, for the benefit of teachers and students, who use the chemical in the laboratory.

  2. Trichloroacetic acid

    Integrated Risk Information System (IRIS)

    Trichloroacetic acid ( TCA ) ; CASRN 76 - 03 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonca

  3. Acrylic acid

    Integrated Risk Information System (IRIS)

    Acrylic acid ( CASRN 79 - 10 - 7 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  4. Selenious acid

    Integrated Risk Information System (IRIS)

    Selenious acid ; CASRN 7783 - 00 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  5. Dichloroacetic acid

    Integrated Risk Information System (IRIS)

    Dichloroacetic acid ; CASRN 79 - 43 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  6. Cacodylic acid

    Integrated Risk Information System (IRIS)

    Cacodylic acid ; CASRN 75 - 60 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  7. Phosphoric acid

    Integrated Risk Information System (IRIS)

    Phosphoric acid ; CASRN 7664 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  8. Benzoic acid

    Integrated Risk Information System (IRIS)

    Benzoic acid ; CASRN 65 - 85 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effec

  9. Formic acid

    Integrated Risk Information System (IRIS)

    Formic acid ; CASRN 64 - 18 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  10. [Hyaluronic acid].

    PubMed

    Pomarede, N

    2008-01-01

    Hyaluronic Acid (HA) is now a leader product in esthetic procedures for the treatment of wrinkles and volumes. The structure of HA, its metabolism, its physiological function are foremost breaking down then its use in aesthetic dermatology: steps of injection, possible side effects, benefits and downsides of the use of HA in aesthetic dermatology.

  11. Vorinostat with sustained exposure and high solubility in poly(ethylene glycol)-b-poly(DL-lactic acid) micelle nanocarriers: characterization and effects on pharmacokinetics in rat serum and urine.

    PubMed

    Mohamed, Elham A; Zhao, Yunqi; Meshali, Mahasen M; Remsberg, Connie M; Borg, Thanaa M; Foda, Abdel Monem M; Takemoto, Jody K; Sayre, Casey L; Martinez, Stephanie E; Davies, Neal M; Forrest, M Laird

    2012-10-01

    The histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anticancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)-b-poly(DL-lactic acid) (PEG-b-PLA) micelles of vorinostat were developed. Vorinostat's pharmacokinetics in rats was investigated after intravenous (i.v.) (10 mg/kg) and oral (p.o.) (50 mg/kg) micellar administrations and compared with a conventional polyethylene glycol 400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 to 8.15 ± 0.60 and 10.24 ± 0.92 mg/mL at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19%, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half-life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG-b-PLA micelles significantly improved the p.o. and i.v. pharmacokinetics and bioavailability of vorinostat, which warrants further investigation.

  12. Hydroxycarboxylic acids and salts

    DOEpatents

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  13. Synthesis of nano-sized stereoselective imprinted polymer by copolymerization of (S)-2-(acrylamido) propanoic acid and ethylene glycol dimethacrylate in the presence of racemic propranolol and copper ion.

    PubMed

    Alizadeh, Taher; Bagherzadeh, Azam; Shamkhali, Amir Nasser

    2016-06-01

    A new chiral functional monomer of (S)-2-(acrylamido) propanoic acid was obtained by reaction of (l)-alanine with acryloyl chloride. The resulting monomer was characterized by FT-IR and HNMR and then utilized for the preparation of chiral imprinted polymer (CIP). This was carried out by copolymerization of (l)-alanine-derived chiral monomer and ethylene glycol dimethacrylate, in the presence of racemic propranolol and copper nitrate, via precipitation polymerization technique, resulting in nano-sized networked polymer particles. The polymer obtained was characterized by scanning electron microscopy and FT-IR. The non-imprinted polymer was also synthesized and used as blank polymer. Density functional theory (DFT) was also employed to optimize the structures of two diasterometric ternary complexes, suspected to be created in the pre-polymerization step, by reaction of optically active isomers of propranolol, copper ion and (S)-2-(acrylamido) propanoic acid. Relative energies and other characteristics of the described complexes, calculated by the DFT, predicted the higher stability of (S)-propranolol involved complex, compared to (R)-propranolol participated complex. Practical batch extraction test which employed CIP as solid phase adsorbent, indicated that the CIP recognized selectively (S)-propranolol in the racemic mixture of propranolol; whereas, the non-imprinted polymer (NIP) showed no differentiation capability between two optically active isomers of propranolol. PMID:27040217

