Sample records for long-acting plga microspheres

  1. IVIVC from Long Acting Olanzapine Microspheres.

    PubMed

    D'Souza, Susan; Faraj, Jabar A; Giovagnoli, Stefano; Deluca, Patrick P

    2014-01-01

    In this study, four PLGA microsphere formulations of Olanzapine were characterized on the basis of their in vitro behavior at 37°C, using a dialysis based method, with the goal of obtaining an IVIVC. In vivo profiles were determined by deconvolution (Nelson-Wagner method) and using fractional AUC. The in vitro and in vivo release profiles exhibited the same rank order of drug release. Further, in vivo profiles obtained with both approaches were nearly superimposable, suggesting that fractional AUC could be used as an alternative to the Nelson-Wagner method. A comparison of drug release profiles for the four formulations revealed that the in vitro profile lagged slightly behind in vivo release, but the results were not statistically significant (P < 0.0001). Using the four formulations that exhibited different release rates, a Level A IVIVC was established using the deconvolution and fractional AUC approaches. A nearly 1?:?1 correlation (R (2) > 0.96) between in vitro release and in vivo measurements confirmed the excellent relationship between in vitro drug release and the amount of drug absorbed in vivo. The results of this study suggest that proper selection of an in vitro method will greatly aid in establishing a Level A IVIVC for long acting injectables. PMID:24578707

  2. IVIVC from Long Acting Olanzapine Microspheres

    PubMed Central

    Faraj, Jabar A.; DeLuca, Patrick P.

    2014-01-01

    In this study, four PLGA microsphere formulations of Olanzapine were characterized on the basis of their in vitro behavior at 37°C, using a dialysis based method, with the goal of obtaining an IVIVC. In vivo profiles were determined by deconvolution (Nelson-Wagner method) and using fractional AUC. The in vitro and in vivo release profiles exhibited the same rank order of drug release. Further, in vivo profiles obtained with both approaches were nearly superimposable, suggesting that fractional AUC could be used as an alternative to the Nelson-Wagner method. A comparison of drug release profiles for the four formulations revealed that the in vitro profile lagged slightly behind in vivo release, but the results were not statistically significant (P < 0.0001). Using the four formulations that exhibited different release rates, a Level A IVIVC was established using the deconvolution and fractional AUC approaches. A nearly 1?:?1 correlation (R2 > 0.96) between in vitro release and in vivo measurements confirmed the excellent relationship between in vitro drug release and the amount of drug absorbed in vivo. The results of this study suggest that proper selection of an in vitro method will greatly aid in establishing a Level A IVIVC for long acting injectables. PMID:24578707

  3. Development of Risperidone PLGA Microspheres.

    PubMed

    D'Souza, Susan; Faraj, Jabar A; Giovagnoli, Stefano; Deluca, Patrick P

    2014-01-01

    The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50?:?50 and 75?:?25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40?mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50?:?50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75?:?25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug. PMID:24616812

  4. Development of Risperidone PLGA Microspheres

    PubMed Central

    D'Souza, Susan; Faraj, Jabar A.; Giovagnoli, Stefano; DeLuca, Patrick P.

    2014-01-01

    The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50?:?50 and 75?:?25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40?mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50?:?50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75?:?25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug. PMID:24616812

  5. PLGA microspheres encapsulating siRNA.

    PubMed

    De Rosa, Giuseppe; Salzano, Giuseppina

    2015-01-01

    The therapeutic use of small interfering RNA (siRNA) represents a new and powerful approach to suppress the expression of pathologically genes. However, biopharmaceutical drawbacks, such as short half-life, poor cellular uptake, and unspecific distribution into the body, hamper the development of siRNA-based therapeutics. Poly(lactide-co-glycolide), (PLGA) microspheres can be a useful tool to overcome these issues. siRNA can be encapsulated into the PLGA microspheres, which protects the loaded nucleic acid against the enzymatic degradation. Moreover, PLGA microspheres can be injected directly into the action site, where the siRNA can be released in controlled manner, thus avoiding the need of frequent invasive administrations. The complete biodegradability of PLGA to monomers easily metabolized by the body, and its approval by FDA and EMA for parenteral administration, assure the safety of this copolymer and do not require the removal of the device after the complete drug release. In chapter, a basic protocol for the preparation of PLGA microspheres encapsulating siRNA is described. This protocol is based on a double emulsion/solvent evaporation technique, a well known and easy to reproduce method. This specific protocol has been developed to encapsulate a siRNA anti-TNF? in PLGA microspheres, and it has been designed and optimized to achieve high siRNA encapsulation efficiency and slow siRNA release in vitro. However, it can be extended also to other siRNA as well as other RNA or DNA-based oligonucleotides (miRNA, antisense, decoy, etc.). Depending on the applications, chemical modifications of the backbone and site-specific modification within the siRNA sequences could be required. PMID:25319645

  6. Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres --A review

    E-print Network

    Braatz, Richard D.

    Review Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres delivery PLGA Autocatalysis Bulk degradation Degradable polymer PLGA microspheres are widely studied for controlled release drug delivery applications, and many models have been proposed to describe PLGA

  7. Effects of formulation parameters on encapsulation efficiency and release behavior of thienorphine loaded PLGA microspheres.

    PubMed

    Yang, Yang; Gao, Yongliang; Mei, Xingguo

    2013-01-01

    To develop a long-acting injectable thienorphine biodegradable poly (d, l-lactide-co-glycolide) (PLGA) microsphere for the therapy of opioid addiction, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The thienorphine loaded PLGA microspheres were prepared by o/w solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, residual solvent content and sterility testing. The microspheres were sterilized by gamma irradiation (2.5 kGy). The results indicated that the morphology of the thienorphine PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 30.19 ± 1.17 to 59.15 ± 0.67 ?m and the drug encapsulation efficiency was influenced by drug/polymer ratio, homogeneous rotation speed, PVA concentration in the water phase and the polymer concentration in the oil phase. These changes were also reflected in drug release. The plasma drug concentration vs. time profiles were relatively smooth for about 25 days after injection of the thienorphine loaded PLGA microspheres to beagle dogs. In vitro and in vivo correlation was established. PMID:21967467

  8. Biodegradation and biocompatibility of PLA and PLGA microspheres

    Microsoft Academic Search

    James M Anderson; Matthew S Shive

    1997-01-01

    A fundamental understanding of the in vivo biodegradation phenomenon as well as an appreciation of cellular and tissue responses which determine the biocompatibility of biodegradable PLA and PLGA microspheres are important components in the design and development of biodegradable microspheres containing bioactive agents for therapeutic application. This chapter is a critical review of biodegradation, biocompatibility and tissue\\/material interactions, and selected

  9. Polymer and microsphere blending to alter the release of a peptide from PLGA microspheres

    Microsoft Academic Search

    Harish B Ravivarapu; Kevin Burton; Patrick P DeLuca

    2000-01-01

    The objective of this study was to evaluate the effect of polymer and microsphere blending in achieving both a sufficient initial release and a desired continuous release of a peptide from poly(d,l-lactide-co-glycolide) microspheres. Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a solvent-extraction\\/evaporation process and were characterized for their drug load, bulk density, size distribution, surface area, surface

  10. PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy

    PubMed Central

    Byeon, Hyeong Jun; Kim, Insoo; Choi, Ji Su; Lee, Eun Seong; Shin, Beom Soo; Youn, Yu Seok

    2015-01-01

    The aim of the current study was to investigate the antitumor potential of poly (D,L-lactic-co-glycolic acid) microspheres (PLGA MSs) containing polyethylene glycol (PEG)-conjugated (PEGylated) tumor necrosis factor–related apoptosis-inducing ligand (PEG-TRAIL). PEG-TRAIL PLGA MSs were prepared by using a water-in-oil-in-water double-emulsion method, and the apoptotic activities of supernatants released from the PLGA MSs at days 1, 3, and 7 were examined. The antitumor effect caused by PEG-TRAIL PLGA MSs was evaluated in pancreatic Mia Paca-2 cell-xenografted mice. PEG-TRAIL PLGA MS was found to be spherical and 14.4±1.06 ?m in size, and its encapsulation efficiency was significantly greater than that of TRAIL MS (85.7%±4.1% vs 43.3%±10.9%, respectively). The PLGA MS gradually released PEG-TRAIL for 14 days, and the released PEG-TRAIL was shown to have clear apoptotic activity in Mia Paca-2 cells, whereas TRAIL released after 1 day had a negligible activity. Finally, PEG-TRAIL PLGA MS displayed remarkably greater antitumor efficacy than blank or TRAIL PLGA MS in Mia Paca-2 cell-xenografted mice in terms of tumor volume and weight, apparently due to increased stability and well-retained apoptotic activity of PEG-TRAIL in PLGA MS. We believe that this PLGA MS system, combined with PEG-TRAIL, should be considered a promising candidate for treating pancreatic cancer. PMID:25632232

  11. Adsorption of Salmon Calcitonin to PLGA Microspheres

    Microsoft Academic Search

    Sema Calis; Ramasubbu Jeyanthi; Tsuimin Tsai; Rahul C. Mehta; Patrick P. DeLuca

    1995-01-01

    Purpose. The interaction of salmon calcitonin (sCT) and poly (d,l-lactide-co-glycolide) was detected during preparation and evaluation of microspheres. The purpose of this study was to quantitate the extent and nature of the interaction.

  12. Active self-healing encapsulation of vaccine antigens in PLGA microspheres

    PubMed Central

    Desai, Kashappa-Goud H.; Schwendeman, Steven P.

    2013-01-01

    Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to “actively” load the protein in the polymer pores and facilitate polymer self-healing at temperature > hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigen in PLGA was investigated. Active self-healing encapsulation of two vaccine antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvant (aluminum hydroxide (Al(OH)3) or calcium phosphate). Active loading of vaccine antigen in Al(OH)3-PLGA microspheres was found to: a) increase proportionally with an increasing loading of Al(OH)3 (0.88-3 wt%) and addition of porosigen, b) decrease when the inner Al(OH)3/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0.2 mL and 63 ?m, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)3 in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt% TT) and encapsulation efficiency (~ 97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer, and d) provide improved in vitro controlled release of antigenic TT. PMID:23103983

  13. Heuristic modeling of macromolecule release from PLGA microspheres

    PubMed Central

    Szl?k, Jakub; Pac?awski, Adam; Lau, Raymond; Jachowicz, Renata; Mendyk, Aleksander

    2013-01-01

    Dissolution of protein macromolecules from poly(lactic-co-glycolic acid) (PLGA) particles is a complex process and still not fully understood. As such, there are difficulties in obtaining a predictive model that could be of fundamental significance in design, development, and optimization for medical applications and toxicity evaluation of PLGA-based multiparticulate dosage form. In the present study, two models with comparable goodness of fit were proposed for the prediction of the macromolecule dissolution profile from PLGA micro- and nanoparticles. In both cases, heuristic techniques, such as artificial neural networks (ANNs), feature selection, and genetic programming were employed. Feature selection provided by fscaret package and sensitivity analysis performed by ANNs reduced the original input vector from a total of 300 input variables to 21, 17, 16, and eleven; to achieve a better insight into generalization error, two cut-off points for every method was proposed. The best ANNs model results were obtained by monotone multi-layer perceptron neural network (MON-MLP) networks with a root-mean-square error (RMSE) of 15.4, and the input vector consisted of eleven inputs. The complicated classical equation derived from a database consisting of 17 inputs was able to yield a better generalization error (RMSE) of 14.3. The equation was characterized by four parameters, thus feasible (applicable) to standard nonlinear regression techniques. Heuristic modeling led to the ANN model describing macromolecules release profiles from PLGA microspheres with good predictive efficiency. Moreover genetic programming technique resulted in classical equation with comparable predictability to the ANN model. PMID:24348037

  14. Enhanced immune response after subcutaneous and oral immunization with biodegradable PLGA microspheres

    Microsoft Academic Search

    M Igartua; R. M Hernández; A Esquisabel; A. R Gascón; M. B Calvo; J. L Pedraz

    1998-01-01

    PLGA microspheres containing bovine serum albumin (BSA) as a model antigen, were prepared by a double emulsion\\/solvent extraction method and their in vitro characterization was performed. The same microspheres were used in a series of in vivo studies to evaluate the immune response induced after subcutaneous or oral inoculation following different immunization protocols. The in vivo data confirm that the

  15. Alginate-chitosan-PLGA composite microspheres induce both innate and adaptive immune response through parenteral immunization in fish.

    PubMed

    Behera, Truptimayee; Swain, Priyabrat

    2013-09-01

    Alginate-chitosan-PLGA composite microspheres encapsulating outer membrane protein antigen of Aeromonas hydrophila as an antigen carrier was explored for the first time in a fish model. This composite microsphere showed distinct advantages over the conventional PLGA microparticles in aspects of the high encapsulation efficiency due to the protein-friendly microenvironment created by the hydrophilic alginate-chitosan cores of the composite microspheres, preventing initial burst release and the elimination of lyophilizing process. The antibody responses significantly increased and persist up to 9 weeks in composite microspheres unlike that PLGA microsphere, native OMP and FIA adjuvant. Moreover, several innate immune parameters as respiratory burst, lysozyme and complement activity were significantly increased in both composite and PLGA microspheres up to 9 weeks than other treated groups. It also gives protection from A. hydrophila infection and brought some hope, for its application in replacement with conventional PLGA microparticle for antigen delivery in fish. PMID:23823131

  16. Effect of protein molecular weight on release from micron-sized PLGA microspheres

    Microsoft Academic Search

    Maryellen Sandor; David Enscore; Paula Weston; Edith Mathiowitz

    2001-01-01

    This study investigates the effect of protein molecular weight on release kinetics from polymeric microspheres (1–3 ?m). Proteins were encapsulated at high and low loadings in poly(lactic-co-glycolic acid) (PLGA) by a phase inversion technique. Mechanism of release from this type of microsphere appeared to be dependent on protein molecular weight for microspheres with low loadings (0.5–1.6%), while independent of protein

  17. Stromal-Derived Factor-1 Alpha-Loaded PLGA Microspheres for Stem Cell Recruitment

    PubMed Central

    Cross, Daisy P.

    2014-01-01

    Purpose Stromal-derived factor-1 alpha (SDF-1?) is a chemo-attractant that has been investigated for treating various diseases, with the goal of recruiting endogenous stem cells to the site of injury. Biodegradable PLGA microspheres were investigated as a means to deliver SDF-1? in a sustained-release manner. Methods We encapsulated SDF-1? into biodegradable poly (lactide-co-glycolide) (PLGA) microspheres using a double-emulsion solvent extraction/evaporation technique. We varied several formulation parameters, characterized the in vitro release profile of SDF-1? and the size and morphology of microspheres, and determined the bioactivity of the released SDF-1? of stimulating migration of mesenchymal stem cells (MSCs). Results We found that microspheres fabricated using end-capped PLGA, BSA as an excipient, and low solvent volumes yielded a high encapsulation efficiency (>64%) and released SDF-1? over a >50-day timeframe. The released SDF-1? was bioactive and caused significant migration of MSCs throughout the duration of release from the microspheres. Conclusions We have identified several variables that led to successful encapsulation of SDF-1? into PLGA microspheres. We envision that SDF-l?-loaded microspheres may serve as injectable sources of sustained-release chemokine for promoting the recruitment of endogenous stem cells to the site of injury. PMID:21614634

  18. Enhanced targeting efficiency of PLGA microspheres loaded with Lornoxicam for intra-articular administration.

    PubMed

    Zhang, Zhiyue; Bi, Xiuli; Li, Hui; Huang, Guihua

    2011-01-01

    Owing to its rationale of targeting the drug to the site of action and minimizing systemic toxic effects of the drug, intra-articular drug delivery system has gained growing interests. In this study, emphasis was placed on intra-articular Lornoxicam-loaded PLGA microspheres (Lnxc-PLGA-MS) preparation and improving the targeting of lornoxicam (Lnxc) in knee joint. The microspheres were prepared by a process involving solid-in-oil-in-water(S/O/W) emulsion, and evaluated for physicochemical properties. Joint cavity's drug leakage into systemic circulation in rabbits was examined to define the drug stagnation. Meanwhile, drug retention in synovial fluid in rats was investigated to further validate the drug targeting. The microspheres were spherical as evidenced by the SEM photographs with mean size of 7.47 ?m, and encapsulation efficiency was observed 82.22% along with drug loading 12.17%. DSC revealed that the drug in the microspheres existed in the phase of uncrystallization. The formulated microspheres could prolong the drug release up to 32 days in vitro. Comparing with animals injected with lornoxicam solution, the plasma drug concentration decreased in rabbits and retention time increased in rats' synovial fluid with intra-articular injections of microspheres, revealing good targeting efficiency. In conclusion, PLGA microspheres could be used to deliver lornoxicam following intra-articular administration for enhancing targeting efficiency. PMID:21812757

  19. Hollow superparamagnetic PLGA/Fe 3O 4 composite microspheres for lysozyme adsorption

    NASA Astrophysics Data System (ADS)

    Yang, Qi; Wu, Yao; Lan, Fang; Ma, Shaohua; Xie, Liqin; He, Bin; Gu, Zhongwei

    2014-02-01

    Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe3O4 composite microspheres composed of an inner cavity, PLGA inner shell and Fe3O4 outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe3O4 nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 ?m showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g-1) and high efficiency in lysozyme adsorption.

  20. Hollow superparamagnetic PLGA/Fe3O4 composite microspheres for lysozyme adsorption.

    PubMed

    Yang, Qi; Wu, Yao; Lan, Fang; Ma, Shaohua; Xie, Liqin; He, Bin; Gu, Zhongwei

    2014-02-28

    Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe(3)O(4) composite microspheres composed of an inner cavity, PLGA inner shell and Fe(3)O(4) outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe(3)O(4) nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 ?m showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g(-1)) and high efficiency in lysozyme adsorption. PMID:24492410

  1. Inhibition of Peptide Acylation in PLGA Microspheres with Water-soluble Divalent Cationic Salts

    Microsoft Academic Search

    Ying Zhang; Andreas M. Sophocleous; Steven P. Schwendeman

    2009-01-01

    Purpose  To test the potential of water-soluble divalent cationic salts to inhibit acylation of octreotide encapsulated in poly(D,L-lactic-co-glycolic\\u000a acid)-star (PLGA) microspheres.\\u000a \\u000a \\u000a \\u000a Methods  The divalent cationic salts, calcium chloride and manganese chloride, previously shown to disrupt peptide sorption, were introduced\\u000a in PLGA microspheres prepared by the double emulsion-solvent evaporation method. Peptide stability was monitored by reversed-phase\\u000a high performance liquid chromatography (RP-HPLC) and identified

  2. Injectable PLGA microsphere\\/calcium phosphate cements: physical properties and degradation characteristics

    Microsoft Academic Search

    W. J. E. M. Habraken; J. G. C. Wolke; A. G. Mikos; J. A. Jansen

    2006-01-01

    Calcium phosphate (CaP) cements show an excellent biocompatibility and often have a high mechanical strength, but in general degrade relatively slow. To increase degradation rates, macropores can be introduced into the cement, e.g., by the inclusion of biodegradable microspheres into the cement. The aim of this research is to develop an injectable PLGA microsphere\\/CaP cement with sufficient setting\\/cohesive properties and

  3. Overexpression of GRF Encapsulated in PLGA Microspheres in Animal Skeletal Muscle Induces Body Weight Gain

    Microsoft Academic Search

    Yong-liang Zhang; Xiao-hui Ren; Song-cai Liu; Jian-wei Dai; Lin-lin Hao; Qing-yan Jiang

    2007-01-01

    Biodegradable nanospheres or microspheres have been widely used as a sustained release system for the delivery of bioagents. In the present study, injectable sustained-release growth hormone-releasing factor (GRF) (1–32) microspheres were prepared by a double emulsion-in liquid evaporation process using biodegradable polylactic-co-glycolic acid (PLGA) as the carrier. The entrapment efficiency was 89.79% and the mean particle size was 4.41 ?m.

  4. The effect of gamma-irradiation on PLGA/PEG microspheres containing ovalbumin.

    PubMed

    Dorati, Rossella; Genta, Ida; Montanari, Luisa; Cilurzo, Francesco; Buttafava, Armando; Faucitano, Antonio; Conti, Bice

    2005-09-20

    Poly(ethylene glycol) (PEG) and sodium chloride (NaCl) are excipients used in PLGA microsphere preparation to stabilize proteins and reduce their burst release. No information is till now available in the literature on the effect due to the use of such excipients on the biopharmaceutical performance of gamma-irradiated microparticulate systems. On this purpose, different batches of microspheres containing ovalbumin (OVA) were prepared by using a PLGA 50:50 (average Mr: 13000), different amounts of PEG (Mr: 400 or 4000) and/or sodium chloride. The non-irradiated and irradiated microspheres were characterized in terms of morphology (SEM, particle size distribution), OVA and PEG content and in vitro OVA release. Radiolysis mechanisms of OVA and OVA loaded microspheres were investigated by EPR analysis. Gamma irradiation affects either microsphere morphology or the release of OVA as a function of the amount of PEG, and the use of NaCl. Irradiation significantly reduces release rate of protein from the microspheres containing 15% and 30% of PEG and from controls (microspheres without additives), while no significative effect on protein release rate is highlighted on microspheres containing lower amounts of PEG. EPR investigation shows that increasing amounts of PEG up to 30% have a perturbation effect on OVA radiolysis path. PMID:16023754

  5. Visual Evidence of Acidic Environment Within Degrading Poly(lactic-co-glycolic acid) (PLGA) Microspheres

    Microsoft Academic Search

    Karen Fu; Daniel W. Pack; Alexander M. Klibanov; Robert Langer

    2000-01-01

    Purpose. In the past decade, biodegradable polymers have becomethe materials of choice for a variety of biomaterials applications. Inparticular, poly(lactic-co-glycolic acid) (PLGA) microspheres havebeen extensively studied for controlled-release drug delivery. However,degradation of the polymer generates acidic monomers, andacidification of the inner polymer environment is a central issue in thedevelopment of these devices for drug delivery.

  6. The Stability of Recombinant Human Growth Hormone in Poly(lactic-co-glycolic acid) (PLGA) Microspheres

    Microsoft Academic Search

    Jeffrey L. Cleland; Anne Mac; Brooks Boyd; Janet Yang; Eileen T. Duenas; Douglas Yeung; Dennis Brooks; Chung Hsu; Herman Chu; Venkat Mukku; Andrew J. S. Jones

    1997-01-01

    Purpose. The development of a sustained release formulation for recombinant human growth hormone (rhGH) as well as other proteins requires that the protein be stable at physiological conditions during its in vivo lifetime. Poly(lactic-co-glycolic acid) (PLGA) microspheres may provide an excellent sustained release formulation for proteins, if protein stability can be maintained.

  7. Chitin/PLGA blend microspheres as a biodegradable drug-delivery system: phase-separation, degradation and release behavior.

    PubMed

    Mi, Fwu-Long; Lin, Yi-Mei; Wu, Yu-Bey; Shyu, Shin-Shing; Tsai, Yi-Hung

    2002-08-01

    A novel chitin-based microsphere was developed for anti-cancer drug-delivery purpose in the present study. These biodegradable microspheres were prepared by directly blending chitin with different contents of poly(D,L-lactide-co-glycolide 50:50) (PLGA 50/50) in dimethylacetamide-lithium chloride solution, and following it by coagulating in water via wet phase inversion. Scanning electron microscopy (SEM) micrography of the blend microsphere showed that there are numerous PLGA particulates homogeneously dispersed in chitin matrix, suggesting the occurrence of obvious phase separation from the blended chitin and PLGA 50/50 phase due to their thermodynamic incompatibility. Degradation of the chitin/PLGA 50/50 blend microsphere depends on the surface erosion of chitin phase and bulk hydrolysis of PLGA phase, according to the examinations of SEM and differential scanning calorimetry studies. Weight loss of the chitin/PLGA 50/50 blend microsphere increases with the increase of chitin content in the microsphere. A two-phase drug-release model is observed from the release of chlorambucil from chitin/PLGA 50/50 blend microspheres. The initial stage of drug-release rate increases with the increased chitin content due to the hydration and surface erosion of hydrophilic chitin phase; however, the following stage of slow release is sustained for several days, mainly contributed by the bulk hydrolysis of hydrophobic PLGA phase. In conclusion, such a chitin/PLGA 50/50 blend microsphere is novel and interesting, and may be used as a special drug-delivery system. PMID:12102197

  8. Influence of particle size and antacid on release and stability of plasmid DNA from uniform PLGA microspheres.

    PubMed

    Varde, Neelesh K; Pack, Daniel W

    2007-12-20

    PLGA microspheres are attractive DNA delivery vehicles due to their controlled release capabilities. One major problem with PLGA microspheres is that they develop an acidic microclimate as the polymer degrades, lowering the intraparticle pH, and potentially damaging the DNA. Antacids have recently shown promise in buffering this acidic microclimate and enhancing protein stability. We manufactured uniform plasmid DNA-encapsulating PLGA microspheres of two sizes (47, 80 microm diameter) and antacid concentrations (0, 3% Mg(OH)2). Microspheres with antacid had a homogeneous surface coverage of small pores, which resulted in a significant reduction of the burst effect. The 47 microm microspheres exhibited complete release of plasmid DNA over the course of two months. Incomplete release was observed from 80 microm spheres, though microspheres with 3% Mg(OH)2 showed a higher cumulative release, suggesting that the antacid at least partially aids in increasing the stability of DNA. SEM was used to visualize the surface pore evolution and cross-sectional microsphere structure over time. Subsequent image analysis was used to quantify the increase of surface pore sizes. Cross-sectional images showed increasing internal degradation and erosion, which resulted in a hollowing-out of microspheres. Our studies show that the incorporation of antacid into the microsphere structure has potential in addressing some of the major problems associated with DNA encapsulation and release in PLGA microspheres. PMID:17928089

  9. Influence of particle size and antacid on release and stability of plasmid DNA from uniform PLGA microspheres

    PubMed Central

    Varde, Neelesh K.; Pack, Daniel W.

    2007-01-01

    PLGA microspheres are attractive DNA delivery vehicles due to their controlled release capabilities. One major problem with PLGA microspheres is that they develop an acidic microclimate as the polymer degrades, lowering the intraparticle pH, and potentially damaging the DNA. Antacids have recently shown promise in buffering this acidic microclimate and enhancing protein stability. We manufactured uniform plasmid DNA-encapsulating PLGA microspheres of two sizes (47, 80 ?m diameter) and antacid concentrations (0, 3% Mg(OH)2). Microspheres with antacid had a homogeneous surface coverage of small pores, which resulted in a significant reduction of the burst effect. The 47 ?m microspheres exhibited complete release of plasmid DNA over the course of two months. Incomplete release was observed from 80 ?m spheres, though microspheres with 3% Mg(OH)2 showed a higher cumulative release, suggesting that the antacid at least partially aids in increasing the stability of DNA. SEM was used to visualize the surface pore evolution and cross-sectional microsphere structure over time. Subsequent image analysis was used to quantify the increase of surface pore sizes. Cross-sectional images showed increasing internal degradation and erosion, which resulted in a hollowing-out of microspheres. Our studies show that the incorporation of antacid into the microsphere structure has potential in addressing some of the major problems associated with DNA encapsulation and release in PLGA microspheres. PMID:17928089

  10. Phagostimulatory effect of uptake of PLGA microspheres loaded with rifampicin on alveolar macrophages.

    PubMed

    Hirota, Keiji; Hasegawa, Taizo; Nakajima, Takehisa; Makino, Kimiko; Terada, Hiroshi

    2011-10-15

    Our previous results on the phagocytic activity of alveolar macrophages (M?s) toward poly(lactic-co-glycolic) acid microspheres (PLGA MS) loaded with the anti-tuberculosis agent rifampicin (R-PLGA MS) suggest that the phagocytosis of R-PLGA MS enhances the phagocytic activity of M? cells. To confirm this possibility, we examined the effect of phagocytosis of R-PLGA MS and polystyrene latex (PSL) MS on the phagocytic uptake of fluorescent PSL (F-PSL) MS by cells of the rat alveolar macrophage cell line NR8383 at 37°C. Phagocytic activity was examined in terms of the population of M? cells that had phagocytosed MS (N(total)) and the total number of MS phagocytosed (n(total)) by counting the phagocytic M? cells and the MS ingested in optical microscopic fields. Phagocytosis of R-PLGA MS enhanced about 1.5 times the values of N(total) and n(total) of the phagocytosis of F-PSL MS under the conditions where the phagocytosis of F-PSL MS did not attain the saturated level. In contrast, the phagocytosis of PSL MS did not enhance the phagocytic activity of M? cells toward F-PSL MS. In conclusion, R-PLGA MS are favorable for drug delivery of anti-tuberculosis agents into alveolar M?s due to their ability to up-regulate the phagocytosis of MS. PMID:21700434

  11. Pegylation enhances protein stability during encapsulation in PLGA microspheres

    Microsoft Academic Search

    Manish Diwan; Tae Gwan Park

    2001-01-01

    During encapsulation of proteins in biodegradable microspheres, a significant amount of the protein reportedly undergoes denaturation to form irreversible insoluble aggregates. Incomplete in vitro release of proteins from the microspheres is a common observation. An attempt was made to overcome this problem by pegylation of the protein to be encapsulated. Lysozyme, a model protein, was conjugated with methoxy polyethylene glycol

  12. In vitro degradation and controlled release behavior of D,L-PLGA50 and PCL-b-D,L-PLGA50 copolymer microspheres.

    PubMed

    Dong, Chang-Ming; Guo, Ying-Zhi; Qiu, Kun-Yuan; Gu, Zhong-Wei; Feng, Xin-De

    2005-09-20

    Blank and bovine serum albumin (BSA)-loaded microspheres based on poly(lactic-acid-alt-glycolic acid) (D,L-PLGA50) and poly(epsilon-caprolactone)-b-poly(lactic-acid-alt-glycolic acid) (PCL-b-D,L-PLGA50) were successfully fabricated using water-in-oil-in-water (w/o/w) double-emulsion extraction/evaporation technique. In vitro degradation of the blank microspheres was characterized by techniques including nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The PCL-b-D,L-PLGA50 copolymer (Mn: number-average molecular weight, Mw: weight-average molecular weight, Mn=44800, Mw/Mn=MWD=1.24, epsilon-caprolactone (CL) %=20.4% in molar ratio) had similar rate of molecular weight reduction compared with the D,L-PLGA50 copolymer before 5 weeks of in vitro degradation. The BSA % loading efficiency of microspheres was mainly controlled by both block copolymer composition and macromolecular architecture, while the sequence structure and the molecular weight of copolymer had no apparent effect on it. Significantly, The PCL-b-D,L-PLGA50 copolymer microspheres showed good release profiles with a nearly constant release during 20-110 days. PMID:16005093

  13. Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

    PubMed Central

    Tai, I-Chun; Fu, Yin-Chih; Wang, Chih-Kuang; Chang, Je-Ken; Ho, Mei-Ling

    2013-01-01

    Statins are used clinically for reduction of cholesterol synthesis to prevent cardiovascular disease. Previous in vitro and in vivo studies have shown that statins stimulate bone formation. However, orally administered statins may be degraded during first-pass metabolism in the liver. This study aimed to prevent this degradation by developing a locally administered formulation of simvastatin that is encapsulated in poly(lactic-co-glycolic acid)/hydroxyapatite (SIM/PLGA/HAp) microspheres with controlled-release properties. The effect of this formulation of simvastatin on bone repair was tested using a mouse model of gap fracture bridging with a graft of necrotic bone. The simvastatin released over 12 days from 3 mg and 5 mg of SIM/PLGA/HAp was 0.03–1.6 ?g/day and 0.05–2.6 ?g/day, respectively. SIM/PLGA/HAp significantly stimulated callus formation around the repaired area and increased neovascularization and cell ingrowth in the grafted necrotic bone at week 2 after surgery. At week 4, both 3 mg and 5 mg of SIM/PLGA/HAp increased neovascularization, but only 5 mg SIM/PLGA/HAp enhanced cell ingrowth into the necrotic bone. The low dose of simvastatin released from SIM/PLGA/HAp enhanced initial callus formation, neovascularization, and cell ingrowth in the grafted bone, indicating that SIM/PLGA/HAp facilitates bone regeneration. We suggest that SIM/PLGA/HAp should be developed as an osteoinductive agent to treat osteonecrosis or in combination with an osteoconductive scaffold to treat severe bone defects. PMID:24143094

  14. Effect of acidic pH on PLGA microsphere degradation and release.

    PubMed

    Zolnik, Banu S; Burgess, Diane J

    2007-10-01

    Polymer degradation and drug release kinetics from PLGA microspheres were investigated under neutral and acidic pH conditions. Two different Mw formulations (Mw: 25,000 and 70,000) were investigated and both exhibited a triphasic release profile at pH 7.4 as well as at pH 2.4. The initial burst and lag phases were similar for both pH values, while the secondary apparent-zero-order phase was substantially accelerated at pH 2.4. The polymer molecular weight change with time for the microspheres followed first order degradation kinetics for both pH values. A linear relationship was established between % drug release (post burst release) and Ln (Mw) for both pH conditions. Most significantly, morphological studies showed that the mechanism of polymer degradation changed from "inside-out" degradation at pH 7.4 to "outside-in" at pH 2.4. At pH 7.4, the microspheres followed the usual morphological changes such as surface pitting and pore formation. Whereas, at pH 2.4 the microspheres maintained smooth surfaces throughout the degradation process and were susceptible to fracturing. The fracturing of the microspheres was attributed to crystallization of oligomeric degradation products as a consequence of their low solubility at this pH. It also appeared that degradation occurred in a more homogeneous pattern at pH 2.4 than is typical of PLGA microspheres at pH 7.4. This may be a result of the entire microspheres experiencing a close-to-uniform pH at 2.4. However, at pH 7.4, the local micro-environmental pH within the microspheres has been reported to vary considerably due to a build up of acid oligomers. This heterogeneous degradation results in the random formation of channels within microspheres degraded at pH 7.4 which was not observed in those degraded at pH 2.4. This is the first time that morphological changes during PLGA microsphere degradation have been compared for low and neutral pH and the data shows a change in the mechanism of degradation at the low pH. PMID:17644208

  15. Controllable promotion of chondrocyte adhesion and growth on PVA hydrogels by controlled release of TGF-?1 from porous PLGA microspheres.

    PubMed

    Nie, Lei; Zhang, Guohua; Hou, Ruixia; Xu, Haiping; Li, Yaping; Fu, Jun

    2015-01-01

    Poly(vinyl alcohol) (PVA) hydrogels have been candidate materials for cartilage tissue engineering. However, the cell non-adhesive nature of PVA hydrogels has been a limit. In this paper, the cell adhesion and growth on PVA hydrogels were promoted by compositing with transform growth factor-?1 (TGF-?1) loaded porous poly(D,L-lactide-co-glycolide) (PLGA) microspheres. The porous microspheres were fabricated by a modified double emulsion method with bovine serum albumin (BSA) as porogen. The average pore size of microspheres was manipulated by changing the BSA/PLGA ratio. Such controllable porous structures effectively influenced the encapsulation efficiency (Eencaps) and release profile of TGF-?1. By compositing PVA hydrogels with such TGF-?1-loaded PLGA microspheres, chondrocyte adhesion and proliferation were significantly promoted in a controllable manner, as confirmed by fluorescent imaging and quantitative CCK-8 assay. That is, the chondrocyte proliferation was favored by using PLGA microspheres with high Eencaps of TGF-?1 or by increasing the PLGA microsphere content in the hydrogels. These results demonstrated a facile method to improve the cell adhesion and growth on the intrinsically cell non-adhesive PVA hydrogels, which may find applications in cartilage substitution. PMID:25437063

  16. Room-temperature attachment of PLGA microspheres to titanium surfaces for implant-based drug release

    NASA Astrophysics Data System (ADS)

    Xiao, Dongqin; Liu, Qing; Wang, Dongwei; Xie, Tao; Guo, Tailin; Duan, Ke; Weng, Jie

    2014-08-01

    Drug release from implant surfaces is an effective approach to impart biological activities, (e.g., antimicrobial and osteogenic properties) to bone implants. Coatings of polylactide-based polymer are a candidate for this purpose, but a continuous (fully covering) coating may be non-optimal for implant-bone fixation. This study reports a simple room-temperature method for attaching poly (lactide-co-glycolide) (PLGA) microspheres to titanium (Ti) surfaces. Microspheres were prepared with polyvinyl alcohol (PVA) or polyvinylpyrrolidone (PVP) as the emulsifier. Microspheres were attached to Ti discs by pipetting as a suspension onto the surfaces followed by vacuum drying. After immersion in shaking water bath for 14 d, a substantial proportion of the microspheres remained attached to the discs. In contrast, if the vacuum-drying procedure was omitted, only a small fraction of the microspheres remained attached to the discs after immersion for only 5 min. Microspheres containing triclosan (a broad-spectrum antibiotic) were attached by porous-surfaced Ti discs. In vitro experiments showed that the microsphere-carrying discs were able to kill Staphylococcus aureus and Escherichia Coli, and support the adhesion and growth of primary rat osteoblasts. This simple method may offer a flexible technique for bone implant-based drug release.

  17. Intra-articular lornoxicam loaded PLGA microspheres: enhanced therapeutic efficiency and decreased systemic toxicity in the treatment of osteoarthritis.

    PubMed

    Zhang, Zhiyue; Huang, Guihua

    2012-01-01

    The aim of this study was to investigate the joint tissue distribution and pharmacodynamics of Lornoxicam (Lnxc) following intra-articular injection of either Lnxc suspensions or sustained release Lnxc-loaded PLGA microspheres (Lnxc-MS), as well as the biocompatibility of PLGA microspheres with or without drugs. In this study, Lnxc suspensions or Lnxc-loaded PLGA microspheres was injected into the knee joint cavity of rats. Blood samples were taken at predetermined times from the jugular vein and the joint tissue (cartilage and synovial membrane) were removed from the rats. Biocompatibility and pharmacodynamics were evaluated by observing the swelling of the joints of the rats and histological analysis following the injection of the microspheres. The plasma drug concentration decreased in rats and retention time increased in rats' joint with intra-articular injections of microspheres, revealing good targeting efficiency and decreased systemic toxicity. After 30 days of intra-articular injection with Lnxc-loaded or blank microspheres, the filtration liquid accumulation, blood vessels and fibrous proliferation were not detected, showing their good compatibility. Furthermore, the articular cartilage damage by papain could also be repaired by the Lnxc-loaded PLGA microspheres. In conclusion, intra-articular Lnxc-MS have considerable potential for creating a sustained release Lnxc delivery system and providing effective healing to Osteoarthritis. PMID:22775466

  18. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury

    PubMed Central

    Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery. PMID:25821803

  19. Mechanism of drug release from double-walled PDLLA(PLGA) microspheres

    PubMed Central

    Xu, Qingxing; Chin, Shi En; Wang, Chi-Hwa; Pack, Daniel W.

    2013-01-01

    The drug release and degradation behavior of two double-walled microsphere formulations consisting of a doxorubicin loaded poly(D,L-lactic-co-glycolic acid) (PLGA) core (~46 kDa) surrounded by a poly(D,L-lactic acid) (PDLLA) shell layer (~55 and 116 kDa) were examined. It was postulated that different molecular weights of the shell layer could modulate the erosion of the outer coating and limit the occurrence of water penetration into the inner drug-loaded core on various time scales, and therefore control the drug release from the microspheres. For both microsphere formulations, the drug release profiles were observed to be similar. The degradation of the microspheres was monitored for a period of about nine weeks and analyzed using scanning electron microscopy, laser scanning confocal microscopy, and gel permeation chromatography. Interestingly, both microsphere formulations exhibited occurrence of bulk erosion of PDLLA on a similar time scale despite different PDLLA molecular weights forming the shell layer. The shell layer of the double-walled microspheres served as an effective diffusion barrier during the initial lag phase period and controlled the release rate of the hydrophilic drug independent of the molecular weight of the shell layer. PMID:23453059

  20. The effect of temozolomide/poly(lactide-co-glycolide) (PLGA)/nano-hydroxyapatite microspheres on glioma U87 cells behavior.

    PubMed

    Zhang, Dongyong; Tian, Ang; Xue, Xiangxin; Wang, Mei; Qiu, Bo; Wu, Anhua

    2012-01-01

    In this study, we investigated the effects of temozolomide (TMZ)/Poly (lactide-co-glycolide)(PLGA)/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the "Solid/Water/Oil" method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, ?(V)?3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, ?(V)?3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma. PMID:22312307

  1. Recombinant human growth hormone poly(lactic-co-glycolic acid) (PLGA) microspheres provide a long lasting effect

    Microsoft Academic Search

    Jeffrey L Cleland; Eileen Duenas; Ann Daugherty; Melinda Marian; Janet Yang; Mark Wilson; Abigail C Celniker; Azin Shahzamani; Valerie Quarmby; Herman Chu; Venkat Mukku; Anne Mac; Melissa Roussakis; Nancy Gillette; Brooks Boyd; Douglas Yeung; Dennis Brooks; Yu-Fun Maa; Chung Hsu; Andrew J. S Jones

    1997-01-01

    The treatment of growth hormone deficiency requires the daily administration of recombinant human growth hormone (rhGH). Long lasting formulations of rhGH have the potential to increase patient compliance, improve quality of life, and increase the efficacy of rhGH (lower total dose). One approach to these formulations is the use of biodegradable, injectable microspheres consisting of poly(lactic-co-glycolic acid) (PLGA). rhGH PLGA

  2. Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings.

    PubMed

    Shen, Jie; Burgess, Diane J

    2012-01-17

    Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under "real-time" and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to "real-time" conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict "real-time" release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under "real-time" and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. PMID:22016033

  3. Chemical and spatial analysis of protein loaded PLGA microspheres for drug delivery applications.

    PubMed

    Rafati, A; Boussahel, A; Shakesheff, K M; Shard, A G; Roberts, C J; Chen, X; Scurr, D J; Rigby-Singleton, S; Whiteside, P; Alexander, M R; Davies, M C

    2012-09-10

    Polymer microspheres for controlled release of therapeutic protein from within an implantable scaffold were produced and analysed using complimentary techniques to probe the surface and bulk chemistry of the microspheres. Time of Flight - Secondary Ion Mass Spectrometry (ToF-SIMS) surface analysis revealed a thin discontinuous film of polyvinyl alcohol (PVA) surfactant (circa 4.5 nm thick) at the surface which was readily removed under sputtering with C(60). Atomic Force Microscopy (AFM) imaging of microspheres before and after sputtering confirmed that the PVA layer was removed after sputtering revealing poly(lactic-co-glycolic) acid(PLGA). Scanning electron microscopy showed the spheres to be smooth with some shallow and generally circular depressions, often with pores in their central region. The occurrence of the protein at the surface was limited to areas surrounding these surface pores. This surface protein distribution is believed to be related to a burst release of the protein on dissolution. Analysis of the bulk properties of the microspheres by confocal Raman mapping revealed the 3D distribution of the protein showing large voids within the pores. Protein was found to be adsorbed at the interface with the PLGA oil phase following deposition on evaporation of the solvent. Protein was also observed concentrated within pores measuring approximately 2 ?m across. The presence of protein in large voids and concentrated pores was further scrutinised by ToF-SIMS of sectioned microspheres. This paper demonstrates that important information for optimisation of such complex bioformulations, including an understanding of the release profile can be revealed by complementary surface and bulk analysis allowing optimisation of the therapeutic effect of such formulations. PMID:22580112

  4. Mechanistic studies for monodisperse exenatide-loaded PLGA microspheres prepared by different methods based on SPG membrane emulsification.

    PubMed

    Qi, Feng; Wu, Jie; Yang, Tingyuan; Ma, Guanghui; Su, Zhiguo

    2014-10-01

    Poly(DL-lactic-co-glycolic acid) (PLGA) microspheres have been widely prepared by many methods, including solvent evaporation, solvent extraction and the co-solvent method. However, very few studies have compared the properties of microspheres fabricated by these methods. This is partly because the broad size distribution of the resultant particles severely complicates the analysis and affects the reliability of the comparison. To this end, uniform-sized PLGA microspheres have been prepared by Shirasu porous glass premix membrane emulsification and used to encapsulate exenatide, a drug for treating Type 2 diabetes. Based on this technique, the influences on the properties of microspheres fabricated by the aforementioned three methods were intensively investigated, including in vitro release, degradation and pharmacology. We found that these microspheres presented totally different release behaviors in vitro and in vivo, but exhibited a similar trend of PLGA degradation. Moreover, the internal structural evolution visually demonstrated these release behaviors. We selected for further examination the microsphere prepared by solvent evaporation because of its constant release rate, and explored its pharmacodynamics, histology, etc., in more detail. This microsphere when injected once showed equivalent efficacy to that of twice-daily injections of exenatide with no inflammatory response. PMID:24952071

  5. Dexamethasone\\/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices

    Microsoft Academic Search

    T Hickey; D Kreutzer; D. J Burgess; F Moussy

    2002-01-01

    The purpose of this research was to develop polylactic-co-glycolic acid (PLGA) microspheres for continuous delivery of dexamethasone for over a 1-month period, in an effort to suppress the acute and chronic inflammatory reactions to implants such as biosensors, which interfere with their functionality. The microspheres were prepared using an oil-in-water emulsion technique. The oil phase was composed of 9:1 dichloromethane

  6. Effect of Polymer Porosity on Aqueous Self-Healing Encapsulation of Proteins in PLGA Microspheres

    PubMed Central

    Reinhold, Samuel E.

    2014-01-01

    Self-healing (SH) poly(lactic-co-glycolic acid) (PLGA) microspheres are a unique class of functional biomaterials capable of microencapsulating process-sensitive proteins by simple mixing and heating the drug-free polymer in aqueous protein solution. Drug-free SH microspheres of PLGA 50/50 with percolating pore networks of varying porosity (? = 0.49–73) encapsulate increasing lysozyme (~1–10% w/w) with increasing ?, with typically ~20–25% pores estimated assessible to entry by the enzyme from the external solution. Release kinetics of lysozyme under physiological conditions is continuous over > 2 weeks and most strongly influenced by ? and protein loading before reaching a lag phase until 28 days at the study completion. Recovered enzyme after release is typically predominantly monomeric and active. Formulations containing acid-neutralizing MgCO3 at >4.3% exhibit >97% monomeric and active protein after the release with full mass balance recovery. Hence, control of SH polymer ? is a key parameter to development of this new class of biomaterials. PMID:24285573

  7. Synchronic release of two hormonal contraceptives for about one month from the PLGA microspheres: in vitro and in vivo studies.

    PubMed

    Sun, Yi; Wang, Jiancheng; Zhang, Xuan; Zhang, Zhijun; Zheng, Yan; Chen, Dawei; Zhang, Qiang

    2008-08-01

    A controlled drug release system based on the injectable PLGA microspheres loaded with gestodene and ethinyl estradiol was prepared and evaluated for the feasibility of monthly synchronic delivery of the two hormonal contraceptives. The scanning electron microscopy, light-scattering analyzer and gel permeation chromatography were used to study the morphology, particle size and molecular weight of the polymer microspheres, respectively. HPLC was utilized to determine the drug loading and the drug released, while a LC-MS-MS system was employed to analyze the plasma drug concentration. Result indicated that the PLGA particles obtained were spherical and appropriate in size. The formulation was stable during the test period. In vitro drug release from the microspheres for both drugs was sustained for about 30 days mostly by the diffusion mechanism. The plasma drug concentration-time profiles of the drug-loaded microspheres were relatively smooth after subcutaneous injection to rats for about 1-month, compared with that for drug suspension. In vitro and in vivo correlation was established. One of the most important facts is the synchronicity of the two contraceptives both in the release kinetics in vitro and the pharmacokinetic behaviors in vivo. Therefore, the synchronic delivery of two contraceptives is achieved for about 1 month by using the injectable PLGA-based microspheres. PMID:18539353

  8. Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction\\/evaporation method

    Microsoft Academic Search

    Yi-Yan Yang; Hui-Hui Chia; Tai-Shung Chung

    2000-01-01

    This study describes the influence of preparation temperature on the various characteristics and release profiles of poly(dl-lactide-co-glycolide) (PLGA) microspheres. The bovine serum albumin (BSA)-loaded microspheres were prepared using the water-in-oil-in-water (w\\/o\\/w) technique with poly(vinyl alcohol) as surfactant in the external aqueous phase. We have varied the preparation temperature to observe its effect on microsphere characteristics such as the microsphere shrinking

  9. MAPs/bFGF-PLGA microsphere composite-coated titanium surfaces promote increased adhesion and proliferation of fibroblasts.

    PubMed

    Wang, Zhongshan; Wu, Guofeng; Bai, Shizhu; Feng, Zhihong; Dong, Yan; Zhou, Jian; Qin, Haiyan; Zhao, Yimin

    2014-06-01

    Infection and epithelial downgrowth are two major problems with maxillofacial transcutaneous implants, and both are mainly due to lack of stable closure of soft tissues at transcutaneous sites. Fibroblasts have been shown to play a key role in the formation of biological seals. In this work, titanium (Ti) model surfaces were coated with mussel adhesive proteins (MAPs) utilizing its unique adhesion ability on diverse inorganic and organic surfaces in wet environments. Prepared basic fibroblast growth factor (bFGF)-poly(lactic-co-glycolic acid) (PLGA) microspheres can be easily synthesized and combined onto MAPs-coated Ti surfaces, due to the negative surface charges of microspheres in aqueous solution, which is in contrast to the positive charges of MAPs. Titanium model surfaces were divided into three groups. Group A: MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces. Group B: MAPs-coated Ti surfaces. Group C: uncoated Ti surfaces. The effects of coated Ti surfaces on adhesion of fibroblasts, cytoskeletal organization, proliferation, and extracellular matrix (ECM)-related gene expressions were examined. The results revealed increased adhesion (P < 0.05), enhanced actin cytoskeletal organization, and up-regulated ECM-related gene expressions in groups A and B compared with group C. Increased proliferation of fibroblasts during five days of incubation was observed in group A compared with groups B and C (P < 0.05). Collectively, the results from this in vitro study demonstrated that MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces had the ability to increase fibroblast functionality. In addition, MAPs/bFGF-PLGA microsphere composite-coated Ti surfaces should be studied further as a method of promoting formation of stable biological seals around transcutaneous sites. PMID:24739496

  10. Hyaluronic acid as an internal phase additive to obtain ofloxacin/PLGA microsphere by double emulsion method.

    PubMed

    Wu, Gang; Chen, Long; Li, Hong; Wang, Ying-jun

    2014-01-01

    Hyaluronic acid (HA) was used as an internal phase additive to improve the loading efficiency of ofloxacin, a hydrophilic drug encapsulated by hydrophobic polylactic-co-glycolic acid (PLGA) materials, through a double emulsion (water-in-oil-in-water) solvent extraction/evaporation method. Results from laser distribution analysis show that polyelectrolyte additives have low impact on the average particle size and distribution of the microspheres. The negatively charged HA increases the drug loading efficiency as well as the amount of HA in microspheres. Burst release can be observed in the groups with the polyelectrolyte additives. The release rate decreases with the amount of HA inside the microspheres in all negatively charged polyelectrolyte-added microsphere groups. PMID:24211960

  11. Release of a Wound-Healing Agent from PLGA Microspheres in a Thermosensitive Gel

    PubMed Central

    Machado, H. A.; Abercrombie, J. J.; You, T.; DeLuca, P. P.; Leung, K. P.

    2013-01-01

    The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4–7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50?:?50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50??m. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries. PMID:24224161

  12. Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel.

    PubMed

    Machado, H A; Abercrombie, J J; You, T; Deluca, P P; Leung, K P

    2013-01-01

    The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50?:?50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 ?m. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries. PMID:24224161

  13. Preparation, Characterization, In Vitro Release and Degradation of Cathelicidin-BF-30-PLGA Microspheres

    PubMed Central

    Li, Hongli; Yuan, Mingwei; Yuan, Minglong

    2014-01-01

    Cathelicidin-BF-30 (BF-30), a water-soluble peptide isolated from the snake venom of Bungarus fasciatus containing 30 amino acid residues, was incorporated in poly(D,L-lactide-co-glycolide) (PLGA) 75?25 microspheres (MS) prepared by a water in oil in water W/O/W emulsification solvent extraction method. The aim of this work was to investigate the stability of BF-30 after encapsulation. D-trehalose was used as an excipient to stabilize the peptide. The MS obtained were mostly under 2 µm in size and the encapsulation efficiency was 88.50±1.29%. The secondary structure of the peptide released in vitro was determined to be nearly the same as the native peptide using Circular Dichroism (CD). The ability of BF-30 to inhibit the growth of Escherichia coli was also maintained. The cellular relative growth and hemolysis rates were 92.16±3.55% and 3.52±0.45% respectively. PMID:24963652

  14. Influence of the co-encapsulation of different non-ionic surfactants on the properties of PLGA insulin-loaded microspheres

    Microsoft Academic Search

    G. De Rosa; R. Iommelli; M. I. La Rotonda; A. Miro; F. Quaglia

    2000-01-01

    The aim of this work was to produce insulin-loaded microspheres allowing the preservation of peptide stability during both particle processing and insulin release. Our strategy was to combine the concepts of using surfactants to improve insulin stability while optimising overall microsphere characteristics such as size, morphology, peptide loading and release. Bovine insulin was encapsulated within poly(lactide-co-glycolide) (PLGA 50:50, Resomer RG504H)

  15. Characterization of the release profile of doxycycline by PLGA microspheres adjunct to non-surgical periodontal therapy.

    PubMed

    Moura, Lucas Alves; Ribeiro, Fernanda Vieira; Aiello, Talita Bianchi; Duek, Eliana Ap De Rezende; Sallum, Enilson Antonio; Nociti Junior, Francisco Humberto; Casati, Márcio Zaffalon; Sallum, Antonio Wilson

    2015-07-01

    The aim of this pilot study was to assess the release of locally delivered doxycycline by poly (l-lactide-co-glycolide) (PLGA) microspheres in the periodontal pocket of patients with chronic periodontitis, treated by non-surgical periodontal therapy. Nineteen sites of non-adjacent teeth of four different patients were evaluated. Five milligram of PLGA microspheres loaded with 16 doxycycline hyclate (DOX) was administered per periodontal site. To quantify DOX released into the periodontal pocket, gingival crevicular fluid (GCF) was collected from the sites on days 2, 5, 7, 10, 15, and 20 after DOX application, and high-performance liquid chromatography was performed. Data were statistically assessed by ANOVA/Tukey test. At days 2, 5, and 7, the DOX concentration was stably sustained (23.33 ± 1.38, 23.4 ± 1.82, and 22.75 ± 1.33 ?g/mL, respectively), with no significant differences over these assessment times (p > 0.05). At days 10 and 15, a tendency was observed toward a decrease in DOX concentration (21.74 ± 0.91 and 20.53 ± 4.88 ?g/mL, respectively), but a significant decrease in GCF drug concentration (19.69 ± 4.70 ?g/mL) was observed only on day 20. The DOX delivery system developed demonstrated a successful sustained release after local administration, as an adjunct to non-surgical periodontal therapy. PMID:25917501

  16. Ultrasound-modulated shape memory and payload release effects in a biodegradable cylindrical rod made of chitosan-functionalized PLGA microspheres.

    PubMed

    Bao, Min; Zhou, Qihui; Dong, Wen; Lou, Xiangxin; Zhang, Yanzhong

    2013-06-10

    Minimally invasive implants and/or scaffolds integrated with multiple functionalities are of interest in the clinical settings. In this paper, chitosan (CTS) functionalized poly(lactic-co-glycolic acid) (PLGA) microspheres containing a model payload, lysozyme (Lyz), were prepared by a water-in-oil-in-water emulsion method, from which cylindrical shaped rod (5 mm in diameter) was fabricated by sintering the composite microspheres in a mold. High-intensity focused ultrasound (HIFU) was then employed as a unique technique to enable shape memory and payload release effects of the three-dimensional (3-D) structure. It was found that incorporation of CTS into PLGA microspheres could regulate the transition temperature Ttrans of the microsphere from 45 to 50 °C and affect shape memory ratio of the fabricated cylindrical rod to some extent. Shape memory test and drug release assay proved that HIFU could modulate the shape recovery process and synchronize the release kinetics of the encapsulated Lyz in the rod in a switchable manner. Moreover, the two processes could be manipulated by varying the acoustic power and insonation duration. Mechanical tests of the microspheres-based rod before and after ultrasound irradiation revealed its compressive properties in the range of trabecular bone. Examination of the degradation behavior indicated that the introduction of CTS into the PLGA microspheres also alleviated acidic degradation characteristic of the PLGA-dominant cylindrical rod. With HIFU, this study thus demonstrated the desired capabilities of shape recovery and payload release effects integrated in one microspheres-based biodegradable cylindrical structure. PMID:23675980

  17. Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres.

    PubMed

    Barat, Ana; Crane, Martin; Ruskin, Heather J

    2008-09-29

    Using poly(lactide-co-glycolide) (PLGA) particles for drug encapsulation and delivery has recently gained considerable popularity for a number of reasons. An advantage in one sense, but a drawback of PLGA use in another, is that drug delivery systems made of this material can provide a wide range of dissolution profiles, due to their internal structure and properties related to particles' manufacture. The advantages of enriching particulate drug design experimentation with computer models, are evident with simulations used to predict and optimize design, as well as indicate choice of best manufacturing parameters. In the present work, we seek to understand the phenomena observed for PLGA micro- and nanospheres, through Cellular Automata (CA) agent-based Monte Carlo (MC) models. Systems are studied both over large temporal scales (capturing slow erosion of PLGA) and for various spatial configurations (capturing initial as well as dynamic morphology). The major strength of this multi-agent approach is to observe dissolution directly, by monitoring the emergent behaviour: the dissolution profile manifested, as a sphere erodes. Different problematic aspects of the modelling process are discussed in details in this paper. The models were tested on experimental data from literature, demonstrating very good performance. Quantitative discussion is provided throughout the text in order to make a demonstration of the use in practice of the proposed model. PMID:18436414

  18. Characterization of PLGA microspheres for the controlled delivery of IL1 ? for tumor immunotherapy

    Microsoft Academic Search

    Limor Chen; Ron N Apte; Smadar Cohen

    1997-01-01

    This paper describes the preparation and characterization of poly(lactic-co-glycolic acid) microspheres for the continuous delivery of a recombinant human interleukin-1? (IL-1?), a cytokine that is investigated for the immunotherapy of tumors. The polymers forming the microspheres were from two different sources, had a comonomer ratio of 50:50 or 75:25 (lactic\\/glycolic acid), and mol. wts. of 5–15 kDa, and were expected

  19. Respirable PLGA Microspheres Containing Rifampicin for the Treatment of Tuberculosis: Screening in An Infectious Disease Model

    Microsoft Academic Search

    Sandra Suarez; Patrick O'Hara; Masha Kazantseva; Christian E. Newcomer; Roy Hopfer; David N. McMurray; Anthony J. Hickey

    2001-01-01

    Purpose. Targeted delivery of rifampicin loaded microspheres to the alveolar macrophage, the host cell for Mycobacterium tuberculosis(MTB), may be an effective targeted approach to pulmonary tuberculosis therapy. A guinea pig infection model has been adopted as a post-treatment screening method for antimicrobial effect. Insufflation and nebulization methods of drug delivery were evaluated.

  20. Respirable PLGA Microspheres Containing Rifampicin for the Treatment of Tuberculosis: Manufacture and Characterization

    Microsoft Academic Search

    Patrick O'Hara; Anthony J. Hickey

    2000-01-01

    Purpose. Particles with aerodynamic diameters of 1–5µm deposit in the periphery of the lungs and are phagocytized by alveolarmacrophages, the primary site of Mycobacterium tuberculosisinfection. Aerosols of biodegradable polymeric microspheres containingantitubercular agents may be delivered to the lungs to improve the treatmentof tuberculosis.

  1. Revisiting PLA\\/PLGA microspheres: an analysis of their potential in parenteral vaccination

    Microsoft Academic Search

    Pål Johansen; Ying Men; Hans P Merkle; Bruno Gander

    2000-01-01

    Poly(lactide) and poly(lactide-co-glycolide) microspheres have been studied for controlled antigen delivery and immune response enhancement for more than a decade. Early developments of such vaccines were basically technology-driven, stemming from the well-established biocompatibility of these polymers in concert with their innate properties to tailor rates of bioerosion and release. More recently, other features have become equally or even more appealing,

  2. Pegylated recombinant human epidermal growth factor (rhEGF) for sustained release from biodegradable PLGA microspheres

    Microsoft Academic Search

    Tae Hyoung Kim; Haeshin Lee; Tae Gwan Park

    2002-01-01

    Recombinant human epidermal growth factor (rhEGF) was conjugated with polyethylene glycol (PEG) to improve its physical stability during microencapsulation in biodegradable poly(lactic-co-glycolic acid) microspheres. rhEGF was conjugated with N-hydroxysuccimide (NHS)-derivatized methoxy-PEG (mPEG) of MW 2000 and 5000 under various reaction conditions to optimize the extent of pegylation. Pegylated rhEGF showed much enhanced physical stability against homogenization. Pegylated rhEGF was encapsulated

  3. Effect of lactoferrin-impregnated porous poly(lactide-co-glycolide) (PLGA) microspheres on osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs).

    PubMed

    Kim, Sung Eun; Yun, Young-Pil; Shim, Kyu-Sik; Park, Kyeongsoon; Choi, Sung-Wook; Suh, Dong Hun

    2014-10-01

    The aim of this study was to develop lactoferrin (LF)-impregnated porous poly(lactide-co-glycolide) (PLGA) microspheres (PMs) to induce osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs). Porous PLGA PMs were fabricated by a fluidic device and their surfaces were modified with heparin-dopamine (Hep-DOPA). Then, LF (100?g, 500?g, and 1000?g) was impregnated on the surface of heparinized PMs (Hep-PMs) via electrostatic interactions to yield LF-impregnated PMs. PMs and modified PMs were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Osteogenic differentiation of rADSCs on PMs and modified PMs was demonstrated by alkaline phosphatase (ALP) activity, calcium deposition, and mRNA expression of osteocalcin and osteopontin. Successful immobilization of Hep-DOPA and LF on the surface of PMs was confirmed by XPS analysis. LF-impregnated PMs generated significantly greater ALP activity, calcium deposition, and mRNA expression of osteocalcin and osteopontin compared with PMs. These results suggested that LF-impregnated PMs effectively induced osteogenic differentiation of rADSCs. PMID:25096719

  4. Modified composite microspheres of hydroxyapatite and poly(lactide-co-glycolide) as an injectable scaffold

    NASA Astrophysics Data System (ADS)

    Hu, Xixue; Shen, Hong; Yang, Fei; Liang, Xinjie; Wang, Shenguo; Wu, Decheng

    2014-02-01

    The compound of hydroxyapatite-poly(lactide-co-glycolide) (HA-PLGA) was prepared by ionic bond between HA and PLGA. HA-PLGA was more stable than the simple physical blend of hydroxyapatite and poly(lactide-co-glycolide) (HA/PLGA). The surface of HA-PLGA microsphere fabricated by an emulsion-solvent evaporation method was rougher than that of HA/PLGA microspheres. Moreover, surface HA content of HA-PLGA microspheres was more than that of HA/PLGA microspheres. In vitro mouse OCT-1 osteoblast-like cell culture results showed that the HA-PLGA microspheres clearly promoted osteoblast attachment, proliferation and alkaline phosphatase activity. It was considered that surface rich HA component and rough surface of HA-PLGA microsphere enhanced cell growth and differentiation. The good cell affinity of the HA-PLGA microspheres indicated that they could be used as an injectable scaffold for bone tissue engineering.

  5. Prevention of local tumor growth with paclitaxel-loaded microspheres

    E-print Network

    resection margin. Methods: Poly-(D,L-lactic-co-glycolic acid) (PLGA) microspheres loaded unloaded (carrier alone) PLGA microspheres, and Lewis lung carcinoma cells com- bined with 50 3 106 or 100 3 106 paclitaxel-loaded PLGA microspheres. After the coinjection of Lewis lung carcinoma cells

  6. PLGA-PEG-PLGA microspheres as a delivery vehicle for antisense oligonucleotides to CTGF: Implications on post-surgical peritoneal adhesion prevention

    NASA Astrophysics Data System (ADS)

    Azeke, John Imuetinyan-Jesu, Jr.

    Abdominal adhesions are the aberrant result of peritoneal wound healing commonly associated with surgery and inflammation. A subject of a large number of studies since the first half of the last century, peritoneal adhesion prevention has, for the most part, evaded the scientific community and continues to cost Americans an estimated $2-4 billion annually. It is known that transforming growth factor-beta (TGF-beta) plays a key role in the wound healing cascade; however, suppression of this multifunctional growth factor's activity may have more harmful consequences than can be tolerated. As a result, much attention has fallen on connective tissue growth factor (CTGF), a downstream mediator of TGF-beta's fibrotic action. It has been demonstrated in several in vitro models, that the suppression of CTGF hinders fibroblast proliferation, a necessary condition for fibrosis. Furthermore, antisense oligonucleotides (antisense oligos, AO) to CTGF have been shown to knock down CTGF mRNA levels by specifically hindering the translation of CTGF protein. Antisense technologies have met with a great deal of excitement as a viable means of preventing diseases such as adhesions by hindering protein translation at the mRNA level. However, the great challenge associated with the use of these drugs lies in the short circulation time when administered "naked". Viral delivery systems, although excellent platforms in metabolic studies, are not ideal for diagnostic use because of the inherent danger associated with viral vectors. Microparticles made of biodegradable polymers have therefore presented themselves as a viable means of delivering these drugs to target cells over extended periods. Herein, we present two in vivo studies confirming the up-regulation of TGF-beta protein and CTGF mRNA following injury to the uterine tissues of female rats. We were able to selectively knockdown post-operative CTGF protein levels following surgery, however, our observations led us to conclude that, while both cytokines are over-expressed within the first day following injury, CTGF protein levels could not be correlated with observed adhesion development. In addition, we synthesized linear triblock copolymers of polyethylene glycol (PEG) and poly(D,L-lactide-co-glycolide) (PLGA), two of the most widely studied biodegradable polymers in use today. Bulk gels and microparticles of the copolymers were then evaluated for gelling behavior, temperature stability, and drug loading and release kinetics in order assess their suitability as potential carriers of antisense therapeutics. A novel approach to affecting the antisense oligonucleotide release kinetics by varying the relative concentrations of co-encapsulated cationic lipid transfection agents was also presented.

  7. Long-acting risperidone injection: efficacy, safety, and cost-effectiveness of the first long-acting atypical antipsychotic

    PubMed Central

    Chue, Pierre

    2007-01-01

    Objective To review the pharmacokinetics, efficacy, safety, and cost-effectiveness of long-acting risperidone. Methods Studies published between January 2000 and October 2006 evaluating the pharmacokinetics, efficacy, safety, and cost-effectiveness of long-acting risperidone were reviewed, as identified from literature searches using Medline and EMBASE. Abstracts and posters on long-acting risperidone presented at key psychiatry congresses and available in the public domain during this time period were also reviewed. Results The unique pharmacokinetic profile of long-acting risperidone is derived from the encapsulation of risperidone in a glycolide/lactide matrix in the form of microspheres such that after a single intramuscular injection, significant plasma levels of the drug are achieved after week 3. Steady state, after repeated administration at 2-week intervals, is achieved after 3 injection cycles. Short- and long-term studies have demonstrated that long-acting risperidone (25, 37.5, or 50 mg) is both efficacious and well tolerated in a wide variety of patients with schizophrenia and related psychoses. Most patients can be switched from other oral and long-acting antipsychotic agents without compromising efficacy and safety. Long-acting risperidone may also reduce overall healthcare costs by decreasing rates of relapse and hospitalization. Conclusion The assured delivery of an atypical antipsychotic medication with long-acting risperidone has important implications for patient compliance, maintenance of stability, consistency of treatment, and improving patient outcomes including the achievement of remission. PMID:19300536

  8. Microencapsulation techniques using ethyl acetate as a dispersed solvent: effects of its extraction rate on the characteristics of PLGA microspheres

    Microsoft Academic Search

    Hongkee Sah

    1997-01-01

    Ethyl acetate solvent evaporation and extraction processes were developed to prepare poly(d,l-lactide-co-glycolide) microspheres. The microencapsulation processes first emulsified a polymer-containing ethyl acetate solution with a 1% aqueous polyvinyl alcohol solution (W1) to make an oil-in-water (O\\/W1) emulsion. The O:W1 phase ratio was carefully chosen so as to saturate the W1 by a small proportion of the dispersed solvent and to

  9. How to achieve sustained and complete protein release from PLGA-based microparticles?

    E-print Network

    Paris-Sud XI, Université de

    - 1 - How to achieve sustained and complete protein release from PLGA-based microparticles? A. Keywords Sustained release; protein; microspheres; poly(lactic-co-glycolic acid) (PLGA); in vitro release in the delivery of therapeutic proteins from PLGA- based microparticles is the sustained and complete release

  10. Inhalable Large Porous Microspheres of Low Molecular Weight Heparin: In Vitro and In Vivo Evaluation

    PubMed Central

    Rawat, Amit; Majumder, Quamrul H.; Ahsan, Fakhrul

    2008-01-01

    This study tests the feasibility of large porous particles as long-acting carriers for pulmonary delivery of low molecular weight heparin (LMWH). Microspheres were prepared with a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), by a double-emulsion–solvent-evaporation technique. The drug entrapment efficiencies of the microspheres were increased by modifying them with three different additives—polyethyleneimine (PEI), Span 60 and stearylamine. The resulting microspheres were evaluated for morphology, size, zeta potential, density, in vitro drug-release properties, cytotoxicity, and for pulmonary absorption in vivo. Scanning electron microscopic examination suggests that the porosity of the particles increased with the increase in aqueous volume fraction. The amount of aqueous volume fraction and the type of core-modifying agent added to the aqueous interior had varying degrees of effect on the size, density and aerodynamic diameter of the particles. When PEI was incorporated in the internal aqueous phase, the entrapment efficiency was increased from 16.22±1.32% to 54.82±2.79%. The amount of drug released in the initial burst phase and the release-rate constant for the core-modified microspheres were greater than those for the plain microspheres. After pulmonary administration, the half-life of the drug from the PEI- and stearylamine-modified microspheres was increased by 5- to 6-fold compared to the drug entrapped in plain microspheres. The viability of Calu-3 cells was not adversely affected when incubated with the microspheres. Overall, the data presented here suggest that the newly developed porous microspheres of LMWH have the potential to be used in a form deliverable by dry-powder inhaler as an alternative to multiple parenteral administrations of LMWH. PMID:18471921

  11. In vitro evaluation of biodegradable microspheres with surface-bound ligands Mark E. Keegan a,b

    E-print Network

    Fahmy, Tarek

    . Keywords: Caco-2; Microsphere; PLGA; Surface modification; Targeted drug delivery 1. Introduction(lactic-co-glycolic acid) (PLGA) microspheres have been described [3,5,6,15,16]. Coupling ligands to the surface (and biologically) inert, aside from the polymer degradation reaction. Protocols for making PLGA

  12. Stability of proteins within biodegradable microspheres

    E-print Network

    Fu, Karen, 1967-

    2000-01-01

    In the past decade, biodegradable polymers have become the materials of choice for a variety of biomaterials applications. In particular, poly(lactic-co-glycolic acid) (PLGA) microspheres have been extensively studied for ...

  13. Prediction of solvent removal profile and effect on properties for peptide-loaded PLGA microspheres prepared by solvent extraction\\/ evaporation method

    Microsoft Academic Search

    Wen-I Li; Kimberly W. Anderson; Rahul C. Mehta; Patrick P. Deluca

    1995-01-01

    Using a predictive mathematical model, several important extrinsic process variables were varied to simulate the process dynamics of microsphere formation. These included the composition profile in the dispersed phase, the solvent concentration profile in the continuous phase and the solvent removal profile in the dispersed phase. By superimposing the composition profile in the dispersed phase with the phase transition boundary,

  14. Influence of different formulations and process parameters during the preparation of drug-loaded PLGA microspheres evaluated by multivariate data analysis.

    PubMed

    Vysloužil, Jakub; Doležel, Petr; Kejdušová, Martina; Mašková, Eliška; Mašek, Josef; Luká?, Robert; Koš?ál, Vratislav; Vetchý, David; Dvo?á?ková, Kate?ina

    2014-12-01

    The main objective of this study was to evaluate the influence of the formulation and process parameters on PLGA microparticles containing a practically insoluble model drug (ibuprofen) prepared by the o/w solvent evaporation method. Multivariate data analysis was used. The effects of altered stirring speed of a mechanical stirrer (600, 1000 rpm), emulsifier concentrations (PVA concentration 0.1 %, 1 %) and solvent selection (dichloromethane, ethyl acetate) on microparticle characteristics (encapsulation efficiency, drug loading, burst effect) were observed. It was found that with increased stirring speed, the PVA concentration or the use of ethyl acetate had a significantly negative effect on encapsulation efficiency. In addition, ethyl acetate had an adverse effect on the burst effect, while increased stirring speed had the opposite effect. Drug load was not affected by any particular variable, but rather by the interactions of evaluated variables. PMID:25531782

  15. On-demand one-step synthesis of monodisperse functional polymeric microspheres with droplet microfluidics.

    PubMed

    Yu, Xu; Cheng, Gong; Zhou, Ming-Da; Zheng, Si-Yang

    2015-04-01

    A simple and robust method for one-step synthesis of monodisperse functional polymeric microspheres was established by generation of reversed microemulsion droplets in aqueous phase inside microfluidic chips and controlled evaporation of the organic solvent. Using this method, water-soluble nanomaterials can be easily encapsulated into biodegradable Poly(D,L-lactic-co-glycolic acid) (PLGA) to form functional microspheres. By controlling the flow rate of microemulsion phase, PLGA polymeric microspheres with narrow size distribution and diameters in the range of ?50-100 ?m were obtained. As a demonstration of the versatility of the approach, high-quality fluorescent CdTe:Zn(2+) quantum dots (QDs) of various emission spectra, superparamagnetic Fe3O4 nanoparticles, and water-soluble carbon nanotubes (CNTs) were used to synthesize fluorescent PLGA@QDs, magnetic PLGA@Fe3O4, and PLGA@CNTs polymeric microspheres, respectively. In order to show specific applications, the PLGA@Fe3O4 were modified with polydopamine (PDA), and then the silver nanoparticles grew on the surfaces of the PLGA@Fe3O4@PDA polymeric microspheres by reducting the Ag(+) to Ag(0). The as-prepared PLGA@Fe3O4@PDA-Ag microspheres showed a highly efficient catalytic reduction of the 4-nitrophenol, a highly toxic substance. The monodisperse uniform functional PLGA polymeric microspheres can potentially be critically important for multiple biomedical applications. PMID:25782525

  16. Temozolomide\\/PLGA microparticles: a new protocol for treatment of glioma in rats

    Microsoft Academic Search

    Yu-Hui Zhang; He Zhang; Jian-min Liu; Zhi-Jian Yue

    Implantable and poly (d,l-lactide-co-glycolide) (PLGA) microparticles were developed to deliver temozolomide (TM) continuously\\u000a in interstitial chemotherapy for glioma. The therapeutic effect of temozolomide\\/PLGA was evaluated in a rat C6 glioma model.\\u000a C6 cells were implanted orthotopically into 100 rat brains in 5 groups (n = 20 each): sham operation group, control group, local delivery of blank PLGA microspheres group, oral TM group,

  17. Delivering neuroactive molecules from biodegradable microspheres for application in central nervous system disorders

    Microsoft Academic Search

    Xudong Cao; Molly S. Shoichet

    1999-01-01

    Nerve growth factor (NGF) may enhance axonal regeneration following injury to the central nervous system (CNS), such as after spinal cord injury. The release profile of NGF, co-encapsulated with ovalbumin, was tailored from biodegradable polymeric microspheres using both polymer degradation and protein loading. Biodegradable polymeric microspheres were prepared from PLGA 50\\/50, PLGA 85\\/15, PCL and a blend of PCL\\/PLGA 50\\/50

  18. Long-Acting Reversible Contraception for Adolescents.

    PubMed

    Fontenot, Holly B; Fantasia, Heidi Collins

    2015-06-01

    In 2013 and 2014, the Centers for Disease Control and Prevention (CDC) publicized its recommendations for the use of long-acting reversible contraception (LARC) (including intrauterine devices and implants) as first-line, highly effective options for pregnancy prevention. The use of LARC by adolescents has had growing support by national health and women's health organizations. Ongoing research is beginning to uncover facilitators and barriers to LARC use in adolescents. The purpose of this column is to highlight two recent U.S.-based studies in which researchers examined perspectives related to and factors associated with LARC use in adolescent and young adult women. PMID:26058908

  19. Long-acting preparations of exenatide

    PubMed Central

    Cai, Yunpeng; Wei, Liangming; Ma, Liuqing; Huang, Xiwen; Tao, Anqi; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Exenatide has been widely used for the treatment of type 2 diabetes mellitus. However, its short plasma half-life of 2.4 hours has limited its clinical application. The exenatide products on the market, twice-daily Byetta™ and once-weekly Bydureon™ (both Amylin Pharmaceuticals, San Diego, CA, USA), are still not perfect. Many researchers have attempted to prolong the acting time of exenatide by preparing sustained-release dosage forms, modifying its structure, gene therapies, and other means. This review summarizes recent advances in long-acting exenatide preparations. PMID:24039406

  20. Development of a 5-fluorouracil-loaded PLGA microsphere delivery system by a solid-in-oil-in-hydrophilic oil (S/O/hO) novel method for the treatment of tumors.

    PubMed

    Lin, Qing; Cai, Yunpeng; Yuan, Minglu; Ma, Lin; Qiu, Mingfeng; Su, Jing

    2014-12-01

    Tumor treatment requires a long-term regimen of chemotherapy, and both surgical tumor resection and radiation therapy are also used. The present study aimed to develop a novel method for 5-fluorouracil (5-FU)-loaded microspheres which enhance the therapeutic effects of chemotherapy, the quality of life of patients and reduce chemotherapy systemic side-effects. The preparation of a 5-FU microsphere delivery system by a solid-in-oil-in-hydrophilic oil (S/O/hO) novel method was carried out and then in vitro and in vivo evaluation of the 5-FU-microsphere delivery system was conducted. The 5-FU microsphere delivery system prepared had sustained-release function and achieved local treatment efficacy for tumors. The encapsulation efficiency of the 5-FU microsphere delivery system was >90% [better than the fabrication method using water-in-oil-in-water (W/O/W)]. The drug release profile from the 5-FU-loaded sustained-release microsphere delivery system matched the pseudo zero-order equation for 30 days in vitro. The plasma concentration of 5-FU was higher than the water solution by subcutaneous injection. The tumor growth rate of rabbits using the 5-FU microsphere delivery system was much lower than the rate in rabbit using a subcutaneous injection of 5-FU water solution. The 5-FU-loaded sustained-release microspheres using the novel method (S/O/hO) is a potential and effective method with which to inhibit tumor growth. PMID:25231485

  1. Protein encapsulation and release from poly(lactide-co-glycolide) microspheres: effect of the protein and polymer properties and of the co-encapsulation of surfactants

    Microsoft Academic Search

    Dolores Blanco; Mar??a J Alonso

    1998-01-01

    Despite the recognised role of the poly(lactide-co-glycolide) (PLGA) in the encapsulation and release of proteins from PLGA microspheres, the importance that the characteristics of the protein have in these processes has not yet been sufficiently investigated. The aim of this work was to study the simultaneous effect of the protein and PLGA properties and of the microencapsulation process on the

  2. Preparation and characterization of poly(D,L-lactide-co-glycolide) microspheres for controlled release of human growth hormone.

    PubMed

    Capan, Yilmaz; Jiang, Ge; Giovagnoli, Stefano; Na, Kyu-Heum; DeLuca, Patrick P

    2003-01-01

    The purpose of this research was to assess the physicochemical properties of a controlled release formulation of recombinant human growth hormone (rHGH) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) composite microspheres. rHGH was loaded in poly(acryloyl hydroxyethyl) starch (acHES) microparticles, and then the protein-containing microparticles were encapsulated in the PLGA matrix by a solvent extraction/evaporation method. rHGH-loaded PLGA microspheres were also prepared using mannitol without the starch hydrogel microparticle microspheres for comparison. The detection of secondary structure changes in protein was investigated by using a Fourier Transfer Infrared (FTIR) technique. The composite microspheres were spherical in shape (44.6 +/- 2.47 microm), and the PLGA-mannitol microspheres were 39.7 +/- 2.50 microm. Drug-loading efficiency varied from 93.2% to 104%. The composite microspheres showed higher overall drug release than the PLGA/mannitol microspheres. FTIR analyses indicated good stability and structural integrity of HGH localized in the microspheres. The PLGA-acHES composite microsphere system could be useful for the controlled delivery of protein drugs. PMID:12916910

  3. Process and formulation variables in the preparation of injectable and biodegradable magnetic microspheres

    Microsoft Academic Search

    Hong Zhao; Jeffrey Gagnon; Urs O Häfeli

    2007-01-01

    The aim of this study was to prepare biodegradable sustained release magnetite microspheres sized between 1 to 2 ?m. The microspheres with or without magnetic materials were prepared by a W\\/O\\/W double emulsion solvent evaporation technique using poly(lactide-co-glycolide) (PLGA) as the biodegradable matrix forming polymer. Effects of manufacturing and formulation variables on particle size were investigated with non-magnetic microspheres. Microsphere

  4. Long-acting risperidone in stable patients with schizoaffective disorder

    Microsoft Academic Search

    A. Mohl; K. Westlye; S. Opjordsmoen; A. Lex; A. Schreiner; M. Benoit; P. Bräunig; R. Medori

    2005-01-01

    Oral and long-acting risperidone has been shown to be effective for acute and maintenance treatment of patients with schizoaffective disorders. The present analysis investigated the efficacy and tolerability of direct transition from other antipsychotics to risperidone long-acting injectable in patients with schizoaffective disorder.Patients aged ? 18 years with schizoaffective disorder (DSM-IV), who required a change of medication, received risperidone long-acting

  5. Development and characterization of GRGDSPC-modified poly(lactide-co-glycolide acid) porous microspheres incorporated with protein-loaded chitosan microspheres for bone tissue engineering.

    PubMed

    Tao, Chun; Huang, Jingbin; Lu, Ying; Zou, Hao; He, Xinyi; Chen, Yan; Zhong, Yanqiang

    2014-10-01

    Scaffolds that can achieve cell adhesion and controlled release of protein drugs are very promising in bone tissue engineering. Due to their biocompatibility and injectablity, poly(lactide-co-glycolide acid) (PLGA) porous microspheres (PLGA-pMS) present potential scaffolds in bone tissue engineering. However, their application is hampered by the burst release of protein drugs and hydrophobicity that leads to poor cell adhesion. To overcome these drawbacks, we developed novel PLGA-pMS by incorporating bovine serum albumin (BSA) loaded chitosan microspheres (CS-MS) in Gly-Arg-Gly-Asp-Ser-Pro-Cys (GRGDSPC) modified PLGA-pMS (CS-MS/PLGA-pMS). GRGDSPC was used to enhance the hydrophilicity and cell affinity of the porous microspheres. Results showed that PLGA-pMS had a size of 446.77±19.46?m, with an average surface pore size of 21.56±3.02?m, whereas CS-MS had a size of 15.98±0.96?m and 16.35±0.38?m (5% and 10% TPP-prepared CS-MS, respectively). A scanning electron microscope (SEM) and a confocal laser scanning microscope (CLSM) revealed that CS-MS were partly embedded in the PLGA matrices and the integrity of CS-MS was retained. Thermogravimetry analyzer (TGA) also demonstrated that CS-MS were incorporated into PLGA-pMS. The CS-MS/PLGA-pMS had a size of 454.02±16.09?m, with a BSA encapsulation efficiency of 53.19±1.67% and 62.16±3.44% (5% and 10% TPP-prepared CS-MS, respectively). CS-MS/PLGA-pMS exhibited a sustained FITC-BSA release for 28 days. Modification of GRGDSPC significantly improved adhesion of MG-63 cells on the porous microspheres. In conclusion, CS-MS/PLGA-pMS may act as potential bifunctional scaffolds for bone tissue engineering. PMID:25074502

  6. Drug-loaded biodegradable microspheres for image-guided combinatory epigenetic therapy in cells

    NASA Astrophysics Data System (ADS)

    Xu, Ronald X.; Xu, Jeff S.; Zuo, Tao; Shen, Rulong; Huang, Tim H.; Tweedle, Michael F.

    2011-02-01

    We synthesize drug-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for image-guided combinatory epigenetic therapy in MCF-10A human mammary epithelial cells. LY294002 and Nile Red are encapsulated in microspheres for sustained drug release and fluorescence microscopic imaging. Drug-loaded microspheres target MCF-10A cells through a three-step binding process involving biotinylated antibody, streptavidin, and biotinylated microspheres. LY294002 loaded microspheres and 5-Aza-2-deoxycytidine are applied to MCF-10A cells for combinatory PI3K/AKT inhibition and deoxyribonucleic acid (DNA) demethylation. Our study implies the technical potential of disease targeting and image-guided combinatory epigenetic therapy using drug-loaded multifunctional biodegradable PLGA microspheres.

  7. Long-acting injectable aripiprazole: how might it fit in our tool box?

    PubMed

    Gopalakrishna, Ganesh; Aggarwal, Arpit; Lauriello, John

    2013-01-01

    Schizophrenia is a severe mental illness with a lifetime prevalence of approximately one percent worldwide. Maintenance antipsychotic treatment has been effective in preventing relapses in long-term follow-up studies. Logically it can be proposed that long-acting injectable antipsychotics (LAI) might reduce both unintentional and intentional nonadherence. Long-acting injectable aripiprazole was approved for the treatment of schizophrenia by the U.S. FDA on 28th February 2013 and will be marketed under the name Abilify Maintena. Aripiprazole LAI (ALAI) is a lyophilized powder that needs to be reconstituted with sterile water to form an injectable suspension without affecting the original molecule. The monthly injection interval is very attractive since patients prefer fewer injections. From a tolerability perspective, ALAI appears to be both weight neutral and lacking metabolic side effects. This can confer an advantage over the other currently available second-generation antipsychotic LAIs. Simple constitution with sterile water and no requirement to refrigerate make storage and administration easier. Like all medications, there are always potential disadvantages to ALAI. There is a period of oral coverage, while not as long as for long-acting risperidone microspheres (RLAI), that is required. Care must be taken to review concomitant medications for the presence of metabolic inducers and inhibitors. One would also expect some patients to be sensitive to extrapyramidal symptoms, especially akathisia which is well documented in the oral preparation. All things considered, we welcome our new tool, ALAI, to our work-place and predict both clinical practice and post marketing analysis and studies will discover its true value. PMID:23644169

  8. Preparation of poly(DL-lactide-co-glycolide) microspheres encapsulating all-trans retinoic acid.

    PubMed

    Jeong, Young-Il; Song, Jin-Gyu; Kang, Sam-Suk; Ryu, Hyang-Hwa; Lee, Young-Hwa; Choi, Chan; Shin, Boo-Ahn; Kim, Kyung-Keun; Ahn, Kyu-Youn; Jung, Shin

    2003-06-18

    Poly(DL-lactide-co-glycolide) (PLGA) microspheres containing all-trans retinoic acid (atRA) were prepared by o/w solvent evaporation method and various preparation parameters, such as poly(vinyl alcohol) (PVA) concentration in aqueous solution, PVA MW, drug weight, solvent, polymer MW, and polymer weight, on the characteristics of microspheres and drug release were investigated. PVA concentration in water phase was a critical factor in making microspheres consistently with smooth surface and round shape. In our study, at least 2% (w/v) of PVA in aqueous solution was necessary for making microspheres with round shape. The particle size of microspheres ranged 10-100 microm. AtRA was slowly released from PLGA microspheres over 30 days. Sterilization of microspheres by ethylene oxide (EO) gas at 37 degrees C did not significantly affect the characteristics of drug release or its morphology. Cell growth inhibition of atRA was affected by preparation process of microspheres rather than the EO-gas sterilization process. These results indicate that PLGA microspheres containing atRA are acceptable for controlled release devices for use in the treatment of brain tumor. PMID:12787638

  9. Poly(ethylene glycol)-poly(lactic-co-glycolic acid) core-shell microspheres with enhanced controllability of drug encapsulation and release rate.

    PubMed

    Cha, Chaenyung; Jeong, Jae Hyun; Kong, Hyunjoon

    2015-09-01

    Poly(lactic-co-glycolic acid) (PLGA) microspheres have been widely used as drug carriers for minimally invasive, local, and sustained drug delivery. However, their use is often plagued by limited controllability of encapsulation efficiency, initial burst, and release rate of drug molecules, which cause unsatisfactory outcomes and several side effects including inflammation. This study presents a new strategy of tuning the encapsulation efficiency and the release rate of protein drugs from a PLGA microsphere by filling the hollow core of the microsphere with poly(ethylene glycol) (PEG) hydrogels of varying cross-linking density. The PEG gel cores were prepared by inducing in situ cross-linking reactions of PEG monoacrylate solution within the PLGA microspheres. The resulting PEG-PLGA core-shell microspheres exhibited (1) increased encapsulation efficiency, (2) decreased initial burst, and (3) a more sustained release of protein drugs, as the cross-linking density of the PEG gel core was increased. In addition, implantation of PEG-PLGA core-shell microspheres encapsulated with vascular endothelial growth factor (VEGF) onto a chicken chorioallantoic membrane resulted in a significant increase in the number of new blood vessels at an implantation site, while minimizing inflammation. Overall, this strategy of introducing PEG gel into PLGA microspheres will be highly useful in tuning release rates and ultimately in improving the therapeutic efficacy of a wide array of protein drugs. PMID:26063500

  10. Long-acting injectable antiretrovirals for HIV treatment and prevention

    PubMed Central

    Spreen, William R.; Margolis, David A.; Pottage, John C.

    2013-01-01

    Purpose of review Long-acting antiretroviral (ARV) drugs may improve adherence to therapy and extend opportunities for therapeutic or prophylactic intervention to underserved patient populations. This review focuses on recent advances in the development of small molecule long-acting injectable ARV agents. Recent findings The need for combination ART and physicochemical and dosing limitations of current ARV drugs impede attempts to redevelop them as long-acting injectable formulations. However, the intrinsic properties of rilpivirine, a nonnucleoside reverse transcriptase inhibitor, and GSK1265744, an HIV-1 integrase strand transfer inhibitor, have enabled crystalline nanoparticle formulations to progress to clinical trials. Summary Investigational long-acting injectable nanoformulations of rilpivirine and GSK1265744 are clinical-stage development candidates. Complementary pharmacologic properties of both agents – different mechanisms of action, resistance profiles, metabolic pathways, lack of drug interactions and low daily oral doses – offer the potential for combination use. Phase I studies of the pharmacokinetics and safety of each long-acting formulation alone and in combination indicate that a monthly dosing regimen is possible for HIV treatment. An ongoing phase IIb trial of oral GSK1265744 and oral rilpivirine is evaluating this two-drug regimen for maintenance of virologic suppression; results will inform future studies using the injectable formulations. Additional preclinical and clinical studies indicate a potential use of each agent for HIV pre-exposure prophylaxis. PMID:24100877

  11. Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin-loaded poly(lactic-co-glycolic acid) microspheres in rats

    PubMed Central

    Zhou, Xiang-lian; He, Jin-tian; Du, Hui-juan; Fan, Yang-yang; Wang, Ying; Zhang, Hong-xia; Jiang, Yang

    2012-01-01

    Aim: To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats. Methods: The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method. Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres. Results: rhEPO was almost completely released from the PLGA microspheres in vitro, following zero-order release kinetics over approximately 30 d. After intramuscular injection (10 000 or 30 000 IU rhEPO/kg) in the rats, the serum rhEPO concentration reached maximum levels on d 1, then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks. Furthermore, the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism. A good linear correlation (R2=0.98) was obtained between the in vitro and in vivo release data. A single intramuscular injection of the rhEPO-loaded PLGA microspheres (10 000 or 30 000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d. Moreover, the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO. Conclusion: The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month. PMID:22139004

  12. Pharmacokinetics of long-acting injectable neuroleptic drugs: clinical implications

    Microsoft Academic Search

    Stephen R. Marder; John W. Hubbard; Theodore Van Putten; Kamal K. Midha

    1989-01-01

    The authors review the literature regarding the pharmacokinetics of long-acting injectable neuroleptic drugs (LINS). There are important differences between LINS and oral neurolepties that affect their pharmacokinetics. By avoiding first pass metabolism in gut and liver, LINS result in lower circulating concentrations of metabolites than are found after oral administration. In addition, LINS take more time to reach a stable

  13. Narcotic tapering in pregnancy using long-acting morphine

    PubMed Central

    Dooley, Roisin; Dooley, Joe; Antone, Irwin; Guilfoyle, John; Gerber-Finn, Lianne; Kakekagumick, Kara; Cromarty, Helen; Hopman, Wilma; Muileboom, Jill; Brunton, Nicole; Kelly, Len

    2015-01-01

    Abstract Objective To document the management of and outcomes for patients receiving narcotic replacement and tapering with long-acting morphine preparations during pregnancy. Design A prospective cohort study over 18 months. Setting Northwestern Ontario. Participants All 600 births at Meno Ya Win Health Centre in Sioux Lookout, Ont, from January 1, 2012, to June 30, 2013, including 166 narcotic-exposed pregnancies. Intervention Narcotic replacement and tapering of narcotic use with long-acting morphine preparations. Main outcome measures Prenatal management of maternal narcotic use, incidence of neonatal abstinence syndrome, and other neonatal outcomes. Results The incidence of neonatal abstinence syndrome fell significantly to 18.1% of pregnancies exposed to narcotics (from 29.5% in a previous 2010 study, P = .003) among patients using narcotic replacement and tapering with long-acting morphine preparations. Neonatal outcomes were otherwise equivalent to those of the nonexposed pregnancies. Conclusion In many patients, long-acting morphine preparations can be safely used and tapered in pregnancy, with a subsequent decrease in observed neonatal withdrawal symptoms. PMID:25821873

  14. Tricyclic antidepressants as long-acting local anesthetics

    Microsoft Academic Search

    Yukari Sudoh; Elaine Elliott Cahoon; Peter Gerner; Ging Kuo Wang

    2003-01-01

    Amitriptyline, nortriptyline, imipramine, doxepin, desipramine, protriptyline, trimipramine, and maprotiline are tricyclic antidepressants (TCAs) used orally in treating major depressive disorders. Recent studies showed that amitriptyline is more potent in blocking the sciatic nerve functions in vivo by local injection than bupivacaine, a long-acting local anesthetic. We therefore tested whether various TCAs could likewise act as local anesthetics in vivo after

  15. Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions

    Microsoft Academic Search

    Hiromitsu Yamamoto; Yoshio Kuno; Shohei Sugimoto; Hirofumi Takeuchi; Yoshiaki Kawashima

    2005-01-01

    Surface-modified dl-lactide\\/glycolide copolymer (PLGA) nanospheres with chitosan (CS) were prepared by the emulsion solvent diffusion method for pulmonary delivery of peptide, i.e., elcatonin. The nanosphere suspension was successfully aerosolized with a nebulizer similar to the drug solution, whereas the microsphere suspensions could not be aerosolized. After pulmonary administration, CS-modified PLGA nanospheres were more slowly eliminated from the lungs than unmodified

  16. The degradation behaviour of nanoscale HA/PLGA and ?-TCP/PLGA composites

    E-print Network

    Ege, Duygu; Best, Serena; Cameron, Ruth

    2014-01-11

    The aim of this work was to prepare and analyze the degradation properties of pure PLGA, homogeneous ?-tricalcium phosphate (?-TCP)/PLGA and hydroxyapatite (HA)/PLGA composites for potential bone replacement applications. ?-TCP and HA powders were...