  14. Methylmalonic acid blood test

    MedlinePlus

    ... acid is a substance produced when proteins, called amino acids, in the body break down. The health care ... Cederbaum S, Berry GT. Inborn errors of carbohydrate, ammonia, amino acid, and organic acid metabolism. In: Gleason CA, Devaskar ...

  15. Folic Acid and Pregnancy

    MedlinePlus

    ... 5 Things to Know About Zika & Pregnancy Folic Acid and Pregnancy KidsHealth > For Parents > Folic Acid and ... before conception and during early pregnancy . About Folic Acid Folic acid, sometimes called folate, is a B ...

  16. Understanding Acid Rain

    ERIC Educational Resources Information Center

    Damonte, Kathleen

    2004-01-01

    The term acid rain describes rain, snow, or fog that is more acidic than normal precipitation. To understand what acid rain is, it is first necessary to know what an acid is. Acids can be defined as substances that produce hydrogen ions (H+), when dissolved in water. Scientists indicate how acidic a substance is by a set of numbers called the pH…

  17. Enhanced toxicity and cellular uptake of methotrexate-conjugated nanoparticles in folate receptor-positive cancer cells by decorating with folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate.

    PubMed

    Junyaprasert, Varaporn Buraphacheep; Dhanahiranpruk, Sirithip; Suksiriworapong, Jiraphong; Sripha, Kittisak; Moongkarndi, Primchanien

    2015-12-01

    Folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FOL) decorated methotrexate (MTX)-conjugated nanoparticles were developed for targeted delivery of MTX to folate receptor-expressed tumor cells. The synthesis of TPGS-FOL followed 3-step process. Firstly, the terminal hydroxyl group of TPGS was converted to sulfonyl chloride using mesyl chloride in comparison with nosyl and tosyl chlorides. The highest conversion efficiency and yield were obtained by mesyl chloride due to the formation of higher reactive intermediate in a presence of triethylamine. Secondly, the substitution of sulfonyl group by sodium azide produced considerably high yield with conversion efficiency of over 90%. Lastly, the coupling reaction of azido-substituted TPGS and propargyl folamide by click reaction resulted in 96% conjugation efficiency without polymer degradation. To fabricate the folate receptor-targeted nanoparticles, 10 and 20%mol MTX-conjugated PEGylated poly(ϵ-caprolactone) nanoparticles were decorated with TPGS-FOL. The size and size distribution of MTX-conjugated nanoparticles relatively increased with %MTX. The MTX release from the nanoparticles was accelerated in acidic medium with an increase of %MTX but retarded in physiological pH medium. The decoration of TPGS-FOL onto the nanoparticles slightly enlarged the size and size distribution of the nanoparticles; however, it did not affect the surface charge. The cytotoxicity and cellular uptake of MCF-7 cells demonstrated that 10% MTX-conjugated nanoparticles and FOL-decorated nanoparticles possessed higher toxicity and uptake efficiency than 20% MTX-conjugated nanoparticles and undecorated nanoparticles, respectively. The results indicated that FOL-10% MTX-conjugated nanoparticles exhibited potential targeted delivery of MTX to folate receptor-expressed cancer cells.

  18. Effects of hypochlorous acid exposure on the rejection of salt, polyethylene glycols, boron and arsenic(V) by nanofiltration and reverse osmosis membranes.

    PubMed

    Do, Van Thanh; Tang, Chuyang Y; Reinhard, Martin; Leckie, James O

    2012-10-15

    The separation layer of polyamide-based (PA) thin film composite (TFC) membranes can be modified by active chlorine species. The PA-TFC membranes, NF90, BW30 and NF270, were exposed to different concentrations of sodium hypochlorite (NaOCl) at pH 5 for 24 h. Elemental composition obtained from X-ray Photoelectron Spectroscopy (XPS) showed that the chlorine content in the PA layer increased with the chlorine concentrations. Treatment of membranes with 10 ppm Cl increased the membrane hydrophilicity. By contrast, when treated with 1000 ppm Cl or more, the membranes became less hydrophilic. Water permeability values for all 3 membrane types declined with increased chlorine concentrations. Filtration of polyethylene glycols (PEGs) with molecular weights of 200, 400 and 600 Daltons (Da) was performed to investigate the influence of chlorine treatment on membrane molecular weight cut off (MWCO) and rejection by size exclusion. Treatment with 10 and 100 ppm Cl lowered the MWCO while treatment with higher concentrations increased the MWCO. All chlorinated membranes experienced higher NaCl rejection compared to virgin ones. The performance of NF90 was tested with respect to the rejection of inorganic contaminants including boron (H(3)BO(3)) and arsenic (H(2)AsO(4)(-)). The boron rejection results paralleled PEG rejection whereas those for arsenic followed NaCl rejection patterns. The changes in membrane performance due to chlorine treatment were explained in terms of competing mechanisms: membrane tightening, bond cleavage by N-chlorination and chlorination promoted polyamide hydrolysis.

  19. Synthesis and characterizations of palladium catalysts with high activity and stability for formic acid oxidation by hydrogen reduction in ethylene glycol at room temperature

    NASA Astrophysics Data System (ADS)

    Wu, Meixia; Li, Muwu; Wu, Xin; Li, Yuexia; Zeng, Jianhuang; Liao, Shijun

    2015-10-01

    In this work, a Pd/C catalyst with high activity as well as excellent stability has been prepared by hydrogen gas reduction of Pd(II) precursor in ethylene glycol solution with the assistance of appropriate amount of sodium citrate. Pd nanoparticles with an average particle size of 3.8 nm and excellent uniformity are obtained. The Pd/C catalyst synthesized in this work shows an electrochemical surface area of 68.6 m2 g-1 and displays activities of 819 A g-1. Strikingly, the Pd/C catalyst also exhibits excellent stability, which has been confirmed by its slow activity decay under repeated potential cycles as well as chronoamperometric test. The activity for Pd/C at the 300th and 500th cycle remains at 5.5 and 2.4 mA cm-2, respectively, which is 25% and 11% of its initial value, respectively. The oxidation currents at the Pd/C and Pd/C-Citrate (control) at 0 V decrease to 44% and 25% of their initial values. Transmission electron microscopy observations on the Pd/C catalyst after 1000 potential cycles reveal that, in addition to carbon support corrosion, Pd agglomeration together with more serious Pd dissolution occur at the same time, leading to a decrease of the electrocatalytic performance.

  20. Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study.

    PubMed

    Yasunami, Noriyuki; Ayukawa, Yasunori; Furuhashi, Akihiro; Atsuta, Ikiru; Rakhmatia, Yunia Dwi; Moriyama, Yasuko; Masuzaki, Tomohiro; Koyano, Kiyoshi

    2016-02-01

    Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site. PMID:26694986

  1. Impact of smoking on guided tissue regeneration using a biocomposite poly (lactic-co-glycolic) acid/sub-micron size hydroxyapatite with a rubber dam as an alternative barrier.

    PubMed

    Stramazzotti, D; Coiana, C; Zizzi, A; Spazzafumo, L; Sauro, S; D'Angelo, A B; Rubini, C; Aspriello, S D

    2015-03-01

    The purpose of our study was to critically evaluate the results obtained from a guided tissue regeneration technique after 12 months using a bocomposite poly (lactic-co-glycolic) acid/sub-micron size hydroxyapatite (PLGA/HA) with a rubber dam as a barrier in smoking and non-smoking patients. We selected 36 patients (18 current smokers and 18 non-smokers) diagnosed with chronic advanced periodontitis with a periodontal site (probing depth [PD] >5) amenable to regenerative surgery. Twelve months after surgery, the periodontal parameters were found to have statistically improved, when non-smokers were compared with smokers, in: PD reduction (6.3 ± 2.1 mm vs. 3.6 ± 1.9 mm); CAL gain (4.4 ± 1.1 vs. 2.8 ± 2.2 mm); recession (1.8 ± 1.4 mm vs. 0.8 ± 0.9 mm); and hard tissue fill (4.7 ± 0.8 mm vs. 2.8 ± 2.1 mm). Furthermore, since we found PD baseline differences between groups, smoking seemed not to influence the outcomes achieved (CAL gain and ΔREC) 12 months post surgery with respect to PD baseline. The use of PLGA/HA with a rubber dam significantly improved the periodontal parameters in both smoking and non-smoking subjects. This improvement was nevertheless lower in smokers than the non-smokers, confirming the negative impact of smoking on periodontal regeneration.