  17. Long-acting risperidone in stable patients with schizoaffective disorder.

    PubMed

    Mohl, A; Westlye, K; Opjordsmoen, S; Lex, A; Schreiner, A; Benoit, M; Bräunig, P; Medori, R

    2005-09-01

    Oral and long-acting risperidone has been shown to be effective for acute and maintenance treatment of patients with schizoaffective disorders. The present analysis investigated the efficacy and tolerability of direct transition from other antipsychotics to risperidone long-acting injectable in patients with schizoaffective disorder. Patients aged > or = 18 years with schizoaffective disorder (DSM-IV), who required a change of medication, received risperidone long-acting injectable 25 mg (increased to 37.5 or 50 mg, if necessary) every 2 weeks for 6 months. The analysis included 249 patients (47% male; mean age 43 years), of whom 74% completed the 6-month study. Mean scores for the total Positive and Negative Syndrome Scale (PANSS) and all three subscales were significantly reduced from baseline to week 4 (p < 0.001), with further improvements until treatment endpoint. Significant improvements from baseline to endpoint were seen in the mood symptom domains of anxiety/depression (10.4+/-4.1 vs 8.7+/-3.9) and uncontrolled hostility/excitement (7.6+/-3.6 vs 6.9+/-3.8). Mean Global Assessment of Function (GAF) score improved significantly from 59.4+/-15.6 at baseline to 66.4+/-17.7 (p < 0.001) at endpoint. Of 87 patients hospitalized at baseline, 67% were discharged at endpoint. Both quality of life (SF-36) and satisfaction with treatment were improved significantly at endpoint. Total ESRS scores fell progressively throughout the study, and the reduction was already statistically significant (p < 0.001) at 4 weeks. Small but statistically significant (p < 0.001) mean shifts of 1.8% were seen in body weight and Body Mass Index (BMI). Patients with schizoaffective disorder derived several benefits from a change to risperidone long-acting injectable, including reductions in psychiatric symptoms (particularly the mood symptom domains) and a reduction in the severity of drug-induced neurological movement disorders. PMID:16144783

  18. Long Acting Contraception Provision by Rural Primary Care Physicians

    PubMed Central

    Smith, Paul; Grewal, Manpreet; Kumaraswami, Tara; Cowett, Allison; Harwood, Bryna

    2014-01-01

    Abstract Objectives: Unplanned pregnancy is a public health problem in the United States, including in rural areas. Primary care physicians are the main providers of health care to women in rural areas and are uniquely positioned to help reduce unplanned pregnancy in rural women. This study documents provision of contraception by rural primary care physicians, focusing on the most effective, long acting methods, intrauterine devices (IUDs) and contraceptive implants. Methods: We surveyed all primary care physicians practicing in rural areas of Illinois and Wisconsin. Bivariate analysis was performed using chi squared and Fisher's exact test, and multivariable analysis was performed with logistic regression to determine factors associated with provision. Results: The response rate was 862 out of 2312 physicians (37%). Nine percent of respondents place implants and 35% place IUDs. Eighty-seven percent of physicians had not had training in implant placement, and 41% had not had training in IUD placement. In multivariable analysis, factors associated with placement of long acting contraception include provision of maternity care, and female gender of the physician. The most common reasons for not providing the methods were lack of training and perceived low demand from patients. Conclusions: Many rural primary care providers do not place long acting contraceptive devices due to lack of training. Female physicians and those providing maternity care are the most likely to place these devices. Increased training for primary care physicians both during and after residency would help increase access to these options for women in rural areas. PMID:24443930

  19. Physicomechanical properties of sintered scaffolds formed from porous and protein-loaded poly(DL-lactic-co-glycolic acid) microspheres for potential use in bone tissue engineering.

    PubMed

    Boukari, Yamina; Scurr, David J; Qutachi, Omar; Morris, Andrew P; Doughty, Stephen W; Rahman, Cheryl V; Billa, Nashiru

    2015-08-01

    An injectable poly(DL-lactic-co-glycolic acid) (PLGA) system comprising both porous and protein-loaded microspheres capable of forming porous scaffolds at body temperature was developed for tissue regeneration purposes. Porous and non-porous (lysozyme loaded) PLGA microspheres were formulated to represent 'low molecular weight' 22-34 kDa, 'intermediate molecular weight' (IMW) 53 kDa and 'high molecular weight' 84-109 kDa PLGA microspheres. The respective average size of the microspheres was directly related to the polymer molecular weight. An initial burst release of lysozyme was observed from both microspheres and scaffolds on day 1. In the case of the lysozyme-loaded microspheres, this burst release was inversely related to the polymer molecular weight. Similarly, scaffolds loaded with 1 mg lysozyme/g of scaffold exhibited an inverse release relationship with polymer molecular weight. The burst release was highest amongst IMW scaffolds loaded with 2 and 3 mg/g. Sustained lysozyme release was observed after day 1 over 50 days (microspheres) and 30 days (scaffolds). The compressive strengths of the scaffolds were found to be inversely proportional to PLGA molecular weight at each lysozyme loading. Surface analysis indicated that some of the loaded lysozyme was distributed on the surfaces of the microspheres and thus responsible for the burst release observed. Overall the data demonstrates the potential of the scaffolds for use in tissue regeneration. PMID:26065672

  20. Polyacrolein microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1986-01-01

    Microspheres of acrolein homopolymers and copolymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

  1. Polyacrolein microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1983-01-01

    Microspheres of acrolein homopolymers and co-polymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

  2. Polyacrolein microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1987-01-01

    Microspheres of acrolein homopolymers and copolymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

  3. Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone tissue engineering

    E-print Network

    Zheng, Yufeng

    Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone. In this study, we prepared mineralized poly(D,L-lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun was deposited on the sur- face of PLGA/gelatin nanofibers rather than PLGA nanofibers because gelatin acted

  4. Long-acting Injectable Antipsychotics in First-episode Schizophrenia

    PubMed Central

    Jeong, Hyun-Ghang

    2013-01-01

    Antipsychotic medications are important for the successful management of schizophrenia. Continuous treatment with medication is superior in relapse prevention and non-adherence to antipsychotic medication is associated with a poor clinical outcome. Long-acting injectable antipsychotics (LAIs) that can guarantee adherence to a treatment regimen could be a useful treatment option. With the introduction of second-generation atypical antipsychotics-long acting injection (SGA-LAI), the risks for extrapyramidal adverse events are decreased. The indications for SGA-LAI have been extended from chronic, stabilized patients to acute psychotic patients. Some studies investigated the use of LAI in first-episode schizophrenia patients and raised the possibility of prescribing LAI as a treatment option. However, there is still limited research using LAI in first-episode schizophrenia. More well-designed, randomized, controlled clinical trials using SGA-LAIs in first episode schizophrenia are needed. Additionally, studies on side effects of SGA-LAI in long-term use are required prior to recommending LAI for patients with first episode schizophrenia. PMID:23678347

  5. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes

    PubMed Central

    Edagwa, Benson J.; Guo, Dongwei; Puligujja, Pavan; Chen, Han; McMillan, JoEllyn; Liu, Xinming; Gendelman, Howard E.; Narayanasamy, Prabagaran

    2014-01-01

    Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 ?g/106 cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 ?g/106 cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens.—Edagwa, B. J., Guo, D., Puligujja, P., Chen, H., McMillan, J., Liu, X., Gendelman, H. E., Narayanasamy, P. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes. PMID:25122556

  6. A Qualitative Analysis of Long-Acting Reversible Contraception.

    PubMed

    Sundstrom, Beth; Baker-Whitcomb, Annalise; DeMaria, Andrea L

    2015-07-01

    Increasing access to long-acting reversible contraception (LARC), including the intrauterine device and the implant is a public health and clinical imperative to reduce rates of unintended pregnancy. In 2012, the American College of Obstetricians and Gynecologists recommended these methods for all women, including adolescents. Little research explores why young women reject these safe, effective contraceptive methods. A total of 53 women aged 18-24 years completed in-depth interviews. Analytical techniques from the grounded theory approach were used to identify patterns and themes across the data. Participants initiated hormonal contraception for "the pill's" beneficial side effects and believed a myth of perfect use, which constructed a false choice of LARC methods. Barriers to LARC options included access, medical resistance, and cost. Participants described a sense of unease about methods perceived as "alien." These women underestimated the risks of oral contraceptive pills and overestimated the risks of long-acting reversible contraception, including infertility. The myth of perfect use emerged as participants wanted to be in control by taking "the pill" every day; however, many described imperfect adherence. Findings include strategies for public health professionals and health care providers to distribute satisfactory and effective contraception for young women. Effective health communication campaigns will emphasize the desirable side effects, safety and increased effectiveness of LARC methods. PMID:25424456

  7. Pharmacokinetics and biodistribution of paclitaxel-loaded microspheres.

    PubMed

    Yan, F; Tang, S; Fu, Q

    2012-04-01

    Paclitaxel(PTX)-loaded microspheres composed of poly(D,L-lactide-co-glycolide) (PLGA) were prepared by an O/W emulsion solvent evaporation method. This study was designed to investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a PTX-loaded microspheres system. Microspheres are characterized according to drug loading, size and shape. With a dynamic light scattering sizer and a transmission electron microscopy, it is shown that the PTX-loaded microspheres had a mean size of approximately 10.24 µm with narrow size distribution and a spherical shape. The in vitro release profiles indicate that the release of PTX from the microspheres exhibit a sustained release behavior. A similar phenomenon is observed in a pharmacokinetic study in rats, in which AUC of the microspheres formulation were 3.7-fold higher than that of PTX injection. The biodistribution study in mice showed that the PTX-loaded microspheres not only decreased drug uptake by liver, but also increased distribution of drug in lung. These results suggest that PTX-loaded microspheres may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for i. v. administration of PTX. PMID:22270845

  8. Polyphosphoester microspheres for sustained release of biologically active nerve growth factor.

    PubMed

    Xu, Xiaoyun; Yu, Hanry; Gao, Shujun; Ma, Hai-Quan; Leong, Kam W; Wang, Shu

    2002-09-01

    Controlled delivery of neurotrophic proteins to a target tissue by biodegradable polymer microspheres has been explored widely for its potential applications in the treatment of various disorders in the nervous system. We investigated in this study the potential of polyphosphoester microspheres as carriers for the sustained release of nerve growth factor (NGF), a water-soluble neurotrophic protein. Two polyphosphoesters (PPEs), P(BHET-EOP/TC) and P(DAPG-EOP), as well as poly(lactide/glycolic acid) (PLGA), were used to fabricate microspheres by a W/O/W emulsion and solvent evaporation/extraction method. With bovine serum albumin as a model protein to optimize processing parameters. P(DAPG-EOP) microspheres exhibited a lower burst effect but similar protein entrapment levels and efficiencies when compared with those made of PLGA. Bioactive NGF could be released for at least 10 weeks from the P(DAPG-EOP) microspheres, as confirmed by a neurite outgrowth assay of the PC12 cells. These NGF containing microspheres were incorporated into the nerve guide conduits that were implanted to bridge a 10 mm gap in a rat sciatic nerve model. Two weeks after implantation, immunostaining with an antibody against the neurofilament protein confirmed the presence of axons at the distal end of regenerated cables within the NGF microsphere-loaded conduits. These results demonstrated the feasibility of using biodegradable PPEs for microencapsulation of NGF and provided a basis for future therapeutic application of the microspheres. PMID:12109702

  9. Process and formulation variables in the preparation of injectable and biodegradable magnetic microspheres.

    PubMed

    Zhao, Hong; Gagnon, Jeffrey; Häfeli, Urs O

    2007-01-01

    The aim of this study was to prepare biodegradable sustained release magnetite microspheres sized between 1 to 2 microm. The microspheres with or without magnetic materials were prepared by a W/O/W double emulsion solvent evaporation technique using poly(lactide-co-glycolide) (PLGA) as the biodegradable matrix forming polymer. Effects of manufacturing and formulation variables on particle size were investigated with non-magnetic microspheres. Microsphere size could be controlled by modification of homogenization speed, PLGA concentration in the oil phase, oil phase volume, solvent composition, and polyvinyl alcohol (PVA) concentration in the outer water phase. Most influential were the agitation velocity and all parameters that influence the kinematic viscosity of oil and outer water phase, specifically the type and concentration of the oil phase. The magnetic component yielding homogeneous magnetic microspheres consisted of magnetite nanoparticles of 8 nm diameter stabilized with a polyethylene glycole/polyacrylic acid (PEG/PAA) coating and a saturation magnetization of 47.8 emu/g. Non-magnetic and magnetic microspheres had very similar size, morphology, and size distribution, as shown by scanning electron microscopy. The optimized conditions yielded microspheres with 13.7 weight% of magnetite and an average diameter of 1.37 microm. Such biodegradable magnetic microspheres seem appropriate for vascular administration followed by magnetic drug targeting. PMID:17407608

  10. Improving the uptake of long acting reversible contraception: a review.

    PubMed

    Michie, L; Cameron, S T

    2013-06-01

    Across the world rates of unintended pregnancy are high. Unintended pregnancy not only results in substantial costs to health services, it can lead to personal distress for women experiencing this. Whilst a large number of unintended pregnancies occur in those not using any method of contraception, a proportion occur in women using a contraceptive method incorrectly or inconsistently. Long acting reversible methods of contraception such as the IUD, IUS, contraceptive implant and contraceptive injectables are the most effective methods of contraception. In spite of this, they are under-utilized by women in developed countries. Educating women and health professionals, and dispelling myths about these methods may improve their acceptability. Furthermore, facilitating uptake by ensuring that a range of contraceptive providers are trained and able to provide to women without undue delay, particularly in the immediate post abortion and postpartum period, may also be effective strategies to improve uptake, and prevent more unintended pregnancies. PMID:23689167

  11. Baclofen-loaded microspheres: preparation and efficacy testing in a new rabbit model

    Microsoft Academic Search

    Frederic Lagarce; Pascal Renaud; Nathalie Faisant; Guillaume Nicolas; Annie Cailleux; Joel Richard; Philippe Menei; Jean-Pierre Benoit

    2005-01-01

    Intrathecal baclofen is the reference treatment for severe spasticity. This drug has to be injected chronically in the intrathecal space by implanted pumps which are very expensive, uncomfortable and sometimes lead to side effects. Previous work has been performed by our group to assess the feasibility of encapsulating baclofen into poly(lactide-co-glycolide) (PLGA) microspheres and injecting these preparations in the intrathecal

  12. Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear

    PubMed Central

    Feng, Liang; Ward, Jonette A.; Li, S. Kevin; Tolia, Gaurav; Hao, Jinsong; Choo, Daniel I.

    2014-01-01

    Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEG-PLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications. PMID:24438444

  13. Near infrared spectroscopic (NIRS) analysis of drug-loading rate and particle size of risperidone microspheres by improved chemometric model.

    PubMed

    Song, Jia; Xie, Jing; Li, Chenliang; Lu, Jia-Hui; Meng, Qing-Fan; Yang, Zhaogang; Lee, Robert J; Wang, Di; Teng, Le-Sheng

    2014-09-10

    Microspheres have been developed as drug carriers in controlled drug delivery systems for years. In our present study, near infrared spectroscopy (NIRS) is applied to analyze the particle size and drug loading rate in risperidone poly(d,l-lactide-co-glycolide) (PLGA) microspheres. Various batches of risperidone PLGA microspheres were designed and prepared successfully. The particle size and drug-loading rate of all the samples were determined by a laser diffraction particle size analyzer and high performance liquid chromatography (HPLC) system. Monte Carlo algorithm combined with partial least squares (MCPLS) method was applied to identify the outliers and choose the numbers of calibration set. Furthermore, a series of preprocessing methods were performed to remove signal noise in NIR spectra. Moving window PLS and radical basis function neural network (RBFNN) methods were employed to establish calibration model. Our data demonstrated that PLS-developed model was only suitable for drug loading analysis in risperidone PLGA microspheres. Comparatively, RBFNN-based predictive models possess better fitting quality, predictive effect, and stability for both drug loading rate and particle size analysis. The correlation coefficients of calibration set (Rc(2)) were 0.935 and 0.880, respectively. The performance of optimum RBFNN models was confirmed by independent verification test with 15 samples. Collectively, our method is successfully performed to monitor drug-loading rate and particle size during risperidone PLGA microspheres preparation. PMID:24954726

  14. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    PubMed Central

    Lindenmayer, JP

    2010-01-01

    Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings where a post-injection observation period for at least 3 hours by medical personnel is available. The overall use of olanzapine LAI will probably be limited by the possibility of a PDSS event. Patients who have a history of good response to oral olanzapine and are in need of assured medication administration may present a good indication for its use, provided that the appropriate mental health delivery setting is available. PMID:20628628

  15. Pharmacokinetics of olanzapine long-acting injection: the clinical perspective

    PubMed Central

    Kraemer, Susanne; Bergstrom, Richard F.; Detke, Holland C.

    2014-01-01

    Olanzapine long-acting injection (OLAI) is a sustained-release depot antipsychotic for the treatment of schizophrenia in adults. Our objective was to explain the pharmacokinetics of OLAI to provide clinical insight. Simulation models and data from clinical trials are presented. Olanzapine concentrations were observed immediately upon injection. Half-life was ?30 days, controlled by the slow rate of intramuscular absorption rather than the 30-h elimination rate-based half-life of oral olanzapine. As each injection builds on the drug still being released from previous injections, concentrations increase gradually until a steady state is reached after ?3 months. Concentrations were similar to oral olanzapine and proportional to the dose; the average steady-state concentrations (10th–90th percentile) for the 150, 210, and 300 mg/2-week doses were 16–32, 15–55, and 20–67 ng/ml, respectively, and those for the 300 and 405 mg/4-week doses were 19–48 and 19–62 ng/ml, respectively. Peak concentrations most often occurred at 2–4 days after injection. Peak-to-trough fluctuation was greater for the 4-week dosing interval than the 2-week one, with no apparent clinical ramifications for these differences. Trough concentrations were above the lower end of the therapeutic range, even at the first injection. Long-term use up to 6 years indicated no additional accumulation. The impact of smoking and sex was similar, but less pronounced than for oral olanzapine. PMID:24815672

  16. Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes.

    PubMed

    Edagwa, Benson J; Guo, Dongwei; Puligujja, Pavan; Chen, Han; McMillan, JoEllyn; Liu, Xinming; Gendelman, Howard E; Narayanasamy, Prabagaran

    2014-12-01

    Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 ?g/10(6) cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 ?g/10(6) cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens. PMID:25122556

  17. Pharmacokinetics of olanzapine long-acting injection: the clinical perspective.

    PubMed

    Heres, Stephan; Kraemer, Susanne; Bergstrom, Richard F; Detke, Holland C

    2014-11-01

    Olanzapine long-acting injection (OLAI) is a sustained-release depot antipsychotic for the treatment of schizophrenia in adults. Our objective was to explain the pharmacokinetics of OLAI to provide clinical insight. Simulation models and data from clinical trials are presented. Olanzapine concentrations were observed immediately upon injection. Half-life was ?30 days, controlled by the slow rate of intramuscular absorption rather than the 30-h elimination rate-based half-life of oral olanzapine. As each injection builds on the drug still being released from previous injections, concentrations increase gradually until a steady state is reached after ?3 months. Concentrations were similar to oral olanzapine and proportional to the dose; the average steady-state concentrations (10th-90th percentile) for the 150, 210, and 300 mg/2-week doses were 16-32, 15-55, and 20-67 ng/ml, respectively, and those for the 300 and 405 mg/4-week doses were 19-48 and 19-62 ng/ml, respectively. Peak concentrations most often occurred at 2-4 days after injection. Peak-to-trough fluctuation was greater for the 4-week dosing interval than the 2-week one, with no apparent clinical ramifications for these differences. Trough concentrations were above the lower end of the therapeutic range, even at the first injection. Long-term use up to 6 years indicated no additional accumulation. The impact of smoking and sex was similar, but less pronounced than for oral olanzapine. PMID:24815672

  18. Possible interaction between letrozole and long-acting injectable zuclopenthixol.

    PubMed

    Lertxundi, Unax; Hernandez, Rafael; Albeniz, Juan Medrano; Echaburu, Saioa Domingo; Ruiz, Borja; García, Montserrat García; Aguirre, Carmelo

    2015-01-01

    Mrs A, a 68-year-old woman with paranoid schizophrenia, was on long-term psychiatric treatment with long-acting intramuscular zuclopenthixol, quetiapine and alprazolam when, in April 2012, she was diagnosed with right breast infiltrating ductal carcinoma. After starting treatment with letrozole on 4 July, Mrs A progressively developed extrapyramidal symptoms and these were particularly evident after each zuclopenthixol administration. On 9 January, both quetiapine and alprazolam were stopped due to excessive lethargy. After the administration of the last dose of zuclopenthixol on 26 January, she presented with sedation, sialorrhea, festinant gait, axial dystonia and dysphagia, all of which were severe. The introduction of letrozole was the only change that had been made to her pharmacotherapeutic regimen in that period. The rest of the findings on neurological examination were normal. Renal function was adequate. Slow symptom onset and progressive worsening until full-blown clinical presentation after 6 months, and the dramatic improvement in the clinical picture achieved 2 days after treatment with biperiden, suggests a long-term insidious interaction leading to zuclopenthixol accumulation. To the best of our knowledge, this is the first report of a possible interaction between letrozole and zuclopenthixol. We consider that it warrants further investigation. In the meanwhile, physicians should be aware of the occurrence of this potentially serious drug-drug interaction. PMID:24831298

  19. Coaxial electrohydrodynamic atomization process for production of polymeric composite microspheres.

    PubMed

    Xu, Qingxing; Qin, Hao; Yin, Zhenyuan; Hua, Jinsong; Pack, Daniel W; Wang, Chi-Hwa

    2013-12-18

    Polymeric composite microspheres consisting of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(D,L-lactic acid) (PDLLA) shell layer were successfully fabricated by coaxial electrohydrodynamic atomization (CEHDA) process. Process conditions, including nozzle voltage and polymer solution flow rates, as well as solution parameters, such as polymer concentrations, were investigated to ensure the formation of composite microspheres with a doxorubicin-loaded PLGA core surrounded by a relatively drug-free PDLLA shell layer. Various microsphere formulations were fabricated and characterized in terms of their drug distribution, encapsulation efficiency and in vitro release. Numerical simulation of CEHDA process was performed based on a computational fluid dynamics (CFD) model in Fluent by employing the process conditions and fluid properties used in the experiments. The simulation results were compared with the experimental work to illustrate the capability of the CFD model to predict the production of consistent compound droplets, and hence, the expected core-shell structured microspheres. PMID:24347672

  20. PLGA microcapsules with novel dimpled surfaces for pulmonary delivery of DNA.

    PubMed

    Mohamed, Farahidah; van der Walle, Christopher F

    2006-03-27

    We describe the fabrication of DNA-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules with novel surface morphologies that will be of use in pulmonary delivery. Our approach was to examine surface morphology and DNA encapsulation efficiency as a function of primary emulsion stability; using two surfactant series based on hydrophile-lipophile balance and hydrophobe molecular weight. Hydrophilic non-ionic surfactants yielded the most stable water-in-dichloromethane emulsions (HLB values >8). These surfactants normally favor convex (o/w) interfacial curvatures and therefore this atypical behavior suggested a relatively high surfactant solvation in the dichloromethane 'oil' phase. This was consistent with the large fall in the glass transition temperature for microspheres prepared with Tween 20, which therefore efficiently penetrated the PLGA matrix and acted as a plasiticizer. Blends of Pluronic triblock copolymers performed poorly as water-in-dichloromethane emulsifiers, and were therefore used to generate hollow microspheres ('microcapsules') with low densities (0.24 g/cm(3)). Although the Pluronic-stabilized emulsions resulted in lower DNA loading (15-28%), microspheres (approximately 8 microm) with novel dimpled surfaces were fabricated. The depth and definition of the dimples was greatest for triblock copolymers with high MW hydrophobe blocks. By cascade impaction, the geometric mean weight diameter of the microcapsules was 3.43 microm, suggesting that they will be of interest as biodegradable pulmonary delivery vehicles. PMID:16414217

  1. Preparation and investigation of sustained drug delivery systems using an injectable, thermosensitive, in situ forming hydrogel composed of PLGA-PEG-PLGA.

    PubMed

    Khodaverdi, Elham; Tekie, Farnaz Sadat Mirzazadeh; Mohajeri, Seyed Ahmad; Ganji, Fariba; Zohuri, Gholamhossein; Hadizadeh, Farzin

    2012-06-01

    In situ gelling systems are very attractive for pharmaceutical applications due to their biodegradability and simple manufacturing processes. The synthesis and characterization of thermosensitive poly(D,L-lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymers as in situ gelling matrices were investigated in this study as a drug delivery system. Ring-opening polymerization using microwave irradiation was utilized as a novel technique, and the results were compared with those using a conventional method of polymerization. The phase transition temperature and the critical micelle concentration (CMC) of the copolymer solutions were determined by differential scanning calorimetry and spectrophotometry, respectively. The size of the micelles was determined with a light scattering method. In vitro drug release studies were carried out using naltrexone hydrochloride and vitamin B12 as model drugs. The rate and yield of the copolymerization process via microwave irradiation were higher than those of the conventional method. The copolymer structure and concentration played critical roles in controlling the sol-gel transition temperature, the CMC, and the size of the nanomicelles in the copolymer solutions. The rate of drug release could be modulated by the molecular weight of the drugs, the concentration of the copolymers, and their structures in the formulations. The amount of release versus time followed zero-order release kinetics for vitamin B12 over 25 days, in contrast to the Higuchi modeling for naltrexone hydrochloride over a period of 17 days. In conclusion, PLGA-PEG1500-PLGA with a lactide-to-glycolide ratio of 5:1 is an ideal system for the long-acting, controlled release of naltrexone hydrochloride and vitamin B12. PMID:22528547

  2. Formulation of sustained-release microspheres of granulocyte macrophage colony stimulating factor by freezing-induced phase separation with dextran and encapsulation with blended polymers.

    PubMed

    Zhang, Xin-ran; Zheng, Ying; Jin, Tuo; Chow, Albert H L

    2011-01-01

    This study aimed to assess the potential merits of formulating sustained-release microspheres of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) via freezing-induced phase separation (FIPS) of the protein with dextran followed by encapsulation with binary mixture of poly(lactic-co-glycolic acid) (PLGA) 2A (MW?12K) and 3A (MW?47K) or of PLGA2A and polylactic acid (PLA; MW?83K). The formulated dextran particles and microspheres were characterized in vitro for loading, aggregation, bioactivity and release behavior of the protein where appropriate. rhGM-CSF retained about 60% of bioactivity with no significant aggregation after each formulation step. Encapsulation of protein-loaded dextran particles attained only 80% with the PLGA2A and PLGA3A blend, but 100% with the PLGA2A and PLA mixture. The former formulation exhibited a triphasic in-vitro release profile typical of PLGA microspheres while the latter revealed a much lower initial burst followed by a steady and complete release of rhGM-CSF with preserved bioactivity over a 15-day period. PMID:21967463

  3. Microradiographic microsphere manipulator

    DOEpatents

    Singleton, Russell M. (Livermore, CA)

    1980-01-01

    A method and apparatus for radiographic characterization of small hollow spherical members (microspheres), constructed of either optically transparent or opaque materials. The apparatus involves a microsphere manipulator which holds a batch of microspheres between two parallel thin plastic films for contact microradiographic characterization or projection microradiography thereof. One plastic film is translated to relative to and parallel to the other to roll the microspheres through any desired angle to allow different views of the microspheres.

  4. In vitro sustained release of recombinant human bone morphogenetic protein-2 microspheres embedded in thermosensitive hydrogels.

    PubMed

    Fu, Yangmu; Du, Lina; Wang, Qi; Liao, Weixiong; Jin, Yiguang; Dong, Anjie; Chen, Chen; Li, Zhongli

    2012-04-01

    Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a critical regulator of osteogenic capacity that is commonly used in bone grafts. The effectiveness of rhBMP-2 may be reduced as it can become unstable and degraded after injection into the body. Microspheres are considered appropriate vehicles for the sustained release of proteins in vivo. In this study, rhBMP-2 microspheres were manufactured using the water-in-oil-in-water (W/O/W) double-emulsion solvent-extraction technique by encapsulation in poly(lactic-co-glycolic) acid (PLGA). The microspheres were then embedded in two hydrogels made of either poloxamer 407 hydrogel or chitosan thioglycolic acid (CS-TA). The encapsulation efficiency and in vitro release of rhBMP-2 were examined and compared with the control release system (rhBMP-2 microspheres alone). The rhBMP-2 microspheres in the CS-TA hydrogel showed the lowest burst release (about 40% in the first 8h) among the three groups. The mechanisms may be the high viscosity of CS-TA hydrogel and the sustained release characteristics of CS-TA itself. The CS-TA hydrogel combined with PLGA microspheres can efficiently encapsulate rhBMP-2, control the burst release at early time points, and provide sustained release in vitro. It may be an appropriate rhBMP-2 vehicle for bone regeneration. PMID:22570935

  5. Hybrid microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Richard C. K. (Inventor)

    1985-01-01

    Substrates, particularly inert synthetic organic resin beads (10) or sheet (12) such as polystyrene are coated with a covalently bound layer (24) of polyacrolein by irradiation a solution (14) of acrolein or other aldehyde with high intensity radiation. Individual microspheres (22) are formed which attach to the surface to form the aldehyde containing layer (24). The aldehyde groups can be converted to other functional groups by reaction with materials such as hydroxylamine. Adducts of proteins such as antibodies or enzymes can be formed by direct reaction with the surface aldehyde groups.

  6. Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease

    PubMed Central

    Karner, Charlotta; Cates, Christopher J

    2014-01-01

    Background Long-acting bronchodilators comprising long-acting beta2-agonists and the anticholinergic agent tiotropium are commonly used for managing persistent symptoms of chronic obstructive pulmonary disease. Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of combining tiotropium and long-acting beta2-agonists for the treatment of chronic obstructive pulmonary (COPD) disease are unclear. Objectives To assess the relative effects of treatment with tiotropium in addition to long-acting beta2-agonist compared to tiotropium or long-acting beta2-agonist alone in patients with chronic obstructive pulmonary disease. Search methods We searched the Cochrane Airways Group Specialised Register of trials and clinicaltrials.gov up to January 2012. Selection criteria We included parallel group, randomised controlled trials of three months or longer comparing treatment with tiotropium in addition to long-acting beta2-agonist against tiotropium or long-acting beta2-agonist alone for patients with chronic obstructive pulmonary disease. Data collection and analysis Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. Main results Five trials were included in this review, mostly recruiting participants with moderate or severe chronic obstructive pulmonary disease. All of them compared tiotropium in addition to long-acting beta2-agonist to tiotropium alone, but only one trial additionally compared a combination of the two types of bronchodilator with long-acting beta2-agonist (formoterol) alone. Two studies used the long-acting beta2-agonist indacaterol, two used formoterol and one used salmeterol. Compared to tiotropium alone (3263 patients), treatment with tiotropium plus long-acting beta2-agonist resulted in a slightly larger improvement in the mean health-related quality of life (St George’s Respiratory Questionnaire (SGRQ) MD ?1.61; 95% CI ?2.93 to ?0.29). In the control arm, tiotropium alone, the SGRQ improved by falling 4.5 units from baseline and with both treatments the improvement was a fall of 6.1 units from baseline (on average). High withdrawal rates in the trials increased the uncertainty in this result, and the GRADE assessment for this outcome was therefore moderate. There were no significant differences in the other primary outcomes (hospital admission or mortality). The secondary outcome of pre-bronchodilator FEV1 showed a small mean increase with the addition of long-acting beta2-agonist (MD 0.07 L; 95% CI 0.05 to 0.09) over the control arm, which showed a change from baseline ranging from 0.03 L to 0.13 L on tiotropium alone. None of the other secondary outcomes (exacerbations, symptom scores, serious adverse events, and withdrawals) showed any statistically significant differences between the groups. There were wide confidence intervals around these outcomes and moderate heterogeneity for both exacerbations and withdrawals. The results from the one trial comparing the combination of tiotropium and long-acting beta2-agonist to long-acting beta2-agonist alone (417 participants) were insufficient to draw firm conclusions for this comparison. Authors’ conclusions The results from this review indicate a small mean improvement in health-related quality of life for patients on a combination of tiotropium and long-acting beta2-agonist compared to tiotropium alone, but it is not clear how clinically important this mean difference may be. Hospital admission and mortality have not been shown to be altered by adding long-acting beta2-agonists to tiotropium as there were not enough data to determine the relative efficacy and safety of tiotropium plus long-acting beta2-agonist compared to long-acting beta2-agonist alone. There were insufficient data to make comparisons between the different long-acting

  7. Bioactivated collagen-based scaffolds embedding protein-releasing biodegradable microspheres: tuning of protein release kinetics.

    PubMed

    Biondi, Marco; Indolfi, Laura; Ungaro, Francesca; Quaglia, Fabiana; La Rotonda, Maria Immacolata; Netti, Paolo A

    2009-10-01

    In tissue engineering, the recapitulation of natural sequences of signaling molecules, such as growth factors, as occurring in the native extracellular matrix (ECM), is fundamental to support the stepwise process of tissue regeneration. Among the manifold of tissue engineering strategies, a promising one is based on the creation of the chrono-programmed presentation of different signaling proteins. This approach is based upon the integration of biodegradable microspheres, loaded with suitable protein molecules, within scaffolds made of collagen and, in case, hyaluronic acid, which are two of the fundamental ECM constituents. However, for the design of bioactivated gel-like scaffolds the determination of release kinetics must be performed directly within the tissue engineering template. In this work, biodegradable poly(lactic-co-glycolic)acid (PLGA) microspheres were produced by the multiple emulsion-solvent evaporation technique and loaded with rhodamine-labelled bovine serum albumin (BSA-Rhod), a fluorescent model protein. The microdevices were dispersed in collagen gels and collagen-hyaluronic acid (HA) semi-interpenetrating networks (semi-IPNs). BSA-Rhod release kinetics were studied directly on single microspheres through confocal laser scanning microscopy (CLSM). To thoroughly investigate the mechanisms governing protein release from PLGA microspheres in gels, BSA-Rhod diffusion in gels was determined by fluorescence correlation spectroscopy (FCS), and water transport through the microsphere bulk was determined by dynamic vapor sorption (DVS). Moreover, the decrease of PLGA molecular weight and glass transition temperature (T(g)) were determined by gel permeation chromatography (GPC) and differential scanning calorimetry (DSC), respectively. Results indicate that protein release kinetics and delivery onset strongly depend on the complex interplay between protein transport through the PLGA matrix and in the collagen-based release media, and water sequestration within the scaffolds, related to the scaffold hydrophilicity, which is dictated by HA content. The proper manipulation of all these features may thus allow the obtainment of a fine control over protein sequential delivery and release kinetics within tissue-engineering scaffolds. PMID:19449203

  8. Sustained release of etanidazole from spray dried microspheres prepared by non-halogenated solvents.

    PubMed

    Wang, Fang Jing; Wang, Chi Hwa

    2002-06-17

    Etanidazole, a kind of radiosensitizer, was encapsulated in the spray-dried microspheres using biodegradable polymer PLGA 65:35 as the carrier for controlled release applications. Two non-halogenated solvents, e.g., ethyl acetate (EA) and ethanol, were tested to modify the properties of microspheres prepared by the commonly used solvent dichloromethane (DCM) alone. Their effects on the release behavior, morphology, particle size, and encapsulation efficiency of etanidazole-loaded microspheres were determined, and results were compared with DCM. The particle formation process via spray drying technique was also analyzed in order to understand the results obtained. It was found that larger percentage of EA (in the solvent mixture consisting of DCM and EA) in the fabrication of PLGA 65:35 microspheres decreases the initial burst, release rate and prolongs the release duration of etanidazole. In contrast to the spherical and porous microspheres prepared by DCM, the microspheres prepared by the solvent EA are all nonporous with a doughnut like surface structure due to its comparatively rapid phase transition (phase inversion) but slow solvent evaporation rate (longer time required to solidify). Increasing the polymer concentration (e.g., 4%, w/v) can bring about much more spherical microspheres by spray drying. Although ethanol, as a co-solvent, can dissolve a higher amount of etanidazole and lead to a higher drug encapsulation efficiency, the addition of ethanol in the DCM solvent can significantly increase the initial burst and the release rate of the microspheres due to the inhomogeneous drug distribution and structure of microspheres caused by phase separation. This study shows that ethyl acetate is an excellent low-toxic solvent that can be used in the spray drying technique for decreasing the initial burst, prolonging the release duration of a highly water-soluble drug like etanidazole. The use of EA provides a promising way to develop a sustained release system for etanidazole and other highly water-soluble drugs. PMID:12044566

  9. Development of Sustained-Release Microspheres for the Delivery of SAR 1118, an LFA-1 Antagonist Intended for the Treatment of Vascular Complications of the Eye

    PubMed Central

    Yandrapu, Sarath

    2013-01-01

    Abstract The objective of this study was to design 1, 3, and 6 month sustained-release poly (lactide-co-glycolide) (PLGA) microspheres of SAR 1118, a lymphocyte function-associated antigen-1 antagonist, using Design of Experiments. A full-factorial design was used to identify the polymers suitable for degradation in 1, 3, and 6 months and the Box-Behnken design was used to study the influence of the polymer type, polymer concentration, and drug to polymer ratio on drug loading, burst release, and particle size. From the full-factorial design, PLGA (50:50), PLGA (75:25), and PLGA (85:15) with an inherent viscosity of 0.3–0.5?dL/g were identified as polymers suitable for degradation in 1, 3, and 6 months, respectively. From the Box-Behnken design, the optimized polymer concentration (12% w/v) and drug to polymer ratio (0.15) were identified and used to prepare the SAR 1118-encapsulated microspheres with the above 3 polymers and evaluated for drug loading, burst release, and sustained drug release. The burst release in these 3 batches was less than 20% and the drug loading ranged from 15%–18%. More than 90% of SAR 1118 release from PLGA (50:50), PLGA (75:25), and PLGA (85:15) microspheres occurred in 1, 3, and 6 months, respectively. Thus, the in vitro cumulative release data are remarkably close to the predicted values. The results demonstrated the potential of the Design of Experiments in designing the SAR 1118 microspheres with a high loading efficiency, low burst release, and sustained release for a desired duration. PMID:23256487

  10. Tuning microcapsules surface morphology using blends of homo-and copolymers of PLGA and PLGA-PEG

    E-print Network

    Raphael, Elie

    Tuning microcapsules surface morphology using blends of homo- and copolymers of PLGA and PLGA-evaporation technique by varying the percentage of PLGA-PEG copolymer in the formulation. As copolymer percentage environment, since PEG and PLGA moieties are not miscible in the solid state. Introduction Although colloids

  11. Contraceptive policies affect post-abortion provision of long-acting reversible contraception

    Microsoft Academic Search

    Kirsten M. J. Thompson; J. Joseph Speidel; Vicki Saporta; Norma Jo Waxman; Cynthia C. Harper

    2011-01-01

    BackgroundPlacement of long-acting reversible contraceptives (LARC) — intrauterine devices (IUDs) and the implant — directly after an abortion provides immediate contraceptive protection and has been proven safe.

  12. Pharmacokinetics in the calf of a long-acting chloramphenicol formulation

    E-print Network

    Boyer, Edmond

    Pharmacokinetics in the calf of a long-acting chloramphenicol formulation administered; In a preliminary study, 3 different chloramphenicol doses were tested by intramuscular (im) route, the highest one interval). pharmacokinetics / chloramphenicol / cattle Résumé - Étude pharmacocinétique d'une formulation

  13. Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair.

    PubMed

    Wood, Matthew D; Gordon, Tessa; Kemp, Stephen W P; Liu, Edward H; Kim, Howard; Shoichet, Molly S; Borschel, Gregory H

    2013-05-01

    The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide-glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation. PMID:23239194

  14. Development of Recombinant Human Growth Hormone (rhGH) sustained-release microspheres by a low temperature aqueous phase/aqueous phase emulsion method.

    PubMed

    Kang, Jian; Wu, Fei; Cai, Yunpeng; Xu, Mingxin; He, Mu; Yuan, Weien

    2014-10-01

    A novel method has been developed to protect Recombinant Human Growth Hormone (rhGH) in poly (lactic-co-glycolic acid) (PLGA) microspheres using an aqueous phase/aqueous phase emulsion and S/O/W multi-emulsion method. This method develops a novel rhGH sustained-release system, which is based on the combination of rhGH-loaded dextran microparticles and PLGA microspheres. The process to fabricate rhGH-loaded dextran microparticles involves an aqueous phase/aqueous phase emulsion system formed at the reduced temperature. RhGH was first dissolved in water together with dextran and polyethylene glycol, followed by stirring at the speed of 2000 rpm for 20-30s at 0°C, and then a freezing process could enable the dextran phase to separate from the continuous PEG phase and rhGH could preferentially be loaded with dextran. The sample after freezing and phase separation was then lyophilized to powder and washed with dichloromethane to remove the PEG. Once loaded in the dextran microparticles (1-4 ?m in diameter), rhGH gained resistance to interface tensions and was encapsulated into PLGA microspheres without aggregation thereafter. RhGH released from PLGA microspheres was in a sustained manner with minimal burst and maximally reduced incomplete release in vitro. Single subcutaneous injection of rhGH-loaded PLGA microspheres to rats resulted in a stable plasma concentration for 30 days avoiding the drug concentration fluctuations after multiple injections of protein solutions. In a hypophysectomized rat model, the IGF-1 and bodyweight results showed that there were higher than the levels obtained for the sustained release formulation by W/O/W for 40 days. These results suggest that the microsphere delivery system had the potential to be an injectable depot for sustained-release of the biocompatible protein of rhGH. PMID:24907681

  15. Formulation and characterization of microspheres loaded with imatinib for sustained delivery.

    PubMed

    Ramazani, F; Chen, W; Van Nostrum, C F; Storm, G; Kiessling, F; Lammers, T; Hennink, W E; Kok, R J

    2015-03-30

    The aim of this study was the development of imatinib-loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres with high loading efficiency which can afford continuous release of imatinib over a prolonged period of time. Imatinib mesylate loaded PLGA microspheres with a size of 6-20 ?m were prepared by a double emulsion (W1/O/W2) method using dichloromethane as volatile solvent. It was found that the microspheres were spherical with a non-porous surface; imatinib loading efficiency (LE) was highly dependent on the pH of the external water phase (W2). By increasing the pH of W2 phase above the highest pKa of imatinib (pKa 8.1), at which imatinib is mainly uncharged, the LE increased from 10% to 90% (pH 5.0 versus pH 9.0). Conversely, only 4% of its counter ion, mesylate, was retained in the microspheres at the same condition (pH 9.0). Since mesylate is highly water soluble, it is unlikely that it partitions into the organic phase. We demonstrated, using differential scanning calorimetry (DSC), that imatinib was molecularly dispersed in the polymeric matrix at loadings up to 8.0%. At higher drug loading, imatinib partially crystallized in the matrix. Imatinib microspheres released their cargo during three months by a combination of diffusion through the polymer matrix and polymer erosion. In conclusion, we have formulated imatinib microspheres with high LE and LC. Although we started with a double emulsion of imatinib mesylate, the obtained microspheres contained imatinib base which was mainly molecularly dispersed in the polymer matrix. These microspheres release imatinib over a 3-month period which is of interest for local treatment of cancer. PMID:25636301

  16. PLGA-lipid liposphere as a promising platform for oral delivery of proteins.

    PubMed

    Ma, Tongtong; Wang, Lianyan; TingyuanYang; Wang, Dong; Ma, Guanghui; Wang, Siling

    2014-05-01

    The main challenge in the oral delivery of protein drugs is to enhance their oral bioavailability. Herein, we report the uniform-sized liposphere prepared by premix membrane emulsification combined with W1/O/W2 double-emulsion method as a potential oral carrier for proteins. The protein-loaded liposphere was composed of a hydrophobic poly (D, L-lactide-co-glycolide) (PLGA) core and the lipid molecules self-assembled at the interface of W1/O and O/W2. During the preparation, the protein structure was effectively maintained. Compared with PLGA microsphere, the liposphere achieved a higher loading capacity (LC, 20.18%), entrapment efficiency (EE, 90.82%) and a lower initial burst (24.73%). Importantly, the lipospheres also showed high transcytotic efficiency with human microfold cell (M cell) model, leading to a potential enhancement of intestinal absorption. This result, together with the above studies supported that the PLGA-lipid liposphere could be a promising platform for enhancing the proteins oral bioavailability. PMID:24698146

  17. 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 (?) 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 electron transfer coefficient (?) 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. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr34355c

  18. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    PubMed

    Winkelman, L A; Overton, T R

    2013-12-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows administered long-acting insulins. Western blot analysis of mammary tissue collected by biopsy indicated that the ratios of phosphorylated protein kinase b (Akt) to total Akt and phosphorylated ribosomal protein S6 (rpS6) to total rpS6 were not affected by long-acting insulins. Modestly elevating insulin activity in lactating dairy cows using long-acting insulins altered milk composition and metabolism. Future research should explore mechanisms by which either insulin concentrations or insulin signaling pathways in the mammary gland can be altered to enhance milk fat and protein production. PMID:24119807

  19. Cartilage Regeneration of Adipose-Derived Stem Cells in the TGF-?1-Immobilized PLGA-Gelatin Scaffold.

    PubMed

    Yin, Feng; Cai, Junfeng; Zen, Wen; Wei, Yanhui; Zhou, Wei; Yuan, Feng; Singh, Shree Ram; Wei, Yiyong

    2015-06-01

    Articular cartilage has restricted self-regenerative capacity; therefore, treatment of cartilage lesions is a great challenge in the field of orthopedics. In the present study, we evaluate the enhancing effect of a transforming growth factor-beta 1 (TGF-?1)-immobilized scaffold, fabricated by incorporating TGF-?1-loaded gelatin microspheres into PLGA framework, on the differentiation of adipose-derived stem cells (ASCs) into chondrocytes. Significant increase in cell proliferation was observed in the TGF-?1-immobilized PLGA-gelatin scaffold, as compared with the ASC-seeded non-TGF-?1-immobilized PLGA-gelatin scaffold. When chondrogenic differentiation of ASCs was evaluated for both constructs, sulfated glycosaminoglycan (sGAG) content was significantly higher in the TGF-?1-immobilized scaffold. This study showed that ASCs containing the TGF-?1-immobilized scaffold better promoted cartilage regeneration in defective articular cartilage, which is assessed by histological observation. Based on the above results, we conclude that TGF-?1-immobilized PLGA-gelatin scaffold seeded with ASCs considerably enhances the quality of the tissue-engineered cartilage, therefore, advancing the field of cartilage tissue engineering. PMID:25267436

  20. microsphere assemblies

    NASA Astrophysics Data System (ADS)

    Peña-Flores, Jesús I.; Palomec-Garfias, Abraham F.; Márquez-Beltrán, César; Sánchez-Mora, Enrique; Gómez-Barojas, Estela; Pérez-Rodríguez, Felipe

    2014-09-01

    The effect of Fe ion concentration on the morphological, structural, and optical properties of TiO2 films supported on silica (SiO2) opals has been studied. TiO2:Fe2O3 films were prepared by the sol-gel method in combination with a vertical dip coating procedure; precursor solutions of Ti and Fe were deposited on a monolayer of SiO2 opals previously deposited on a glass substrate by the same procedure. After the dip coating process has been carried out, the samples were thermally treated to obtain the TiO2:Fe2O3/SiO2 composites at the Fe ion concentrations of 1, 3, and 5 wt%. Scanning electron microscopy (SEM) micrographs show the formation of colloidal silica microspheres of about 50 nm diameter autoensembled in a hexagonal close-packed fashion. Although the X-ray diffractograms show no significant effect of Fe ion concentration on the crystal structure of TiO2, the ?-Raman and reflectance spectra do show that the intensity of a phonon vibration mode and the energy bandgap of TiO2 decrease as the Fe+3 ion concentration increases.

  1. Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: Preparation, pharmacokinetics and distribution in vivo.

    PubMed

    Song, Zhimei; Feng, Runliang; Sun, Min; Guo, Chenyu; Gao, Yan; Li, Lingbing; Zhai, Guangxi

    2011-02-01

    The aim of this study was to assess the potential of new copolymeric micelles to modify the pharmacokenetics and tissue distribution of Curcumin (CUR), a hydrophobic drug. In the present study, a poly (d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer was synthesized and characterized by (1)H NMR, gel permeation chromatography and FTIR analysis. The CUR-loaded PLGA-PEG-PLGA micelles were prepared by dialysis method and the physicochemical parameters of the micelles such as zeta potential, size distribution and drug encapsulation were characterized. The pharmacokinetics and biodistribution of CUR-loaded micelles in vivo were evaluated. The results showed that the zeta potential of CUR-loaded micelles was about -0.71mV and the average size was 26.29nm. CUR was encapsulated into PLGA-PEG-PLGA micelles with loading capacity of 6.4±0.02% and entrapment efficiency of 70±0.34%. The plasma AUC((0-)(?)), t(1/2?), t(1/2?) and MRT of CUR micelles were increased by 1.31, 2.48, 4.54 and 2.67 fold compared to the CUR solution, respectively. The biodistribution study in mice showed that the micelles decreased drug uptake by liver and spleen and enhanced drug distribution in lung and brain. These results suggested that PLGA-PEG-PLGA micelles would be a potential carrier for CUR. PMID:21044788

  2. A Review of Long-Acting Medications for ADHD in Canada

    PubMed Central

    Hosenbocus, Sheik; Chahal, Raj

    2009-01-01

    Objective: To review and comment on the long-acting medications presently marketed in Canada for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in terms of design, composition, mode of action and efficacy including other long-acting products that are not yet available in Canada. Method: A literature review was conducted using MEDLINE, PsycInfo, CINAHL, and PubMed with additional information gathered from other sources. Results: The American Academy of Pediatrics (AAP), the American Academy of Child and Adolescent Psychiatry (AACAP) and the Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA) while endorsing the stimulants as first line medications to treat ADHD also recommended the use of long-acting once-a-day medication for better efficacy, convenience and adherence. Most studies rated the controlled release and the immediate release medications as similar in efficacy. However, long-acting medication was shown to be superior in terms of remission rates. Conclusion: When a child is receiving a long-acting medication for treatment of ADHD, he may feel less stigmatized, is more likely to be adherent and achieve remission. A child in remission can benefit from other treatment modalities thus improving long-term prognosis. PMID:19881943

  3. Controlled release of bioactive TGF-beta 1 from microspheres embedded within biodegradable hydrogels.

    PubMed

    DeFail, Alicia J; Chu, Constance R; Izzo, Nicholas; Marra, Kacey G

    2006-03-01

    Transforming growth factor-beta1 (TGF-beta1) is of great relevance to cartilage development and regeneration. A delivery system for controlled release of growth factors such as TGF-beta1 may be therapeutic for cartilage repair. We have encapsulated TGF-beta1 into poly(DL-lactide-co-glycolide) (PLGA) microspheres, and subsequently incorporated the microspheres into biodegradable hydrogels. The hydrogels are poly(ethylene glycol) based, and the degradation rate of the hydrogels is controlled by the non-toxic cross-linking reagent, genipin. Release kinetics of TGF-beta1 were assessed using ELISA and the bioactivity of the released TGF-beta1 was evaluated using a mink lung cell growth inhibition assay. The controlled release of TGF-beta1 encapsulated within microspheres embedded in scaffolds is better controlled when compared to delivery from microspheres alone. ELISA results indicated that TGF-beta1 was released over 21 days from the delivery system, and the burst release was decreased when the microspheres were embedded in the hydrogels. The concentration of TGF-beta1 released from the gels can be controlled by both the mass of microspheres embedded in the gel, and by the concentration of genipin. Additionally, the scaffold permits containment and conformation of the spheres to the defect shape. Based on these in vitro observations, we predict that we can develop a microsphere-loaded hydrogel for controlled release of TGF-beta1 to a cartilage wound site. PMID:16140372

  4. Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague.

    PubMed

    Huang, Shih-shiung; Li, I-Hsun; Hong, Po-da; Yeh, Ming-kung

    2014-01-01

    Yersinia pestis F1 antigen-loaded poly(DL-lactide-co-glycolide)/polyethylene glycol (PEG) (PLGA/PEG) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1 antigen-loaded microspheres (mean particle size 3.8 ?m) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1 antigen over 70 days. The distribution (%) of Y. pestis F1 on the microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 ?g Y. pestis F1 antigen/mg microspheres/day of Y. pestis F1 antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 ?g Y. pestis F1 antigen/mg microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by intraperitoneal injection challenge in mice test, in which mice received one dose of 40 ?g F1 antigen content of PLGA/PEG microspheres, F1 antigen in Al(OH)3, and in comparison with F1 antigen in Al(OH)3 vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH)3 vaccine (100%). In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764 ± 3,124) to 7 weeks (126,468 ± 19,176) after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers. PMID:24550673

  5. Evaluation of quinidine short and long-acting in control of arrhythmias.

    PubMed

    Coodley, E; Pugash, N; Toppo, F

    1984-09-01

    Twenty-one patients with arrhythmias responsive to quinidine were studied both with regard to consistency of response as determined by repeat Holter Monitoring and in half of these patients a comparison of short and long-acting quinidine was made. Holter Monitoring demonstrated greater than 60% reduction of ectopic activity in all but one patient and reproducibility varied by less than 10% in nineteen of twenty-one patients. Nine of eleven patients showed the same response to long-acting quinidine as compared to short-acting. Eight of nine patients having significant numbers of ectopic pairs showed a significant reduction with quinidine therapy, both short-acting and long-acting. PMID:6486521

  6. Fabrication of Nanostructured PLGA Scaffolds Using Anodic Aluminum Oxide Templates

    E-print Network

    Hsueh, Cheng-Chih; Hsu, Shan-Hui; Hung, Huey-Shan

    2008-01-01

    PLGA (poly(lactic-co-glycolic acid)) is one of the most used biodegradable and biocompatible materials. Nanostructured PLGA even has great application potentials in tissue engineering. In this research, a fabrication technique for nanostructured PLGA membrane was investigated and developed. In this novel fabrication approach, an anodic aluminum oxide (AAO) film was use as the template ; the PLGA solution was then cast on it ; the vacuum air-extraction process was applied to transfer the nano porous pattern from the AAO membrane to the PLGA membrane and form nanostures on it. The cell culture experiments of the bovine endothelial cells demonstrated that the nanostructured PLGA membrane can double the cell growing rate. Compared to the conventional chemical-etching process, the physical fabrication method proposed in this research not only is simpler but also does not alter the characteristics of the PLGA. The nanostructure of the PLGA membrane can be well controlled by the AAO temperate.

  7. Biodegradable Nanoparticles Containing Doxorubicin-PLGA Conjugate for Sustained Release

    Microsoft Academic Search

    Hyuk Sang Yoo; Jong Eun Oh; Keun Hyeung Lee; Tae Gwan Park

    1999-01-01

    Purpose. Doxorubicin was chemically conjugated to a terminal end group of poly(D,L-lactic-co-glycolic acid) [PLGA] and the doxorubicin-PLGA conjugate was formulated into nanoparticles to sustain the release of doxorubicin.

  8. 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?m 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. PMID:26057730

  9. Degradation behaviour of microspheres prepared by spray-drying poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers.

    PubMed

    Blanco, M Dolores; Sastre, Roberto L; Teijón, César; Olmo, Rosa; Teijón, José M

    2006-12-01

    Polymeric microsphere degradation must be taken into account in the design of drug delivery systems to be injected in in vivo systems, thus a prior analysis of in vitro degradation behaviour of microspheres appears to be necessary. In this study degradation characteristics of poly(lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) microspheres prepared by the spray-drying technique have been examined. It was found that a slow decrease in molecular weight took place during the first stage of degradation, and the value of the rate constant decreased with the increase of the percentage of lactic acid of the polymer in a linear way. Thus, the period of time of this first stage decreased with the increase of content of glycolidyl units of the polymer, and it was the unique stage observed in PLA microspheres after 5 months of study. During this period of time, significant mass loss was not observed in the microspheres. The second stage of degradation of PLGA microspheres showed a larger rate constant, whose value increased with the content of glycolidyl units of the polymer. Mass loss was observed from number-average molecular weight about 6000. A sharp decrease of glass transition temperature (T(g)) was observed coinciding with the start of mass loss. This fact was accompanied by a physical change of the samples, fusion of microspheres to form large particles, which also fusion to form a unique mass of polymer; moment from that the degradation process was quicker. PMID:16971074

  10. Hydrogen microsphere hazard evaluation

    NASA Astrophysics Data System (ADS)

    Zalosh, R. G.; Bajpai, S. N.

    1981-03-01

    Progress on a preliminary hazard evaluation of hollow glass microspheres for hydrogen transport and storage is reported. The flammability and explosibility of representative hydrogen filled microspheres was assessed. The tests include dust cloud explosion; flame propagation; impact sensitivity; spark ignition; and autoignition furnace. The microspheres can be ignited and propagate flame either in the quiescent bulk form or as a suspended cloud. A preliminary comparison with flammability data for gaseous hydrogen and iron titanium hydride powder indicate that the autoignition temperature of hydrogen filled microspheres is comparable to that or the other forms of hydrogen, but suspended clouds of microspheres produce lower explosion pressures than hydride dust or hydrogen gas. Safety codes and government regulations pertinent to hydrogen filled microspheres are also reviewed.

  11. Generational PipeLined Genetic Algorithm (PLGA) using Stochastic Selection

    E-print Network

    De, Rajat Kumar

    Generational PipeLined Genetic Algorithm (PLGA) using Stochastic Selection Malay K. Pakhira and Rajat K. De Abstract-- In this paper, a pipelined version of genetic algorithm, called PLGA (PLGA). A number of benchmark problems are used to compare the performances of conventional roulette

  12. A short term quality control tool for biodegradable microspheres.

    PubMed

    D'Souza, Susan; Faraj, Jabar A; Dorati, Rossella; DeLuca, Patrick P

    2014-06-01

    Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C. PMID:24519488

  13. Treatment of Pancreatic Ascites and External Pancreatic Fistulas with a Long-Acting Somatostatin Analogue (Sandostatin)

    Microsoft Academic Search

    I. Segal; D. Parekh; J. Lipschitz; G. Gecelter; J. A. Myburgh

    1993-01-01

    Prior to the advent of somatostatin conservative therapy for pancreatic fistulas, treatment included intravenous nutritional therapy with nothing per mouth and therapeutic agents to diminish pancreatic secretions. None of these modalities were uniformly successful. A prospective study to evaluate the efficacy of a long-acting somatostatin analogue (Sandostatin) was carried out. 18 patients – 10 with pancreatic ascites and 8 with

  14. EFFICACY OF A LONG-ACTING OXYTETRACYCLINE* AGAINST CHLAMYDIAL OVINE ABORTION

    E-print Network

    Paris-Sud XI, Université de

    EFFICACY OF A LONG-ACTING OXYTETRACYCLINE* AGAINST CHLAMYDIAL OVINE ABORTION Annie RODOLAKIS1 A ABORTIVE OVINE. ― Le traitement de la chlamydiose abortive ovine par la Terramycine/L A 200 a été-bas. La transposition d'un tel traitement à la pratique et son intérêt sont discutés. Chlamydial abortion

  15. Risperidone Long-Acting Injection: Safety and Efficacy in Elderly Patients with Schizophrenia

    PubMed Central

    Catalán, Rosa; Penadés, Rafael

    2011-01-01

    Antipsychotic medication is considered the cornerstone of the treatment in elderly patients with schizophrenia. Long acting risperidone injection was the first antipsychotic available for use in this group of patients. Current scientific literature revealed that long-acting risperidone is effective in treating the positive and negative symptoms of schizophrenia and some improvements in cognition and functioning have also been found. In terms of efficacy, there is a paucity of randomized trials but the studies suggest that long-acting risperidone is efficient in the long-term management of schizophrenia, with a safety profile similar to that of oral risperidone. It seems that patient acceptance of treatment is greater when patients are switched from a traditional oral medication to depot risperidone and some improvements in cognition and functioning might be related. Further long-term comparisons with other oral and long-acting antipsychotic medications are needed. These studies should include cost-effectiveness data. Research into metabolic side effects is also needed. PMID:23861642

  16. Risperidone Long-acting Injection (RLAI) – real world outcomes from the United Kingdom high-secure hospitals

    Microsoft Academic Search

    Simon Gibbon; Edward Silva; Rupinder Kaler; Inti Qurashi; Mrigendra Das; Jon Patrick; Manjit Gahir; Douglas Gray; Lakshmanan Ramachandran; Anthony Maden

    2011-01-01

    Purpose – High-secure hospital patients often have complex presentations that are marked by co-morbidity, violence, histories of poor concordance with oral medication, and treatment resistance. The ability to give a long-acting medication with a low propensity for extra pyramidal side effects is of potential value to clinicians treating these patients. Risperidone Long-acting Injection (RLAI) is the first long-acting atypical antipsychotic

  17. Evaluating Appropriateness of Prescribing of Long-Acting Risperidone for Injection in Acute Care Settings

    PubMed Central

    Mah, Greg T; Dumontet, Jane; Lakhani, Anisha; Corrigan, Susan

    2010-01-01

    Background Long-acting risperidone for injection is a second-generation antipsychotic indicated for the treatment of schizophrenia and related psychotic disorders. It is a relatively new agent with pharmacokinetic and dosing properties unlike those of conventional long-acting antipsychotic drugs administered by injection. Objective To determine the proportion of patients for whom long-acting risperidone for injection was prescribed appropriately in acute care settings in the Fraser Health Authority of British Columbia, according to the following 4 criteria: approved indication for therapy, 2-week dosing intervals, dose increases no sooner than every 4 weeks, and initial overlap supplementation with another antipsychotic for at least 3 weeks. A variety of other variables, including documented approval under special authority from the provincial drug coverage program, length of hospital stay, initial dose of risperidone, and total number of doses, were assessed as secondary outcomes. Methods A chart review was conducted for all patients for whom therapy with long-acting risperidone for injection was prescribed during stays in 8 acute care hospitals between July 1, 2007, and July 22, 2008. The appropriateness of prescribing was assessed according to the 4 prespecified criteria. Results Long-acting risperidone for injection was prescribed for 116 patients during the study period, and 82 of these started therapy and were included in the evaluation. The primary outcome could not be assessed for 27 of these 82 patients, because they were discharged early, and data for some or all of the 4 criteria were not available. For 33 (60%) of the 55 remaining patients, long-acting risperidone for injection had been prescribed appropriately. In contrast, for 22 (40%) of the patients, prescription of risperidone was deemed inappropriate because of failure to meet at least 1 of the 4 criteria. Premature escalation of the dose and inadequate overlap with antipsychotic supplementation were the most common reasons for designation of the prescription as inappropriate. Conclusions Opportunities exist to improve prescribing practices for long-acting risperidone for injection in acute care institutions in this health authority. PMID:22479015

  18. PLGA: a unique polymer for drug delivery.

    PubMed

    Kapoor, Deepak N; Bhatia, Amit; Kaur, Ripandeep; Sharma, Ruchi; Kaur, Gurvinder; Dhawan, Sanju

    2015-01-01

    Biodegradable polymers have played an important role in the delivery of drugs in a controlled and targeted manner. Polylactic-co-glycolic acid (PLGA) is one of the extensively researched synthetic biodegradable polymers due to its favorable properties. It is also known as a 'Smart Polymer' due to its stimuli sensitive behavior. A wide range of PLGA-based drug delivery systems have been reported for the treatment or diagnosis of various diseases and disorders. The present review provides an overview of the chemistry, physicochemical properties, biodegradation behavior, evaluation parameters and applications of PLGA in drug delivery. Different drug-polymer combinations developed into drug delivery or carrier systems are enumerated and discussed. PMID:25565440

  19. Deltoid Injections of Risperidone Long-acting Injectable in Patients with Schizophrenia

    PubMed Central

    Quiroz, Jorge A.; Rusch, Sarah; Thyssen, An; Kushner, Stuart

    2011-01-01

    Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Methods Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. Results In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites. PMID:21779538

  20. Testing the effects of long-acting steroids in edema and ecchymosis after closed rhinoplasty

    PubMed Central

    Gutierrez, Santiago; Wuesthoff, Carolina

    2014-01-01

    BACKGROUND: Steroids have proven to be of some benefit in rhinoplasty edema and ecchymosis when administered at a high and repeated dose. OBJECTIVE: To evaluate the effects of single-dose, long-acting intramuscular steroids on postoperative edema and ecchymosis after closed rhinoplasty with osteotomies compared with placebo. METHODS: A randomized, double-blinded, placebo-controlled trial was performed. Fifty-four patients were randomly assigned to two groups: 28 received a single dose of long-acting dexamethasone (mean [± SD] dose 16±4 mg) immediately before anesthetic induction; the remaining 26 received an intramuscular injection of saline solution. The same surgeon performed all surgeries, with patients under general anesthesia. Acetaminophen was the only analgesic used to control postoperative pain. High-resolution digital photographs were taken on postoperative days 1, 3, 7 and 14. Scoring was performed separately for eyelid swelling and ecchymosis by an independent observer using a graded scale (0 to 5) for edema and a scoring system (0 to 13) for ecchymosis. RESULTS: No statistically significant differences in terms of age, sex or amount of bleeding during surgery were found between the two groups. No statistically significant difference was observed in the decrease of both ecchymosis and edema between placebo and high-dose, long-acting dexamethasone. A statistically significant difference in operation time was found, favouring the steroid group. No severe complications were observed due to steroid use. DISCUSSION: Osteotomies are basically a form of (controlled) trauma, with considerable disruption of the abundant blood vessels in this facial region and, therefore, are associated with with undesirable effects. A recent meta-analysis failed to show benefits of the use of steroids after postoperative day 3. Only a trend toward reduction in edema and ecchymosis with the use of long-acting steroids compared with placebo was demonstrated in the present study. CONCLUSION: There was no benefit in administering single-dose, long-acting steroids in patients undergoing closed rhinoplasty with osteotomies. PMID:25114618

  1. Risperidone Long-Acting Injections: Successful Alternative Deltoid Muscle Injections for Refractory Schizophrenia

    PubMed Central

    Saxena, Arjun; Grace, Jeffery; Olympia, Josie L.; Trigoboff, Eileen; Watson, Thomas; Cushman, Sharon; Newcomer, David

    2008-01-01

    Treatment-resistant paranoid schizophrenia is often addressed with long-term intramuscular preparations of conventional antipsychotics (haloperidol and fluphenazine), which can be associated with the development of painful, lumpy nodules at the injection site. In this article, we present a case example of a 58-year-old male patient with paranoid schizophrenia who was treated with risperidone long-acting injection given into the deltoid muscle instead of the US Food and Drug Administration (FDA)-approved gluteal muscle injection site. Use of this agent in the deltoid muscle facilitated healing of the numerous painful lumpy nodules associated with prior trials of conventional long-acting injections. In addition, the patient’s psychiatric outcome was improved relative to what had been observed with the previous agents. PMID:19727259

  2. Efficacy and safety of risperidone long-acting injection in elderly people with schizophrenia

    PubMed Central

    Singh, Dhiren; O’Connor, Daniel W

    2009-01-01

    Antipsychotic medication is the mainstay of treatment in elderly patients with psychosis. In recent years, second generation antipsychotics have come to be preferred. Long-acting risperidone is the first such antipsychotic available for use in this vulnerable group of patients and offers an attractive alternative to traditional medications. The available literature revealed that long-acting risperidone is generally well tolerated and is effective in treating both the positive and negative symptoms of schizophrenia. Despite a lack of randomized trials and head-to-head studies, it appears to be a useful addition to the treatment armory for patients with chronic psychosis who require a depot preparation. Further research into its endocrine and metabolic side effects is needed. PMID:19750235

  3. Effectiveness of risperidone long-acting injection in first-episode schizophrenia: In naturalistic setting

    Microsoft Academic Search

    Borah Kim; Sang-Hyuk Lee; Tae Kyou Choi; ShinYoung Suh; Yong Woo Kim; EunHee Lee; Ki Hwan Yook

    2008-01-01

    Patients with first-episode schizophrenia frequently relapse during the first years of the illness. This may be associated with clinical deterioration. It is important to prevent relapses in first-episode schizophrenia. We examine whether risperidone long-acting injection (RLAI) could effectively act to prevent relapse in first-episode schizophrenia. We conducted a prospective, naturalistic, controlled, and open-label study over 2 years in 50 patients with

  4. Long-acting reversible contraception in the pediatric emergency department: clinical implications and common challenges.

    PubMed

    Koyama, Atsuko; Dorfman, David H; Forcier, Michelle M

    2015-04-01

    Long-acting reversible contraception (LARC) is recommended as first-line contraception for adolescents and young adults. As the use of LARC increases, pediatric emergency medicine clinicians should be able to recognize different types of LARC and address their common adverse effects, adverse reactions, and complications. This continuing medical education activity provides an overview of LARC and will assist clinicians in the evaluation and management of patients with LARC-associated complaints. PMID:25831033

  5. Ivermectin (3.15%) long-acting formulations in cattle: Absorption pattern and pharmacokinetic considerations

    Microsoft Academic Search

    A. Lifschitz; G. Virkel; M. Ballent; J. Sallovitz; F. Imperiale; A. Pis; C. Lanusse

    2007-01-01

    Ivermectin (IVM) is a broad-spectrum antiparasitic drug extensively used in veterinary medicine. The composition of the pharmaceutical preparation affects IVM absorption and its systemic availability. After the introduction of the first approved IVM formulation (propylene glycol\\/glycerol formal 60:40) used at 200?g\\/kg, different pharmaceutical modifications have been assayed to extend IVM persistent endectocide activity. Recently, IVM 3.15% long-acting (IVM-LA) preparations to

  6. Long-acting nifedipine in the management of the hypertensive patient

    PubMed Central

    Snider, Morgan E; Nuzum, Donald S; Veverka, Angie

    2008-01-01

    Hypertension is a global condition affecting billions worldwide. It is a significant contributor to cardiovascular events, cardiac death and kidney disease. A number of medication classes exist to aid healthcare providers and their patients in controlling hypertension. Nifedipine, a dihydropyridine calcium channel blocker, was once one of the most widely used medications for hypertension, but safety and tolerability concerns along with the introduction of new classes of antihypertensive medications and an increasing pool of data showing mortality benefit of other classes caused nifedipine to fall out of favor. More recently, long-acting formulations were developed and made available to clinicians. These newer formulations were designed to address many of the concerns raised by earlier formulations of nifedipine. Numerous clinical trials have been conducted comparing long-acting nifedipine to many of the more commonly prescribed antihypertensive medications. This review will address the pharmacology, pharmacokinetics and the available clinical trial data on long-acting nifedipine and summarize its role in the management of hypertension. PMID:19337538

  7. Repair of rat cranial bone defect by using bone morphogenetic protein-2-related peptide combined with microspheres composed of polylactic acid/polyglycolic acid copolymer and chitosan.

    PubMed

    Li, Jingfeng; Jin, Lin; Wang, Mingbo; Zhu, Shaobo; Xu, Shuyun

    2015-01-01

    The effects of the transplanted bone morphogenetic protein-2 (BMP2) -related peptide P24 and rhBMP2 combined with poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS) microspheres were investigated in promoting the repair of rat cranial bone defect. Forty white rats were selected and equally divided into four groups (group A: 1??g of rhBMP2/PLGA/CS composite; group B: 3?mg of P24/PLGA/CS composite; group C: 0.5??g of rhBMP2 + 1.5?mg of P24/PLGA/CS composite; group D: blank PLGA/CS material), and rat cranial bone defect models with a diameter of 5?mm were established. The materials were transplanted to the cranial bone defects. The animals were sacrificed on weeks 6 and 12 post-operation. Radiographic examinations (x-ray imaging and 3D CT scanning) and histological evaluations were performed. The repaired areas of cranial bone defects were measured, and the osteogenetic abilities of various materials were compared. Cranial histology, imaging, and repaired area measurements showed that the osteogenetic effects at two time points (weeks 6 and 12) in group C were better than those in groups A and B. The effects in groups A and B were similar. Group D achieved the worst repair effect of cranial bone defects, where a large number of fibrous connective tissues were observed. The PLGA/CS composite microspheres loaded with rhBMP2 and P24 had optimal concrescence and could mutually increase their osteogenesis capability. rhBMP2 + P24/PLGA/CS composite is a novel material for bone defect repair with stable activity to induce bone formation. PMID:26154695

  8. Microsphere Insulation Panels

    NASA Technical Reports Server (NTRS)

    Mohling, R.; Allen, M.; Baumgartner, R.

    2006-01-01

    Microsphere insulation panels (MIPs) have been developed as lightweight, longlasting replacements for the foam and vacuum-jacketed systems heretofore used for thermally insulating cryogenic vessels and transfer ducts. The microsphere core material of a typical MIP consists of hollow glass bubbles, which have a combination of advantageous mechanical, chemical, and thermal-insulation properties heretofore available only separately in different materials. In particular, a core filling of glass microspheres has high crush strength and low density, is noncombustible, and performs well in soft vacuum.

  9. Organic aerogel microspheres

    DOEpatents

    Mayer, S.T.; Kong, F.M.; Pekala, R.W.; Kaschmitter, J.L.

    1999-06-01

    Organic aerogel microspheres are disclosed which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonstick gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  10. Organic aerogel microspheres

    DOEpatents

    Mayer, Steven T. (San Leandro, CA); Kong, Fung-Ming (Pleasanton, CA); Pekala, Richard W. (Pleasant Hill, CA); Kaschmitter, James L. (Pleasanton, CA)

    1999-01-01

    Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  11. Accelerated chondrocyte functions on NaOH-treated PLGA scaffolds

    Microsoft Academic Search

    Grace E. Park; Megan A. Pattison; Thomas J. Webster

    2005-01-01

    Compared to conventional poly(lactic-co-glycolic acid) (PLGA), previous studies have shown that NaOH-treated PLGA two-dimensional substrates enhanced functions of osteoblasts (bone-forming cells), vascular and bladder smooth muscle cells, and chondrocytes (cartilage-synthesizing cells). In this same spirit, the purpose of this in vitro study was to fabricate three-dimensional NaOH-treated PLGA scaffolds and determine their efficacy toward articular cartilage applications. To improve functions

  12. Hydrolytic degradation characteristics of irradiated multi-layered PLGA films.

    PubMed

    Joachim Loo, Say Chye; Jason Tan, Wei Li; Khoa, Shu Min; Chia, Ngeow Khing; Venkatraman, Subbu; Boey, Freddy

    2008-08-01

    Poly(lactide-co-glycolide) (PLGA) has been extensively investigated for controlled drug release. Because they undergo bulk degradation, they do not allow for a good controlled-release of drugs. The objective of this study is therefore to understand if a multi-layer-cum-irradiation technique would elicit surface erosion from PLGA polymers. A linear loss of mass and film thinning from PLGA films were observed. Also, the erosion of the top layer, of this multi-layered structure, accelerates degradation of the underlying layers. It is this effect that results in the observed pseudo-surface erosion for irradiated multi-layered PLGA. PMID:18514448

  13. Characteristics of patients with COPD newly prescribed a long-acting bronchodilator: a retrospective cohort study

    PubMed Central

    Wurst, Keele E; St Laurent, Samantha; Mullerova, Hana; Davis, Kourtney J

    2014-01-01

    Introduction This study aimed to characterize patients with chronic obstructive pulmonary disease (COPD) newly prescribed a long-acting bronchodilator (LABD), and to assess changes in medication over 24 months. Methods A cohort of patients with COPD aged ?40 years newly prescribed an LABD between January 1, 2007 and December 31, 2009 were identified from the Truven Marketscan® Commercial Database (Truven Health Analytics, Ann Arbor, MI, USA) and followed for 24 months. Inclusion criteria included no prior prescription for an LABD or inhaled corticosteroids for 12 months prior to the LABD index date (baseline). Patient characteristics were examined. As LABDs were mainly long-acting muscarinic antagonists (LAMAs), additions, switches, discontinuation, adherence to (medication possession ratio), and persistence (proportion of days covered) with LAMA monotherapy were assessed for 24 months following the index date. Adherence and persistence with long-acting ?2-agonists (LABAs) were also assessed. Results A cohort of 3,268 patients aged 40–65 years was identified (mean age 55.8 years, 48% male). LAMA monotherapy was prescribed to 93% of patients who received an LABD. During the 24-month follow-up, 16% of these patients added COPD medication, 10% switched to an inhaled corticosteroid-containing medication, and 25% discontinued after one LAMA prescription at baseline. Over 12 and 24 months, adherence to LAMA was 40% and 33%, respectively, and adherence to LABA was 29% and 24%, respectively. Over the same time periods, persistence with LAMA monotherapy was 19% and 15%, respectively, and persistence with LABA was 9% and 7%, respectively. Conclusion Adherence to newly initiated LAMA monotherapy was low, with one in four patients adding to or switching from LAMA and many patients discontinuing therapy. Adherence to LABA was also low. These results suggest that additional medication to a single LABD may be required in some patients with COPD to achieve optimal disease control. PMID:25285002

  14. Prevention of unintended pregnancy: a focus on long-acting reversible contraception.

    PubMed

    Pickle, Sarah; Wu, Justine; Burbank-Schmitt, Edith

    2014-06-01

    This article summarizes the literature regarding the epidemiology and prevention of unintended pregnancy in the United States. Because of the Affordable Care Act and its accompanying contraceptive provision, there is a need for more primary care clinicians to provide family planning services. Office-based interventions to incorporate family planning services in primary care are presented, including clinical tools and electronic health record use. Special attention is paid to long-acting reversible contraceptive methods (the subdermal implant and intrauterine devices); these highly effective and safe methods have the greatest potential to decrease the rate of unintended pregnancy, but have been underused. PMID:24830607

  15. Growth Factor Gradients via Microsphere Delivery in Biopolymer Scaffolds for Osteochondral Tissue Engineering

    PubMed Central

    Wang, Xiaoqin; Wenk, Esther; Zhang, Xiaohui; Meinel, Lorenz; Vunjak-Novakovic, Gordana; Kaplan, David L.

    2009-01-01

    Temporally and spatially controlled delivery of growth factors in polymeric scaffolds is crucial for engineering composite tissue structures, such as osteochondral constructs. In the present study, microsphere-mediated growth factor delivery in polymer scaffolds and its impact on osteochondral differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) was evaluated. Two growth factors, bone morphogenetic protein 2 (rhBMP-2) and insulin-like growth factor I (rhIGF-I), were incorporated as a single concentration gradient or reverse gradient combining two factors in the scaffolds. To assess the gradient making system and the delivery efficiency of polylactic-co-glycolic acid (PLGA) and silk fibroin microspheres, initially an alginate gel was fabricated into a cylinder shape with microspheres incorporated as gradients. Compared to PLGA microspheres, silk microspheres were more efficient in delivering rhBMP-2, probably due to sustained release of the growth factor, while less efficient in delivering rhIGF-I, likely due to loading efficiency. The growth factor gradients formed were shallow, inducing non-gradient trends in hMSC osteochondral differentiation. Aqueous-derived silk porous scaffolds were used to incorporate silk microspheres using the same gradient process. Both growth factors formed deep and linear concentration gradients in the scaffold, as shown by enzyme-linked immunosorbent assay (ELISA). After seeding with hMSCs and culturing for 5 weeks in a medium containing osteogenic and chondrogenic components, hMSCs exhibited osteogenic and chondrogenic differentiation along the concentration gradients of rhBMP-2 in the single gradient of rhBMP-2 and reverse gradient of rhBMP-2/rhIGF-I, but not the rhIGF-I gradient system, confirming that silk microspheres were more efficient in delivering rhBMP-2 than rhIGF-I for hMSCs osteochondrogenesis. This novel silk microsphere/scaffold system offers a new option for the delivery of multiple growth factors with spatial control in a 3D culture environment for both understanding natural tissue growth process and in vitro engineering complex tissue constructs. PMID:19071168

  16. The effects of long-acting bronchodilators on total mortality in patients with stable chronic obstructive pulmonary disease

    Microsoft Academic Search

    Agnes Kliber; Larry D Lynd; Don D Sin

    2010-01-01

    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD. METHODS: Using MEDLINE, EMBASE and

  17. Long-acting ? 2-adrenoceptor agonists or tiotropium bromide for patients with COPD: is combination therapy justified?

    Microsoft Academic Search

    Rachel C Tennant; Edward M Erin; Peter J Barnes; Trevor T Hansel

    2003-01-01

    Bronchodilators are the mainstay of therapy for patients with established chronic obstructive pulmonary disease (COPD) but, at present, the majority of patients use short-acting agents. There is increasing evidence that long-acting agents, such as the ?2-adrenoceptor agonists salmeterol and formeterol, and the new anticholinergic tiotropium bromide provide a better therapeutic option. In the treatment of COPD, long-acting ?2-adrenoceptor agonists (LABAs)

  18. Protein encapsulation into biodegradable microspheres by a novel S/O/W emulsion method using poly(ethylene glycol) as a protein micronization adjuvant.

    PubMed

    Morita, T; Sakamura, Y; Horikiri, Y; Suzuki, T; Yoshino, H

    2000-12-01

    A new method for preparing protein-loaded biodegradable microspheres by a process involving solid-in-oil-in-water (S/O/W) emulsion was established using poly(ethylene glycol) (PEG). In the first step, a protein solution was lyophilized with PEG, which resulted in the formation of spherical protein microparticles, less than 5 microm in diameter, dispersed in a continuous PEG phase. This process was well explained by the aqueous phase separation phenomenon induced by freezing-condensation. Since this lyophilizate could be directly dispersed in an organic phase containing biodegradable polymer by dissolving PEG with methylene chloride, a conventional in-water drying method could be adopted in the second step. Through this S/O/W emulsion process, horseradish peroxidase was effectively entrapped into monolithic-type microspheres of poly(DL-lactic-co-glycolic acid) (PLGA), without significant loss of activity. Bovine superoxide dismutase (bSOD), as another model protein, could be encapsulated into reservoir-type microspheres by the 'polymer-alloys method' using both poly(DL-lactic acid) (PLA) and PLGA. The initial release of bSOD from this reservoir-type microsphere was efficiently reduced. Further, the bSOD release kinetics could be suitably modified by adjusting the loading amounts of PEG or polymer composition. In this study, the multi-functional nature of PEG was successfully utilized in the preparation and designing of protein-loaded microspheres. PMID:11102683

  19. Thermal Transpiration in Microsphere Membranes

    Microsoft Academic Search

    Marcus Young; Yen Lin Han; E. P. Muntz; G. Shiflett; Andrew Ketsdever; Amanda Green

    2003-01-01

    Self-assembled glass microsphere membranes as an alternative transpiration membrane for application in a Knudsen Compressor are discussed. A performance model is constructed and used to compare the performance of glass microsphere membranes to silicon aerogel membranes for this application. An initial experimental Knudsen Compressor stage based on glass microsphere membranes has been designed and experimentally tested. Preliminary performance results show

  20. The use of short- and long-acting hypnotics in clinical medicine.

    PubMed

    Nicholson, A N

    1981-01-01

    1 Activity of short- and long-acting benzodiazepines is reviewed with reference to pharmacokinetics and residual sequelae, and to efficacy and adverse effects. 2 Some benzodiazepines may not lead to obvious effects on performance, such as nordiazepam and clobazam, and the persistence of residual sequelae may not relate obviously to elimination half-lives (as with diazepam and possibly flunitrazepam). However, benzodiazepines with mean half-lives less than 8 h may have residual sequelae, whereas hypnotics with mean half-lives greater than 16 h are likely to lead to impared performance and/or anxiolytic effects the next day. 3 Potassium chlorazepate 15 mg, with its long-acting metabolite nordiazepam, would seem to be the drug of choice for insomnia secondary to anxiety. For the insomniac without significant psychopathology, temazepam 10-20 mg, triazolam 0.125-0.25 mg and for occasional use, diazepam 5-10 mg, provide the initial approach. Flurazepam hydrochloride 15-30 mg, nitrazepam 5-10 mg and flunitrazepam 1 mg and above, have persistent residual effects and should be reserved for refractory patients, and for those in whom some impairment of performance the next day would be acceptable. 4 There is little or no evidence to suggest that the proper use of the short-acting hypnotics, triazolam and temazepam, leads to a worsening of sleep on withdrawal. However, some benzodiazepines may lead to disturbances of sleep and/or rebound insomnia, and nitrazepam and flunitrazepam may be implicated. PMID:6133538

  1. Biodistribution of PLGA and PLGA/chitosan nanoparticles after repeat-dose oral delivery in F344 rats for 7 days

    PubMed Central

    Navarro, Sara M; Darensbourg, Caleb; Cross, Linda; Stout, Rhett; Coulon, Diana; Astete, Carlos E; Morgan, Timothy; Sabliov, Cristina M

    2015-01-01

    Aim To quantify in vivo the biodistribution of poly(lactic-co-glycolic) acid (PLGA) and PLGA/chitosan nanoparticles (PLGA/Chi NPs) and assess if the positive charge of chitosan significantly enhances nanoparticle absorption in the GI tract. Material & methods PLGA and PLGA/Chi NPs covalently linked to tetramethylrhodamine-5-isothiocyanate (TRITC) were orally administered to F344 rats for 7 days, and the biodistribution of fluorescent NPs was analyzed in different organs. Results The highest amount of particles (% total dose/g) was detected for both treatments in the spleen, followed by intestine and kidney, and then by liver, lung, heart and brain, with no significant difference between PLGA and PLGA/Chi NPs. Conclusion Only a small percentage of orally delivered NPs was detected in the analyzed organs. The positive charge conferred by chitosan was not sufficient to improve the absorption of the PLGA/Chi NPs over that of PLGA NPs. PMID:25491670

  2. The effect of adding inhaled corticosteroids to tiotropium and long-acting beta2-agonists for chronic obstructive pulmonary disease

    PubMed Central

    Karner, Charlotta; Cates, Christopher J

    2014-01-01

    Background Long-acting bronchodilators comprising long-acting beta2-agonists and the anticholinergic agent tiotropium are commonly used, either on their own or in combination, for managing persistent symptoms of chronic obstructive pulmonary disease. Patients with severe chronic obstructive pulmonary disease who are symptomatic and who suffer repeated exacerbations are recommended to add inhaled corticosteroids to their bronchodilator treatment. However, the benefits and risks of adding inhaled corticosteroid to tiotropium and long-acting beta2-agonists for the treatment of chronic obstructive pulmonary disease are unclear. Objectives To assess the relative effects of adding inhaled corticosteroids to tiotropium and long-acting beta2-agonists treatment in patients with chronic obstructive pulmonary disease. Search methods We searched the Cochrane Airways Group Specialised Register of trials (February 2011) and reference lists of articles. Selection criteria We included parallel group, randomised controlled trials of three months or longer comparing inhaled corticosteroid and long-acting beta2-agonist combination therapy in addition to inhaled tiotropium against tiotropium and long-acting beta2-agonist treatment for patients with chronic obstructive pulmonary disease (COPD). Data collection and analysis Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials. Main results One trial (293 patients) was identified comparing tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy to tiotropium plus long-acting beta2-agonist. The study was of good methodological quality, however it suffered from high and uneven withdrawal rates between the treatment arms. There is currently insufficient evidence to know how much difference the addition of inhaled corticosteroids makes to people who are taking tiotropium and a long-acting beta2-agonist for COPD. Authors’ conclusions The relative efficacy and safety of adding inhaled corticosteroid to tiotropium and a long-acting beta2-agonist for chronic obstructive pulmonary disease patients remains uncertain and additional trials are required to answer this question. PMID:21901729

  3. A Novel Technique for Loading of Paclitaxel-PLGA Nanoparticles onto ePTFE Vascular Grafts

    E-print Network

    Park, Jong-Sang

    A Novel Technique for Loading of Paclitaxel-PLGA Nanoparticles onto ePTFE Vascular Grafts Hyun Jung(lactic-co- glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-NPs) were prepared by the emulsion-solvent evaporation method and spin penetration techniques. Scanning electron microscope (SEM) images of various stages of Ptx-PLGA

  4. The cost associated with administering risperidone long-acting injections in the Australian community

    PubMed Central

    2011-01-01

    Background Risperidone long-acting injection (LAI) is mostly administered twice weekly to people with schizophrenia by nurses at community mental health centres (CMHC) or through mobile outreach visits. This study estimates the cost of resource utilisation associated with the administration of risperidone LAI and the potential savings from substituting two-weekly injections with a longer interval product of therapeutic equivalence. Methods A survey of mental health staff overseeing the administration of risperidone LAI at 253 distinct Australian CMHCs was undertaken in November 2009. For the two-week period prior to the survey, respondents were asked questions on injection time (and related tasks) and, for mobile outreach visits, distance and time travelled as well as reduction in visits. Results were stratified by Australian Standard Geographical Classification (ASGC) region. Resource use was quantified and valued in Australian dollars. Results Results are derived from 74 CMHCs, representing approximately 26% of the national average risperidone LAI unit two-week sales. Stratified average injection time (including related tasks) for risperidone LAI ranged from 18-29 minutes, with a national average of 20.12 minutes. For mobile outreach visits, average distance per patient ranged from 19.4 to 55.5 km for One Staff Visits and 15.2 to 218.1 km for More Than One Staff Visits, and average time travelled ranged from 34.1 to 54.5 minutes for One Staff Visits and 29.2 to 136.3 minutes for More Than One Staff visits. The upper range consistently reflected greater resource utilisation in rural areas compared to urban areas. If administration of risperidone LAI had not been required, 20% fewer mobile outreach visits would have occurred. Conclusions The national average saving per two-weekly risperidone long-acting injection avoided is $75.14. In 2009 in Australia, this would have saved ~$11 million for injection administration costs alone if all patients taking two-weekly risperidone LAI had instead been treated with a therapeutically equivalent long-acting injectable antipsychotic requiring one less injection per month. PMID:21943060

  5. The role of combination inhaled corticosteroid/long-acting beta-agonist therapy in COPD management.

    PubMed

    Mapel, Douglas W; Hurley, Judith S; Dalal, Anand A; Blanchette, Christopher M

    2010-06-01

    Chronic obstructive pulmonary disease (COPD) is now the fourth leading cause of death, affects an estimated 24 million Americans, and accounts for over ten million physician and emergency department (ED) visits and hospitalisations each year. The diagnosis and management of COPD falls largely to primary care practitioners. Previously, COPD management options were limited, but newer treatments have been shown to slow lung deterioration, reduce symptoms and preserve quality of life. Combination therapy with an inhaled corticosteroid and a long-acting beta2-agonist (ICS/LABA) is an effective therapy for COPD that, compared to other therapies, has been shown to reduce exacerbations, hospitalisations, ED visits and health care costs. This review focuses on the role of combination ICS/LABA therapy in managing COPD, including indications, potential benefits and considerations that affect therapy decisions. PMID:20339822

  6. Role of combination inhaled corticosteroids and long acting beta agonists in the treatment of adult asthma.

    PubMed

    Mayers I; Damant R

    2005-06-01

    An inhaled corticosteroid (ICS) and a long acting beta agonist (LABA) are combined in an inhaler for treatment of persistent asthma. There is evidence that maintenance therapy with a combination ICS/LABA inhaler improves clinical outcomes and reduces airflow obstruction in patients with persistent asthma, who are not well controlled even when using ICS maintenance therapy. There is evidence that a combination ICS/LABA inhaler may also play a role in initial maintenance therapy for patients with mild persistent asthma, who have never used ICS therapy. There is no evidence regarding the use of combination therapy in intermittent asthma. Oral candidal infections, hoarseness and pharyngolaryngeal pain are the most frequently reported adverse events. Combination inhaler therapy can improve compliance with guidelines that recommend a LABA only be used with concurrent ICS administration. PMID:15966131

  7. [Pharmacoeconomics aspects of long-acting beta-2 agonists in COPD patients].

    PubMed

    Jahnz-Rózyk, Karina; Targowski, Tomasz

    2010-04-01

    Pharmacoeconomics is the scientific discipline that assess the overall value of pharmaceutical health care products, services, and programs. Several potential uses for pharmacoeconomic analysis are pharmaceutical reimbursement, price negotiations, formulary discussions, clinical practice guideline developments, and communications to prescribing physicians. Bronchodilatator medications, including SABA (slow acting beta-2 agonists) and LABA (long acting beta-2 agonists) are central to the symptomatic management of COPD. LABA in Evidence Based Medicine related treatment of COPD patients is presented in this article. In the second part issues regarding the limitations and interpretations of COPD clinical trials have been discussed. The important role of cost-effectiveness analyses in LABA reimbursement and drug pricing strategy in Poland have been stressed. PMID:20491347

  8. A pediatric non-protein losing Menetrier's disease successfully treated with octreotide long acting release

    PubMed Central

    Nardo, Giovanni Di; Oliva, Salvatore; Aloi, Marina; Ferrari, Federica; Frediani, Simone; Marcheggiano, Adriana; Cucchiara, Salvatore

    2012-01-01

    Pediatric Menetrier’s disease (MD) is an uncommon, acute, self-limited hypertrophic gastropathy characterized by enlarged gastric folds associated with epithelial hyperplasia and usually accompanied by protein losing gastropathy. Gastric cytomegalovirus infection is found in one third of MD children and its treatment is often associated with remission. Diagnosis often requires full-thickness biopsy due to inability to detect typical histological findings with conventional endoscopic biopsy. We report an uncommon case of non self-limited pediatric MD needing endoscopic mucosal resection for diagnosis which was then successfully treated with octreotide long-acting release (LAR). To the best of our knowledge, this is the first pediatric MD case successfully treated with octreotide LAR. Our experience suggests octreotide LAR as treatment for refractory MD before gastrectomy. PMID:22690084

  9. [Long-acting injectable antipsychotics. Overview and advice for daily routine care].

    PubMed

    Köhler, S; Heinz, A; Sterzer, P

    2014-09-01

    Recent investigations have demonstrated a significant reduction of relapse and hospitalization rates associated with the use of long-acting injectable antipsychotics (LAIs) in the treatment of schizophrenia. There are only marginal differences in the effectiveness of different specific LAIs. Furthermore, LAIs are comparable to the oral equivalents with respect to effectiveness and side effects. The occurrence of extrapyramidal motor disorders (EPD) is less frequent in second generation (SG) LAIs than in first generation (FG) LAIs. Moreover, specific characteristics of some substances should be considered: In SG-LAIs immediate onset of action is only applicable for olanzapine and paliperidone and FG-LAIs should always be given as a test dose first to assure a general tolerance. All LAIs have a high variability of plasma levels which complicates the dose titration. Last but not least, current research concerning long-term consequences of continuous treatment with antipsychotics and the potentially poorer response to antipsychotics should be considered. PMID:24113854

  10. Safety of the long-acting neuraminidase inhibitor laninamivir octanoate hydrate in post-marketing surveillance.

    PubMed

    Kashiwagi, Seizaburo; Yoshida, Sanae; Yamaguchi, Hiroki; Niwa, Shinpei; Mitsui, Noriko; Tanigawa, Masatoshi; Shiosakai, Kazuhito; Yamanouchi, Naoki; Shiozawa, Tomoo; Yamaguchi, Fumie

    2012-11-01

    Laninamivir octanoate hydrate (laninamivir) is a long-acting neuraminidase inhibitor (NAI) that completes treatment with only a single inhalation. It was launched in Japan in October 2010 as an anti-influenza agent. A post-marketing surveillance study was conducted in the 2010/2011 influenza season to assess the safety of this drug in clinical settings. Adverse drug reactions (ADRs) were observed in 50 patients (59 events) out of 3542 patients subjected to safety evaluation (incidence 1.41%). Commonly reported ADRs were psychiatric disorders (abnormal behaviour, etc.), gastrointestinal disorders (diarrhoea, nausea, etc.) and nervous system disorders (dizziness, etc.), with incidences of 0.48% (n=17), 0.45% (n=16) and 0.17% (n=6), respectively. No serious ADRs occurred. ADRs usually emerged on the day on which laninamivir was inhaled (52.5%) and ADRs emerged within 3 days after inhalation in >90% of adversely affected patients. ADRs resolved or improved within 3 days in >85% of patients. The incidence of adverse events involving abnormal behaviour was 3.1% (30/959) among patients <10 years of age, 0.7% (8/1088) among patients aged 10-19 years, 0.1% (2/1431) among adult patients aged 20-64 years and 0.0% (0/64) among patients aged ?65 years. It was confirmed that laninamivir is unlikely to cause delayed ADRs or a prolonged duration of ADRs despite this drug being a long-acting NAI. Furthermore, the incidence of ADRs was not found to have increased compared with that observed during clinical trials, and the types of ADR observed during this study were similar to those previously observed. Thus, laninamivir octanoate hydrate was confirmed to have no noticeable problem with safety. PMID:22871369

  11. Differences in acute anorectic effects of long-acting GLP-1 receptor agonists in rats.

    PubMed

    Sisley, Stephanie; Smith, Kathleen; Sandoval, Darleen A; Seeley, Randy J

    2014-08-01

    Long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists have both glucose- and weight-lowering effects. The brain is poised to mediate both of these actions since GLP-1Rs are present in key areas known to control weight and glucose. Although some research has been performed on the effects of exendin-4 in the brain, little data exists on the central effects of liraglutide, a long-acting GLP-1R agonist with much closer structural homology to native GLP-1. In lean, Long-Evans rats, we found that direct intra-third cerebroventricular (i3vt) administration of 0.26 nmol liraglutide caused a 50% reduction in food intake. However, exendin-4 produced the same reduction in food intake with 10-fold greater potency (0.02 nmol). These data are supported by similar c-Fos immunoreactivity in the hypothalamic paraventricular nuclei by exendin-4 as compared to liraglutide despite differing doses. The anorectic effects of both drugs were blocked with i3vt pre-treatment of a GLP-1R competitive antagonist, exendin(9-39), indicating that both drugs required the GLP-1R for their effects. Exendin-4, and not liraglutide, caused hyperglycemia when given i3vt prior to an oral glucose tolerance test, although liraglutide did not lower glucose. Thus, these data show that GLP-1R agonists have differing anorectic potencies in the CNS, which may account for some of their clinical differences. Additionally, we show here that the glucose lowering properties of acute administration of GLP-1R agonists are not accounted for by their central effects. PMID:24879927

  12. Pharmacokinetics of injectable, long-acting nevirapine for HIV prophylaxis in breastfeeding infants.

    PubMed

    Cortez, John M; Quintero, Rafaela; Moss, John A; Beliveau, Martin; Smith, Thomas J; Baum, Marc M

    2015-01-01

    Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 ?m), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 ?g ml(-1)) for 6 weeks or longer. PMID:25313219

  13. Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

    PubMed

    Hu, Xi; Lin, Xia; Gu, Yuechen; Liu, Zitong; Tang, Yilin; Zhang, Yu; Chen, Xi; Wang, Yanjiao; Tang, Xing

    2014-08-01

    The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-?-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 ?m millipore membrane filter. PMID:24188474

  14. Development of coated nifedipine dry elixir as a long acting oral delivery with bioavailability enhancement.

    PubMed

    Choi, Jae-Yoon; Jin, Su-Eon; Park, Youmie; Lee, Hyo-Jong; Park, Yohan; Maeng, Han-Joo; Kim, Chong-Kook

    2011-10-01

    To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68-8.75 ?m of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the C(max) and AUC(0?8h) of nifedipine in rat increased about 13- and 7-fold, respectively, and the Tmax of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC(0?8h) and T(max) of nifedipine in CNDE increased markedly and the C(max) of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine. PMID:22076771

  15. [A history of antipsychotic long-acting injections in the treatment of schizophrenia].