  2. Ameliorative effects of Syzygium jambolanum extract and its poly (lactic-co-glycolic) acid nano-encapsulated form on arsenic-induced hyperglycemic stress: a multi-parametric evaluation.

    PubMed

    Samadder, Asmita; Das, Sreemanti; Das, Jayeeta; Paul, Avijit; Khuda-Bukhsh, Anisur Rahman

    2012-12-01

    In South East Asia, groundwater arsenic contamination has become a great menace. Chronic arsenic intoxication leads to a hyperglycemic condition in animals and man. Because of undesirable side-effects and affordability, orthodox medicine, like insulin, is not preferred by many who like natural products instead. Unfortunately, such natural products mostly lack scientific validation. Therefore, we became interested in assessing the efficacy of the ethanolic seed extract of Syzygium jambolanum (SJ), traditionally used against diabetic conditions. We also formulated poly (lactic-co-glycolic) acid (PLGA)-encapsulated nano-SJ (NSJ) and tested whether the ameliorative potentials of SJ could be enhanced by nano-encapsulation. In this study, we conducted both in vitro (in L6 cells) and in vivo (in mice) experiments to assess the relative efficacy of SJ and NSJ. We characterized the physico-chemical features of NSJ by atomic force microscopy and critically analyzed several bio-markers and signal proteins associated with arsenic-induced stress and hyperglycemia. We also determined the relative ameliorative potentials of SJ and NSJ by using standard protocols. NSJ could cross the blood brain barrier in mice. Overall results suggested that NSJ had a greater potential than that of SJ, indicating the possibility of using NSJ in the future drug design and management of arsenic-induced hyperglycemia and stress.

  3. A free-standing, sheet-shaped, "hydrophobic" biomaterial containing polymeric micelles formed from poly(ethylene glycol)-poly(lactic acid) block copolymer for possible incorporation/release of "hydrophilic" compounds.

    PubMed

    Moroishi, Hitomi; Yoshida, Chikara; Murakami, Yoshihiko

    2013-02-01

    Sheet-shaped materials with a large contact area relative to the drug targeting site lead to advantages over conventional particle-shaped drug carriers and have several advantages for their biomedical applications. The present study proposes a methodology for preparing a novel sheet-shaped "hydrophobic" and biocompatible biomaterial in which polymeric micelles are uniformly dispersed for the incorporation of "hydrophilic" compounds into the sheet. The methoxy-terminated poly(ethylene glycol)-block-poly(lactic acid) block copolymer (CH(3)O-PEG-b-PLA) was successfully synthesized by means of the anionic ring-opening polymerization of both ethylene oxide and dl-lactide. CH(3)O-PEG-b-PLA was self-assembled and formed stable micelle-like w/o emulsion with a hydrophilic inner core in organic solvents. A sheet-shaped material containing a hydrophilic inner space for incorporating hydrophilic compounds was obtained by spin-coating both the micelle solution and a sheet-forming polymer. Fluorescent images of the sheet proved that polymeric micelles providing hydrophilic spaces were uniformly dispersed in the hydrophobic sheet. The facile technique presented in this paper can be a tool for fabricating sheet-shaped biomaterials that have a hydrophilic inner core and, consequently, that are suitable for the sustained release of hydrophilic compounds.

  4. Quantitative three-dimensional analysis of poly (lactic-co-glycolic acid) microsphere using hard X-ray nano-tomography revealed correlation between structural parameters and drug burst release.