    PubMed

    Crocq, M-A

    2015-02-01

    From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors. PMID:25598520

  16. Pharmacokinetics of Injectable, Long-Acting Nevirapine for HIV Prophylaxis in Breastfeeding Infants

    PubMed Central

    Cortez, John M.; Quintero, Rafaela; Moss, John A.; Beliveau, Martin; Smith, Thomas J.

    2014-01-01

    Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 ?m), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 ?g ml?1) for 6 weeks or longer. PMID:25313219

  17. Oral Delivery of DMAB-Modified Docetaxel-Loaded PLGA-TPGS Nanoparticles for Cancer Chemotherapy

    Microsoft Academic Search

    Hongbo Chen; Yi Zheng; Ge Tian; Yan Tian; Xiaowei Zeng; Gan Liu; Kexin Liu; Lei Li; Zhen Li; Lin Mei; Laiqiang Huang

    2011-01-01

    Three types of nanoparticle formulation from biodegradable PLGA-TPGS random copolymer were developed in this research for oral administration of anticancer drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS random copolymer was synthesized and characterized. DMAB was used to increase retention time at the cell surface, thus increasing the chances of particle uptake

  18. Polyvinyl pyridine microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

    1980-01-01

    Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

  19. Polyvinyl pyridine microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

    1979-01-01

    Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

  20. Doped zinc oxide microspheres

    DOEpatents

    Arnold, Jr., Wesley D. (Oak Ridge, TN); Bond, Walter D. (Knoxville, TN); Lauf, Robert J. (Oak Ridge, TN)

    1993-01-01

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

  1. Microsphere insulation systems

    NASA Technical Reports Server (NTRS)

    Allen, Mark S. (Inventor); Willen, Gary S. (Inventor); Mohling, Robert A. (Inventor)

    2005-01-01

    A new insulation system is provided that contains microspheres. This insulation system can be used to provide insulated panels and clamshells, and to insulate annular spaces around objects used to transfer, store, or transport cryogens and other temperature-sensitive materials. This insulation system provides better performance with reduced maintenance than current insulation systems.

  2. Doped zinc oxide microspheres

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-12-14

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

  3. Electrospinning growth factor releasing microspheres into fibrous scaffolds.

    PubMed

    Whitehead, Tonya J; Sundararaghavan, Harini G

    2014-01-01

    This procedure describes a method to fabricate a multifaceted substrate to direct nerve cell growth. This system incorporates mechanical, topographical, adhesive and chemical signals. Mechanical properties are controlled by the type of material used to fabricate the electrospun fibers. In this protocol we use 30% methacrylated Hyaluronic Acid (HA), which has a tensile modulus of ~500 Pa, to produce a soft fibrous scaffold. Electrospinning on to a rotating mandrel produces aligned fibers to create a topographical cue. Adhesion is achieved by coating the scaffold with fibronectin. The primary challenge addressed herein is providing a chemical signal throughout the depth of the scaffold for extended periods. This procedure describes fabricating poly(lactic-co-glycolic acid) (PLGA) microspheres that contain Nerve Growth Factor (NGF) and directly impregnating the scaffold with these microspheres during the electrospinning process. Due to the harsh production environment, including high sheer forces and electrical charges, protein viability is measured after production. The system provides protein release for over 60 days and has been shown to promote primary nerve cell growth. PMID:25178038

  4. Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

    PubMed

    Shin, Seung-Hwa; Lee, Jangwook; Lim, Kwang Suk; Rhim, Taiyoun; Lee, Sang Kyung; Kim, Yong-Hee; Lee, Kuen Yong

    2013-02-28

    Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease. In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis. Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems. Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems. TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days. The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres. Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model. This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis. PMID:23262200

  5. Porous microsphere and its applications

    PubMed Central

    Cai, Yunpeng; Chen, Yinghui; Hong, Xiaoyun; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Porous microspheres have drawn great attention in the last two decades for their potential applications in many fields, such as carriers for drugs, absorption and desorption of substances, pulmonary drug delivery, and tissue regeneration. The application of porous microspheres has become a feasible way to address existing problems. In this essay, we give a brief introduction of the porous microsphere, its characteristics, preparation methods, applications, and a brief summary of existing problems and research tendencies. PMID:23515359

  6. Influence of storage temperature and moisture on the performance of microsphere/hydrogel composites.

    PubMed

    Wang, Yan; Burgess, Diane J

    2013-09-15

    The current study involved investigation of the effect of storage temperature and moisture on the performance of poly(lactide-co-glycolide) (PLGA) microsphere/poly(vinyl-alcohol) (PVA) hydrogel composites. Physical aging occurred in composites stored at 25°C due to structural relaxation. The glass transition temperature (Tg) and enthalpy of relaxation of the composites increased leading to a slower cumulative % release. The Tg of composites incubated at 40°C, 75% RH decreased significantly due to the plasticization effect of absorbed water, whereas no change was observed in the Tg of microspheres alone; indicating that the hydrogel component enhanced water absorption. PLGA degradation occurred leading to significantly faster dexamethasone release following incubation at 40°C, 75% RH for 1 month. No significant change was observed in the in vitro release profiles of composites after 6 months storage at 25°C, 60% RH, however, release was accelerated following 12 months storage. Accordingly, exposure of the composites to ambient temperature/moisture during storage, shipping or handling may cause physical aging, plasticization, and degradation and hence, their performance may be affected. The extent to which the performance of the composite is affected by storage temperature and moisture is a net effect of physical aging and moisture induced plasticization/hydrolytic degradation. PMID:23811131

  7. [Study on compound levonorgestrel microspheres].

    PubMed

    Guo, R; Lu, B

    1993-12-01

    Levonorgestrel (LNG) and estradiol (E2) were mixed in the ratio of 5:2 by weight. Compound LNG gelatin-microspheres were prepared by phase-separation method, natural biodegradable gelatin being used as the core material. The experimental conditions were optimized, the mean diameter of the microspheres obtained being 10-40 microns, and the rate of encapsulation 65-75%. Storage observations and acceleration tests of the compound LNG gelatin-microsphere injection prepared showed that the microspheres have good stability. The thermal degradation activation energy of the injection was determined to be 134.4 kJ/mol, based on differential scanning colorimetry (DSC). T1/2 values for dissolution in vitro of LNG and E2 from the compound LNG gelatin-microsphere injection and from the unencapsulated injection showed significant difference (P < 0.01), indicating that the microspheres have good sustained release action. Effects of the pure LNG microsphere injection and compound LNG microsphere injection on the mouse ovary were compared histologically. The results showed that the compound LNG microsphere injection reduced some of the side effects such as ovary congestion. This points out that the compound dosage form can clinically alleviate the irregular bleeding caused by the administration of LNG alone. PMID:8150435

  8. 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

  9. Profile of olanzapine long-acting injection for the maintenance treatment of adult patients with schizophrenia

    PubMed Central

    Di Lorenzo, Rosaria; Brogli, Alice

    2010-01-01

    Olanzapine long-acting injection (OLAI) is a crystalline salt composed of olanzapine and pamoic acid, which permits a depot intramuscular formulation of olanzapine. The half-life of olanzapine pamoate is 30 days, and its steady state is reached approximately at 12 weeks. Oral supplementation of olanzapine is not required during OLAI initiation, according to Eli Lilly recommendations, although a study indicated that ?60% of D2 receptor occupancy was reached only by the fifth injection cycle. To date, a short-term, placebo-controlled study of 8 weeks in acutely ill patients and a long-term, controlled trial of 24 weeks in stabilized patients have been conducted. In both the studies, efficacy and safety were similar to those of oral olanzapine, with the exception of an acute adverse effect, the so-called inadvertent intravascular injection event, which occurred 1–3 hours after the injection with an incidence rate of 0.07% per injection. It consisted of symptoms that are similar to those reported in cases of oral olanzapine overdose. The most significant studies published to date, on the use of olanzapine pamoate in schizophrenia, are reviewed in this article. The pharmacodynamic and pharmacokinetic profile and related side effects of OLAI are reported. PMID:20856920

  10. Laninamivir and its prodrug, CS-8958: long-acting neuraminidase inhibitors for the treatment of influenza.

    PubMed

    Yamashita, Makoto

    2010-01-01

    Oseltamivir and zanamivir are currently licensed worldwide for influenza treatment and chemoprophylaxis. Both drugs require twice-daily administration for 5 days for treatment. A new influenza drug, laninamivir (code name R-125489), and its prodrug form, CS-8958 (laninamivir octanoate or laninamivir prodrug), which are long-acting neuraminidase inhibitors, are introduced in this review. Laninamivir potently inhibited the neuraminidase activities of various influenza A and B viruses, including subtypes N1-N9, pandemic (2009) H1N1 virus, highly pathogenic avian influenza (HPAI) H5N1 viruses and oseltamivir-resistant viruses. Because of the long retention of laninamivir in mouse lungs after an intranasal administration of CS-8958, therapeutic administration of a single dose of CS-8958 showed superior efficacy to repeated administrations of zanamivir or oseltamivir in animal infection models for influenza A and B viruses. These include pandemic (2009) H1N1 virus and HPAI H5N1 virus. Prophylactic single administration of CS-8958, as early as 7 days prior to infection, also showed superior efficacy. Finally, the potential of a single inhalation of CS-8958 for influenza patients was demonstrated by clinical studies, and CS-8958 has been approved and is commercially available as Inavir(®) (Daiichi Sankyo Co., Ltd, Tokyo) in Japan. PMID:21107016

  11. Contraceptive implants: long acting and provider dependent contraception raises concerns about freedom of choice.

    PubMed

    Thompson, M S

    1996-11-30

    David Bromham's editorial on contraceptive implants ignores the wider issues to voice concern that trial by media could limit contraceptive choice by jeopardising research into new methods. However, it is more beneficial to the public for points of conflict to be debated openly. Furthermore, the impetus for research into new contraceptive technology is driven by profit and political motives and is only marginally affected by the media. Implanted contraceptives may increase the choice of contraceptive methods, but they put control of fertility increasingly into the hands of the medical profession. Herein lies their greatest problem: their potential to increase providers' control over clients' choice. There is the danger that certain groups of women may be targeted for their use: in the United States the coercive use of Norplant for mothers receiving welfare benefit has been suggested. Long acting contraceptives are a contraceptive of choice only when they are available without pressure, as part of a wider menu; when instant removal on request is guaranteed; and when there is an open and free flow of information and opinions between users, health professionals, and special interest groups. PMID:8956712

  12. Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

    PubMed

    McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

    2015-07-01

    Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-?-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. PMID:26094124

  13. Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility.

    PubMed

    Loutradis, Dimitris; Drakakis, Petros; Vlismas, Antonis; Antsaklis, Aristidis

    2009-04-01

    Corifollitropin alfa is being developed by Schering-Plough Corp as an injectable, long-acting follicle-stimulating hormone (FSH) agonist for the treatment of infertility. A single dose of corifollitropin alfa could initiate and sustain multifollicular growth in patients undergoing controlled ovarian stimulation, such as during in vitro fertilization or intracytoplasmic sperm injection. The agent comprises an alpha-subunit, which is identical to that of FSH, and a beta-subunit, which is produced by the fusion of the C-terminal peptide from the beta-subunit of chorionic gonadotropin to the beta-subunit of FSH. Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing. The drug was well tolerated and does not appear to be associated with any serious adverse events or the formation of antibodies. The initial results from a large, phase III, double-blind clinical trial indicated that the ongoing pregnancy rate achieved with corifollitropin alfa treatment was high and similar to the rate established with daily treatment of recombinant FSH. The number of oocytes retrieved following the administration of corifollitropin alfa was slightly higher compared with the number observed with daily recombinant FSH treatment. Thus, corifollitropin alfa has the potential to serve as a viable fertility agent and to gain a place in the infertility market. PMID:19337959

  14. Dual use of long-acting reversible contraceptives and condoms among adolescents.

    PubMed

    Williams, Rebekah L; Fortenberry, J Dennis

    2013-04-01

    Unintended pregnancy and sexually transmitted infections (STI) continue to be significant public health problems, and adolescents are disproportionately affected by both. With national attention and funding directed toward adolescent pregnancy prevention, promotion of long-acting reversible contraceptive (LARC) use among adolescents is both timely and relevant. However, LARCs provide no protection against STIs, requiring dual-method use of both LARC and barrier methods, most commonly the male latex condom, to address these issues simultaneously. Rates of both LARC and dual-method contraception are low in the United States, but have increased in recent years. Dual-method contraception is highest among younger women and adolescents with multiple or new sex partners. Consistent condom use remains a major barrier to dual-method use, as it necessitates admission of STI risk by both partners, and use is dependent upon two decision-makers rather than a single contraceptive user. Promoting the initiation and maintenance of LARC and condom use across multiple partnered sexual encounters requires understanding of individual, dyadic, and social influences. Successful maintenance of contraceptive and STI prevention behaviors requires individualized, longitudinal reinforcement, and social supports, but can ultimately reduce the burden of unintended pregnancy and STI among adolescents. PMID:23535054

  15. Kaposi's sarcoma after long-acting steroids: time until remission and drug washout.

    PubMed

    Nassar, D; Schartz, N E C; Bouché, C; Lévy, A; Kerob, D; Agbalika, F; Lafaurie, M; Lebbé, C

    2010-01-01

    Long-acting steroids (LAS) are widely used to treat various inflammatory diseases and allergies. They have many adverse effects including the inhibition of the hypothalamopituitary axis that can last several months. LAS are also strong immunosuppressors and can result in severe opportunistic infections and immunodeficiency-related malignancies. However, the time needed for immune recovery after withdrawal of LAS is unknown. Here we report a case of Kaposi's sarcoma (KS) and severe immunosuppression after a chronic triamcinolone acetonide (TA) treatment. Six months after withdrawal, traces of TA were still detected in the serum by HPLC mass spectrometry. At 8 months, the drug became undetectable, and clinical and biological signs of immune recovery - beginning of KS regression, normalization of IgG levels and CD4 T lymphocyte counts - became noticeable. We then provide a review of the literature on the time until remission of KS after immunosuppression reduction. We also reviewed the cases of KS induced by TA, and the metabolic side effects of TA when compared to standard glucocorticoids. PMID:20110636

  16. Aclidinium bromide provides long-acting bronchodilation in patients with COPD.

    PubMed

    Chanez, P; Burge, P S; Dahl, R; Creemers, J; Chuchalin, A; Lamarca, R; Garcia Gil, E

    2010-02-01

    Aclidinium bromide is a novel, long-acting, muscarinic antagonist in phase III development for the maintenance treatment of COPD. This phase IIb study investigated the efficacy and safety of aclidinium for the treatment of moderate to severe COPD to establish the optimal dose for phase III studies. A total of 464 patients with moderate to severe stable COPD were randomised to double-blind, once-daily treatment with aclidinium (25, 50, 100, 200, or 400microg), placebo, or open-label tiotropium (18microg) for 4 weeks. Spirometric measurements were performed at 22-24h after the first dose and then at weekly intervals, and from 0.5 to 6h post-dose on day 1 and day 29. Compared with placebo, aclidinium 200microg and 400microg significantly increased trough FEV(1) on day 29 versus baseline. During the first 6h post-dose, the bronchodilatory effect of aclidinium (all doses) on day 1 was comparable to that on day 29. Time to peak FEV(1) was 3h for aclidinium 100-400microg. Aclidinium was well tolerated, with no dose-dependent effect on ECG, laboratory parameters, or adverse events. The incidence of AEs was generally comparable to placebo. Aclidinium produced sustained bronchodilation over 24h and was well tolerated during this short-term study. Based on these data, aclidinium 200microg was selected as the investigational dose for future clinical trials in COPD. PMID:19683590

  17. Functional magnetic microspheres

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Landel, Robert F. (Inventor)

    1981-01-01

    Functional magnetic particles are formed by dissolving a mucopolysaccharide such as chitosan in acidified aqueous solution containing a mixture of ferrous chloride and ferric chloride. As the pH of the solution is raised magnetite is formed in situ in the solution by raising the pH. The dissolved chitosan is a polyelectrolyte and forms micelles surrounding the granules at pH of 8-9. The chitosan precipitates on the granules to form microspheres containing the magnetic granules. On addition of the microspheres to waste aqueous streams containing dissolved ions, the hydroxyl and amine functionality of the chitosan forms chelates binding heavy metal cations such as lead, copper, and mercury and the chelates in turn bind anions such as nitrate, fluoride, phosphate and borate.

  18. PEGylated PLGA nanoparticles for the improved delivery of doxorubicin

    Microsoft Academic Search

    Jason Park; Peter M. Fong; Jing Lu; Kerry S. Russell; Carmen J. Booth; W. Mark Saltzman; Tarek M. Fahmy

    2009-01-01

    We hypothesize that the efficacy of doxorubicin (DOX) can be maximized and dose-limiting cardiotoxicity minimized by controlled release from PEGylated nanoparticles. To test this hypothesis, a unique surface modification technique was used to create PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating DOX. An avidin-biotin coupling system was used to control poly(ethylene glycol) conjugation to the surface of PLGA nanoparticles, of diameter

  19. Preparation and characterization of cationic PLGA nanospheres as DNA carriers

    Microsoft Academic Search

    M. N. V. Ravi Kumar; U. Bakowsky; C. M. Lehr

    2004-01-01

    Nanoparticles formulated from biodegradable polymers such as poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) are being extensively investigated as non-viral gene delivery systems due to their controlled release characteristics and biocompatibility. PLGA nanoparticles for DNA delivery are mainly formulated by an emulsion-solvent evaporation technique using PVA as a stabilizer generating negatively charged particles and heterogeneous size distribution. The objective of the

  20. Barium Vanadate Microspheres

    NASA Astrophysics Data System (ADS)

    Yosinski, Shari; Tweeton, Landon; Feller, Steve; Affatigato, Mario

    2009-11-01

    It has been found that many glass powders can form micro- or nanospheres when heated in a flame or by a laser. Much of the research in this area of microspheres has concentrated on making hollow spheres, called microballoons, of silica and borosilicate glasses. Our aim was to create highly porous barium vanadate microspheres for possible future applications in material storage. The surface area of porous spheres would provide a greater amount of bonding surface area for dopants than hollow spheres. Barium vanadate glass with a molar fraction of 0.4 to 0.6 barium oxide was used because this glass is stable and has a low Tg. Size distributions of the spheres were quantified and the extent of sphere formation and porosity was examined using a scanning electron microscope. The size of spheres formed is affected by powder size, dropping method, and flame position. The porosity of the microspheres is affected by flame temperature, time spent in flame, and the material onto which the spheres fall. The greatest porosity was achieved by first heating the glass powder at a low temperature and then immediately sending it through the flames of two MAPP gas torches at approximately 2100^oC onto a metal sheet.

  1. Role of indacaterol and the newer very long-acting ?2-agonists in patients with stable COPD: a review

    PubMed Central

    Ridolo, Erminia; Montagni, Marcello; Olivieri, Elisa; Riario-Sforza, Gian Galeazzo; Incorvaia, Cristoforo

    2013-01-01

    Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting ?2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting ?2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting ?2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting ?2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far. PMID:24082783

  2. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model

    Microsoft Academic Search

    Leanne Groban

    2003-01-01

    With the development of the newer long-acting amide local anesthetics,ropivacaine and levobupivacaine, numerous animal studies of LA systemic toxicity have emerged. Because of the complex nature of the human response to LA intoxication, the task of designing and interpreting these animal studies of LA toxicity can be difficult. Accordingly, this report will review the selection of an animal model for

  3. A Controlled, Evidence-Based Trial of Paliperidone Palmitate, A Long-Acting Injectable Antipsychotic, in Schizophrenia

    Microsoft Academic Search

    Henry A Nasrallah; Srihari Gopal; Cristiana Gassmann-Mayer; Jorge A Quiroz; Pilar Lim; Mariëlle Eerdekens; Eric Yuen; David Hough

    2010-01-01

    Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and

  4. Effect of functionalized micropatterned PLGA on guided neurite growth.

    PubMed

    Yao, Li; Wang, Shenguo; Cui, Wenjin; Sherlock, Richard; O'Connell, Claire; Damodaran, Gopinath; Gorman, Adrienne; Windebank, Anthony; Pandit, Abhay

    2009-02-01

    When coaptation is not possible in the repair of nerve injuries, a bridge of biomaterial scaffold provides a structural support for neuronal cell growth and guides nerve regeneration. Poly(lactide-co-glycolide) (PLGA) scaffolds have been widely investigated for neural tissue engineering applications. In order to investigate guided neurite growth, we have fabricated micropatterns on PLGA films using laser ablation methods. The micropatterned PLGA films were coated with collagen type I or laminin peptide (PPFLMLLKGSTR) to promote axon growth. Micropatterned PLGA films provide a guidance effect on both early stage neurite outgrowth and elongation. Small (5 microm) grooves showed more statistically significant parallel neurite growth compared with larger size grooves (10 microm). Micropatterned PLGA films coated with laminin peptide showed more parallel neurite growth compared with those coated with collagen type I. Primary neurite number and total neurite length per cell decreased on micropatterned PLGA films compared with the controls. Neurites showed a preference for growth in the microgrooves rather than on the spaces. This study indicates that surface micropatterned structures with conjugated functional molecules can be used to guide neurite growth. PMID:18835227

  5. 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. PMID:26044202

  6. Encapsulation of immunoglobulin G by solid-in-oil-in-water: effect of process parameters on microsphere properties.

    PubMed

    Marquette, Sarah; Peerboom, Claude; Yates, Andrew; Denis, Laurence; Goole, Jonathan; Amighi, Karim

    2014-04-01

    Antibodies (Abs) are prone to a variety of physical and chemical degradation pathways, which require the development of stable formulations and specific delivery strategies. In this study, injectable biodegradable and biocompatible polymeric particles were employed for controlled-release dosage forms and the encapsulation of antibodies into polylactide-co-glycolide (PLGA) based microspheres was explored. In order to avoid stability issues which are commonly described when water-in-oil (w/o) emulsion is used, a solid-in-oil-in-water (s/o/w) method was developed and optimized. The solid phase was made of IgG microparticles and the s/o/w process was evaluated as an encapsulation method using a model Ab molecule (polyclonal bovine immunoglobulin G (IgG)). The methylene chloride (MC) commonly used for an encapsulation process was replaced by ethyl acetate (EtAc), which was considered as a more suitable organic solvent in terms of both environmental and human safety. The effects of several processes and formulation factors were evaluated on IgG:PLGA microsphere properties such as: particle size distribution, drug loading, IgG stability, and encapsulation efficiency (EE%). Several formulations and processing parameters were also statistically identified as critical to get reproducible process (e.g. the PLGA concentration, the volume of the external phase, the emulsification rate, and the quantity of IgG microparticles). The optimized encapsulation method has shown a drug loading of up to 6% (w/w) and an encapsulation efficiency of up to 60% (w/w) while preserving the integrity of the encapsulated antibody. The produced microspheres were characterized by a d(0.9) lower than 110 ?m and showed burst effect lower than 50% (w/w). PMID:24184674

  7. Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging

    E-print Network

    Mieszawska, Aneta J.

    Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles ...

  8. Stem Cells Grown in Osteogenic Medium on PLGA, PLGA/HA, and Titanium Scaffolds for Surgical Applications

    PubMed Central

    Asti, Annalia; Gastaldi, Giulia; Dorati, Rossella; Saino, Enrica; Conti, Bice; Visai, Livia; Benazzo, Francesco

    2010-01-01

    Pluripotent adipose tissue-derived stem cells (hASCs) can differentiate into various mesodermal cell types such as osteoblasts, chondroblasts, and myoblasts. We isolated hASCs from subcutaneous adipose tissue during orthopaedic surgery and induced the osteogenic differentiation for 28 days on three different synthetic scaffolds such as polylactide-co-glycolide (PLGA), polylactide-co-glycolide/hydroxyapatite (PLGA/HA), and trabecular titanium scaffolds (Ti6Al4V). Pore size can influence certain criteria such as cell attachment, infiltration, and vascularization. The aim of this study was to investigate the performance of PLGA and PLGA/HA scaffolds with a higher porosity, ranging between 75% and 84%, with respect to Ti scaffolds but with smaller pore size, seeded with hASCs to develop a model that could be used in the treatment of bone defects and fractures. Osteogenesis was assessed by ELISA quantitation of extracellular matrix protein expression, von Kossa staining, X-ray microanalysis, and scanning electron microscopy. The higher amount of protein matrix on the Ti scaffold with respect to PLGA and PLGA/HA leads to the conclusion that not only the type of material but the structure significantly affects cell proliferation. PMID:21234383

  9. Physical Characteristics of Polymer Magnetic Microspheres

    Microsoft Academic Search

    Rasim A. Ali-Zade

    2004-01-01

    In this study the structure and the magnetic properties of polymer microspheres, filled with magnetite nanoparticles are investigated. Average particle size of magnetite nanoparticles before and after being introduced into polymer microspheres, and the distance between nanoparticles in the polymer microspheres, are measured. Magnetization curve of polymer magnetic microspheres (PMMS) is determined. The magnetic susceptibility of PMMS with various diameters,

  10. Clinical efficacy of long-acting neuraminidase inhibitor laninamivir octanoate hydrate in postmarketing surveillance.

    PubMed

    Kashiwagi, Seizaburo; Yoshida, Sanae; Yamaguchi, Hiroki; Mitsui, Noriko; Tanigawa, Masatoshi; Shiosakai, Kazuhito; Yamanouchi, Naoki; Shiozawa, Tomoo; Yamaguchi, Fumie

    2013-04-01

    Laninamivir octanoate hydrate (laninamivir) is a long-acting neuraminidase inhibitor which requires only a single inhaled dose to fully treat infection by the influenza virus. In Japan, this drug was launched in October 2010 as a new treatment for the influenza virus. A postmarketing surveillance study was conducted in the 2010/2011 influenza season to assess the efficacy of this drug in clinical settings. For 3542 patients evaluated for efficacy (type A, n = 3179; type B, n = 342, unknown type, n = 3), including the day of drug administration, the median duration to fever resolution was three days, and the median duration to relief from influenza symptoms was four days. Based on the judgment of participating physicians, the efficacy rate was 97.6 % for type A influenza, 93.3 % for type B influenza, and 100 % in unknown types. "Treatment failure," as judged by participating physicians, was most closely correlated with the inhalation status of laninamivir. Despite laninamivir requiring only the administration of a single dose, it was confirmed to be an effective treatment in more than 90 % of patients with type A or type B influenza virus infections. This drug was considered to be useful for the treatment of influenza infections due to ease of use and its improvement of compliance. It became clear that the efficacy of laninamivir depended strongly on the status of inhalation, and thus careful and detailed instructions on the correct method of inhalation were considered to be important in order to obtain reliable therapeutic effects. PMID:23085742

  11. Long-acting reversible contraception: a practical solution to reduce unintended pregnancy.

    PubMed

    Secura, G

    2013-06-01

    Unintended pregnancy remains a significant global public health problem; 41% of all pregnancies worldwide in 2008 were unintended. The unintended pregnancy rate is greater in less developed regions (57 per 1000 women aged 15-44 years) than in more developed regions (42 per 1000), with the United States a notable exception at a rate of 52 per 1000 women. Among US women, nearly half of unintended pregnancies are due to incorrect or inconsistent use of a contraceptive method. Long-acting reversible contraception (LARC) includes the intrauterine device and subdermal implant and offers the potential to address the problem of unintended pregnancy. LARC is extremely safe and over 99% effective at preventing pregnancy. In real-world tests LARC methods were over 20 times more effective at preventing unintended pregnancy (HRadj=21.8, 95% confidence interval, 13.7 to 34.9) compared to the contraceptive pill, patch, or ring. Despite their level of effectiveness, less than 15% of contracepting women worldwide use LARC. LARC are only infrequently contraindicated, even among younger and nulliparous women. Instead education, access, and cost are the primary barriers. In a US study of nearly 10000 women aged 14-45 years, when the three barriers were removed 75% of study participants chose a LARC method. As a result, the study reported an 80% reduction in teen births and 75% reduction in abortions among women in the cohort compared to national statistics. If we are serious about reducing unintended pregnancy, we need to be serious about increasing the use of methods that we know work. Greater LARC use and continuation has been proven to effectively reduce unintended pregnancy, including abortion and teen pregnancy. PMID:23689169

  12. Depletion of long-acting ampicillin in goat milk following intramuscular administration.

    PubMed

    Ferrini, Anna Maria; Trenta, Simona; Mannoni, Veruscka; Rosati, Remo; Coni, Ettore

    2010-12-01

    Although goat milk production represents today a very small percentage of the world milk market, this percentage has been growing continuously during the past 20 years. Goat milk is the basic milk supply in many developing countries and provides tasteful derivative products in developed countries. Goats, as well as all milk-producing animals, can be affected by mastitis, but goats being considered a minor species, few drugs are specifically registered for these animals; most, at least for mastitis treatment, are usually tested and registered for use in cows. This situation leads often to the adoption for goat milk of withdrawal periods defined for cows even if these extrapolations prove almost never valid for goats. In the present study, the elimination of the ?-lactam antibacterial agent ampicillin in goat milk was investigated. Ampicillin was chosen because it is one of the most common antibiotics used by goat farmers against mastitis due to the fact that it is well tolerated and has short elimination times in cows. Goats were treated with long-acting ampicillin at 15 mg (kg of body weight)(-1) by double intramuscular injection at 72 h interval. Milk was collected in a 12 h milking scheme. The method used to determine the levels of ampicillin in goat milk was based on a liquid-liquid extraction of this drug from the matrix, successive derivatization with formaldehyde, and final separation by HPLC with fluorescence detection. The results point out a slow depletion of ampicillin and, consequently, a withdrawal period (13 milkings) longer than that extrapolated and authorized for cows and sheep. PMID:21070070

  13. Pharmacological profile of a new, potent, and long-acting gonadotropin-releasing hormone antagonist: degarelix.

    PubMed

    Broqua, Pierre; Riviere, Pierre J-M; Conn, P Michael; Rivier, Jean E; Aubert, Michel L; Junien, Jean-Louis

    2002-04-01

    We describe the pharmacological profile in rats and monkeys of degarelix (FE200486), a member of a new class of long-acting gonadotropin-releasing hormone (GnRH) antagonists. At single subcutaneous injections of 0.3 to 10 microg/kg in rats, degarelix produced a dose-dependent suppression of the pituitary-gonadal axis as revealed by the decrease in plasma luteinizing hormone (LH) and testosterone levels. Duration of LH suppression increased with the dose: in the rat, significant suppression of LH lasted 1, 2, and 7 days after a single subcutaneous injection of degarelix at 12.5, 50, or 200 microg/kg, respectively. Degarelix fully suppressed plasma LH and testosterone levels in the castrated and intact rats as well as in the ovariectomized rhesus monkey for more than 40 days after a single 2-mg/kg subcutaneous injection. In comparative experiments, degarelix showed a longer duration of action than the recently developed GnRH antagonists abarelix, ganirelix, cetrorelix, and azaline B. The in vivo mechanism of action of degarelix was consistent with competitive antagonism, and the prolonged action of degarelix was paralleled by continued presence of radioimmunoassayable degarelix in the general circulation. In contrast to cetrorelix and similarly to ganirelix and abarelix, degarelix had only weak histamine-releasing properties in vitro. These results demonstrate that the unique and favorable pharmacological properties of degarelix make it an ideal candidate for the management of sex steroid-dependent pathologies requiring long-term inhibition of the gonadotropic axis. PMID:11907162

  14. Association between long-acting reversible contraceptive use, teenage pregnancy, and abortion rates in England

    PubMed Central

    Connolly, Anne; Pietri, Guilhem; Yu, Jingbo; Humphreys, Samantha

    2014-01-01

    Background Since the late 1990s, the British government has launched major strategies to address high teenage pregnancy and abortion rates in England. These have focused in part on improving access to contraception through national campaigns. This study assessed teenage pregnancy and abortion rate trends since 1998 and possible associations with usage of long-acting reversible contraceptives (LARCs). Methods Teenage conception rates and age-specific abortion rates were obtained from the Office for National Statistics and the Department of Health. LARC usage data was obtained for Depo-Provera, Implanon/Nexplanon, intrauterine devices, Mirena, and Noristerat from the IMS British Pharmaceutical Index, IMS Hospital Pharmacy Audit, IMS Disease Analyzer, and KT-31 reports. Through linear regression methods, changes in conception and abortion-related outcomes during 1998–2011 and the associations with LARC usage were assessed. Results Conception rates for girls younger than 18 years of age decreased significantly between 1998–2011, from 46.6 to 30.7 per 1,000 girls. A statistically significant association was observed between this decrease and increased LARC usage (P=0.0024) in this population. Abortion rates among females aged <18 years or aged 18–19 years decreased between 1998–2011, and their associations with increased LARC usage were statistically significant (P=0.0029 and P=0.0479, respectively). The pattern in older women was complex; abortion rates in women aged 20–24 years or 25–34 years increased slightly from 1998 to 2011, with stabilization during 2007–2011. Conclusion Increased LARC usage in England was significantly associated with decreased teenage pregnancy rates and abortion rates in females aged <20 years. Government strategies appears to have a positive impact on these outcomes; however, abortion rates among women over 20 years of age remain an issue. PMID:25473316

  15. Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis.

    PubMed

    Gunawardana, Manjula; Remedios-Chan, Mariana; Miller, Christine S; Fanter, Rob; Yang, Flora; Marzinke, Mark A; Hendrix, Craig W; Beliveau, Martin; Moss, John A; Smith, Thomas J; Baum, Marc M

    2015-07-01

    Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day(-1) in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml(-1); interquartile range [IQR], 0.60 to 1.50 ng ml(-1)) and tenofovir (TFV; median, 15.0 ng ml(-1); IQR, 8.8 to 23.3 ng ml(-1)), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/10(6) cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. PMID:25896688

  16. Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation.

    PubMed

    Varol, Chen; Zvibel, Isabel; Spektor, Lior; Mantelmacher, Fernanda Dana; Vugman, Milena; Thurm, Tamar; Khatib, Marian; Elmaliah, Elinor; Halpern, Zamir; Fishman, Sigal

    2014-10-15

    Obesity induces low-grade chronic inflammation, manifested by proinflammatory polarization of adipose tissue innate and adaptive resident and recruited immune cells that contribute to insulin resistance (IR). The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that mediates postprandial insulin secretion and has anabolic effects on the adipose tissue. Importantly, recent evidence suggested that GIP is a potential suppressor of inflammation in several metabolic models. In this study, we aimed to investigate the immunoregulatory role of GIP in a murine model of diet-induced obesity (DIO) using the long-acting GIP analog [d-Ala(2)]GIP. Administration of [d-Ala(2)]GIP resulted in adipocytes of increased size, increased levels of adipose tissue lipid droplet proteins, indicating better lipid storage capacity, and reduced adipose tissue inflammation. Flow cytometry analysis revealed reduced numbers of inflammatory Ly6C(hi) monocytes and F4/80(hi)CD11c(+) macrophages, associated with IR. In addition, [d-Ala(2)]GIP reduced adipose tissue infiltration of IFN-?-producing CD8(+) and CD4(+) T cells. Furthermore, [d-Ala(2)]GIP treatment induced a favorable adipose tissue adipokine profile, manifested by a prominent reduction in key inflammatory cytokines (TNF-?, IL-1?, IFN-?) and chemokines (CCL2, CCL8, and CCL5) and an increase in adiponectin. Notably, [d-Ala(2)]GIP also reduced the numbers of circulating neutrophils and proinflammatory Ly6C(hi) monocytes in mice fed regular chow or a high-fat diet. Finally, the beneficial immune-associated effects were accompanied by amelioration of IR and improved insulin signaling in liver and adipose tissue. Collectively, our results describe key beneficial immunoregulatory properties for GIP in DIO and reveal that its augmentation ameliorates adipose tissue inflammation and improves IR. PMID:25217161

  17. Long-acting Reversible Contraception for Adolescents and Young Adults: Patient and Provider Perspectives

    PubMed Central

    Kavanaugh, Megan L.; Frohwirth, Lori; Jerman, Jenna; Popkin, Ronna; Ethier, Kathleen

    2013-01-01

    Study objective To describe and explore provider- and patient-level perspectives regarding long-acting reversible contraception (LARC) for teens and young adults (ages 16-24). Methods Data collection occurred between June – December 2011. We first conducted telephone interviews with administrative directors at 20 publicly funded facilities that provide family planning services. At six of these sites, we conducted a total of six focus group discussions (FGDs) with facility staff and forty-eight in-depth interviews (IDIs) with facility clients ages 16-24. Results Staff in the FGDs did not generally equate being a teen with ineligibility for IUDs. In contrast to staff, one quarter of the young women did perceive young age as rendering them ineligible. Clients and staff agreed that the “forgettable” nature of the methods and their duration were some of LARC’s most significant advantages. They also agreed that fear of pain associated with both insertion and removal and negative side effects were disadvantages. Some aspects of IUDs and implants were perceived as advantages by some clients but disadvantages by others. Common challenges to providing LARC-specific services to younger patients included extra time required to counsel young patients about LARC methods, outdated clinic policies requiring multiple visits to obtain IUDs, and a perceived higher removal rate among young women. The most commonly cited strategy for addressing many of these challenges was securing supplementary funding to support the provision of these services to young patients. Conclusion Incorporating young women’s perspectives on LARC methods into publicly funded family planning facilities’ efforts to provide these methods to a younger population may increase their use among young women. PMID:23287602

  18. Preclinical Pharmacokinetics and Tissue Distribution of Long-Acting Nanoformulated Antiretroviral Therapy

    PubMed Central

    Gautam, Nagsen; Roy, Upal; Balkundi, Shantanu; Puligujja, Pavan; Guo, Dongwei; Smith, Nathan; Liu, Xin-Ming; Lamberty, Benjamin; Morsey, Brenda; Fox, Howard S.; McMillan, JoEllyn; Gendelman, Howard E.

    2013-01-01

    Long-acting injectable nanoformulated antiretroviral therapy (nanoART) was developed with the explicit goal of improving medicine compliance and for drug targeting of viral tissue reservoirs. Prior nanoART studies completed in humanized virus-infected mice demonstrated sustained antiretroviral responses. However, the pharmacokinetics (PK) and tissue distribution of nanoART were not characterized. To this end, the PK and tissue distribution of nanoformulated atazanavir (ATV) and ritonavir (RTV) injected subcutaneously or intramuscularly in mice and monkeys were evaluated. Fourteen days after injection, ATV and RTV levels were up to 13-, 41-, and 4,500-fold higher than those resulting from native-drug administration in plasma, tissues, and at the site of injection, respectively. At nanoART doses of 10, 50, 100, and 250 mg/kg of body weight, relationships of more- and less-than-proportional increases in plasma and tissue levels with dose increases were demonstrated with ATV and RTV. Multiple-dose regimens showed serum and tissue concentrations up to 270-fold higher than native-drug concentrations throughout 8 weeks of study. Importantly, nanoART was localized in nonlysosomal compartments in tissue macrophages, creating intracellular depot sites. Reflective data were obtained in representative rhesus macaque studies. We conclude that nanoART demonstrates blood and tissue antiretroviral drug levels that are enhanced compared to those of native drugs. The sustained and enhanced PK profile of nanoART is, at least in part, the result of the sustained release of ATV and RTV from tissue macrophases and at the site of injection. PMID:23612193

  19. PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats

    Microsoft Academic Search

    Ya-Ping Li; Yuan-Ying Pei; Xian-Ying Zhang; Zhou-Hui Gu; Zhao-Hui Zhou; Wei-Fang Yuan; Jian-Jun Zhou; Jian-Hua Zhu; Xiu-Jian Gao

    2001-01-01

    The aim of the present work was to assess the merits of PEGylated poly(lactic-co-glycolic acid) (PEG–PLGA) nanoparticles as protein and peptide drugs (PPD) carriers. PEG–PLGA copolymer, which could be used to prepare the stealth nanoparticles or long-circulating nanoparticles, was synthesized with methoxypolyethyleneglycol (MePEG) and PLGA. The structure of PEG–PLGA was confirmed with 1H NMR and Fourier transform infrared (FTIR) spectrum,

  20. Lanreotide 60 mg, a new long-acting formulation: effectiveness in the chronic treatment of acromegaly.

    PubMed

    Attanasio, Roberto; Baldelli, Roberto; Pivonello, Rosario; Grottoli, Silvia; Bocca, Liliana; Gasco, Valentina; Giusti, Massimo; Tamburrano, Guido; Colao, Annamaria; Cozzi, Renato

    2003-11-01

    Lanreotide (LAN) 60 mg (LAN60), a new long-acting formulation of LAN alleged to suppress GH/IGF-I hypersecretion for 28 d in acromegalic patients, was administered in a prospective open multicenter study to 92 patients with active acromegaly (61 women and 31 men, aged 20-79 yr). LAN60 was given as adjuvant treatment (AT) in 62 patients; the other 30 patients [primary treatment (PT)] were de novo (n = 20) or previously treated only by pharmacotherapy (n = 10). After wash-out from previous treatments, LAN60 was started im every 28 d for 3 injections; the dose was then individually tailored, aiming at lowering GH to less than 2.5 micro g/liter and IGF-I to the normal range. After a median follow-up of 24 months (range, 6-48 months), IGF-I normalized in 65% of patients, decreasing from 199 +/- 8% (expressed as a percentage of the upper limit of normal range; mean +/- SE) to 87 +/- 4% (P < 0.0001). GH fell to less than 2.5 microg/liter in 63% of patients and to less than 1 microg/liter in 25%, decreasing from 20 +/- 3 to 3 +/- 0.4 microg/liter (P < 0.0001). A progressive increase in the rate of IGF-I normalization was observed (from 49% at 1 yr to 77% at 3 yr). The rate of GH/IGF-I normalization was 72% at 36 months by Kaplan-Meier analysis. No tachyphylaxis was observed throughout the study. Shortening the interval between injections to 21 d improved GH/IGF-I suppression. PT and AT patients achieved similar final GH/IGF-I levels and rates of normalization. Tumor shrank in 39% of assessable patients and in 50% of PT. Plasma glucose levels did not change, and high density lipoprotein cholesterol increased (by 19.3 +/- 5.1%; P = 0.0215). Gallstones appeared or worsened in 13% of patients. LAN60 is a new, very effective and long-lasting formulation for the treatment of acromegaly. The persistence of a powerful suppression of GH/IGF-I levels, the progressive increase in the rate of IGF-I normalization, and the similarity in the efficacy achieved in PT and AT patients point to a role for LAN60 in the primary treatment of acromegaly. PMID:14602759

  1. Microfabricated PLGA scaffolds: a comparative study for application to tissue engineering

    E-print Network

    Bhatia, Sangeeta

    Microfabricated PLGA scaffolds: a comparative study for application to tissue engineering Giovanni two simple methods for fabricating poly(DL-lactide-co-glycolide) (PLGA) scaffolds with feature sizes of motor speeds and position. A PLGA solution is drawn from the needle of the syringe by the application

  2. 1 Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic 2 ligand conjugates

    E-print Network

    Fahmy, Tarek

    U N C O R R E C T E D P R O O F 1 Enhancement of surface ligand display on PLGA nanoparticles: 17 PLGA 18 Nanoparticle 19 Modification 20 Targeted 21 Drug delivery 22 T cells 23Biodegradable of avidin and palmitic acid can be used to modify poly(lactic-co-glycolic acid) (PLGA) particle 27surfaces

  3. Controlling the morphology of electrospray-generated PLGA microparticles for drug delivery

    E-print Network

    Gomez, Alessandro

    Controlling the morphology of electrospray-generated PLGA microparticles for drug delivery Begoña-controlled method to generate PLGA microparticles of different morphologies using the electrospray drying route) and their copolymer, poly (lactide-co-glycolide) (PLGA) [1­4]. Recent ad- vances in the design of these type of drug

  4. Research Article PEGylated PLGA nanoparticles for the improved delivery of doxorubicin

    E-print Network

    Fahmy, Tarek

    Research Article PEGylated PLGA nanoparticles for the improved delivery of doxorubicin Jason Park(lactic-co- glycolic acid) (PLGA) nanoparticles encapsulating DOX. An avidin-biotin coupling system was used to control poly(ethylene glycol) conjugation to the surface of PLGA nanoparticles, of diameter ~130 nm, loaded

  5. Ultrasound Characterization of Mechanical Properties of Nanometric Contrast Agents with PLGA Shell in

    E-print Network

    Paris-Sud XI, Université de

    Ultrasound Characterization of Mechanical Properties of Nanometric Contrast Agents with PLGA Shell the endothelial barrier, their shell made up of biocompatible polymer (PLGA) is stiffer to undergo a longer time frequency). Obtained values are compatible with literature data and offer insight into the behaviour of PLGA

  6. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

    PubMed

    Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

    2015-03-18

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers. PMID:25650634

  7. In vivo biocompatibility of the PLGA microparticles in parotid gland

    PubMed Central

    Cantín, Mario; Miranda, Patricio; Suazo Galdames, Iván; Zavando, Daniela; Arenas, Patricia; Velásquez, Luis; Vilos, Cristian

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) microparticles are used in various disorders for the controlled or sustained release of drugs, with the management of salivary gland pathologies possible using this technology. There is no record of the response to such microparticles in the glandular parenchyma. The purpose of this study was to assess the morphological changes in the parotid gland when injected with a single dose of PLGA microparticles. We used 12 adult female Sprague Dawley rats (Rattus norvegicus) that were injected into their right parotid gland with sterile vehicle solution (G1, n=4), 0.5 mg PLGA microparticles (G2, n=4), and 0.75 mg PLGA microparticles (G3, n=4); the microparticles were dissolved in a sterile vehicle solution. The intercalar and striated ducts lumen, the thickness of the acini and the histology aspect in terms of the parenchyma organization, cell morphology of acini and duct system, the presence of polymeric residues, and inflammatory response were determined at 14 days post-injection. The administration of the compound in a single dose modified some of the morphometric parameters of parenchyma (intercalar duct lumen and thickness of the glandular acini) but did not induce tissue inflammatory response, despite the visible presence of polymer waste. This suggests that PLGA microparticles are biocompatible with the parotid tissue, making it possible to use intraglandular controlled drug administration. PMID:24228103

  8. Preparation and physicochemical characterization of naproxen-PLGA nanoparticles.

    PubMed

    Javadzadeh, Yousef; Ahadi, Fatemeh; Davaran, Soodabeh; Mohammadi, Ghobad; Sabzevari, Araz; Adibkia, Khosro

    2010-12-01

    Naproxen is a non-steroidal anti-inflammatory drug which can be used for the treatment of inflammatory disorders like uveitis and arthirit rheumatoid. The aim of the present study was to investigate the physicochemical characteristics of naproxen-PLGA nanoparticles. The nanoparticles of naproxen with PLGA were formulated using the solvent evaporation/extraction technique (the single emulsion technique). Several process parameters i.e., drug/polymer ratio, aqueous phase volume and speed of homogenization were considered with the aim of achieve optimal preparation conditions. The physicochemical characteristics of nanoparticles were studied applying particle size analysis, differential scanning calorimetry, X-ray crystallography, Fourier transform infrared spectroscopy and scanning electron microscopy. The release rate of naproxen from various drug/polymer nanoparticles was investigated as well. All the prepared formulations using PLGA resulted in nano-range size particles (352-571 nm) with spherical smooth morphology. The nanoparticles of naproxen-PLGA displayed lower crystallinity with no chemical interactions between the drug and polymer molecules. The nanoparticles exhibited the slower release of drug in comparison with the intact drug and the physical mixtures. According of these findings, formulation of the naproxen-PLGA nanoparticles was able to improve the physicochemical characteristics of the drug and possibly will increase the anti-inflammatory effects of drug following its ocular or intra-joint administration. PMID:20719477

  9. Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives

    Microsoft Academic Search

    Eun Ju Oh; Ki Su Kim; Jiseok Kim; Jeong-A Yang; Ji-Hyun Kong; Min Young Lee; Allan S. Hoffman; Sei Kwang Hahn

    2010-01-01

    Hyaluronic acid (HA) is a biodegradable, biocompatible, non-toxic, non-immunogenic and non-inflammatory linear polysaccharide, which has been used for various medical applications such as arthritis treatment, ocular surgery, tissue augmentation, and so on. In this review, the effect of chemical modification of HA on its distribution throughout the body was reported for target specific and long-acting delivery applications of protein, peptide,

  10. A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia

    Microsoft Academic Search

    Gahan Pandina; Srihari Gopal; Cristiana Gassmann-Mayer; David Hough; Bart Remmerie; George Simpson

    2011-01-01

    This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N=1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150mgeq.), day 8 (100mgeq.), and once-monthly flexible dosing as deltoid or gluteal injections on

  11. Microsphere based saliva diagnostics

    NASA Astrophysics Data System (ADS)

    Rissin, David M.; DiCesare, Christopher; Hayman, Ryan B.; Blicharz, Timothy M.; Walt, David R.