    PubMed

    Huang, Xiaozhou; Li, Na; Wang, Dajiang; Luo, Yuyan; Wu, Ziyu; Guo, Zhefei; Jin, Qixing; Liu, Zhuying; Huang, Yafei; Zhang, Yongming; Wu, Chuanbin

    2015-08-10

    The objective of this study was to investigate the use of transmission hard X-ray nano-computed-tomography (nano-CT) for characterization of the pore structure and drug distribution in poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating bovine serum albumin and to study the correlation between drug distribution and burst release. The PLGA microspheres were fabricated using a double-emulsion method. The results of pore structure analysis accessed with nano-CT were compared with those acquired by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Surface pore interconnectivity and surface protein interconnectivity were obtained using combined nano-CT and pixel analysis. The correlation between surface protein interconnectivity with the initial burst release across various tested formulations was also analyzed. The size, shape, and distribution of the pores and protein could be clearly observed in the whole microsphere using nano-CT, whereas only the sectional information was observed using SEM or CLSM. Interconnected pores and surface connected pores could be clearly distinguished in nano-CT, which enables the quantitative analysis of surface pore interconnectivity and surface protein interconnectivity. The surface protein interconnectivity in different formulations correlated well with the burst release at 5-10h. Nano-CT provided a nondestructive, high-resolution, and three-dimensional analysis method to characterize the porous microsphere.

  5. Poly(propylene fumarate) and poly(DL-lactic-co-glycolic acid) as scaffold materials for solid and foam-coated composite tissue-engineered constructs for cranial reconstruction.

    PubMed

    Dean, David; Topham, Neal S; Meneghetti, S Cristina; Wolfe, Michael S; Jepsen, Karl; He, Shulin; Chen, Jeffrey E-K; Fisher, John P; Cooke, Malcolm; Rimnac, Clare; Mikos, Antonios G

    2003-06-01

    This pilot study investigates the osseointegration of four types of critical-size (1.5-cm diameter) rabbit cranial defect (n = 35) bone graft scaffolds. The first is a solid poly(propylene fumarate)/beta-tricalcium phosphate(PPF/beta-TCP) disk; the three remaining constructs contain a PPF/beta-TCP core coated with a 1-mm resorptive porous foam layer of PPF or PLGA [poly(DL-lactic-co-glycolic acid)], and bone marrow. Animals were killed at 6, 12, and 20 weeks. There was no evidence of a foreign body inflammatory response at any time during the study. Histomorphometric analyses of new bone formation sorted lineal and areal measures of new bone into three cranial layers (i.e., external, middle, and internal). Statistical analyses revealed significantly more bone in the PLGA foam-coated constructs than in the PPF foam-coated constructs (p < 0.03). No implant fixation was used; there is no strength at time 0. Twenty percent of all explants were tested for incorporation strength with a one-point "push-in" test, and failure ranged from 8.3 to 34.7 lb. The results of this study support the use of PPF as a biocompatible material that provides both a structural and osteogenic substrate for the repair of cranial defects.

  6. Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study.

    PubMed

    Yasunami, Noriyuki; Ayukawa, Yasunori; Furuhashi, Akihiro; Atsuta, Ikiru; Rakhmatia, Yunia Dwi; Moriyama, Yasuko; Masuzaki, Tomohiro; Koyano, Kiyoshi

    2015-12-23

    Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site.

  7. Swelling properties of copolymeric hydrogels of poly(ethylene glycol) monomethacrylate and monoesters of itaconic acid for use in drug delivery.