    2005-11-01

    Saliva presents a minimally invasive alternative medium to blood for performing diagnostics1. Microsphere sensors for ions, small organic molecules, and proteins are currently being developed and optical microarrays containing thousands of these sensors will be used for simultaneous multi-analyte analysis. The fiber bundle platform in use is 1mm in diameter and contains approximately 50,000 individually addressable 3.1?m fibers, each with an etched well capable of housing a single 3.1?m microsphere sensor. Micron-sized bead-based chemistries are produced in house, followed by deposition onto a fiber-optic bundle platform, allowing for multiplexed analysis. The ultimate goal is to develop a universal diagnostic system using saliva as the diagnostic medium. This platform will permit multiplexed analysis of a sample by integrating microfluidics with the optical arrays loaded with sensors capable of detecting relevant biomarkers associated with a wide range of disease states. Disease states that are currently under investigation include end stage renal disease (ESRD) and Sjoegrens Syndrome (SS).

  12. Microsphere delivery of Risperidone as an alternative to combination therapy.

    PubMed

    D'Souza, Susan; Faraj, Jabar; DeLuca, Patrick

    2013-11-01

    The purpose of this study was to develop a parenteral delivery system of Risperidone that would provide initial and extended drug release and thereby avoid the need for co-administration of oral tablets. Key formulation parameters utilized to achieve desired therapeutic levels in vivo were particle size and drug loading. Three poly (D,L-lactide-co-glycolide) (PLGA) microsphere formulations (Formulations A, B, and C) that encapsulated Risperidone were prepared by varying particle size (19-49 ?m) and drug loading parameters (31-37%) but with a uniform bulk density (0.66-0.69)g/cc and internal porosity, utilizing the solvent extraction/evaporation method. The microspheres were characterized for drug content by HPLC, particle size by laser diffractometry, surface morphology by scanning electron microscopy (SEM), and in vivo drug release. In vivo studies were performed in male Sprague-Dawley rats, and levels of the active moiety (Risperidone and its metabolite, 9-hydroxyrisperidone) were assessed. In vivo release profiles from the three microsphere formulations were dependent on particle size and drug loading. The smaller sized microspheres (Formulation A) exhibited a large initial burst and a shorter duration of action, while the larger particles exhibited a smaller initial burst (Formulations B and C) but released drug for a much longer period in vivo. Extended duration of drug release was ascribed to higher drug content in the microspheres. A biweekly simulation of multiple dosing revealed that Formulation C, the selected formulation, with a high load and large particle size would provide adequate initial and maintenance levels of the active moiety (Risperidone and its metabolite, 9-hydroxyrisperidone). A comparison of biweekly dosing in vivo of Formulation C with the marketed product showed that at steady state, though average concentrations for both preparations were similar, the time taken to achieve steady state was much faster for Formulation C. The delay in attaining steady state with Risperdal Consta® was attributed to the 3 week latency in drug release from the microspheres and was in accordance with previous studies indicating a good corroboration with clinical findings. Calculated cumulative AUC (area under the curve) levels for Formulation C were similar to the Risperdal Consta®, though there were marked differences in AUC levels at the early time points. Comparison of Risperidal Consta® and Formulation C by multiple dosing in vivo experiments revealed that the marketed preparation demonstrated a substantial delay in providing an initial loading dose, continuous circulating levels, and attainment of steady state; all of which were observed rapidly with Formulation C. Findings from the current study strongly suggest that a microsphere dosage form of Risperidone can be formulated with an optimum particle size and drug loading to provide an initial bolus followed by maintenance levels, thereby eliminating combination therapy and improving patient compliance. PMID:23892159

  13. Knowledge and Perception on Long Acting and Permanent Contraceptive Methods in Adigrat Town, Tigray, Northern Ethiopia: A Qualitative Study

    PubMed Central

    Addissie, Adamu

    2014-01-01

    Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice. PMID:25140252

  14. Controlled Release of Dutasteride from Biodegradable Microspheres: In Vitro and In Vivo Studies

    PubMed Central

    Xie, Xiangyang; Yang, Yanfang; Chi, Qiang; Li, ZhiPing; Zhang, Hui; Li, Ying; Yang, Yang

    2014-01-01

    The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH), into poly(lactide-co-glycolide) (PLGA). A response surface method (RSM) with central composite design (CCD) was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods. PMID:25541985

  15. Microencapsulation of curcumin in PLGA microcapsules by coaxial flow focusing

    NASA Astrophysics Data System (ADS)

    Lei, Fan; Si, Ting; Luo, Xisheng; Xu, Ronald X.

    2014-03-01

    Curcumin-loaded PLGA microcapsules are fabricated by a liquid-driving coaxial flow focusing device. In the process, a stable coaxial cone-jet configuration is formed under the action of a coflowing liquid stream and the coaxial liquid jet eventually breaks up into microcapsules because of flow instability. This process can be well controlled by adjusting the flow rates of three phases including the driving PVA water solution, the outer PLGA ethyl acetate solution and the inner curcumin propylene glycol solution. Confocal and SEM imaging methods clearly indicate the core-shell structure of the resultant microcapsules. The encapsulation rate of curcumin in PLGA is measured to be more than 70%, which is much higher than the tranditional methods such as emulsion. The size distribution of resultant microcapsules under different conditions is presented and compared. An in vitro release simulation platform is further developed to verify the feasibility and reliability of the method.

  16. Glass microsphere lubrication

    NASA Technical Reports Server (NTRS)

    Geiger, Michelle; Goode, Henry; Ohanlon, Sean; Pieloch, Stuart; Sorrells, Cindy; Willette, Chris

    1991-01-01

    The harsh lunar environment eliminated the consideration of most lubricants used on earth. Considering that the majority of the surface of the moon consists of sand, the elements that make up this mixture were analyzed. According to previous space missions, a large portion of the moon's surface is made up of fine grained crystalline rock, about 0.02 to 0.05 mm in size. These fine grained particles can be divided into four groups: lunar rock fragments, glasses, agglutinates (rock particles, crystals, or glasses), and fragments of meteorite material (rare). Analysis of the soil obtained from the missions has given chemical compositions of its materials. It is about 53 to 63 percent oxygen, 16 to 22 percent silicon, 10 to 16 percent sulfur, 5 to 9 percent aluminum, and has lesser amounts of magnesium, carbon, and sodium. To be self-supporting, the lubricant must utilize one or more of the above elements. Considering that the element must be easy to extract and readily manipulated, silicon or glass was the most logical choice. Being a ceramic, glass has a high strength and excellent resistance to temperature. The glass would also not contaminate the environment as it comes directly from it. If sand entered a bearing lubricated with grease, the lubricant would eventually fail and the shaft would bind, causing damage to the system. In a bearing lubricated with a solid glass lubricant, sand would be ground up and have little effect on the system. The next issue was what shape to form the glass in. Solid glass spheres was the only logical choice. The strength of the glass and its endurance would be optimal in this form. To behave as an effective lubricant, the diameter of the spheres would have to be very small, on the order of hundreds of microns or less. This would allow smaller clearances between the bearing and the shaft, and less material would be needed. The production of glass microspheres was divided into two parts, production and sorting. Production includes the manufacturing of the microspheres, while sorting entails deciphering the good microspheres from the bad ones. Each process is discussed in detail.

  17. Oral Delivery of DMAB-Modified Docetaxel-Loaded PLGA-TPGS Nanoparticles for Cancer Chemotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Hongbo; Zheng, Yi; Tian, Ge; Tian, Yan; Zeng, Xiaowei; Liu, Gan; Liu, Kexin; Li, Lei; Li, Zhen; Mei, Lin; Huang, Laiqiang

    2011-12-01

    Three types of nanoparticle formulation from biodegradable PLGA-TPGS random copolymer were developed in this research for oral administration of anticancer drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS random copolymer was synthesized and characterized. DMAB was used to increase retention time at the cell surface, thus increasing the chances of particle uptake and improving oral drug bioavailability. Nanoparticles were found to be of spherical shape with an average particle diameter of around 250 nm. The surface charge of PLGA-TPGS nanoparticles was changed to positive after DMAB modification. The results also showed that the DMAB-modified PLGA-TPGS nanoparticles have significantly higher level of the cellular uptake than that of DMAB-modified PLGA nanoparticles and unmodified PLGA-TPGS nanoparticles. In vitro, cytotoxicity experiment showed advantages of the DMAB-modified PLGA-TPGS nanoparticle formulation over commercial Taxotere® in terms of cytotoxicity against MCF-7 cells. In conclusion, oral chemotherapy by DMAB-modified PLGA-TPGS nanoparticle formulation is an attractive and promising treatment option for patients.

  18. Emulsion Electrospinning as an Approach to Fabricate PLGA/Chitosan Nanofibers for Biomedical Applications

    PubMed Central

    Tavanai, Hossein; Hilborn, Jöns; Donzel-Gargand, Olivier; Leifer, Klaus; Arpanaei, Ayyoob

    2014-01-01

    Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94?MPa and 4.21?MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction. PMID:24689041

  19. Posterolateral Spinal Fusion in Rabbits Using a RP-based PLGA\\/ TCP\\/Col\\/BMSCs-OB Biomimetic Grafting Material

    Microsoft Academic Search

    Xing Ma; Xiaoming Wu; Yaoping Wu; Jian Liu; Zhuo Xiong; Rong Lv; Yongnian Yan; Jun Wang; Dan Li

    2009-01-01

    Three-dimensional highly porous poly(DL-lactic-co-glycolic acid)\\/ tricalcium phosphate (PLGA\\/TCP) scaffolds were fabricated using a rapid prototyping technique (RP). The 3D rhombic lamellar PLGA\\/TCP carriers (20 mm × 20 mm × 3 mm) subsequently were coated with collagen type I (Col) to produce PLGA\\/TCP\\/Col composites. Both the RP-based PLGA\\/TCP scaffolds and the PLGA\\/TCP\\/Col composites were observed by scanning electron microscopy. Forty New

  20. Prevalence and factors affecting use of long acting and permanent contraceptive methods in Jinka town, Southern Ethiopia: a cross sectional study

    PubMed Central

    Mekonnen, Getachew; Enquselassie, Fikre; Tesfaye, Gezahegn; Semahegn, Agumasie

    2014-01-01

    Introduction In Ethiopia, knowledge of contraceptive methods is high though there is low contraceptive prevalence rate. This study was aimed to assess prevalence and associated factors of long acting and permanent contraceptive methods in Jinka town, southern Ethiopia. Methods Community based cross sectional survey was conducted to assess the prevalence and factors affecting long acting and permanent methods of contraceptives utilization from March to April 2008. Eight hundred child bearing age women were participated in the quantitative study and 32 purposively selected focus group discussants were participated in the qualitative study. Face to face interview was used for data collection. Data were analyzed by SPSS version 13.0 statistical software. Descriptive statistics and logistic regression were computed to analyze the data. Results The prevalence of long acting and permanent contraceptive method was 7.3%. Three fourth (76.1%) of the women have ever heard about implants and implant 28 (50%) were the most widely used method. Almost two third of women had intention to use long acting and permanent methods. Knowledge of contraceptive and age of women have significant association with the use of long acting and permanent contraceptive methods. Conclusion The overall prevalence of long acting and permanent contraceptive method was low. Knowledge of contraceptive and age of women have significant association with use of long acting and permanent contraceptive. Extensive health information should be provided. PMID:25404960

  1. 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. PMID:25951620

  2. A biodegradable polymeric system for peptide–protein delivery assembled with porous microspheres and nanoparticles, using an adsorption/infiltration process

    PubMed Central

    Alcalá-Alcalá, Sergio; Urbán-Morlán, Zaida; Aguilar-Rosas, Irene; Quintanar-Guerrero, David

    2013-01-01

    A biodegradable polymeric system is proposed for formulating peptides and proteins. The systems were assembled through the adsorption of biodegradable polymeric nanoparticles onto porous, biodegradable microspheres by an adsorption/infiltration process with the use of an immersion method. The peptide drug is not involved in the manufacturing of the nanoparticles or in obtaining the microspheres; thus, contact with the organic solvent, interfaces, and shear forces required for the process are prevented during drug loading. Leuprolide acetate was used as the model peptide, and poly(d,l-lactide-co-glycolide) (PLGA) was used as the biodegradable polymer. Leuprolide was adsorbed onto different amounts of PLGA nanoparticles (25 mg/mL, 50 mg/mL, 75 mg/mL, and 100 mg/mL) in a first stage; then, these were infiltrated into porous PLGA microspheres (100 mg) by dipping the structures into a microsphere suspension. In this way, the leuprolide was adsorbed onto both surfaces (ie, nanoparticles and microspheres). Scanning electron microscopy studies revealed the formation of a nanoparticle film on the porous microsphere surface that becomes more continuous as the amount of infiltrated nanoparticles increases. The adsorption efficiency and release rate are dependent on the amount of adsorbed nanoparticles. As expected, a greater adsorption efficiency (~95%) and a slower release rate were seen (~20% of released leuprolide in 12 hours) when a larger amount of nanoparticles was adsorbed (100 mg/mL of nanoparticles). Leuprolide acetate begins to be released immediately when there are no infiltrated nanoparticles, and 90% of the peptide is released in the first 12 hours. In contrast, the systems assembled in this study released less than 44% of the loaded drug during the same period of time. The observed release profiles denoted a Fickian diffusion that fit Higuchi’s model (t1/2). The manufacturing process presented here may be useful as a potential alternative for formulating injectable depots for sensitive hydrophilic drugs such as peptides and proteins, among others. PMID:23788833

  3. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children

    PubMed Central

    Ni Chroinin, Muireann; Lasserson, Toby J; Greenstone, Ilana; Ducharme, Francine M

    2014-01-01

    Background Long-acting ß2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed in asthmatic children. Objectives To compare the safety and benefit of adding LABA to ICS with the same or an increased dose of ICS in children with persistent asthma. Search methods We searched the Cochrane Airways Group Asthma Trials Register (May 2008). Selection criteria We included randomised controlled trials testing the combination of LABA and ICS versus the same or an increased dose of ICS for minimum of at least 28 days in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included pulmonary function, symptoms, adverse events, and withdrawals. Data collection and analysis Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. Main results A total of 25 trials representing 31 control-intervention comparisons were included in the review randomising 5572 children. Most of the participants were inadequately controlled on current ICS dose. We assessed the addition of LABA to the same dose of ICS and to an increased dose of ICS: (1)The addition of LABA to ICS was compared to same dose ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The mean age of participants was 10 years and males accounted for 64% of the study populations. The mean FEV1 at baseline was 80% of predicted or above in 10 studies; FEV1 61% to 79% of predicted in eight studies; and unreported in the remaining study. Participants were inadequately controlled before randomisation in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was not associated with a significant reduction in exacerbations requiring oral steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone, there was a significantly greater improvement in FEV1 with the addition of LABA (nine studies; 0.08 Litres, 95% CI 0.06 to 0.11) but no statistically significant group differences in symptom-free days, hospital admission, quality of life, use of reliever medication, and adverse events. Withdrawals occurred significantly less frequently with the addition of LABA.(2)A total of seven studies assessed the addition of LABA to ICS therapy compared with an increased dose of ICS randomising 1021 children. The mean age of participants was 8 years with 67% of males. The baseline mean FEV1 was 80% of predicted or above in 2 of the 3 studies reporting this characteristic. All trials enrolled participants who were inadequately controlled on a baseline dose equivalent to 400 mcg/day of beclomethasone or less. There was no group significant difference in the risk of an exacerbation requiring oral steroids with the combination of LABA and ICS compared to a double dose of ICS (two studies, RR 1.5 95% CI 0.65 to 3.48). The increased risk of hospital admission with combination therapy was also not statistically significant (RR 2.21 95% CI 0.74 to 6.64). Compared to double dose ICS, use of LABA was associated with a significantly greater improvement in morning PEF (four studies; MD 7.55 L/min 95% CI: 3.57 to 11.53) and evening PEF L/min (three studies, MD 5.5 L/min; 95% CI 1.21 to 9.79), but there were insufficient data to aggregate data on FEV1, symptoms, rescue reliever use, and quality of life. There was no statistically significant difference in the overall risk of all cause withdrawals (five studies; RR 0.71; 95% CI 0.42 to 1.20. There was no group difference in the risk of overall adverse effects detected. Short term growth was significantly greater in children treated with combination therapy compared to double dose ICS (two studies: MD 1.2 cm/year; 95% CI 0.72 to 1.7). Authors’ conclusions In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but was superior for improving lung function compared to t

  4. Biocompatibility and characteristics of chitosan/cellulose acetate microspheres for drug delivery

    NASA Astrophysics Data System (ADS)

    Zhou, Hui-Yun; Zhou, Dong-Ju; Zhang, Wei-Fen; Jiang, Ling-Juan; Li, Jun-Bo; Chen, Xi-Guang

    2011-12-01

    In this work, chitosan/cellulose acetate microspheres (CCAM) were prepared by the method of W/O/W emulsion with no toxic reagents. The microspheres were spherical, free flowing, and non-aggregated, which had a narrow size distribution. More than 90% of the microspheres had the diameter ranging from 200 to 280 ?m. The hemolytic analysis indicated that CCAM was safe and had no hemolytic effect. The implanted CCAM did not produce any significant changes in the hematology of Sprague-Dawley (SD) rats, such as white blood cell, red blood cell, platelet, and the volume of hemoglobin. In addition, the levels of serum alanine aminotransferase, blood urea nitrogen, and creatinine had no obvious changes in SD rats implanted with CCAM, surger thread, or normal SD rats without any implantation. Thus, the CCAM had good blood compatibility and had no hepatotoxicity or renal toxicity to SD rats. Furthermore, CCAM with or without the model drug had good tissue compatibility with respect to the inflammatory reaction in SD rats and showed no significant difference from that of SD rats implanted with surgery thread. CCAM shows promise as a long-acting delivery system, which had good biocompatibility and biodegradability.

  5. Fabrication of glass microspheres with conducting surfaces

    DOEpatents

    Elsholz, William E. (Acampo, CA)

    1984-01-01

    A method for making hollow glass microspheres with conducting surfaces by adding a conducting vapor to a region of the glass fabrication furnace. As droplets or particles of glass forming material pass through multiple zones of different temperature in a glass fabrication furnace, and are transformed into hollow glass microspheres, the microspheres pass through a region of conducting vapor, forming a conducting coating on the surface of the microspheres.

  6. Phase inversion dynamics of PLGA solutions related to drug delivery

    Microsoft Academic Search

    P. D. Graham; K. J. Brodbeck; A. J. McHugh

    1999-01-01

    Dark ground optical microscopy, electron microscopy, and high performance liquid chromatography (HPLC) have been used to quantify the effects of formulation changes on the phase inversion dynamics and in vitro drug release properties of a PLGA-based drug delivery system. Gel growth rates and water influx rates are determined from plots of the square of the respective front motion with time.

  7. Simulation of Drug Release from PLGA Particles In Vivo

    PubMed Central

    Sasaki, Kaori; Igarashi, Martha; Hinata, Manami; Komori, Yuna

    2013-01-01

    Specific targeting of tissues and/or cells is essential for any type of drug delivery system because this determines the efficacy and side effects of the drug. Poly lactic-co-glycolic acids (PLGA) have long been used as biomaterials for drug delivery due to their excellent biocompatibility and biodegradability. Direct visualization of PLGA particles is feasible even within tissues, and cell specificity of the drug delivery system is normally assessed by using labeled particles. However, particle labeling alone does not address factors such as the release and distribution of the drug. Thus, it is desirable to set up a simulation system of drug release and distribution in vivo. In the present study, we aimed to establish a method to simulate drug distribution in PLGA drug delivery by using Hoechst 33342 as an imitating drug. Our approach enabled us to identify, isolate, and characterize cells exposed to Hoechst 33342 and to deduce the concentration of this fluorescent dye around both targeted and nontargeted cells. We believe that the method described herein will provide essential information regarding the specificity of cell targeting in any type of PLGA drug delivery system. PMID:24222857

  8. RESEARCH ARTICLE Facile synthesis of PEGylated PLGA nanoparticles

    E-print Network

    Sridhar, Srinivas

    RESEARCH ARTICLE Facile synthesis of PEGylated PLGA nanoparticles encapsulating doxorubicin and its K. Nagesha & Robert Cormack & Mike G. Makrigiorgos & Srinivas Sridhar Published online: 9 January of nanoparticle-based platforms for different bio- medical applications. A better understanding for engineer- ing

  9. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model.

    PubMed

    Groban, Leanne

    2003-01-01

    With the development of the newer long-acting amide local anesthetics,ropivacaine and levobupivacaine, numerous animal studies of LA systemic toxicity have emerged. Because of the complex nature of the human response to LA intoxication, the task of designing and interpreting these animal studies of LA toxicity can be difficult. Accordingly, this report will review the selection of an animal model for the study of LA toxicity; examine the pertinent in vivo animal studies that compare the central nervous system toxicity, cardiovascular toxicity, and the ease of resuscitation of the single enantiomer local anesthetics to racemic bupivacaine; and extrapolate these findings to the clinical setting. PMID:12567336

  10. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate

    PubMed Central

    Gupta, Vineet; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.

    2015-01-01

    Extracellular matrix (ECM) components, such as chondroitin sulfate (CS) and tricalcium phosphate, serve as raw materials, and thus spatial patterning of these raw materials may be leveraged to mimic the smooth transition of physical, chemical, and mechanical properties at the bone-cartilage interface. We hypothesized that encapsulation of opposing gradients of these raw materials in high molecular weight poly(d,l-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds would enhance differentiation of rat bone marrow–derived stromal cells. The raw material encapsulation altered the microstructure of the microspheres and also influenced the cellular morphology that depended on the type of material encapsulated. Moreover, the mechanical properties of the raw material encapsulating microsphere-based scaffolds initially relied on the composition of the scaffolds and later on were primarily governed by the degradation of the polymer phase and newly synthesized ECM by the seeded cells. Furthermore, raw materials had a mitogenic effect on the seeded cells and led to increased glycosaminoglycan (GAG), collagen, and calcium content. Interestingly, the initial effects of raw material encapsulation on a per-cell basis might have been overshadowed by medium-regulated environment that appeared to favor osteogenesis. However, it is to be noted that in vivo, differentiation of the cells would be governed by the surrounding native environment. Thus, the results of this study demonstrated the potential of the raw materials in facilitating neo-tissue synthesis in microsphere-based scaffolds and perhaps in combination with bioactive signals, these raw materials may be able to achieve intricate cell differentiation profiles required for regenerating the osteochondral interface.

  11. Preparation and properties of PLGA nanofiber membranes reinforced with cellulose nanocrystals.

    PubMed

    Mo, Yunfei; Guo, Rui; Liu, Jianghui; Lan, Yong; Zhang, Yi; Xue, Wei; Zhang, Yuanming

    2015-08-01

    Although extensively used in the fields of drug-carrier and tissue engineering, the biocompatibility and mechanical properties of polylactide-polyglycolide (PLGA) nanofiber membranes still limit their applications. The objective of this study was to improve their utility by introducing cellulose nanocrystals (CNCs) into PLGA nanofiber membranes. PLGA and PLGA/CNC composite nanofiber membranes were prepared via electrospinning, and the morphology and thermodynamic and mechanical properties of these nanofiber membranes were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The cytocompatibility and cellular responses of the nanofiber membranes were also studied by WST-1 assay, SEM, and confocal laser scanning microscopy (CLSM). Incorporation of CNCs (1, 3, 5, and 7wt.%) increased the average fiber diameter of the prepared nanofiber membranes from 100nm (neat PLGA) to ?400nm (PLGA/7wt.% CNC) and improved the thermal stability of the nanofiber membranes. Among the PLGA/CNC composite nanofiber membranes, those loaded with 7wt.% CNC nanofiber membranes had the best mechanical properties, which were similar to those of human skin. Cell culture results showed that the PLGA/CNC composite nanofiber membranes had better cytocompatibility and facilitated fibroblast adhesion, spreading, and proliferation compared with neat PLGA nanofiber membranes. These preliminary results suggest that PLGA/CNC composite nanofiber membranes are promising new materials for the field of skin tissue engineering. PMID:26047881

  12. Development of sulfadiazine-decorated PLGA nanoparticles loaded with 5-fluorouracil and cell viability.

    PubMed

    Guimarães, Pedro Pires Goulart; Oliveira, Sheila Rodrigues; de Castro Rodrigues, Gabrielle; Gontijo, Savio Morato Lacerda; Lula, Ivana Silva; Cortés, Maria Esperanza; Denadai, Ângelo Márcio Leite; Sinisterra, Rubén Dario

    2015-01-01

    The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = -32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future. PMID:25580685

  13. Advances in Microsphere Insulation Systems

    NASA Astrophysics Data System (ADS)

    Allen, M. S.; Baumgartner, R. G.; Fesmire, J. E.; Augustynowicz, S. D.

    2004-06-01

    Microsphere insulation, typically consisting of hollow glass bubbles, combines in a single material the desirable properties that other insulations only have individually. The material has high crush strength, low density, is noncombustible, and performs well in soft vacuum. Microspheres provide robust, low-maintenance insulation systems for cryogenic transfer lines and dewars. They also do not suffer from compaction problems typical of perlite that result in the necessity to reinsulate dewars because of degraded thermal performance and potential damage to its support system. Since microspheres are load bearing, autonomous insulation panels enveloped with lightweight vacuum-barrier materials can be created. Comprehensive testing performed at the Cryogenics Test Laboratory located at the NASA Kennedy Space Center demonstrated competitive thermal performance with other bulk materials. Test conditions were representative of actual-use conditions and included cold vacuum pressure ranging from high vacuum to no vacuum and compression loads from 0 to 20 psi. While microspheres have been recognized as a legitimate insulation material for decades, actual implementation has not been pursued. Innovative microsphere insulation system configurations and applications are evaluated.

  14. Long-Acting Forms of Growth Hormone-Releasing Hormone and Growth Hormone: Effects in Normal Volunteers and Adults with Growth Hormone Deficiency

    Microsoft Academic Search

    David R. Clemmons

    2007-01-01

    Background: Growth hormone (GH) replacement therapy in adults and children has found broad acceptance by endocrinologists and patients, but the need for daily injections remains a significant barrier to more widespread use. Long-acting Formulations: Several approaches have been taken to develop long-acting forms of GH and to extend the half-life of GH-releasing factor. Each of these preparations has been tested

  15. Cost Effectiveness of Leukotriene Receptor Antagonists versus Long-Acting Beta2 Agonists as Add-On Therapy to Inhaled Corticosteroids for Asthma: A Pragmatic Trial

    Microsoft Academic Search

    Edward C. F. Wilson; David Price; Stanley D. Musgrave; Erika J. Sims; Lee Shepstone; Jamie Murdoch; H. Miranda. Mugford; Annie Blyth; Elizabeth F. Juniper; Jon G. Ayres; Stephanie Wolfe; Daryl Freeman; Richard F. T. Gilbert; Elizabeth V. Hillyer; Ian Harvey

    2010-01-01

    Background:Background: Information is lacking on the relative effectiveness and cost effectiveness - in a real-life primary-care setting - of leukotriene receptor antagonists (LTRAs) and long-acting ?2 adrenergic receptor agonists (?2 agonists) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids (ICS). Abstract: Objective:Objective: To estimate the cost effectiveness of LTRAs compared with long-acting ?2

  16. Dose-response effects of long-acting injectable vitamin B12 plus selenium (Se) on the vitamin B12 and Se status of ewes and their lambs

    Microsoft Academic Search

    ND Grace; SO Knowles

    2006-01-01

    AIM: To determine the effect of increasing doses of long-acting injectable vitamin B12 plus selenium (Se) given pre-mating on the vitamin B12 and Se status of ewes and their lambs from birth to weaning.METHODS: Four groups of 24 Poll Dorset ewes each were injected 4 weeks pre-mating with different doses of a long-acting vitamin B12 + Se product, containing 3

  17. Long-Acting Reversible Contraceptive Use in Urban Women From a Title X–Supported Boston Community Health Center

    PubMed Central

    Ricciotti, Hope A.; Dodge, Laura E.; Ramirez, Christina I.; Barnes, Katherine; Hacker, Michele R.

    2015-01-01

    Background Unintended and adolescent pregnancy disproportionately affects minority populations, but the effect of age, race and ethnicity on the use of long-acting reversible contraception (LARC) has not been well studied. Objective The objective of this pilot study was to examine LARC use over a 5-year period among women receiving care at a Boston community health center. Methods Retrospective cohort study of LARC method use among black, Hispanic, and white women receiving care at the Dimock Center from 2006 to 2010. Results This study included 276 women (60.1% black, 18.5% Hispanic, and 9.1% white). LARC was not used as a first-line method in the majority (96.0%), regardless of age, race, and ethnicity; yet nearly half identified a long-acting contraceptive as their method of choice. Conclusions The findings of this pilot study reveal opportunities to reduce unintended pregnancy through increased LARC use, which may be accomplished by provider and patient education. PMID:25301380

  18. LAPS-FSH: a new and effective long-acting follicle-stimulating hormone analogue for the treatment of infertility.

    PubMed

    Jung, Sunyoung; Park, Youngjin; Kim, YoungHoon; Kim, Yu Yon; Choi, Hyun-Ji; Son, Woo-Chan; Kwon, SeChang

    2014-10-01

    Although several long-acting follicle-stimulating hormone (FSH) therapies have been developed to enhance the ovarian response, a disadvantage of FSH therapy is its relatively short half-life, which requires women to receive one to two injections per day for almost 2 weeks. In the present study, we developed a novel FSH analogue by conjugating recombinant human FSH (rhFSH) and the constant region of the human immunoglobulin G4 fragment via non-peptidyl linkers. The efficacy of the FSH analogue was evaluated in vitro by cAMP level assessments, pharmacokinetic studies and a determination of ovarian weight and by comparing these findings with the results from other FSH analogues. In addition, the total number of antral and Graafian follicles was determined after 7 days of treatment with control, 6µgkg(-1) follitropin ?, 6, 12 or 42µgkg(-1) corifollitropin ? or 3, 6 or 12µgkg(-1) long acting protein/peptide discovery-follicle-stimulating hormone (LAPS-FSH). As a result, the animals treated with 12µgkg(-1) LAPS-FSH produced additional and larger healthy follicles. These data demonstrate that LAPS-FSH promotes growth and inhibits atresia of the ovarian follicle compared with other available drugs, suggesting that our new drug enhances the efficacy and duration of treatment. It is expected that our new FSH analogue will result in a higher chance of pregnancy in patients who are unresponsive to other drugs. PMID:24044514

  19. Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment.

    PubMed

    Baert, Lieven; van 't Klooster, Gerben; Dries, Willy; François, Marc; Wouters, Alfons; Basstanie, Esther; Iterbeke, Koen; Stappers, Fred; Stevens, Paul; Schueller, Laurent; Van Remoortere, Pieter; Kraus, Guenter; Wigerinck, Piet; Rosier, Jan

    2009-08-01

    Long-acting parenteral formulations of antiretrovirals could facilitate maintenance and prophylactic treatment in HIV. Using the poorly water- and oil-soluble non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 (rilpivirine) as base or hydrochloride (HCl), nanosuspensions were prepared by wet milling (Elan NanoCrystal technology) in an aqueous carrier. Laser diffraction showed that the average particles size were (1) close to the targeted size proportionality (200-400-800 nm), with increasing distributions the larger the average particle size, and (2) were stable over 6 months. Following single-dose administration, the plasma concentration profiles showed sustained release of TMC278 over 3 months in dogs and 3 weeks in mice. On comparison of intramuscular and subcutaneous injection of 5mg/kg (200 nm) in dogs, the subcutaneous route resulted in the most stable plasma levels (constant at 25 ng/mL for 20 days, after which levels declined slowly to 1-3 ng/mL at 3 months); 200 nm nanosuspensions achieved higher and less variable plasma concentration profiles than 400 and 800 nm nanosuspensions. In mice, the pharmacokinetic profiles after a single 20mg/kg dose (200 nm) were similar with two different surfactants used (poloxamer 338, or d-alpha-tocopheryl polyethylene glycol 1000 succinate). In conclusion, this study provides proof-of-concept that 200-nm sized TMC278 nanosuspensions may act as long-acting injectable. PMID:19328850

  20. Curcumin-Loaded PLGA Nanoparticles Coating onto Metal Stent by EPD Bull. Korean Chem. Soc. 2007, Vol. 28, No. 3 397 Curcumin-Loaded PLGA Nanoparticles

    E-print Network

    Park, Jong-Sang

    Curcumin-Loaded PLGA Nanoparticles Coating onto Metal Stent by EPD Bull. Korean Chem. Soc. 2007, Vol. 28, No. 3 397 Curcumin-Loaded PLGA Nanoparticles Coating onto Metal Stent by Electrophoretic) nanoparticles embedded with curcumin, which was done by a modified spontaneous emulsification method and used

  1. Development and evaluation of a novel biodegradable sustained release microsphere formulation of paclitaxel intended to treat breast cancer

    PubMed Central

    Shiny, Jacob; Ramchander, Thadkapally; Goverdhan, Puchchakayala; Habibuddin, Mohammad; Aukunuru, Jithan Venkata

    2013-01-01

    Objective: The objective of this study was to develop a novel 1 month depot paclitaxel (PTX) microspheres that give a sustained and complete drug release. Materials and Methods: PTX loaded microspheres were prepared by o/w emulsion solvent evaporation technique using the blends of poly(lactic-co-glycolic acid) (PLGA) 75/25, polycaprolactone 14,000 and polycaprolactone 80,000. Fourier transform infrared spectroscopy was used to investigate drug excipient compatibility. Compatible blends were used to prepare F1-F6 microspheres, the process was characterised and the optimum formulation was selected based on the release. Optimised formulation was characterised for solid state of the drug using the differential scanning calorimetry (DSC) studies, surface morphology using the scanning electron microscopy (SEM), in vivo drug release, in vitro in vivo correlation (IVIVC) and anticancer activity. Anticancer activity of release medium was determined using the cell viability assay in Michigan Cancer Foundation (MCF-7) cell line. Results: Blend of PLGA with polycaprolactone (Mwt 14,000) at a ratio of 1:1 (F5) resulted in complete release of the drug in a time frame of 30 days. F5 was considered as the optimised formulation. Incomplete release of the drug resulted from other formulations. The surface of the optimised formulation was smooth and the drug changed its solid state upon fabrication. The formulation also resulted in 1-month drug release in vivo. The released drug from F5 demonstrated anticancer activity for 1-month. Cell viability was reduced drastically with the release medium from F5 formulation. A 100% IVIVC was obtained with F5 formulation suggesting the authenticity of in vitro release, in vivo release and the use of the formulation in breast cancer. Conclusions: From our study, it was concluded that with careful selection of different polymers and their combinations, PTX 1 month depot formulation with 100% drug release and that can be used in breast cancer was developed. PMID:24167783

  2. Production of monodisperse, polymeric microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Rhim, Won-Kyu (Inventor); Hyson, Michael T. (Inventor); Chang, Manchium (Inventor)

    1990-01-01

    Very small, individual polymeric microspheres with very precise size and a wide variation in monomer type and properties are produced by deploying a precisely formed liquid monomer droplet, suitably an acrylic compound such as hydroxyethyl methacrylate into a containerless environment. The droplet which assumes a spheroid shape is subjected to polymerizing radiation such as ultraviolet or gamma radiation as it travels through the environment. Polymeric microspheres having precise diameters varying no more than plus or minus 5 percent from an average size are recovered. Many types of fillers including magnetic fillers may be dispersed in the liquid droplet.

  3. Fabrication and characterization of aligned nanofibrous PLGA\\/Collagen blends as bone tissue scaffolds

    Microsoft Academic Search

    Moncy V. Jose; Vinoy Thomas; Derrick R. Dean; Elijah Nyairo

    2009-01-01

    Aligned nanofibrous blends of poly (d, l-lactide-co-glycolide) (PLGA) and collagen with various PLGA\\/collagen compositions (80\\/20, 65\\/35 and 50\\/50) were fabricated by electrospinning and characterized for bone tissue engineering. Morphological characterization showed that the addition of collagen to PLGA resulted in narrowing of the diameter distribution and a reduction in average diameter. Differential scanning calorimetric (DSC) studies showed that the triple

  4. Altered responses of chondrocytes to nanophase PLGA\\/nanophase titania composites

    Microsoft Academic Search

    Jennifer K Savaiano; Thomas J Webster

    2004-01-01

    Chondrocyte (cartilage-synthesizing cells) cell density and synthesis of select intracellular proteins by chondrocytes were investigated on novel nanophase poly-lactic\\/glycolic acid (PLGA) and titania composites in the present in vitro study. Nanophase PLGA films were created by chemically treating conventional (or micron-structured) PLGA films with 10n NaOH for 1h. Titania particle dimensions in ceramic compacts were controlled by utilizing either conventional

  5. Biodegradable polymeric micelles composed of doxorubicin conjugated PLGA–PEG block copolymer

    Microsoft Academic Search

    Hyuk Sang Yoo; Tae Gwan Park

    2001-01-01

    Biodegradable polymeric micelles containing doxorubicin in the core region were prepared from a di-block copolymer composed of doxorubicin-conjugated poly(dl-lactic-co-glycolic acid) (PLGA) and polyethyleneglycol (PEG). The di-block copolymer of PLGA–PEG was first synthesized and the primary amino group of doxorubicin was then conjugated to the terminal hydroxyl group of PLGA, which had been pre-activated using p-nitrophenyl chloroformate. The resulting polymeric micelles

  6. Development of a respirable, sustained release microcarrier for 5-fluorouracil I: In vitro assessment of liposomes, microspheres, and lipid coated nanoparticles.

    PubMed

    Hitzman, Cory J; Elmquist, William F; Wattenberg, Lee W; Wiedmann, Timothy S

    2006-05-01

    The release rate of 5-fluorouracil (5-FU) from liposomes, microspheres, and lipid-coated nanoparticles (LNPs) was determined by microdialysis to investigate their use as a respirable delivery system for adjuvant (postsurgery) therapy of lung cancer. 5-FU was incorporated into liposomes using thin film hydration and into microspheres and LNPs by spray drying. Primary particle size distributions were measured by dynamic light scattering. Liposomes released 5-FU in 4-10 h (k(1) = 0.44-2.31/h, first-order release model). Extruded vesicles with diameters less than one micron released 5-FU more quickly than nonextruded vesicles. With poly-(lactide) (PLA) and Poly-(lactide-co-glycolide) (PLGA) microspheres, slower release rates were observed (k(1) = 0.067-0.202/h). Increasing the lactide:glycolide ratio (50:50-100:0) resulted in a progressive decrease in the release rate of 5-FU. poly-(lactide-co-caprolactone) (PLCL) microspheres released 5-FU more rapidly compared to PLGA systems (k(1) = 0.254-0.259/h). LNPs formulated with polymeric core excipients had lower release rates compared to monomeric excipients (k(1) = 0.043-0.105/h vs. k(1) = 0.192-0.345/h). Changing the lipid chain length of the shell lipid components had a relatively minor effect (k(1) = 0.043-0.129/h). Overall, these systems yielded a wide range of delivery durations that may be suitable for use as an inhalation delivery system for adjuvant therapy of lung cancer. PMID:16570302

  7. Optimization of maghemite-loaded PLGA nanospheres for biomedical applications.

    PubMed

    Silva, Marcela Fernandes; Winkler Hechenleitner, Ana Adelina; de Oliveira, Daniela Martins Fernandes; Agüeros, Maite; Peñalva, Rebeca; Irache, Juan Manuel; Pineda, Edgardo Alfonso Gómez

    2013-06-14

    Magnetic nanoparticles have been proposed as interesting tools for biomedical purposes. One of their promising utilization is the MRI in which magnetic substances like maghemite are used in a nanometric size and encapsulated within locally biodegradable nanoparticles. In this work, maghemite has been obtained by a modified sol-gel method and encapsulated in polymer-based nanospheres. The nanospheres have been prepared by single emulsion evaporation method. The different parameters influencing the size, polydispersity index and zeta potential surface of nanospheres were investigated. The size of nanospheres was found to increase as the concentration of PLGA increases, but lower sizes were obtained for 3 min of sonication time and surfactant concentration of 1%. Zeta potential response of magnetic nanospheres towards pH variation was similar to that of maghemite-free nanospheres confirming the encapsulation of maghemite within PLGA nanospheres. The maghemite entrapment efficiency and maghemite content for nanospheres are 12% and 0.59% w/w respectively. PMID:23602998

  8. Severe withdrawal syndrome after substitution of a short-acting benzodiazepine for a long-acting benzodiazepine.

    PubMed

    Bond, W S; Berwish, N J; Swift, B

    1985-10-01

    A severe withdrawal syndrome occurred in a patient after oxazepam 10 mg bid was substituted for diazepam 5 mg bid. The onset of symptoms was consistent with the rate of decline of diazepam and its active metabolite, desmethyldiazepam. Reintroduction of diazepam produced prompt symptom remission. This report and others suggest the need for caution when substituting a short-acting drug for a long-acting one, even when usual doses of each are used. The chronic use of benzodiazepines for eight months or longer prior to substitution or withdrawal appears to place the patient at a higher risk of incurring withdrawal phenomena. Slow and careful tapering of drug is required in such patients to reduce the risk of withdrawal symptoms. PMID:3932057

  9. Formoterol, a new long acting beta 2 agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma.

    PubMed Central

    Wallin, A; Melander, B; Rosenhall, L; Sandström, T; Wåhlander, L

    1990-01-01

    Sixteen patients with stable chronic asthma participated in a double blind crossover study comparing the new inhaled long acting beta 2 agonist formoterol with salbutamol. Inhaled (n = 15) and oral steroid (n = 1) treatment were maintained at the same daily dose throughout the study. For four weeks the patients received either formoterol 24 micrograms twice daily or salbutamol 400 micrograms twice daily, plus additional puffs (with the same drug) when needed. Asthma symptoms, additional puffs of beta 2 agonist, peak expiratory flow (PEF), and side effects were recorded daily. During treatment with formoterol the patients used fewer additional puffs of beta 2 agonist, had better symptom scores, less disturbed sleep, more days without additional aerosol, and higher PEF both morning and evening than during salbutamol treatment. Thus formoterol 24 micrograms twice daily gave long lasting bronchodilatation and asthma symptoms were well controlled with regular twice daily administration. PMID:1972599

  10. Paliperidone Palmitate Long-Acting Injectable Given Intramuscularly in the Deltoid Versus the Gluteal Muscle: Are They Therapeutically Equivalent?

    PubMed

    Yin, John; Collier, Abby C; Barr, Alasdair M; Honer, William G; Procyshyn, Ric M

    2015-08-01

    Paliperidone palmitate long-acting injectable is a second-generation antipsychotic indicated for the treatment of schizophrenia. According to the product monograph, the monthly maintenance dose of paliperidone palmitate can be given in either the deltoid or gluteal muscle. Unfortunately, many clinicians may misinterpret these directions to mean that these intramuscular sites are interchangeable, and thus therapeutically equivalent. Currently, the literature on this topic is sparse, but the published pharmacokinetic studies and Food and Drug Administration submission data on paliperidone palmitate show discrepancies in the elimination half-life, peak plasma concentration, and absorption rate that are dependent on the site of injection. The degree of shifts in pharmacokinetic parameters suggests that paliperidone palmitate injections via the deltoid and gluteal muscle are not bioequivalent and therefore are not therapeutically equivalent. Thus, using the same maintenance dosing regimen at both sites or switching between sites of injection may result in unforeseen consequences in patient outcomes. PMID:26061612

  11. Preparation of hollow hydroxyapatite microspheres.

    PubMed

    Wang, Qing; Huang, Wenhai; Wang, Deping; Darvell, Brian W; Day, Delbert E; Rahaman, Mohamed N

    2006-07-01

    The preparation of hollow hydroxyapatite (HA) microspheres as potential drug-delivery vehicles was investigated. A lithium-calcium-borate (10Li(2)O-15CaO-75B(2)O(3)) (mol%) glass, made by fusing the components at 1100 degrees C for 1 h, was ground to a powder and passed through a flame at approximately 1400 degrees Celsius to spheroidize the particles. The resulting glass microspheres (106-125 microm in diameter) were reacted in 0.25 M K(2)HPO(4) solution for 5 days at 37 degrees Celsius and pH 10-12, resulting in the formation of porous, hollow microspheres of a calcium phosphate (Ca-P) material with external diameters similar to those of the original glass particles. Heat treatment at 600 degrees Celsius for 4 h partially converted the Ca-P material to HA, as confirmed by X-ray diffraction, and also increased the strength of the hollow microspheres. PMID:16770549

  12. The safety of long-acting ?2-agonists in the treatment of stable chronic obstructive pulmonary disease

    PubMed Central

    Decramer, Marc L; Hanania, Nicola A; Lötvall, Jan O; Yawn, Barbara P

    2013-01-01

    Background Inhaled long-acting bronchodilators are the mainstay of pharmacotherapy for chronic obstructive pulmonary disease (COPD). Both the twice-daily long-acting ?2-adrenoceptor agonists (LABAs) salmeterol and formoterol and the once-daily LABA indacaterol are indicated for use in COPD. This review examines current evidence for the safety of LABAs in COPD, focusing on their effect on exacerbations and deaths. Methods We searched PubMed for placebo-controlled studies evaluating long-term (?24 weeks) use of formoterol, salmeterol, or indacaterol in patients with stable COPD, published between January 1990 and September 2012. We summarized data relating to exacerbations and adverse events, particularly events related to COPD. Results From 20 studies examined (8774 LABA-treated patients), there was no evidence of an association between LABA treatment and increased exacerbations, COPD-related adverse events, or deaths. Where analyzed as an efficacy outcome, LABA treatment was generally associated with significant or numerical reductions in COPD exacerbations compared with placebo. Incidences of COPD-related adverse events were similar for active and placebo treatments. The incidence of adverse events typically associated with the ?2-agonist drug class such as skeletal muscle tremors and palpitations was low (often <1% of patients), and there were no reports of increased incidence of cardiac arrhythmias. The systemic effects of ?2-adrenoceptor stimulation, such as high glucose and potassium levels, were considered minor. Conclusion Current evidence from clinical studies of the safety and tolerability profile of LABAs supports their long-term use in COPD. PMID:23378756

  13. End-of-dose pain in chronic pain: does it vary with the use of different long-acting opioids?

    PubMed

    Zimmermann, Michael; Richarz, Ute

    2014-11-01

    A large percentage of patients with chronic pain on around-the-clock (ATC) opioids may experience increased pain occurring at the end of a scheduled dose, also known as end-of-dose pain. Despite the significant prevalence and impact of end-of-dose pain in patients using extended-release (ER) opioids, there are no detailed analyses examining how the frequency of end-of-dose pain is linked to the formulations of long-acting opioids. Consequently, we performed a systematic review to evaluate how many published studies on patients with chronic cancer or noncancer pain identified end-of-dose pain. As only a few studies mentioned end-of-dose pain explicitly, we used breakthrough pain (BTP) as a surrogate parameter. We determined if any opioid formulation had a greater association with the frequency of BTP, the use of rescue medication for BTP, and the frequency of end-of-dose pain. Of the 39 studies entered in the final analysis, 14 studies across different formulations showed that ER opioids were effective in the prevention of BTP. The opioids most frequently studied were hydromorphone (26%), followed by morphine (23%), and transdermal buprenorphine (23%). Only 5% of the studies used immediate-release preparations. Overall, most studies showed that patients using ER preparations experienced fewer episodes of BTP compared with patients on placebo or an active comparator. This could reflect the favorable duration of action of these opioids compared with short-acting formulations. Future studies should examine the incidence of end-of-dose pain and use of rescue medicine in a longitudinal manner in patients with chronic pain taking short- vs. long-acting ATC opioids. PMID:24373184

  14. Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition

    Microsoft Academic Search

    Giovanni Vozzi; Christopher Flaim; Arti Ahluwalia; Sangeeta Bhatia

    2003-01-01

    Construction of biodegradable, three-dimensional scaffolds for tissue engineering has been previously described using a variety of molding and rapid prototyping techniques. In this study, we report and compare two methods for fabricating poly(dl-lactide-co-glycolide) (PLGA) scaffolds with feature sizes of approximately 10–30?m. The first technique, the pressure assisted microsyringe, is based on the use of a microsyringe that utilizes a computer-controlled,

  15. Biodegradable thermosensitive micelles of PEG-PLGA-PEG triblock copolymers

    Microsoft Academic Search

    Byeongmoon Jeong; You Han Bae; Sung Wan Kim

    1999-01-01

    Micellization of poly(ethylene glycol-b-(DL-lactic acid-co-glycolic acid)-b-ethylene glycol), PEG-PLGA-PEG, triblock copolymers in water was studied by 13C-NMR (nuclear magnetic resonance), dye solubilization method, and light scattering. Critical micelle concentration was decreased by half by increasing temperature from 20 to 50°C. Enthalpy of micellization was calculated to be 10–20 KJ\\/mole. Apparent aggregation number, diameter of a micelle abruptly increased while second viral

  16. Controlled cellular orientation on PLGA microfibers with defined diameters

    Microsoft Academic Search

    C. M. Hwang; J. Y. Park; K. Lee; K. Sun; A. Khademhosseini; S. H. Lee

    2009-01-01

    s  In this study, we investigated the effects of the diameter of microfibers on the orientation (angle between cells’ major axis\\u000a and the substrate fiber long axis) of adhered cells. For this purpose, mouse fibroblast L929 cells were cultured on the surface\\u000a of PLGA fibers of defined diameters ranging from 10 to 242 ?m, and their adhesion and alignment was quantitatively analyzed.

  17. Microspheres and nanoparticles from ultrasound

    NASA Astrophysics Data System (ADS)

    Suh, Won Hyuk

    Improved preparations of various examples of monodispersed, porous, hollow, and core-shell metal and semiconductor nanoparticles or nanowires have been developed. Now titania microspheres and nanoparticles and silica microspheres can be synthesized using an inexpensive high frequency (1.7 MHz) ultrasonic generator (household humidifier; ultrasonic spray pyrolysis; USP). Morphology and pore size of titania microspheres were controlled by the silica to Ti(IV) ratio and silica particle size. Fine tuning the precursor ratio affords sub-50 nm titania nanoparticles as well. In terms of silica microspheres, morphology was controlled by the silica to organic monomer ratio. In liquids irradiated with high intensity ultrasound (20 kHz; HIUS), acoustic cavitation produces high energy chemistry through intense local heating inside the gas phase of collapsing bubbles in the liquid. HIUS and USP confine the chemical reactions to isolated sub-micron reaction zones, but sonochemistry does so in a heated gas phase within a liquid, while USP uses a hot liquid droplet carried by a gas flow. Thus, USP can be viewed as a method of phase-separated synthesis using submicron-sized droplets as isolated chemical reactors for nanomaterial synthesis. While USP has been used to create both titania and silica spheres separately, there are no prior reports of titania-silica composites. Such nanocomposites of metal oxides have been produced, and by further manipulation, various porous structures with fascinating morphologies were generated. Briefly, a precursor solution was nebulized using a commercially available household ultrasonic humidifier (1.7 MHz ultrasound generator), and the resulting mist was carried in a gas stream of air through a quartz glass tube in a hot furnace. After exiting the hot zone, these microspheres are porous or hollow and in certain cases magnetically responsive. In the case of titania microspheres, they are rapidly taken up into the cytoplasm of mammalian cells and nearly noncytoxic. Small molecules like Rhodamine and DHED (dehydroevodiamine HCl; Alzheimer's disease therapeutic) can be delivered along with them. Furthermore, synthesis of carbon nanoparticles and titanate nanotube species are possible utilizing these microspheres. Characterizations were done by SEM, (S)TEM, optical/confocal microscopy, XRD, XPS, EDS, SAED, zeta potential, and BET.

  18. Modeling scattered intensity from microspheres in evanescent field 

    E-print Network

    Shah, Suhani Kiran

    2009-05-15

    of the microsphere/surface separation. Additionally, larger microspheres have the ability to resonantly confine light and produce spectrally narrow Whispering Gallery Modes (WGMs). It is hypothesized that WGMs may be excited in microspheres with the DCPM system...

  19. Initial Development and Characterization of PLGA Nanospheres Containing Ropivacaine

    PubMed Central

    Moraes, Carolina Morales; de Matos, Angélica Prado; de Lima, Renata; Rosa, André Henrique; de Paula, Eneida

    2008-01-01

    Local anesthetics are able to induce pain relief by binding to the sodium channels of excitable membranes, blocking the influx of sodium ions and the propagation of the nervous impulse. Ropivacaine (RVC) is an amino amide, enantiomerically pure, local anesthetic largely used in surgical procedures, which present physico-chemical and therapeutic properties similar to those of bupivacaine but decreased toxicity and motor blockade. The present work focuses on the preparation and characterization of nanospheres containing RVC; 0.25% and 0.50% RVC were incorporated in poly(d,l-lactide-co-glycolide (PLGA) 50:50) nanospheres (PLGA-NS), prepared by the nanoprecipitation method. Characterization of the nanospheres was conducted through the measurement of pH, particle size, and zeta potential. The pH of the nanoparticle system with RVC was 6.58. The average diameters of the RVC-containing nanospheres was 162.7 ± 1.5 nm, and their zeta potentials were negative, with values of about ?10.81 ± 1.16 mV, which promoted good stabilization of the particles in solution. The cytotoxicity experiments show that RVC-loaded PLGA-NS generate a less toxic formulation as compared with plain RVC. Since this polymer drug-delivery system can effectively generate an even less toxic RVC formulation, this study is fundamental due to its characterization of a potentially novel pharmaceutical form for the treatment of pain with RVC. PMID:19669531

  20. Preparation and characterization of rapamycin-loaded PLGA coating stent.

    PubMed

    Pan, C J; Tang, J J; Weng, Y J; Wang, J; Huang, N

    2007-11-01

    In this study, using polylactic acid-co-glycolic acid (PLGA) with a molecular weight of 95,800 Da as drug carrier, three dose (low, moderate, high) rapamycin-eluting stents and the corresponding coating films were prepared. The pre- and post-expansion morphology of the rapamycin-eluting stent was examined by scanning electron microscopy (SEM), indicating that the coating was very smooth and uniform. The coating had the ability to withstand the compressive and tensile strains imparted without cracking from the stent during expansion process. There were many voids on stent coating surface after released for 18 days in release medium. The thermodynamics data of the stent coating film measured by differential scanning calorimetry (DSC) showed a lack of measurable solubility of rapamycin in the PLGA matrix. The release behavior of rapamycin from stent surface had a two phase release profile with a burst release period of about 2 days, followed by a sustained and slow release phase. The mass loss behavior of PLGA appeared linear throughout most of the degradation period, corresponding to an approximately constant mass loss rate. The platelet adhesion tests showed that the rapamycin-eluting films may have a good blood compatibility compared with control samples. Take into these results account, this novel rapamycin-eluting may be a good candidate to resolve in-stent restenosis. PMID:17607513

  1. NanoCipro Encapsulation in Monodisperse Large Porous PLGA Microparticles

    PubMed Central

    Arnold, Matthew M.; Gorman, Eric M.; Schieber, Loren J.; Munson, Eric J.; Berland, Cory

    2007-01-01

    Pulmonary drug delivery of controlled release formulations may provide an effective adjunct approach to orally delivered antibiotics for clearing persistent lung infections. Dry powder formulations for this indication should possess characteristics including; effective deposition to infected lung compartments, persistence at the infection site, and steady release of antibiotic. Large porous particles (?10-15 ?m) have demonstrated effective lung deposition and enhanced lung residence as a result of their large diameter and reduced clearance by macrophages in comparison to small microparticles (?1-5 ?m). In this report, Precision Particle Fabrication technology was used to create monodisperse large porous particles of poly(D,L-lactic-co-glycolic acid) (PLGA) utilizing oils as extractable porogens. After extraction, the resulting large porous PLGA particles exhibited a low density and a web-like or hollow interior depending on porogen concentration and type, respectively. Ciprofloxacin nanoparticles (nanoCipro) created by homogenization in dichloromethane, possessed a polymorph with a decreased melting temperature. Encapsulating nanoCipro in large porous PLGA particles resulted in a steady release of ciprofloxacin that was extended for larger particle diameters and for the solid particle morphology in comparison to large porous particles. The encapsulation efficiency of nanoCipro was quite low and factors impacting the entrapment of nanoparticles during particle formation were elucidated. A dry powder formulation with the potential to control particle deposition and sustain release to the lung was developed and insight to improve nanoparticle encapsulation is discussed. PMID:17604870

  2. Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition.

    PubMed

    Vozzi, Giovanni; Flaim, Christopher; Ahluwalia, Arti; Bhatia, Sangeeta

    2003-06-01

    Construction of biodegradable, three-dimensional scaffolds for tissue engineering has been previously described using a variety of molding and rapid prototyping techniques. In this study, we report and compare two methods for fabricating poly(DL-lactide-co-glycolide) (PLGA) scaffolds with feature sizes of approximately 10-30 microm. The first technique, the pressure assisted microsyringe, is based on the use of a microsyringe that utilizes a computer-controlled, three-axis micropositioner, which allows the control of motor speeds and position. A PLGA solution is deposited from the needle of a syringe by the application of a constant pressure of 20-300 mm Hg, resulting in a controlled polymer deposition. The second technique is based on 'soft lithographic' approaches that utilize a poly(dimethylsiloxane) mold. Three variations of the second technique are presented: polymer casting, microfluidic perfusion, and spin coating. Polymer concentration, solvent composition, and mold dimensions influenced the resulting scaffolds as evaluated by light and electron microscopy. As a proof-of-concept for scaffold utility in tissue engineering applications, multilayer structures were formed by thermal lamination, and scaffolds were rendered porous by particulate leaching. These simple methods for forming PLGA scaffolds with microscale features may serve as useful tools to explore structure/function relationships in tissue engineering. PMID:12695080

  3. Synthesis of hydrophilic intra-articular microspheres conjugated to ibuprofen and evaluation of anti-inflammatory activity on articular explants.

    PubMed

    Bédouet, Laurent; Moine, Laurence; Pascale, Florentina; Nguyen, Van-Nga; Labarre, Denis; Laurent, Alexandre

    2014-01-01

    The main limitation of current microspheres for intra-articular delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is a significant initial burst release, which prevents a long-term drug delivery. In order to get a sustained delivery of NSAIDs without burst, hydrogel degradable microspheres were prepared by co-polymerization of a methacrylic derivative of ibuprofen with oligo(ethylene-glycol) methacrylate and poly(PLGA-PEG) dimethacrylate as degradable crosslinker. Microspheres (40-100 ?m) gave a low yield of ibuprofen release in saline buffer (?2% after 3 months). Mass spectrometry analysis confirmed that intact ibuprofen was regenerated indicating that ester hydrolysis occurred at the carboxylic acid position of ibuprofen. Dialysis of release medium followed by alkaline hydrolysis show that in saline buffer ester hydrolysis occurred at other positions in the polymer matrix leading to the release of water-soluble polymers (>6-8000 Da) conjugated with ibuprofen showing that degradation and drug release are simultaneous. By considering the free and conjugated ibuprofen, 13% of the drug is released in 3 months. In vitro, ibuprofen-loaded MS inhibited the synthesis of prostaglandin E2 in articular cartilage and capsule explants challenged with lipopolysaccharides. Covalent attachment of ibuprofen to PEG-hydrogel MS suppresses the burst release and allows a slow drug delivery for months and the cyclooxygenase-inhibition property of regenerated ibuprofen is preserved. PMID:24231051

  4. Controlled delivery of heat shock protein using an injectable microsphere/hydrogel combination system for the treatment of myocardial infarction.

    PubMed

    Lee, Jangwook; Tan, Cheau Yih; Lee, Sang-Kyung; Kim, Yong-Hee; Lee, Kuen Yong

    2009-08-01

    Myocardial infarction causes a high rate of morbidity and mortality worldwide, and heat shock proteins as molecular chaperones have been attractive targets for protecting cardiomyoblasts under environmental stimuli. In this study, in order to enhance the penetration of heat shock protein 27 (HSP27) across cell membranes, we fused HSP27 with transcriptional activator (TAT) derived from human immunodeficiency virus (HIV) as a protein transduction domain (PTD). We loaded the fusion protein (TAT-HSP27) into microsphere/hydrogel combination delivery systems to control the release behavior for prolonged time periods. We found that the release behavior of TAT-HSP27 was able to be controlled by varying the ratio of PLGA microspheres and alginate hydrogels. Indeed, the released fusion protein maintained its bioactivity and could recover the proliferation of cardiomyoblasts cultured under hypoxic conditions. This approach to controlling the release behavior of TAT-HSP27 using microsphere/hydrogel combination delivery systems may be useful for treating myocardial infarction in a minimally invasive manner. PMID:19374930

  5. PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery

    PubMed Central

    Zou, Peng; Stern, Stephan T.; Sun, Duxin

    2014-01-01

    Purpose Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly( lactic-coglycolicacid) (PLGA). Methods BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor). Results FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 minutes. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 hours. Conclusions The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs. PMID:24065591

  6. Understanding greater cardiomyocyte functions on aligned compared to random carbon nanofibers in PLGA

    PubMed Central

    Asiri, Abdullah M; Marwani, Hadi M; Khan, Sher Bahadar; Webster, Thomas J

    2015-01-01

    Previous studies have demonstrated greater cardiomyocyte density on carbon nanofibers (CNFs) aligned (compared to randomly oriented) in poly(lactic-co-glycolic acid) (PLGA) composites. Although such studies demonstrated a closer mimicking of anisotropic electrical and mechanical properties for such aligned (compared to randomly oriented) CNFs in PLGA composites, the objective of the present in vitro study was to elucidate a deeper mechanistic understanding of how cardiomyocyte densities recognize such materials to respond more favorably. Results showed lower wettability (greater hydrophobicity) of CNFs embedded in PLGA compared to pure PLGA, thus providing evidence of selectively lower wettability in aligned CNF regions. Furthermore, the results correlated these changes in hydrophobicity with increased adsorption of fibronectin, laminin, and vitronectin (all proteins known to increase cardiomyocyte adhesion and functions) on CNFs in PLGA compared to pure PLGA, thus providing evidence of selective initial protein adsorption cues on such CNF regions to promote cardiomyocyte adhesion and growth. Lastly, results of the present in vitro study further confirmed increased cardiomyocyte functions by demonstrating greater expression of important cardiomyocyte biomarkers (such as Troponin-T, Connexin-43, and ?-sarcomeric actin) when CNFs were aligned compared to randomly oriented in PLGA. In summary, this study provided evidence that cardiomyocyte functions are improved on CNFs aligned in PLGA compared to randomly oriented in PLGA since CNFs are more hydrophobic than PLGA and attract the adsorption of key proteins (fibronectin, laminin, and vironectin) that are known to promote cardiomyocyte adhesion and expression of important cardiomyocyte functions. Thus, future studies should use this knowledge to further design improved CNF:PLGA composites for numerous cardiovascular applications. PMID:25565806

  7. Combined modality doxorubicin-based chemotherapy and chitosan-mediated p53 gene therapy using double-walled microspheres for treatment of human hepatocellular carcinoma

    PubMed Central

    Xu, Qingxing; Leong, Jiayu; Chua, Qi Yi; Chi, Yu Tse; Chow, Pierce Kah-Hoe; Pack, Daniel W.; Wang, Chi-Hwa

    2013-01-01

    The therapeutic efficiency of combined chemotherapy and gene therapy on human hepatocellular carcinoma HepG2 cells was investigated using double-walled microspheres that consisted of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(L-lactic acid) (PLLA) shell layer and fabricated via the precision particle fabrication (PPF) technique. Here, double-walled microspheres were used to deliver doxorubicin (Dox) and/or chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53), loaded in the core and shell phases, respectively. Preliminary studies on chi-DNA nanoparticles were performed to optimize gene transfer to HepG2 cells. The transfection efficiency of chi-DNA nanoparticles was optimal at an N/P ratio of 7. In comparison to the 25-kDa branched polyethylenimine (PEI), chitosan showed no inherent toxicity towards the cells. Next, the therapeutic efficiencies of Dox and/or chi-p53 in microsphere formulations were compared to free drug(s) and evaluated in terms of growth inhibition, and cellular expression of tumor suppressor p53 and apoptotic caspase 3 proteins. Overall, the combined Dox and chi-p53 treatment exhibited enhanced cytotoxicity as compared to either Dox or chi-p53 treatments alone. Moreover, the antiproliferative effect was more substantial when cells were treated with microspheres than those treated with free drugs. High p53 expression was maintained during a five-day period, and was largely due to the controlled and sustained release of the microspheres. Moreover, increased activation of caspase 3 was observed, and was likely to have been facilitated by high levels of p53 expression. Overall, double-walled microspheres present a promising dual anticancer delivery system for combined chemotherapy and gene therapy. PMID:23578555

  8. Microsphere coated substrate containing reactive aldehyde groups

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Richard C. K. (Inventor)

    1984-01-01

    A synthetic organic resin is coated with a continuous layer of contiguous, tangential, individual microspheres having a uniform diameter preferably between 100 Angstroms and 2000 Angstroms. The microspheres are an addition polymerized polymer of an unsaturated aldehyde containing 4 to 20 carbon atoms and are covalently bonded to the substrate by means of high energy radiation grafting. The microspheres contain reactive aldehyde groups and can form conjugates with proteins such as enzymes or other aldehyde reactive materials.

  9. Evaluation of the permeability of hair growing ingredient encapsulated PLGA nanospheres to hair follicles and their hair growing effects

    Microsoft Academic Search

    Hiroyuki Tsujimoto; Kaori Hara; Yusuke Tsukada; C. C. Huang; Yoshiaki Kawashima; Minoru Arakaki; Hajime Okayasu; Haruko Mimura; Nobuhiko Miwa

    2007-01-01

    This paper describes the process of encapsulating hair growing ingredients in the PLGA nanospheres by emulsion solvent diffusion method and investigates the feasibility of using the PLGA nanospheres as the DDS (Drug delivery System) carriers for delivering various hair growing ingredients to hair follicles. In-vitro and in-vivo tests were conducted to verify the performances of encapsulated PLGA nanospheres with three

  10. Long-acting beta-agonists reduce mortality of patients with severe and very severe chronic obstructive pulmonary disease: a propensity score matching study

    PubMed Central

    2013-01-01

    Background Long-acting beta-agonists were one of the first-choice bronchodilator agents for stable chronic obstructive pulmonary disease. But the impact of long-acting beta-agonists on mortality was not well investigated. Methods National Emphysema Treatment Trial provided the data. Severe and very severe stable chronic obstructive pulmonary disease patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in United States during 1988–2002. We used the 6–10 year follow-up data of patients randomized to non-surgery treatment. Hazard ratios for death by long-acting beta-agonists were estimated by three models using Cox proportional hazard analysis and propensity score matching were measured. Results The pre-matching cohort was comprised of 591 patients (50.6% were administered long-acting beta-agonists. Age: 66.6?±?5.3 year old. Female: 35.4%. Forced expiratory volume in one second (%predicted): 26.7?±?7.1%. Mortality during follow-up: 70.2%). Hazard ratio using a multivariate Cox model in the pre-matching cohort was 0.77 (P?=?0.010). Propensity score matching was conducted (C-statics: 0.62. No parameter differed between cohorts). The propensity-matched cohort was comprised of 492 patients (50.0% were administered long-acting beta-agonists. Age: 66.8?±?5.1 year old. Female: 34.8%. Forced expiratory volume in one second (%predicted) 26.5?±?6.8%. Mortality during follow-up: 69.1%). Hazard ratio using a univariate Cox model in the propensity-matched cohort was 0.77 (P?=?0.017). Hazard ratio using a multivariate Cox model in the propensity-matched cohort was 0.76 (P?=?0.011). Conclusions Long-acting beta-agonists reduce mortality of severe and very severe chronic obstructive pulmonary disease patients. PMID:23725215

  11. Strategies for microsphere-mediated cellular delivery 

    E-print Network

    Cardenas-Maestre, Juan Manuel

    2011-11-23

    Amino-functionalised polystyrene microspheres are promising candidates as delivery systems due to their unique features, tunable surface functionalities, and controllable release of the cargo. Herein several strategies ...

  12. Brain-Targeted Nasal Clonazepam Microspheres

    PubMed Central

    Shaji, J.; Poddar, A.; Iyer, S.

    2009-01-01

    Gelatin-chitosan mucoadhesive microspheres of clonazepam were prepared using the emulsion cross linking method. Mirospheres were evaluated using the in vitro and ex vivo drug release patterns. In vivo CNS drug distribution studies were carried out in rats by administering the clonazepam microspheres intra-nasally and clonazepam solution intravenously. From the drug levels in plasma and CSF, drug targeting index and drug targeting efficiency were calculated. Results obtained indicated that intranasally administered clonazepam microspheres resulted in higher brain levels with a drug targeting index of 2.12. Gelatin-chitosan cross linked mucoadhesive microspheres have the potential to be developed as a brain-targeted drug delivery system for clonazepam.

  13. Preclinical Development and In Vivo Efficacy of Ceftiofur-PLGA Microparticles.

    PubMed

    Vilos, Cristian; Velasquez, Luis A; Rodas, Paula I; Zepeda, Katherine; Bong, Soung-Jae; Herrera, Natalia; Cantin, Mario; Simon, Felipe; Constandil, Luis

    2015-01-01

    Drug delivery systems based on polymeric microparticles represent an interesting field of development for the treatment of several infectious diseases for humans and animals. In this work, we developed PLGA microparticles loaded with ceftiofur (PLGA-cef), a third- generation cephalosporin that is used exclusively used in animals. PLGA-cef was prepared by the double emulsion w/o/w method, and exhibited a diameter in the range of 1.5-2.2 ?m, and a negative ? potential in the range of -35 to -55 mV. The loading yield of PLGA-cef was ~7% and encapsulation efficiency was approximately 40%. The pharmacokinetic study demonstrated a sustained release profile of ceftiofur for 20 days. PLGA-cef administrated in a single dose was more effective than ceftiofur non-encapsulated in rats challenged with S. Typhimurium. The in vivo toxicological evaluation showed that PLGA-cef did not affect the blood biochemical, hematological and hemostasis parameters. Overall, the PLGA-cef showed slow in vivo release profile, high antibacterial efficacy, and low toxicity. The results obtained supports the safe application of PLGA-cef as sustained release platform in the veterinary industry. PMID:25915043

  14. Concepts and practices used to develop functional PLGA-based nanoparticulate systems

    PubMed Central

    Sah, Hongkee; Thoma, Laura A; Desu, Hari R; Sah, Edel; Wood, George C

    2013-01-01

    The functionality of bare polylactide-co-glycolide (PLGA) nanoparticles is limited to drug depot or drug solubilization in their hard cores. They have inherent weaknesses as a drug-delivery system. For instance, when administered intravenously, the nanoparticles undergo rapid clearance from systemic circulation before reaching the site of action. Furthermore, plain PLGA nanoparticles cannot distinguish between different cell types. Recent research shows that surface functionalization of nanoparticles and development of new nanoparticulate dosage forms help overcome these delivery challenges and improve in vivo performance. Immense research efforts have propelled the development of diverse functional PLGA-based nanoparticulate delivery systems. Representative examples include PEGylated micelles/nanoparticles (PEG, polyethylene glycol), polyplexes, polymersomes, core-shell–type lipid-PLGA hybrids, cell-PLGA hybrids, receptor-specific ligand-PLGA conjugates, and theranostics. Each PLGA-based nanoparticulate dosage form has specific features that distinguish it from other nanoparticulate systems. This review focuses on fundamental concepts and practices that are used in the development of various functional nanoparticulate dosage forms. We describe how the attributes of these functional nanoparticulate forms might contribute to achievement of desired therapeutic effects that are not attainable using conventional therapies. Functional PLGA-based nanoparticulate systems are expected to deliver chemotherapeutic, diagnostic, and imaging agents in a highly selective and effective manner. PMID:23459088

  15. Magnetic poly(lactide-co-glycolide) (PLGA) and cellulose particles for MRI-based cell tracking

    PubMed Central

    Nkansah, Michael K.; Thakral, Durga; Shapiro, Erik M.

    2010-01-01

    Biodegradable, superparamagnetic micro- and nanoparticles of poly(lactide-co-glycolide) (PLGA) and cellulose were designed, fabricated and characterized for magnetic cell labeling. Monodisperse nanocrystals of magnetite were incorporated into micro- and nanoparticles of PLGA and cellulose with high efficiency using an oil-in-water single emulsion technique. Superparamagnetic cores had high magnetization (72.1 emu/g). The resulting polymeric particles had smooth surface morphology and high magnetite content (43.3 wt% for PLGA and 69.6 wt% for cellulose). While PLGA and cellulose nanoparticles displayed highest r2* values per millimole of iron (399 s-1mM-1 for cellulose and 505 s-1mM-1 for PLGA), micron-sized PLGA particles had a much higher r2* per particle than either. After incubation for a month in citrate buffer (pH 5.5), magnetic PLGA particles lost close to 50% of their initial r2* molar relaxivity, while magnetic cellulose particles remained intact, preserving over 85% of their initial r2* molar relaxivity. Lastly, mesenchymal stem cells and human breast adenocarcinoma cells were magnetically labeled using these particles with no detectable cytotoxicity. These particles are ideally suited for non-invasive cell tracking in vivo via MRI and due to their vastly different degradation properties, offer unique potential for dedicated use for either short (PLGA-based particles) or long term (cellulose-based particles) experiments. PMID:21404328

  16. PLGA microparticle-embedded thermosensitive hydrogels for sustained release of hydrophobic drugs.

    PubMed

    Joung, Yoon Ki; Choi, Jong Hoon; Park, Kyung Min; Park, Ki Dong

    2007-12-01

    The release profile of a hydrophobic drug, indomethacin (IMC), from poly(lactic-co-glycolic acid) (PLGA) particles embedded in a chitosan-Pluronic (CP) hydrogel matrix was investigated. The PLGA particles were prepared by an oil-in-water (O/W) emulsion method, and were mixed with IMC. The average diameter of the prepared PLGA particles was determined as 41.6 +/- 35.8 microm by dynamic light scattering (DLS). The loading amount and loading efficiency were 0.023 +/- 0.01 mg/mg and 14.8 +/- 0.67%, respectively. The CP solution (16 wt%) was transformed into a thermosensitive hydrogel under increasing temperature above a lower critical solution temperature (LCST). In this process, the IMC-loaded PLGA particles were mixed and uniformly dispersed in the solution phase, following thermosensitive gelation. SEM observation revealed that the added IMC-loaded PLGA particles were uniformly dispersed in a three-dimensional matrix of the CP hydrogel, observed by SEM. The PLGA particles embedded in the CP hydrogel released about 30% of loaded IMC for 25 days, showing a significantly sustained release as compared with the PLGA particles only (approximately 50% for the same period). Therefore, it is assumed that this sustained release of IMC results from the retardation effect of the CP hydrogel matrix on the degradation and release of the PLGA particles. PMID:18458485

  17. Concepts and practices used to develop functional PLGA-based nanoparticulate systems.

    PubMed

    Sah, Hongkee; Thoma, Laura A; Desu, Hari R; Sah, Edel; Wood, George C

    2013-01-01

    The functionality of bare polylactide-co-glycolide (PLGA) nanoparticles is limited to drug depot or drug solubilization in their hard cores. They have inherent weaknesses as a drug-delivery system. For instance, when administered intravenously, the nanoparticles undergo rapid clearance from systemic circulation before reaching the site of action. Furthermore, plain PLGA nanoparticles cannot distinguish between different cell types. Recent research shows that surface functionalization of nanoparticles and development of new nanoparticulate dosage forms help overcome these delivery challenges and improve in vivo performance. Immense research efforts have propelled the development of diverse functional PLGA-based nanoparticulate delivery systems. Representative examples include PEGylated micelles/nanoparticles (PEG, polyethylene glycol), polyplexes, polymersomes, core-shell-type lipid-PLGA hybrids, cell-PLGA hybrids, receptor-specific ligand-PLGA conjugates, and theranostics. Each PLGA-based nanoparticulate dosage form has specific features that distinguish it from other nanoparticulate systems. This review focuses on fundamental concepts and practices that are used in the development of various functional nanoparticulate dosage forms. We describe how the attributes of these functional nanoparticulate forms might contribute to achievement of desired therapeutic effects that are not attainable using conventional therapies. Functional PLGA-based nanoparticulate systems are expected to deliver chemotherapeutic, diagnostic, and imaging agents in a highly selective and effective manner. PMID:23459088

  18. Rationale-Based Engineering of a Potent Long-Acting FGF21 Analog for the Treatment of Type 2 Diabetes

    PubMed Central

    Hecht, Randy; Li, Yue-Sheng; Sun, Jeonghoon; Belouski, Ed; Hall, Michael; Hager, Todd; Yie, Junming; Wang, Wei; Winters, Dwight; Smith, Stephen; Spahr, Chris; Tam, Lei-Ting; Shen, Zhongnan; Stanislaus, Shanaka; Chinookoswong, Narumol; Lau, Yvonne; Sickmier, Allen; Michaels, Mark Leo; Boone, Thomas; Véniant, Murielle M.; Xu, Jing

    2012-01-01

    Fibroblast growth factor 21 (FGF21) is a promising drug candidate for the treatment of type 2 diabetes. However, the use of wild type native FGF21 is challenging due to several limitations. Among these are its short half-life, its susceptibility to in vivo proteolytic degradation and its propensity to in vitro aggregation. We here describe a rationale-based protein engineering approach to generate a potent long-acting FGF21 analog with improved resistance to proteolysis and aggregation. A recombinant Fc-FGF21 fusion protein was constructed by fusing the Fc domain of human IgG1 to the N-terminus of human mature FGF21 via a linker peptide. The Fc positioned at the N-terminus was determined to be superior to the C-terminus as the N-terminal Fc fusion retained the ?Klotho binding affinity and the in vitro and in vivo potency similar to native FGF21. Two specific point mutations were introduced into FGF21. The leucine to arginine substitution at position 98 (L98R) suppressed FGF21 aggregation at high concentrations and elevated temperatures. The proline to glycine replacement at position 171 (P171G) eliminated a site-specific proteolytic cleavage of FGF21 identified in mice and cynomolgus monkeys. The derived Fc-FGF21(RG) molecule demonstrated a significantly improved circulating half-life while maintaining the in vitro activity similar to that of wild type protein. The half-life of Fc-FGF21(RG) was 11 h in mice and 30 h in monkeys as compared to 1-2 h for native FGF21 or Fc-FGF21 wild type. A single administration of Fc-FGF21(RG) in diabetic mice resulted in a sustained reduction in blood glucose levels and body weight gains up to 5-7 days, whereas the efficacy of FGF21 or Fc-FGF21 lasted only for 1 day. In summary, we engineered a potent and efficacious long-acting FGF21 analog with a favorable pharmaceutical property for potential clinical development. PMID:23209571

  19. Compression molding of aerogel microspheres

    DOEpatents

    Pekala, R.W.; Hrubesh, L.W.

    1998-03-24

    An aerogel composite material produced by compression molding of aerogel microspheres (powders) mixed together with a small percentage of polymer binder to form monolithic shapes in a cost-effective manner is disclosed. The aerogel composites are formed by mixing aerogel microspheres with a polymer binder, placing the mixture in a mold and heating under pressure, which results in a composite with a density of 50--800 kg/m{sup 3} (0.05--0.80 g/cc). The thermal conductivity of the thus formed aerogel composite is below that of air, but higher than the thermal conductivity of monolithic aerogels. The resulting aerogel composites are attractive for applications such as thermal insulation since fabrication thereof does not require large and expensive processing equipment. In addition to thermal insulation, the aerogel composites may be utilized for filtration, ICF target, double layer capacitors, and capacitive deionization. 4 figs.

  20. Compression molding of aerogel microspheres

    DOEpatents

    Pekala, Richard W. (Pleasant Hill, CA); Hrubesh, Lawrence W. (Pleasanton, CA)

    1998-03-24

    An aerogel composite material produced by compression molding of aerogel microspheres (powders) mixed together with a small percentage of polymer binder to form monolithic shapes in a cost-effective manner. The aerogel composites are formed by mixing aerogel microspheres with a polymer binder, placing the mixture in a mold and heating under pressure, which results in a composite with a density of 50-800 kg/m.sup.3 (0.05-0.80 g/cc). The thermal conductivity of the thus formed aerogel composite is below that of air, but higher than the thermal conductivity of monolithic aerogels. The resulting aerogel composites are attractive for applications such as thermal insulation since fabrication thereof does not require large and expensive processing equipment. In addition to thermal insulation, the aerogel composites may be utilized for filtration, ICF target, double layer capacitors, and capacitive deionization.

  1. Nonaggregating Microspheres Containing Aldehyde Groups

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan

    1989-01-01

    Cobalt gamma irradiation of hydrophilic monomers in presence of acrolein yields exceptionally-stable, nonaggregating microspheres. Mixtures of 2-hydroxyethyl methacrylate (HEMA) and acrolein form homogeneous solutions in distilled water containing 0.4 percent polyethylene oxide (PEO). After deaeration with nitrogen, mixtures irradiated at room temperature with gamma rays from cobalt source; total exposure time 4 hours, at rate of 0.2 milliroentgen per hour. Reaction product centrifuged three times for purification and kept in distilled water.

  2. Pharmacokinetics and disposition of CS-8958, a long-acting prodrug of the novel neuraminidase inhibitor laninamivir in rats.

    PubMed

    Koyama, K; Takahashi, M; Nakai, N; Takakusa, H; Murai, T; Hoshi, M; Yamamura, N; Kobayashi, N; Okazaki, O

    2010-03-01

    CS-8958, a prodrug of laninamivir (R-125489), is currently under development as an inhaled anti-influenza drug. In this study, the pharmacokinetics and disposition of CS-8958 were characterized in rats. After intratracheal administration of 14C-CS-8958, radioactivity was retained over long periods in the target tissues (trachea and lung) as its active metabolite R-125489 - 19.12% of the dose was retained in the lung at 24 h. After intratracheal administration of CS-8958, plasma R-125489 concentration was slowly eliminated, and its half-life (14.1 h) was considerably longer than that after intravenous administration of R-125489. The radioactivity of intratracheally administered 14C-CS-8958 was mainly excreted into the urine (67.5% of dose), and this excretion lasted over long periods. R-125489 accounted for most of the urinary radioactivity recovered after 24 h. These results demonstrated that CS-8958 administered intratracheally to rats was converted/hydrolysed to R-125489 in the target tissues, and that the R-125489 was slowly excreted into the urine via an absorption rate-limiting process. Such distinctive pharmacokinetics attributed to the slow release of R-125489 suggests the potential for a long-acting anti-influenza drug. PMID:20146556

  3. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.

    PubMed

    Yamashita, Makoto; Tomozawa, Takanori; Kakuta, Masayo; Tokumitsu, Akane; Nasu, Hatsumi; Kubo, Shuku

    2009-01-01

    Two neuraminidase (NA) inhibitors, zanamivir (Relenza) and oseltamivir phosphate (Tamiflu), have been licensed for the treatment of and prophylaxis against influenza. In this paper, the new potent NA inhibitor R-125489 is reported for the first time. R-125489 inhibited the NA activities of various type A and B influenza viruses, including subtypes N1 to N9 and oseltamivir-resistant viruses. The survival effect of R-125489 was shown to be similar to that of zanamivir when administered intranasally in a mouse influenza virus A/Puerto Rico/8/34 infection model. Moreover, we found that the esterified form of R-125489 showed improved efficacy compared to R-125489 and zanamivir, depending on the acyl chain length, and that 3-(O)-octanoyl R-125489 (CS-8958) was the best compound in terms of its life-prolonging effect (P < 0.0001, compared to zanamivir) in the same infection model. A prolonged survival effect was observed after a single administration of CS-8958, even if it was given 7 days before infection. It is suggested that intranasally administered CS-8958 works as a long-acting NA inhibitor and shows in vivo efficacy as a result of a single intranasal administration. PMID:18955520

  4. Modeling the budget impact of long-acting injectable paliperidone palmitate in the treatment of schizophrenia in Japan

    PubMed Central

    Mahlich, Jörg; Nishi, Masamichi; Saito, Yoshimichi

    2015-01-01

    Background The cost of schizophrenia in Japan is high and new long-acting injectable (LAI) antipsychotics might be able to reduce costs by causing a reduction of hospital stays. We aim to estimate budget effects of the introduction of a new 1-month LAI, paliperidone palmitate, in Japan. Methods A budget impact analysis was conducted from a payer perspective. The model took direct costs of illness into account (ie, costs for inpatient and outpatient services, as well as drug costs). The robustness of the model was checked using a sensitivity analysis. Results According to our calculations, direct total costs of schizophrenia reach 710,500 million yen a year (US$6 billion). These costs decrease to 691,000 million yen (US$5.9 billion) 3 years after the introduction of paliperidone palmitate. Conclusion From a payer point of view, the introduction of a new treatment for schizophrenia in Japan helps to save resources and is not associated with a higher financial burden.

  5. Hospitalisation Utilisation and Costs in Schizophrenia Patients in Finland before and after Initiation of Risperidone Long-Acting Injection

    PubMed Central

    Asseburg, Christian; Willis, Michael; Löthgren, Mickael; Seppälä, Niko; Hakala, Mika; Persson, Ulf

    2012-01-01

    Objectives. Quantify changes in hospital resource use in Finland following initiation of risperidone long-acting injection (RLAI). Materials and Methods. A retrospective multi-center chart review (naturalistic setting) was used to compare annual hospital bed-days and hospital episodes for 177 schizophrenia patients (mean age 47.1 years, 52% female, 72% hospitalized) before and after initiation of RLAI (between January 2004 and June 2005) using the within-patient “mirror-image” study design. The base case analytical approach allocated hospital episodes overlapping the start date entirely to the preinitiation period. In order to investigate the impact of inpatient care ongoing at baseline, the change in bed-days was also estimated using an alternative analytical approached related to economic modelling. Results. In the conventional analysis, the mean annual hospitalisation costs declined by €11,900 and the number of bed-days was reduced by 40%, corresponding to 0.19 fewer hospital episodes per year. The reductions in bed-days per patient-year were similar for patients switched to RLAI as inpatients and as outpatients. In the modelling-based analysis, an 8% reduction in bed-days per year was observed. Conclusion. Despite uncertainty in the choice of analytic approach for allocating inpatient episodes that overlapping this initiation, consistent reductions in resource use are associated with the initiation of RLAI in Finland. PMID:22966445

  6. Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.

    PubMed

    Wei, Xiao-Lan; Han, Ying-Rui; Quan, Li-Hui; Liu, Chun-Yu; Liao, Yong-Hong

    2013-05-13

    The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 ?m), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect. PMID:23542494

  7. Counseling and provision of long-acting reversible contraception in the US: National survey of nurse practitioners

    PubMed Central

    Harper, Cynthia C.; Stratton, Laura; Raine, Tina R.; Thompson, Kirsten; Henderson, Jillian T.; Blum, Maya; Postlethwaite, Debbie; Speidel, J Joseph

    2013-01-01

    Objective Nurse practitioners (NPs) provide frontline care in women’s health, including contraception, an essential preventive service. Their importance for contraceptive care will grow, with healthcare reforms focused on affordable primary care. This study assessed practice and training needs to prepare NPs to offer high-efficacy contraceptives - IUDs and implants. Method A US nationally representative sample of nurse practitioners in primary care and women’s health was surveyed in 2009 (response rate 69%, n=586) to assess clinician knowledge and practices, guided by the CDC US Medical Eligibility Criteria for Contraceptive Use. Results Two-thirds of women’s health NPs (66%) were trained in IUD insertions, compared to 12% of primary care NPs. Contraceptive counseling that routinely included IUDs was low overall (43%). Nurse practitioners used overly restrictive patient eligibility criteria, inconsistent with CDC guidelines. Insertion training (aOR=2.4, 95%CI: 1.10 5.33) and knowledge of patient eligibility (aOR=2.9, 95%CI: 1.91 4.32) were associated with IUD provision. Contraceptive implant provision was low: 42% of NPs in women’s health and 10% in primary care . Half of NPs desired training in these methods. Conclusion Nurse practitioners have an increasingly important position in addressing high unintended pregnancy in the U.S., but require specific training in long-acting reversible contraceptives. PMID:24128950

  8. Within-drug benefit-risk evaluation of olanzapine long-acting injection at one and two years of treatment.

    PubMed

    Detke, Holland C; Lauriello, John; Landry, John; McDonnell, David P

    2014-12-01

    We sought to evaluate the within-drug benefit-risk of olanzapine long-acting injection (LAI) using both quantitative and qualitative methods. Subjects included 1192 adult patients with schizophrenia or schizoaffective disorder who participated in clinical trials with the opportunity for at least two years of continuous treatment with olanzapine LAI (45-405?mg every two to four weeks). Using the Benefit Risk Action Team (BRAT) framework, we evaluated frequency versus duration of benefits and risks commonly observed with atypical antipsychotics. We then used the Transparent Uniform Risk/Benefit Overview (TURBO) method, which weighs the drug's two most medically serious and/or frequent adverse events versus its primary benefit (effectiveness) and an ancillary benefit. The most frequent events among all patients were remaining free of relapse (91.4% for an average of 306?days at one year, 88.4% for 546?days at two years) and symptomatic remission (81.7% for an average of 239?days at one year, 84.1% for 438?days at two years). One- and two-year incidence of ?7% weight gain was 33.3% and 41.7%. Incidences for sexual dysfunction, hyperprolactinemia, and post-injection delirium/sedation syndrome (PDSS) were <2%. TURBO ratings unanimously selected PDSS and weight gain as key risks and resulted in an average score in the acceptable benefit-risk balance range. PMID:24996038

  9. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    PubMed Central

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery.

  10. Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging.

    PubMed

    Mieszawska, Aneta J; Gianella, Anita; Cormode, David P; Zhao, Yiming; Meijerink, Andries; Langer, Robert; Farokhzad, Omid C; Fayad, Zahi A; Mulder, Willem J M

    2012-06-14

    Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable bioimaging features. We accomplished this through esterification reactions of PLGA to generate polymers modified with nanocrystals. The PLGA nanoparticles formed from modified PLGA polymers that were functionalized with either gold nanocrystals or quantum dots exhibited favorable features for computed tomography and optical imaging, respectively. PMID:22555311

  11. Inhaled PLGA Particles of Prostaglandin E1 Ameliorate Symptoms and Progression of Pulmonary Hypertension at a Reduced Dosing Frequency

    PubMed Central

    Gupta, Vivek; Gupta, Nilesh; Shaik, Imam H.; Mehvar, Reza; Nozik-Grayck, Eva; McMurtry, Ivan F.; Oka, Masahiko; Komatsu, Masanobu; Ahsan, Fakhrul

    2014-01-01

    This study sought to investigate the efficacy of a noninvasive and long acting polymeric particle based formulation of prostaglandin E1 (PGE1), a potent pulmonary vasodilator, in alleviating the signs of pulmonary hypertension (PH) and reversing the biochemical changes that occur in the diseased lungs. PH rats, developed by a single subcutaneous injection of monocrotaline (MCT), were treated with two types of polymeric particles of PGE1, porous and nonporous, and intratracheal or intravenous plain PGE1. For chronic studies, rats received either intratracheal porous poly (lactic-co-glycolic acid) (PLGA) particles, once- or thrice-a-day, or plain PGE1 thrice-a-day for 10 days administered intratracheally or intravenously. The influence of formulations on disease progression was studied by measuring the mean pulmonary arterial pressure (MPAP), evaluating right ventricular hypertrophy and assessing various molecular and cellular makers including the degree of muscularization, platelet aggregation, matrix metalloproteinase-2 (MMP-2) and proliferating cell nuclear antigen (PCNA). Both plain PGE1 and large porous particles of PGE1 reduced MPAP and right ventricular hypertrophy (RVH) in rats that received the treatments for 10 days. Polymeric porous particles of PGE1 produced the same effects at a reduced dosing frequency compared to plain PGE1 and caused minimal off-target effects on systemic hemodynamics. Microscopic and immunohistochemical studies revealed that porous particles of PGE1 also reduced the degree of muscularization, von Willebrand factor (vWF) and PCNA expression in the lungs of PH rats. Overall, our study suggests that PGE1 loaded inhalable particulate formulations improve PH symptoms and arrest the progression of disease at a reduced dosing frequency compared to plain PGE1. PMID:23485062

  12. Evaluation of drug release from PLGA nanospheres containing bethametasone

    NASA Astrophysics Data System (ADS)

    Khosroshahi, Mohammad E.; Enayati, Marjan; Shafiei, Sara; Tavakoli, Javad

    2007-07-01

    In this research poly (d,l-lactide-coglycolide acid) (PLGA) as polymeric nanospheres, poly(vinyl alcohol) (PVA) with 87-89% hydrolysis degree as surfactant and distilled water as suspending medium were used. The encapsulated drug was Bethametasone. The nanospheres were prepared by an emulsion-solvent evaporation method. The nanospheres characterized by photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM). The amount of drug release was determined by HPLC. In emulsion-solvent evaporation technique, time of ultrasound exposure, surfactant content in the formulation and evaporation rate of organic solvents were considered as formulation variables.

  13. Efficacy and blood sera analysis of a long-acting formulation of moxidectin against Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)on treated cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The therapeutic and persistent efficacy of a single subcutaneous injection of a long-acting (LA) formulation of moxidectin at a concentration of 1 mg per kg of body weight were determined against Rhipicephalus (Boophilus) microplus (Canestrini), along with the concentration-time blood sera profile i...

  14. The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

    PubMed Central

    Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

    1999-01-01

    Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

  15. Impact of CYP2D6 genotype on steady-state serum concentrations of risperidone and 9-hydroxyrisperidone in patients using long-acting injectable risperidone.

    PubMed

    Hendset, Magnhild; Molden, Espen; Refsum, Helge; Hermann, Monica

    2009-12-01

    An increased risk of adverse effects and discontinuation of risperidone therapy is observed in patients with impaired cytochrome P450 2D6 (CYP2D6) function on oral risperidone therapy. The present study is the first to investigate the impact of CYP2D6 genotype on serum concentrations of risperidone and 9-hydroxyrisperidone in patients using injectable long-acting risperidone. Two hundred three patients were divided into groups according to administered risperidone formulation (long-acting injection; n = 90) and CYP2D6 genotype. Dose-adjusted serum concentrations were compared using the CYP2D6*1/*1 subgroup as reference. The total serum concentration of risperidone plus 9-hydroxyrisperidone was 80% (P < 0.03) and 32% (P < 0.03) higher, whereas the risperidone-9-hydroxyrisperidone ratios were 6.3-fold (P < 0.01) and 12.5-fold (P < 0.01) higher in the CYP2D6def/def (def means defective allele, ie, CYP2D6*3, *4, *5, or *6) subgroup for long-acting and oral risperidone, respectively. In conclusion, CYP2D6 genotype significantly affects the pharmacokinetics of both oral and long-acting risperidone formulations. PMID:19910717

  16. POROUS WALL, HOLLOW GLASS MICROSPHERES

    SciTech Connect

    Sexton, W.