    PubMed

    Teijón, César; Guerrero, Sandra; Olmo, Rosa; Teijón, José M; Blanco, M Dolores

    2009-11-01

    Copolymeric hydrogels of poly(ethylene glycol) monomethacrylate (PEGMA) (P) have been synthesized for use in drug-delivery. New copolymeric hydrogels were prepared by free radical solution polymerization of PEGMA and monomethyl itaconate (MMI) or monoethyl itaconate (MEI), using ethyleneglycol dimethacrylate and tetraethyleneglycol dimethacrylate, respectively, as cross-linkers. The effect of copolymer composition on swelling behavior, thermal decomposition and drug release was studied. Three compositions of each copolymer were studied: 70P/30MMI (or MEI), 80P/20MMI (or MEI) and 90P/10MMI (or MEI). The largest equilibrium swelling degree was observed in gels containing the highest content of MMI or MEI (84.22 +/- 0.22 wt % for 70P/30MEI; 79.56 +/- 0.64 wt % for 70P/30MMI). The swelling process was in accordance with Fick's Second Law. Methotrexate (MTX), an anticancer agent used in the treatment of different hyperproliferative epithelial diseases, was chosen to be loaded in the gels. The drug was included by immersion of the copolymeric disks in an aqueous solution of the drug. The amount of MTX in the xerogels was between 5.34 +/- 0.06 mg MTX/g (90P/10MMI) and 14.94 +/- 0.91 mg MTX/g (80P/20MEI). Two stages of thermal degradation for unloaded and MTX-loaded gels were determined; the presence of the drug in the polymeric matrices decreased the temperature of the first stage of thermal degradation. MTX release was also in accordance with Fick's Second Law. The length of total drug release (340 +/- 30 min-1502 +/- 81 min) could be modulated as a function of the comonomer composition of the hydrogel.

  8. Effects of hypochlorous acid exposure on the rejection of salt, polyethylene glycols, boron and arsenic(V) by nanofiltration and reverse osmosis membranes.

    PubMed

    Do, Van Thanh; Tang, Chuyang Y; Reinhard, Martin; Leckie, James O

    2012-10-15

    The separation layer of polyamide-based (PA) thin film composite (TFC) membranes can be modified by active chlorine species. The PA-TFC membranes, NF90, BW30 and NF270, were exposed to different concentrations of sodium hypochlorite (NaOCl) at pH 5 for 24 h. Elemental composition obtained from X-ray Photoelectron Spectroscopy (XPS) showed that the chlorine content in the PA layer increased with the chlorine concentrations. Treatment of membranes with 10 ppm Cl increased the membrane hydrophilicity. By contrast, when treated with 1000 ppm Cl or more, the membranes became less hydrophilic. Water permeability values for all 3 membrane types declined with increased chlorine concentrations. Filtration of polyethylene glycols (PEGs) with molecular weights of 200, 400 and 600 Daltons (Da) was performed to investigate the influence of chlorine treatment on membrane molecular weight cut off (MWCO) and rejection by size exclusion. Treatment with 10 and 100 ppm Cl lowered the MWCO while treatment with higher concentrations increased the MWCO. All chlorinated membranes experienced higher NaCl rejection compared to virgin ones. The performance of NF90 was tested with respect to the rejection of inorganic contaminants including boron (H(3)BO(3)) and arsenic (H(2)AsO(4)(-)). The boron rejection results paralleled PEG rejection whereas those for arsenic followed NaCl rejection patterns. The changes in membrane performance due to chlorine treatment were explained in terms of competing mechanisms: membrane tightening, bond cleavage by N-chlorination and chlorination promoted polyamide hydrolysis. PMID:22818949

  9. Precipitation: its acidic nature.

    PubMed

    Frohliger, J O; Kane, R

    1975-08-01

    A comparison of the free hydrogen ion concentration and the total hydrogen ion concentration of rain samples shows that rain is a weak acid. The weak acid nature of rain casts doubt on the concepts that the acidity of rain is increasing and that these increases are due to strong acids such as sulfuric acid.

  10. Functional properties and biodistribution of poly(triethylenetetramine/cystamine bisacrylamide) and poly(triethylenetetramine/cystamine bisacrylamide)- poly(ethylene glycol) mixtures formed with nucleic acid.

    PubMed

    Brumbach, Jonathan H; Lee, Yong Won; Kim, Sung Wan; Yockman, James W

    2012-04-10

    The clinical success of non-viral gene delivery reagents is hampered by their inefficient cellular transgene delivery, which is largely influenced by carrier properties that are currently undefined and misunderstood. In an attempt to further define and understand the requirements for a safe and efficient non-viral gene delivery reagent, research labs often engineer and evaluate many putative products with subtle physiochemical differences in order to delineate requirements for improved in vitro and in vivo success. The synthesis of many putative reagents is often time-intensive, laborious and costly. In a previous manuscript published by our lab, different amounts of poly(triethylenetetramine/cystamine bisacrylamide) (p(TETA/CBA) and its pegylated counterpart, poly(triethylenetetramine/cystamine bisacrylamide)- poly(ethylene glycol) (p(TETA/CBA)-g-PEG) were mixed together to easily identify optimal reagent properties and candidates in vitro, while avoiding the synthesis of many putative candidates for study. This report uses the aforementioned facile approach to evaluate reagent properties of products that were obtained via one-pot synthesis, which improved synthetic ease. As such, synthesis time was reduced from 6days to 3days and had comparable or improved transfection and viability compared to previous works. Moreover, this synthesis resulted in higher molecular weight products than were used in the previous study and allow for lower polymer doses to be used for complexation, which is useful for systemic delivery that is used herein. The physiochemical properties of the formulations derived using these novel reagents was studied prior to investigating their in vivo biodistribution profiles in a murine colon adenocarcinoma model. Interestingly, negatively charged complexes exhibited greater passive tumor accumulation compared to positively charged complexes following their systemic administration. These studies warrant further investigation for the use of

  11. [An experimental study on a slow-release complex with rifampicin-polylactic-co-glycolic acid-calcium 
phosphate cement].

    PubMed

    Wu, Jianhuang; Ding, Zhou; Lei, Qing; Li, Miao; Liang, Yan; Lu, Tao

    2016-09-28

    目的:制备利福平(rifampicin,RFP)-聚乳酸-羟基乙酸(polylactic-co-glycolic acid,PLGA)-磷酸钙骨水泥(calcium phosphate cement,CPC)缓释复合体(RFP-PLGA-CPC复合体),并研究其理化性质及体外释药性能。方法:采用乳化-溶剂挥发法制备RFP-PLGA缓释微球。实验分为CPC组、包埋了RFP的CPC组(RFP-CPC组)、载有RFP的PLGA缓释微球与自固化CPC复合体组(RFP-PLGA-CPC复合体组)。测定3组材料的凝固时间﹑孔隙率。通过体外药物释放实验观察释药前后的抗压强度、断面形态的变化以及体外释药情况。结果:CPC组的凝固时间最短,RFP-PLGA-CPC复合体组的凝固时间最长。CPC组的孔隙率同RFP-CPC组比较,差异有统计学意义(P<0.05);CPC组和RFP-CPC组的孔隙率与RFP-PLGA-CPC复合体组比较,差异均有统计学意义(均P<0.01)。RFP-PLGA-CPC复合体组的抗压强度与CPC组比较,差异有统计学意义(P<0.01);而RFP-CPC组和CPC组之间的抗压强度随着时间的变化逐渐表现出显著性差异(3 d: P<0.05;30和60 d:P<0.01)。CPC组在降解过程中的抗压强度的变化不大。PLGA微球的大小均一,粒径基本在100~150 μm之间,微球的形态呈现出球体或是类球体,微球的表面圆润光滑,无杂质附着; CPC组的断面空隙在浸泡3 d直至60 d都没有明显变化;而RFP-CPC组的微结构变化亦不大,其断面均是小的微粒形成的;RFP-PLGA-CPC复合体组断面的孔隙明显增多,一直到60 d时PLGA微球逐渐消失,剩下空洞。RFP-PLGA-CPC复合体组无明显短时间内药物大量释放现象,60 d累计释药率达到近95%,将该复合体释药行为进行线性拟合,发现药物以恒速进行局部释放,符合零级动力学方程F=0.168×t。结论:RFP-PLGA-CPC复合体孔隙率显著高于CPC,能够持续缓慢释放有效抗结核药物,并能较长时间维持一定的力学强度。.

  12. Amino Acid Metabolism Disorders

    MedlinePlus

    ... defects & other health conditions > Amino acid metabolism disorders Amino acid metabolism disorders E-mail to a friend Please ... baby’s newborn screening may include testing for certain amino acid metabolism disorders. These are rare health conditions that ...

  13. Carbolic acid poisoning

    MedlinePlus

    Phenol poisoning; Phenylic acid poisoning; Hydroxybenzene poisoning; Phenic acid poisoning; Benzenol poisoning ... Below are symptoms of carbolic acid poisoning in different parts of the ... urine Decreased urine output No urine output EYES, EARS, ...

  14. Azelaic Acid Topical

    MedlinePlus

    Azelaic acid gel is used to clear the bumps, lesions, and swelling caused by rosacea (a skin disease that ... redness, flushing, and pimples on the face). Azelaic acid cream is used to treat acne. Azelaic acid ...

  15. Uric acid test (image)

    MedlinePlus

    Uric acid urine test is performed to check for the amount of uric acid in urine. Urine is collected over a 24 ... testing. The most common reason for measuring uric acid levels is in the diagnosis or treatment of ...

  16. Facts about Folic Acid

    MedlinePlus

    ... Information For... Media Policy Makers Facts About Folic Acid Language: English Español (Spanish) Recommend on Facebook Tweet ... of the baby's brain and spine. About folic acid Folic acid is a B vitamin. Our bodies ...

  17. Acid Lipase Disease

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Acid Lipase Disease Information Page Synonym(s): Cholesterol Ester Storage ... Trials Related NINDS Publications and Information What is Acid Lipase Disease ? Acid lipase disease or deficiency occurs ...

  18. Acid distribution in phosphoric acid fuel cells

    SciTech Connect

    Okae, I.; Seya, A.; Umemoto, M.

    1996-12-31

    Electrolyte acid distribution among each component of a cell is determined by capillary force when the cell is not in operation, but the distribution under the current load conditions had not been clear so far. Since the loss of electrolyte acid during operation is inevitable, it is necessary to store enough amount of acid in every cell. But it must be under the level of which the acid disturbs the diffusion of reactive gases. Accordingly to know the actual acid distribution during operation in a cell is very important. In this report, we carried out experiments to clarify the distribution using small single cells.

  19. Reduction-responsive disassemblable core-cross-linked micelles based on poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide)-lipoic acid conjugates for triggered intracellular anticancer drug release.

    PubMed

    Wei, Rongran; Cheng, Liang; Zheng, Meng; Cheng, Ru; Meng, Fenghua; Deng, Chao; Zhong, Zhiyuan

    2012-08-13

    Reduction-sensitive reversibly core-cross-linked micelles were developed based on poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide)-lipoic acid (PEG-b-PHPMA-LA) conjugates and investigated for triggered doxorubicin (DOX) release. Water-soluble PEG-b-PHPMA block copolymers were obtained with M(n,PEG) of 5.0 kg/mol and M(n,HPMA) varying from 1.7 and 4.1 to 7.0 kg/mol by reversible addition-fragmentation chain transfer (RAFT) polymerization. The esterification of the hydroxyl groups in the PEG-b-PHPMA copolymers with lipoic acid (LA) gave amphiphilic PEG-b-PHPMA-LA conjugates with degrees of substitution (DS) of 71-86%, which formed monodispersed micelles with average sizes ranging from 85.3 to 142.5 nm, depending on PHPMA molecular weights, in phosphate buffer (PB, 10 mM, pH 7.4). These micelles were readily cross-linked with a catalytic amount of dithiothreitol (DTT). Notably, PEG-b-PHPMA(7.0k)-LA micelles displayed superior DOX loading content (21.3 wt %) and loading efficiency (90%). The in vitro release studies showed that only about 23.0% of DOX was released in 12 h from cross-linked micelles at 37 °C at a low micelle concentration of 40 μg/mL, whereas about 87.0% of DOX was released in the presence of 10 mM DTT under otherwise the same conditions. MTT assays showed that DOX-loaded core-cross-linked PEG-b-PHPMA-LA micelles exhibited high antitumor activity in HeLa and HepG2 cells with low IC(50) (half inhibitory concentration) of 6.7 and 12.8 μg DOX equiv/mL, respectively, following 48 h incubation, while blank micelles were practically nontoxic up to a tested concentration of 1.0 mg/mL. Confocal laser scanning microscope (CLSM) studies showed that DOX-loaded