    2012-06-30

    Hollow Glass Microspheres (HGM) is not a new technology. All one has to do is go to the internet and Google{trademark} HGM. Anyone can buy HGM and they have a wide variety of uses. HGM are usually between 1 to 100 microns in diameter, although their size can range from 100 nanometers to 5 millimeters in diameter. HGM are used as lightweight filler in composite materials such as syntactic foam and lightweight concrete. In 1968 a patent was issued to W. Beck of the 3M{trademark} Company for 'Glass Bubbles Prepared by Reheating Solid Glass Particles'. In 1983 P. Howell was issued a patent for 'Glass Bubbles of Increased Collapse Strength' and in 1988 H. Marshall was issued a patent for 'Glass Microbubbles'. Now Google{trademark}, Porous Wall, Hollow Glass Microspheres (PW-HGMs), the key words here are Porous Wall. Almost every article has its beginning with the research done at the Savannah River National Laboratory (SRNL). The Savannah River Site (SRS) where SRNL is located has a long and successful history of working with hydrogen and its isotopes for national security, energy, waste management and environmental remediation applications. This includes more than 30 years of experience developing, processing, and implementing special ceramics, including glasses for a variety of Department of Energy (DOE) missions. In the case of glasses, SRS and SRNL have been involved in both the science and engineering of vitreous or glass based systems. As a part of this glass experience and expertise, SRNL has developed a number of niches in the glass arena, one of which is the development of porous glass systems for a variety of applications. These porous glass systems include sol gel glasses, which include both xerogels and aerogels, as well as phase separated glass compositions, that can be subsequently treated to produce another unique type of porosity within the glass forms. The porous glasses can increase the surface area compared to 'normal glasses of a 1 to 2 order of magnitude, which can result in unique properties in areas such as hydrogen storage, gas transport, gas separations and purifications, sensors, global warming applications, new drug delivery systems and so on. One of the most interesting porous glass products that SRNL has developed and patented is Porous Wall, Hollow Glass Microspheres (PW-HGMs) that are being studied for many different applications. The European Patent Office (EPO) just recently notified SRS that the continuation-in-part patent application for the PW-HGMs has been accepted. The original patent, which was granted by the EPO on June 2, 2010, was validated in France, Germany and the United Kingdom. The microspheres produced are generally in the range of 2 to 100 microns, with a 1 to 2 micron wall. What makes the SRNL microspheres unique from all others is that the team in Figure 1 has found a way to induce and control porosity through the thin walls on a scale of 100 to 3000 {angstrom}. This is what makes the SRNL HW-HGMs one-of-a-kind, and is responsible for many of their unique properties and potential for various applications, including those in tritium storage, gas separations, H-storage for vehicles, and even a variety of new medical applications in the areas of drug delivery and MRI contrast agents. SRNL Hollow Glass Microspheres, and subsequent, Porous Wall, Hollow Glass Microspheres are fabricated using a flame former apparatus. Figure 2 is a schematic of the apparatus.

  17. Assembly of ordered magnetic microsphere arrays

    NASA Astrophysics Data System (ADS)

    Xu, Wanling; Ketterson, John

    2008-08-01

    We have developed a straightforward technique to assemble ordered arrays of magnetic microspheres on patterned thin Permalloy (Py) films deposited on the surface of a silicon wafer. Droplets containing micrometer-sized carboxyl paramagnetic microspheres are placed on a horizontally oriented wafer. The field produced by a permanent magnet placed under the wafer is rendered inhomogeneous by the patterned Py features and the resulting field gradients attract and hold the paramagnetic microspheres to these features. While the magnetic microspheres are being attracted to and secured on the pattered Permalloy features, a horizontal flow is created by a pipette, which also removes loose (unsecured) microspheres. By applying this technique to a cocktail of individually functionalized microspheres, a sensor could be realized, which will screen, in parallel, for a large number of targets per unit area. The ability to resolve individual microspheres is close to 100%. A desirable feature is that the substrate is reusable; removing the magnet allows an existing batch of microspheres, which may have lost sensitivity due to environmental exposure, to be flushed from the substrate and replaced with a new batch. The technique complements existing approaches in the field of microarrays widely used in immunoassay, DNA fragment detection, pathogen detection, and other applications in functional genomics and diagnostics.

  18. Thermal response of chalcogenide microsphere resonators

    SciTech Connect

    Ahmad, H; Aryanfar, I; Lim, K S; Chong, W Y; Harun, S W

    2012-05-31

    A chalcogenide microsphere resonator (CMR) used for temperature sensing is proposed and demonstrated. The CMR is fabricated using a simple technique of heating chalcogenide glass and allowing the molten glass to form a microsphere on the waist of a tapered silica fibre. The thermal responses of the CMR is investigated and compared to that of a single-mode-fibre (SMF) based microsphere resonator. It is observed that the CMR sensitivity to ambient temperature changes is 8 times higher than that of the SMF-based microsphere resonator. Heating the chalcogenide microsphere with a laser beam periodically turned on and off shows periodic shifts in the transmission spectrum of the resonator. By injecting an intensity-modulated cw signal through the resonator a thermal relaxation time of 55 ms is estimated.

  19. Integrated Cryogenic Experiment (ICE) microsphere investigation

    SciTech Connect

    Spradley, I.; Read, D.

    1989-09-01

    The main objective is to determine the performance of microsphere insulation in a 0-g environment and compare its performance to reference insulations such as multilayer insulation. The Lockheed Helium Extended-Life Dewar (HELD) is used to provide superfluid-helium cold sink for the experiment. The use of HELD allows the low-g dynamic properties of Passive Orbital Disconnect Struts (PODS) to be characterized and provides a flight demonstration of the PODS system. The thermal performance of microspheres in 1 and 0 g was predicted, a flight experiment was designed to determine microsphere thermal performance, and the interface was also designed between the experimental package and the shuttle through HELD and the Hitchhiker-M carrier. A single test cell was designed and fabricated. The cell was filled with uncoated glass microspheres and tested with a liquid-nitrogen cold sink. The data were found to agree with predictions of microsphere performance in 1 g.

  20. Polymer microspheres carrying fluorescent DNA probes

    NASA Astrophysics Data System (ADS)

    Chen, Xiaoyu; Dai, Zhao; Zhang, Jimei; Xu, Shichao; Wu, Chunrong; Zheng, Guo

    2010-07-01

    A polymer microspheres carried DNA probe, which was based on resonance energy transfer, was presented in this paper when CdTe quantum dots(QDs) were as energy donors, Au nanoparticles were as energy accepters and poly(4- vinylpyrindine-co-ethylene glycol dimethacrylate) microspheres were as carriers. Polymer microspheres with functional group on surfaces were prepared by distillation-precipitation polymerization when ethylene glycol dimethacrylate was as crosslinker in acetonitrile. CdTe QDs were prepared when 3-mercaptopropionic acid(MPA) was as the stabilizer in aqueous solution. Because of the hydrogen-bonding between the carboxyl groups of MPA on QDs and the pyrindine groups on the microspheres, the QDs were self-assembled onto the surfaces of microspheres. Then, the other parts of DNA probe were finished according to the classic method. The DNA detection results indicated that this novel fluorescent DNA probe system could recognize the existence of complementary target DNA or not.

  1. Hydrogels composed of cyclodextrin inclusion complexes with PLGA-PEG-PLGA triblock copolymers as drug delivery systems.

    PubMed

    Khodaverdi, Elham; Mirzazadeh Tekie, Farnaz Sadat; Hadizadeh, Farzin; Esmaeel, Haydar; Mohajeri, Seyed Ahmad; Sajadi Tabassi, Sayyed A; Zohuri, Gholamhossein

    2014-02-01

    Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEGPLGA and ?-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined. PMID:24234803

  2. Physicochemical characterization of camptothecin membrane binding properties and polymeric microsphere formulations

    NASA Astrophysics Data System (ADS)

    Selvi, Bilge

    In an effort to design novel formulation strategies to optimize the antitumor activity of camptothecin (CPT), the physicochemical and membrane binding properties of the drug, were investigated by various techniques in acidic and physiological pH. The intrinsic solubility of the CPT-lactone free base was determined to be 3.44 muM and 5.11 muM at 22°C and 37°C, respectively. The equilibrium solubility of the drug was found to increase with increasing temperature and decreasing pH. The enhanced solubility of the drug at very low pH is attributed to the protonation of the nitrogen atom in the ring B and the increased solvency of the highly acidic media. The logarithmic value of the intrinsic partition coefficient P of the free base CPT-lactone form was estimated to be 1.65, characteristic of a molecule suitable for oral absorption. The association constants Kf of the drug for bilayers composed of the zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and the negatively-charged 1,2-dioleoyl-sn-glycero-3-phospho- rac-(1-glycerol) (DOPG) were studied at acidic pH by fluorescence anisotropy and determined to be 35.4 +/- 4.5 M-1 and 93.1 +/- 11.0 M-1 for DOPC and DOPG, respectively, indicating a tendency of CPT to preferentially bind to negatively charged membranes. The energy of activation for the hydrolysis of CPT at physiological pH was found to be 114.3 +/- 33.4 kj/mole. The calculated t½ of the reaction at pH 7.2 at temperatures 25°C and 10°C was found to be 0.07 days and 5.12 days, respectively, whereas the time required for 1% of CPT-lactone to hydrolyze to CPT-carboxylate (t99%) was determined to be 1.8 hours, thus offering enough time to safely handle CPT-lactone at low temperatures. The preformulation results indicated that at highly acidic media CPT is positively charged and exists at its stable lactone form of increased solubility and has a capacity to bind to negatively charged membranes. Taking advantage of the increased stability of CPT in acidic media CPT-loaded microspheres were prepared in a 10 N HCl-methylene chloride mixture using the H-series of poly(D,L-lactide-co-glycolide) (H-PLGA). The system was then compared with a standard microsphere formation method and the results were evaluated with respect to particle morphology and drug release profile. Rough surface of the particles were obtained from the preparation method where a 10 N HCl solution was used. The release pattern of CPT was biphasic comprising a first burst effect followed by zero order release for all the formulations. However, the release of the drug was slightly faster from the microspheres formed with the modified method compared to the standard. Until now clinical application of CPT has been highly restricted by the insolubility and instability of the drug in its active lactone form, resulting in less antitumor potency and poor bioavailability. The pH-dependent release of the CPT-loaded microspheres was also compared and faster initial release (burst phase) was found at neutral pH, whereas at low pH the release was zero order for all the formulations. The results indicate that the stabilization and sustained release of CPT from H-PLGA microspheres might reduce local toxicity while simultaneously prolonging efficiency, suggesting new perspectives in CPT chemotherapy.

  3. PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors

    PubMed Central

    Figueiredo, Marxa; Esenaliev, Rinat

    2012-01-01

    This paper focuses on novel approaches in the field of nanotechnology-based carriers utilizing ultrasound stimuli as a means to spatially target gene delivery in vivo, using nanoparticles made with either poly(lactic-co-glycolic acid) (PLGA) or other polymers. We specifically discuss the potential for gene delivery by particles that are echogenic (amenable to destruction by ultrasound) composed either of polymers (PLGA, polystyrene) or other contrast agent materials (Optison, SonoVue microbubbles). The use of ultrasound is an efficient tool to further enhance gene delivery by PLGA or other echogenic particles in vivo. Echogenic PLGA nanoparticles are an attractive strategy for ultrasound-mediated gene delivery since this polymer is currently approved by the US Food and Drug Administration for drug delivery and diagnostics in cancer, cardiovascular disease, and also other applications such as vaccines and tissue engineering. This paper will review recent successes and the potential of applying PLGA nanoparticles for gene delivery, which include (a) echogenic PLGA used with ultrasound to enhance local gene delivery in tumors or muscle and (b) PLGA nanoparticles currently under development, which could benefit in the future from ultrasound-enhanced tumor targeted gene delivery. PMID:22506124

  4. Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection.

    PubMed

    Sugaya, Norio; Ohashi, Yasuo

    2010-06-01

    We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness. PMID:20368393

  5. Design Rationale and Development Approach for Pegfilgrastim as a Long-Acting Granulocyte Colony-Stimulating Factor.

    PubMed

    Arvedson, Tara; O'Kelly, James; Yang, Bing-Bing

    2015-06-01

    Filgrastim, a recombinant methionyl human granulocyte colony-stimulating factor (G-CSF) (r-metHuG-CSF), is efficacious in stimulating neutrophil production and maturation to prevent febrile neutropenia (FN) in response to chemotherapy. Because of its relatively short circulating half-life, daily filgrastim injections are required to stimulate neutrophil recovery. In an effort to develop a long-acting form of filgrastim that was as safe and efficacious as filgrastim but had a longer in vivo residence time, a number of strategies were considered. Ultimately, fusion of filgrastim to polyethylene glycol (PEG) was selected. Following extensive analysis of conjugation chemistries as well as in vitro and in vivo characterization of a panel of PEGylated proteins, a construct containing a 20 kDa PEG moiety covalently conjugated to the N-terminus of filgrastim was chosen for advancement as pegfilgrastim. Pegfilgrastim is primarily cleared by neutrophils and neutrophil precursors (rather than the kidneys), meaning that clearance from the circulation is self-regulating and pegfilgrastim is eliminated only after neutrophils start to recover. Importantly, addition of PEG did not alter the mechanism of action and safety profile compared to filgrastim. Clinical evaluation revealed that a single 6 mg dose effectively reduces the duration of neutropenia and risk of FN in patients receiving chemotherapy. This work demonstrates the benefit of using PEGylation to generate pegfilgrastim, which allows for once-per-chemotherapy cycle administration while maintaining similar safety and efficacy profiles as those for multiple daily administration of filgrastim. Approaches that may provide advances for therapeutic agonists of G-CSF receptor are also discussed. PMID:25998211

  6. A Long-Acting Integrase Inhibitor Protects Female Macaques from Repeated High-Dose Intravaginal SHIV Challenge

    PubMed Central

    Andrews, Chasity D.; Yueh, Yun Lan; Spreen, William R.; St. Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D.; Markowitz, Martin

    2015-01-01

    GSK1265744 long-acting (GSK744 LA) is a strand-transfer inhibitor of HIV/SIV integrase and was shown to be an effective pre-exposure prophylaxis agent in a low-dose intrarectal SHIV rhesus macaque challenge model. Here, we examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with 50 mg/kg of GSK744 LA monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were 5-fold lower on average in cervical tissues than rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected 6 of 8 female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for pre-exposure prophylaxis. PMID:25589630

  7. Provision of long-acting reversible contraception in HIV-prevalent countries: results from nationally representative surveys in southern Africa

    PubMed Central

    Morse, J; Chipato, T; Blanchard, K; Nhemachena, T; Ramjee, G; McCulloch, C; Blum, M; Saleeby, E; Harper, CC

    2013-01-01

    Objective To analyse the current provision of long-acting reversible contraception (LARC) and clinician training needs in HIV-prevalent settings. Design Nationally representative survey of clinicians. Setting HIV-prevalent settings in South Africa and Zimbabwe. Population Clinicians in South Africa and Zimbabwe. Methods Nationally representative surveys of clinicians were conducted in South Africa and Zimbabwe (n = 1444) to assess current clinical practice in the provision of LARC in HIV-prevalent settings. Multivariable logistic regression was used to analyse contraceptive provision and clinician training needs. Main outcome measure Multivariable logistic regression of contraceptive provision and clinician training needs. Results Provision of the most effective reversible contraceptives is limited: only 14% of clinicians provide copper intrauterine devices (IUDs), 4% levonorgestrel-releasing IUDs and 16% contraceptive implants. Clinicians’ perceptions of patient eligibility for IUD use were overly restrictive, especially related to HIV risks. Less than 5% reported that IUDs were appropriate for women at high risk of HIV or for HIV-positive women, contrary to evidence-based guidelines. Only 15% viewed implants as appropriate for women at risk of HIV. Most clinicians (82%), however, felt that IUDs were underused by patients, and over half desired additional training on LARC methods. Logistic regression analysis showed that LARC provision was largely restricted to physicians, hospital settings and urban areas. Results also showed that clinicians in rural areas and clinics, including nurses, were especially interested in training. Conclusions Clinician competency in LARC provision is important in southern Africa, given the low use of methods and high rates of unintended pregnancy among HIV-positive and at-risk women. Despite low provision, clinician interest is high, suggesting the need for increased evidence-based training in LARC to reduce unintended pregnancy and associated morbidities. PMID:23721413

  8. Clinical pharmacokinetics of AZD3199, an inhaled ultra-long-acting ?2-adrenoreceptor agonist (uLABA)

    PubMed Central

    Bjermer, Leif; Kuna, Piotr; Jorup, Carin; Bengtsson, Thomas; Rosenborg, Johan

    2015-01-01

    Objective The clinical pharmacokinetics of AZD3199, an ultra-long-acting ?2-agonist, were investigated in healthy volunteers and patients with asthma or chronic obstructive pulmonary disease (COPD). Materials and methods Five studies are presented: one single ascending dose study in healthy Caucasian males; two multiple ascending dose studies in healthy males, one in Caucasians and one in Japanese; a Phase IIA asthma study; and a Phase IIB COPD study. Subjects received AZD3199 via a Spira nebulizer (Turbuhaler; equivalent delivered doses 5–3200 ?g) or Turbuhaler (single delivered doses of 120–1920 ?g or repeated delivered once-daily doses 240–1,680 ?g). AZD3199 pharmacokinetics were assessed using total plasma concentration and urinary excretion, and tolerability using adverse events, clinical laboratory tests, and physical examinations. Results AZD3199 appeared rapidly in the systemic circulation following single and multiple dosing in healthy volunteers and patients (maximum plasma concentration within 30 minutes), with dose-proportional time-independent pharmacokinetics. Plasma exposure to unmetabolized drug was similar in healthy volunteers and patients with asthma, but relatively lower in patients with COPD. Estimated terminal half-life was up to 142 hours in healthy Caucasian males. AZD3199 was well tolerated and showed no or at most mild systemic effects. Conclusion AZD3199 plasma exposure in healthy volunteers and patients suggested linear pharmacokinetics and a long half-life. Systemic availability was similar in healthy subjects and patients with asthma, but was lower in patients with COPD. These clinical trials suggest that AZD3199 is well-tolerated in healthy male volunteers and patients, with no safety concerns identified to preclude further evaluation. PMID:25709399

  9. Short-acting cocaine and long-acting GBR-12909 both elicit rapid dopamine uptake inhibition following intravenous delivery

    PubMed Central

    España, Rodrigo A.; Roberts, David C.S.; Jones, Sara R.

    2008-01-01

    The rewarding effects of cocaine have been reported to occur within seconds of administration. Extensive evidence suggests that these actions involve the ability of cocaine to inhibit the dopamine (DA) transporter. We recently showed that 1.5 mg/kg intravenous (i.v.) cocaine inhibits DA uptake within 5 sec. Despite this evidence there remains a lack of consensus regarding how quickly i.v. cocaine and other DA uptake inhibitors elicit DA uptake inhibition. The current studies sought to better characterize the onset of cocaine-induced DA uptake inhibition and to compare these effects to those obtained with the high-affinity, long-acting DA transporter inhibitor, 1-(2-bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl)piperazine (GBR-12909). Using in vivo fast scan cyclic voltammetry, we showed that i.v. cocaine (0.75, 1.5, and 3.0 mg/kg) significantly inhibited DA uptake in the nucleus accumbens of anesthetized rats within 5 sec. DA uptake inhibition peaked at 30 sec and returned to baseline levels in approximately one hour. The effects of cocaine were dose-dependent, with the 3.0 mg/kg dose producing greater uptake inhibition at the early time points and exhibiting a longer latency to return to baseline. Further, the blood-brain barrier impermiant cocaine-methiodide had no effect on DA uptake or peak height, indicating that the generalized peripheral effects of cocaine do not contribute to the CNS alterations measured here. Finally, we show that GBR-12909 (0.75, 1.5, and 3.0 mg/kg) also significantly inhibited DA uptake within 5 sec post-injection, although the peak effect and return to baseline were markedly delayed compared to cocaine, particularly at the highest dose. Combined, these observations indicate that the central effects of dopamine uptake inhibitors occur extremely rapidly following i.v. drug delivery. PMID:18597947

  10. Concurrent Oral Antipsychotic Drug Use Among Schizophrenia Patients Initiated on Long-Acting Injectable Antipsychotics Post-Hospital Discharge.

    PubMed

    Doshi, Jalpa A; Pettit, Amy R; Stoddard, Jeffrey J; Zummo, Jacqueline; Marcus, Steven C

    2015-08-01

    Pharmacological treatment is central to effective management of schizophrenia. Prescribing clinicians have an increasing array of options from which to choose, and oral antipsychotic polypharmacy is common in routine clinical practice. Practice guidelines recommend long-acting injectable (LAI) formulations, typically viewed as monotherapeutic alternatives, for patients with established nonadherence. Yet there are limited data on the prevalence and nature of concurrent oral antipsychotic prescriptions in patients receiving LAIs. Our observational, claims-based study examined the frequency and duration of concurrent oral prescriptions in 340 Medicaid patients receiving LAI therapy. Specifically, we examined patients with a recent history of nonadherence and hospitalization for schizophrenia and included both first-generation antipsychotic depot medications (fluphenazine decanoate, haloperidol decanoate) and more recently available second-generation injectables (LAI risperidone, paliperidone palmitate). Of all patients initiated on LAIs, 75.9% had a concurrent oral antipsychotic prescription in the 6 months post-hospital discharge. Patients receiving concurrent prescriptions were frequently prescribed an oral formulation of their LAI agent, but many first-generation LAI users received a concurrent second-generation oral medication. The lowest rate of concurrent prescribing (58.8%) was found with paliperidone palmitate, whereas the highest rate was with LAI risperidone (88.9%). Overlap in oral and LAI prescriptions typically occurred for a substantial period of time (ie, >30 days) and for a notable percentage of the days covered by LAIs (often 50% or more). Our findings highlight the need to further examine such prescribing patterns, to probe the reasons for them, and to clarify the optimal roles of different antipsychotic treatments in clinical practice. PMID:26075492

  11. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein

    PubMed Central

    McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

    2014-01-01

    Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. PMID:24811361

  12. Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

    PubMed

    McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

    2014-07-01

    Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. PMID:24811361

  13. Spectroscopy techniques for analyzing the hydrolysis of PLGA and PLLA.

    PubMed

    Tan, Hwee Yun; Widjaja, Effendi; Boey, Freddy; Loo, Say Chye Joachim

    2009-10-01

    The in vitro hydrolytic degradation of irradiated biodegradable polymers was studied. Poly(L-lactide), poly(lactide-co-glycolic acid) (PLGA)(80:20), and PLGA(50:50) polymers were first electron beam irradiated at 5 Mrad before hydrolytic degradation. Hydrolysis of these films was characterized through their physical properties--mass loss, average molecular weight, and thermal properties. Changes to the chemical structures of these polyesters were also analyzed using Fourier-transformed infrared (FTIR) and Raman spectroscopy, and the spectra results were correlated to their physical properties. The results showed that an increase in hydroxyl (OH) group, observed from the FTIR spectroscopy, indicates that the polymer is degrading through hydrolysis--first-stage degradation. Subsequently, a decrease in C==O group, observed from Raman spectroscopy, indicates that the polymer is experiencing mass loss--second-stage degradation. Therefore, a good correlation exists in determining the extent of polymer degradation through the use of FTIR and Raman spectroscopy by observing changes to the OH and C==O groups from the spectra of these nondestructive techniques. PMID:19489010

  14. Adsorption of plasma proteins on uncoated PLGA nanoparticles.

    PubMed

    Sempf, Karim; Arrey, Tabiwang; Gelperina, Svetlana; Schorge, Tobias; Meyer, Björn; Karas, Michael; Kreuter, Jörg

    2013-09-01

    The biodistribution of nanoparticles is significantly influenced by their interaction with plasma proteins. In order to optimize and possibly monitor the delivery of drugs bound to nanoparticles across the blood-brain barrier (BBB), the protein adsorption pattern of uncoated poly(lactic-co-glycolic acid) (PLGA) nanoparticles after their incubation in human plasma was studied by mass spectrometry. After washing of the particles with water, the proteins were directly digested on the nanoparticle surface using trypsin and then analyzed by nLC MALDI-TOF/TOF. Up to now, the standard method for investigation into the plasma protein adsorption to the particles was 2D gel electrophoresis (2D-PAGE), in certain cases followed by mass spectrometry. The non-gel-based method proposed in the present study provides novel insights into the protein corona surrounding the nanoparticles. The proteins adsorbed on the PLGA nanoparticles after incubation that gave the best signal in terms of quality (high MASCOT score) in human plasma were apolipoprotein E, vitronectin, histidine-rich glycoprotein and kininogen-1. These proteins also are constituents of HDL. PMID:23395970

  15. Microencapsulation of a synbiotic into PLGA/alginate multiparticulate gels.

    PubMed

    Cook, Michael T; Tzortzis, George; Charalampopoulos, Dimitris; Khutoryanskiy, Vitaliy V

    2014-05-15

    Probiotic bacteria have gained popularity as a defence against disorders of the bowel. However, the acid sensitivity of these cells results in a loss of viability during gastric passage and, consequently, a loss of efficacy. Probiotic treatment can be supplemented using 'prebiotics', which are carbohydrates fermented specifically by probiotic cells in the body. This combination of probiotic and prebiotic is termed a 'synbiotic'. Within this article a multiparticulate dosage form has been developed, consisting of poly(d,l-lactic-co-glycolic acid) (PLGA) microcapsules containing prebiotic Bimuno™ incorporated into an alginate-chitosan matrix containing probiotic Bifidobacterium breve. The aim of this multiparticulate was that, in vivo, the probiotic would be protected against gastric acid and the release of the prebiotic would occur in the distal colon. After microscopic investigation, this synbiotic multiparticulate was shown to control the release of the prebiotic during in vitro gastrointestinal transit, with the release of galacto-oligosaccharides (GOS) initially occurred over 6h, but with a triphasic release pattern giving further release over 288 h. Encapsulation of B. breve in multiparticulates resulted in a survival of 8.0 ± 0.3 logCFU/mL cells in acid, an improvement over alginate-chitosan microencapsulation of 1.4 logCFU/mL. This was attributed to increased hydrophobicity by the incorporation of PLGA particles. PMID:24657143

  16. Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content.

    PubMed

    Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

    2012-01-01

    Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties' effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property-biodistribution relationships. PMID:22419876

  17. Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

    PubMed Central

    Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

    2012-01-01

    Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships. PMID:22419876

  18. Porous magnesium/PLGA composite scaffolds for enhanced bone regeneration following tooth extraction.

    PubMed

    Brown, Andrew; Zaky, Samer; Ray, Herbert; Sfeir, Charles

    2015-01-01

    Sixty percent of implant-supported dental prostheses require bone grafting to enhance bone quantity and quality prior to implant placement. We have developed a metallic magnesium particle/PLGA composite scaffold to overcome the limitations of currently used dental bone grafting materials. This is the first report of porous metallic magnesium/PLGA scaffolds synthesized using a solvent casting, salt leaching method. We found that incorporation of varying amounts of magnesium into the PLGA scaffolds increased the compressive strength and modulus, as well as provided a porous structure suitable for cell infiltration, as measured by mercury intrusion porosimetry. Additionally, combining basic-degrading magnesium with acidic-degrading PLGA led to an overall pH buffering effect and long-term release of magnesium over the course of a 10-week degradation assay, as measured with inductively coupled plasma-atomic emission spectroscopy. Using an indirect proliferation assay adapted from ISO 10993:5, it was found that extracts of medium from degrading magnesium/PLGA scaffolds increased bone marrow stromal cell proliferation in vitro, a phenomenon observed by other groups investigating magnesium's impact on cells. Finally, magnesium/PLGA scaffold biocompatibility was assessed in a canine socket preservation model. Micro-computed tomography and histological analysis showed the magnesium/PLGA scaffolds to be safer and more effective at preserving bone height than empty controls. Three-dimensional magnesium/PLGA composite scaffolds show promise for dental socket preservation and also, potentially, orthopedic bone regeneration. These scaffolds could decrease inflammation observed with clinically used PLGA devices, as well as enhance osteogenesis, as observed with previously studied magnesium devices. PMID:25234156

  19. Effects of ball-milling on PLGA polymer and its implication on lansoprazole-loaded nanoparticles

    PubMed Central

    Shabir, Anjumn; Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R.

    2011-01-01

    PLGA is a biodegradable polymer utilised widely in pharmaceutical research for the encapsulation of a wide range of drugs as nano particulate systems. This study investigates the impact of rotary ball milling on the physical properties of PLGA and its influence on nanoparticle formation prepared using the solvent displacement technique. By applying mechanical stress to the polymer and altering its physical appearance and molecular weight, the loading of lansoprazole within the nanoparticles was increased to 96%, with a reduction in particle size. The results indicate that rotary ball milling significantly reduces particle size, increases lansoprazole loading and improves the release profile for lansoprazole loaded PLGA nanoparticles PMID:24826005

  20. Development and characterization of hyaluronic acid-anchored PLGA nanoparticulate carriers of doxorubicin

    Microsoft Academic Search

    Pradeep Mishra; Anil K. Mishra; Pushpa Mishra; Govind Prasad Agrawal; Hari Singh

    A novel hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA) copo- lymer was synthesized and characterized by infrared and nuclear magnetic resonance spectroscopy. The nanoparticles of doxorubicin (DOX)-loaded HA-PEG-PLGA were prepared and compared with monomethoxy(polyethylene glycol) (MPEG)-PLGA nanoparticles. Nanoparticles were prepared using drug-to-polymer ratios of 1:1 to 1:3. Drug-to-polymer ratio of 1:1 is considered the optimum formulation on the basis of low particle size

  1. Solid evacuated microspheres of hydrogen

    DOEpatents

    Turnbull, Robert J. (Urbana, IL); Foster, Christopher A. (Champaign, IL); Hendricks, Charles D. (Livermore, CA)

    1982-01-01

    A method is provided for producing solid, evacuated microspheres comprised of hydrogen. The spheres are produced by forming a jet of liquid hydrogen and exciting mechanical waves on the jet of appropriate frequency so that the jet breaks up into drops with a bubble formed in each drop by cavitation. The drops are exposed to a pressure less than the vapor pressure of the liquid hydrogen so that the bubble which is formed within each drop expands. The drops which contain bubbles are exposed to an environment having a pressure just below the triple point of liquid hydrogen and they thereby freeze giving solid, evacuated spheres of hydrogen.

  2. Maintenance therapy with once-monthly administration of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder: a pilot study of an extended dosing interval

    PubMed Central

    Gharabawi, Georges M; Gearhart, Natalie C; Lasser, Robert A; Mahmoud, Ramy A; Zhu, Young; Mannaert, Erik; Naessens, Ineke; Bossie, Cynthia A; Kujawa, Mary; Simpson, George M

    2007-01-01

    Background Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly) administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder. Methods Clinically stable patients participated in a 1-year, open-label, single-arm, multicenter pilot study. During the 4-week lead-in phase, patients received long-acting risperidone 50 mg injections every 2 weeks, with 2 weeks of oral risperidone supplementation. Injections of long-acting risperidone 50 mg every 4 weeks followed for up to 48 weeks, without oral supplementation. The primary endpoint was relapse; other assessments included PANSS, CGI-S, adverse event reports, and determination of risperidone and 9-hydroxyrisperidone plasma concentrations. Results Twelve patients in the intent-to-treat population (n = 67) met relapse criteria (17.9%). Relapse risk at 1 year was estimated as 22.4%. Non-statistically significant improvements in symptoms (PANSS) and clinical status (CGI-S) at endpoint were observed. The most common adverse events included schizophrenia aggravated not otherwise specified (19.5%), anxiety (16.1%), insomnia (16.1%), and headache (11.5%). There were no unexpected safety and tolerability findings. Mean plasma concentrations for risperidone and 9-hydroxyrisperidone were generally stable during the study. Conclusion Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients. Although the results suggest that some symptomatically stable patients with schizophrenia or schizoaffective disorder might be safely managed with long-acting risperidone 50 mg once monthly, these findings alone do not identify which patients will have a sufficient therapeutic benefit nor do they quantify comparative effects of standard and altered dosing. Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results. Controlled studies would be required to support a recommendation for alternative dosing regimens. PMID:17261186

  3. Co-delivery of docetaxel and Poloxamer 235 by PLGA-TPGS nanoparticles for breast cancer treatment.

    PubMed

    Tang, Xiaolong; Liang, Yong; Feng, Xiaojun; Zhang, Rongbo; Jin, Xu; Sun, Leilei

    2015-04-01

    Multidrug resistance (MDR) is a major hurdle to the success of cancer chemotherapy. Poloxamers have been shown to reverse MDR by inhibiting the P-glycoprotein (P-gp) pump. The objective of this research is to test the feasibility of docetaxel-loaded PLGA-TPGS/Poloxamer 235 nanoparticles to overcome MDR in docetaxel-resistant human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by a modified nanoprecipitation method using PLGA-TPGS and PLGA-TPGS/Poloxamer 235 mixture, respectively. The PLGA-TPGS/Poloxamer 235 nanoparticles were of spherical shape and have a rough and porous surface. The docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles which had an average size of around 180nm with a narrow size distribution were stable, showing almost no change in particle size and surface charge during the 3-month storage period. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PLGA-TPGS/Poloxamer 235 porous nanoparticles (PPNPs) in docetaxel-resistant human breast cancer cell line, MCF-7/TXT, in comparison with PLGA-TPGS nanoparticles (PTNPs). The PLGA-TPGS/Poloxamer 235 porous nanoparticles produced significantly higher level of toxicity than both of PLGA-TPGS nanoparticle formulation and Taxotere® both in vitro and in vivo, indicating docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles have significant potential for the treatment of breast cancer. PMID:25686959

  4. Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity.

    PubMed

    Pawar, Dilip; Mangal, Sharad; Goswami, Roshan; Jaganathan, K S

    2013-11-01

    In this study, the efficacy of mucoadhesive polymers, i.e., chitosan and glycol chitosan as a mucoadhesive coating material in nasal vaccine delivery was investigated. The Hepatitis B surface Antigen (HBsAg) encapsulated PLGA, chitosan coated PLGA (C-PLGA), and Glycol chitosan coated PLGA (GC-PLGA) nanoparticles (NPs) were prepared. The formulations were characterized for particle size, shape, surface charge, and entrapment efficiency. The mucoadhesive ability of coated and non-coated NPs was determined using in vitro mucoadhesion and nasal clearance test. In addition, the systemic uptake and bio-distribution were also evaluated to understand the fate of NPs following nasal delivery. The immuno-adjuvant ability of various formulations was compared by measuring specific antibody titer in serum and secretory. The results indicated that PLGA NPs exhibit negative surface charge, whereas C-PLGA and GC-PLGA NPs exhibited positive surface charge. The GC-PLGA NPs demonstrated lower clearance and better local and systemic uptake compared to chitosan coated and uncoated PLGA NPs. In vivo immunogenicity studies indicated that GC-PLGA NPs could induce significantly higher systemic and mucosal immune response compared to PLGA and C-PLGA NPs. In conclusion, GC-PLGA NPs could be a promising carrier adjuvant for the nasal vaccine delivery for inducing a potent immune response at mucosal surface(s) and systemic circulation. PMID:23831265

  5. Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans.

    PubMed

    Brunner, G A; Sendhofer, G; Wutte, A; Ellmerer, M; Søgaard, B; Siebenhofer, A; Hirschberger, S; Krejs, G J; Pieber, T R

    2000-01-01

    NN304 is a long-acting insulin analogue that is acylated with a 14-C-fatty acid chain. Protraction of action of this novel insulin analogue is due not to slow absorption after subcutaneous administration but to reversible binding to albumin. We investigated the pharmacokinetic and pharmacodynamic properties of insulin analogue NN304 (0.3 and 0.6 U/kg) in comparison to NPH insulin (0.3 and 0.6 IU/kg) in 10 healthy volunteers performing a randomised, double-blind, cross-over, placebo-controlled glucose clamp study. During the observation period of 24 hours the areas under the insulin curve for NPH[0.3 IU/kg] vs. NPH[0.6 IU/kg] were 60 vs. 102 nmol min l(-1) (p<0.01) and for insulin analogue NN304[0.3 U/kg] vs. NN304[0.6 U/kg] 490 vs. 932 nmol min l(-1) (p <0.001), suggesting a clear dose-response relationship for both NPH insulin and NN304. The amount of disposed glucose (area under the curve of glucose infusion) differed with statistical significance between the five treatments and was highest with NPH[0.6 IU/kg] (2671 mg/kg) and lowest with placebo (265 mg/kg). However, area under the curve of glucose infusion after treatment with NN304 was only 36% (dose of 0.3 U/kg) and 24% (dose of 0.6 U/kg) of that observed with corresponding doses of NPH insulin. Moreover, increasing dosages of NN304 failed to demonstrate a significant dose-response with regard to the area under the curve of glucose infusion. This study demonstrates that the principle of protracted insulin action of NN304 by reversible binding to albumin is effective in humans albeit at a much lower rate of glucose utilisation when compared to NPH insulin. Thus, in contrast to animal studies NN304 and NPH insulin can not be considered equipotent in humans. PMID:10826516

  6. Characterization of a Polyamine Microsphere and Its Adsorption for Protein

    PubMed Central

    Wang, Feng; Liu, Pei; Nie, Tingting; Wei, Huixian; Cui, Zhenggang

    2013-01-01

    A novel polyamine microsphere, prepared from the water-in-oil emulsion of polyethylenimine, was characterized. The investigation of scanning electron microscopy showed that the polyamine microsphere is a regular ball with a smooth surface. The diameter distribution of the microsphere is 0.37–4.29 ?m. The isoelectric point of the microsphere is 10.6. The microsphere can adsorb proteins through the co-effect of electrostatic and hydrophobic interactions. Among the proteins tested, the highest value of adsorption of microsphere, 127.8 mg·g?1 microsphere, was obtained with lipase. In comparison with other proteins, the hydrophobic force is more important in promoting the adsorption of lipase. The microsphere can preferentially adsorb lipase from an even mixture of proteins. The optimum temperature and pH for the selective adsorption of lipase by the microsphere was 35 °C and pH 7.0. PMID:23344018

  7. Current advances in research and clinical applications of PLGA-based nanotechnology

    PubMed Central

    Lü, Jian-Ming; Wang, Xinwen; Marin-Muller, Christian; Wang, Hao; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2009-01-01

    Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases. PMID:19435455

  8. Clinical Pharmacokinetics of Laninamivir, a Novel Long-Acting Neuraminidase Inhibitor, After Single and Multiple Inhaled Doses of Its Prodrug, CS8958, in Healthy Male Volunteers

    Microsoft Academic Search

    Hitoshi Ishizuka; Satoshi Yoshiba; Hiromi Okabe; Kazutaka Yoshihara

    2010-01-01

    Phase 1 studies of laninamivir, a novel long-acting neuraminidase inhibitor, were carried out to assess its safety, tolerability, and pharmacokinetics after inhaled administration of its prodrug, CS-8958. Healthy male volunteers (total N = 76) participated in double-blind, randomized, placebo-controlled trials and received 5, 10, 20, 40, 80, or 120 mg of a single dose or 20 or 40 mg of

  9. A 3Month Course of Long-Acting Repeatable Octreotide (Sandostatin LAR) Improves Portal Hypertension in Patients With Cirrhosis: A Randomized Controlled Study

    Microsoft Academic Search

    Laurent Spahr; Emiliano Giostra; Jean-Louis Frossard; Isabelle Morard; Gilles Mentha; Antoine Hadengue

    2007-01-01

    OBJECTIVE:In patients with cirrhosis, acute octreotide administration may transiently decrease the hepatic venous pressure gradient (HVPG). Information on long-term effects of octreotide is limited and controversial. We evaluated portal and systemic hemodynamics following a prolonged administration of long-acting octreotide in patients with cirrhosis.METHODS:Eighteen cirrhotic patients (alcoholic 12; age 55 yr [44–69]; Pugh's score 7.8; HVPG 17.3 mmHg [12–22]), no steatohepatitis

  10. Effect of a Long-Acting Somatostatin Derivative SMS 201-995 (Sandostatin) on Glucose Homeostasis in Type I Diabetes mellitus

    Microsoft Academic Search

    I. Navascues; J. Gil; C. Pascau; D. Senén; E. del Pozo; M. Serrano-Ríos

    1988-01-01

    The infusion of natural somatostatin (SRIF) has been able to partially correct postprandial hyperglycemic reactions in insulin-dependent diabetes mellitus (IDDM). SMS 201-995 (Sandostatin) is a long-acting derivative with a growth hormone-suppressive effect 10-60 times more potent than the native peptide. The effect of SMS 201-995 (50 ?g s.c.) on glucose control by exogenous insulin has been documented in a series

  11. Partial Inhibition of the Growth of Transplanted Dunning Rat Prostate Tumors with the Long-Acting Somatostatin Analogue Sandostatin (SMS 201-995)

    Microsoft Academic Search

    R. A. Siegel; L. Tolcsvai; M. Rudin

    The growth-inhibiting effects of the long-acting somatostatin analogue Sandostatin on the transplanted Dunning R3327-H androgen-sensitive rat prostate tumor were investigated. Recipient animals were male Co penhagen x Fischer !•', rats (\\\\ = 36). When mean tumor volume reached 700 mm3(20 weeks following transplantation), the rats were divided into four groups: control; Sandostatin (100 fig\\/kg s.c. twice a day); castrate; castrate\\/Sandostatin.

  12. Bone Remodeling, Bone Mass and Weight Gain in Patients with Stabilized Schizophrenia in Real-Life Conditions Treated with Long-Acting Injectable Risperidone

    Microsoft Academic Search

    Mirjana Doknic; Nadja P. Maric; Dubravka Britvic; Sandra Pekic; Aleksandar Damjanovic; Dragana Miljic; Marko Stojanovic; Zoran Radojicic; Miroslava Jasovic Gasic; Vera Popovic

    2011-01-01

    Background: Prolactin-raising antipsychotics, risperidone (antidopaminergic activity), may be associated with low bone mass. On the other hand, risperidone may cause an increase in body weight thought to be favorable for bone. Objectives: (1) To determine bone remodeling parameters and bone mass in patients with schizophrenia on long-term treatment with long-acting injectable risperidone (LAIR) in naturalistic settings, and (2) to evaluate

  13. Critical Factors Influencing the In Vivo Performance of Long-acting Lipophilic Solutions—Impact on In Vitro Release Method Design

    Microsoft Academic Search

    Susan Weng Larsen; Claus Larsen

    2009-01-01

    Parenteral long-acting lipophilic solutions have been used for decades and might in the future be used in the design of depots\\u000a with tailored delivery characteristics. The present review highlights major factors influencing the in vivo performance of lipophilic solutions. Furthermore, an account is given of the characteristics of employed in vitro release methods with a focus on the “state” of

  14. Tadalafil, a long-acting type 5 phosphodiesterase isoenzyme inhibitor, improves neurological functional recovery in a rat model of embolic stroke

    Microsoft Academic Search

    Li Zhang; Zhenggang Zhang; Rui Lan Zhang; Yisheng Cui; Margot C. LaPointe; Brian Silver; Michael Chopp

    2006-01-01

    Sildenafil, a type 5 phosphodiesterase isoenzyme (PDE5) inhibitor with a short half-life, increases brain cyclic guanosine monophosphate (cGMP) levels and improves neurological functional recovery when administered after stroke. In the present study, we investigated the effects of tadalafil (Cialis), a long acting PDE5 inhibitor, on brain cGMP levels, neurogenesis, angiogenesis, and neurological function during stroke recovery in a rat model

  15. Anti-inflammatory effects of a short-acting and a long-acting ? 2-adrenoceptor agonist in guinea pig skin

    Microsoft Academic Search

    Mauro M. Teixeira; Timothy J. Williams; Paul G. Hellewell

    1995-01-01

    The pharmacological modulation of the accumulation and function of eosinophils in tissues may have a significant impact in the treatment of allergic diseases such as asthma, atopic dermatitis and rhinitis. In this study, we have investigated the acute anti-inflammatory effects of a short-acting (salbutamol) and a long-acting (salmeterol) ?2-adrenoceptor agonist on 111In-accumulation and oedema formation in allergic and mediator-induced inflammation

  16. Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study

    Microsoft Academic Search

    N Nathan; T Borel; A Djibo; D Evans; S Djibo; JF Corty; M Guillerm; KP Alberti; L Pinoges; PJ Guerin; D Legros

    2005-01-01

    Summary Background In sub-Saharan Africa in the 1990s, more than 600 000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior

  17. Low-Dose Therapy With the Long-Acting Erythropoietin Analogue Darbepoetin Alpha Persistently Activates Endothelial Akt and Attenuates Progressive Organ Failure

    Microsoft Academic Search

    Ferdinand H. Bahlmann; Rong Song; Sascha M. Boehm; Michael Mengel; Reinhard von Wasielewski; Carsten Lindschau; Torsten Kirsch; Kirsten de Groot; Robert Laudeley; Eva Niemczyk; Faikah Güler; Jan Menne; Hermann Haller; Danilo Fliser

    2010-01-01

    Background—The hematopoietic cytokine erythropoietin has cytoprotective effects in endothelial cells in vitro that are mediated through direct activation of the pro-survival Akt tyrosine kinase signaling pathway. We tested the hypothesis that low-dose therapy with the long-acting recombinant human erythropoietin analogue darbepoetin alpha protects vascular endothelium in vivo in a classic remnant kidney rat model characterized by severe endothelial damage, progressive

  18. Effects of the Long-Acting Insulin Analog Insulin Glargine on Cultured Human Skeletal Muscle Cells: Comparisons to Insulin and IGF-I

    Microsoft Academic Search

    T. P. Ciaraldi; L. CARTER; G. SEIPKE; S. MUDALIAR; R. R. HENRY

    2001-01-01

    The aim of this study was to determine whether the long- acting insulin analog, insulin glargine, behaves like human insulin for metabolic and mitogenic responses in differenti- ated cultured human skeletal muscle cells from nondiabetic and diabetic subjects. Human insulin and insulin glargine were equipotent in their ability to compete for (125I)insulin binding. Insulin glargine displaced (125I)IGF-I from the IGF-

  19. Tissue-engineered cartilage by in vivo culturing of chondrocytes in PLGA–collagen hybrid sponge

    Microsoft Academic Search

    Takashi Sato; Guoping Chen; Takashi Ushida; Tomoo Ishii; Naoyuki Ochiai; Tetsuya Tateishi

    2001-01-01

    Bovine chondrocytes were isolated from the shoulder articular joints of a calf, seeded in biodegradable porous polymer scaffolds, and implanted subcutaneously in the dorsum of athymic nude mice to tissue engineer articular cartilage in vivo. Hybrid sponge of poly(dl-lactic-co-glycolic acid) (PLGA) and collagen was used as the porous scaffold with PLGA sponge and collagen sponge used as the controls. Chondrocytes

  20. Fabricating PLGA sponge scaffold integrated with gelatin\\/hyaluronic acid for engineering cartilage

    Microsoft Academic Search

    N. J. Chang; M. L. Yeh; Y. R. Jhung

    2009-01-01

    The aim of present study is to characterize the physical properties of the PLGA-gelatin\\/HA composite scaffold and its ability for chondrocytes' attachment for cartilage tissue engineering applications. The 3D porous PLGA scaffold was fabricated by salt leaching method, and surface was integrated with gelatin and hyaluronic acid by crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide EDC solution. Water uptake ratio and element

  1. Effect of polymer viscosity on physicochemical properties and ocular tolerance of FB-loaded PLGA nanospheres

    Microsoft Academic Search

    J. Araújo; E. Vega; C. Lopes; M. A. Egea; M. L. Garcia; E. B. Souto

    2009-01-01

    Poly(lactide-co-glycolide) acid (PLGA) nanospheres incorporating flurbiprofen (FB) were produced by the solvent displacement technique, for ocular applications aiming to avoid\\/minimize inflammation induced by surgical trauma. In this work, a PLGA of low viscosity has been tested and the results obtained were compared with those previously reported by Vega et al. The physicochemical properties of the developed formulations were evaluated by

  2. Biofabrication of a PLGA-TCP-based porous bioactive bone substitute with sustained release of icaritin.

    PubMed

    Xie, Xin-Hui; Wang, Xin-Luan; Zhang, Ge; He, Yi-Xin; Leng, Yang; Tang, Ting-Ting; Pan, Xiaohua; Qin, Ling

    2012-12-18

    A phytomolecule, icaritin, has been identified and shown to be osteopromotive for the prevention of osteoporosis and osteonecrosis. This study aimed to produce a bioactive poly (l-lactide-co-glycolide)-tricalcium phosphate (PLGA-TCP)-based porous scaffold incorporating the osteopromotive phytomolecule icaritin, using a fine spinning technology. Both the structure and the composition of icaritin-releasing PLGA-TCP-based scaffolds were evaluated by scanning electron microscopy (SEM). The porosity was quantified by both water absorption and micro-computed tomography (micro-CT). The mechanical properties were evaluated using a compression test. In vitro release of icaritin from the PLGA-TCP scaffold was quantified by high-performance liquid chromatography (HPLC). The attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the composite scaffold were evaluated. Both an in vitro cytotoxicity test and an in vivo test via muscular implantation were conducted to confirm the scaffold's biocompatibility. The results showed that the PLGA-TCP-icaritin composite scaffold was porous, with interconnected macro- (about 480?µm) and micropores (2-15?µm). The mechanical properties of the PLGA-TCP-icaritin scaffold were comparable with those of the pure PLGA-TCP scaffold, yet was spinning direction-dependent. Icaritin content was detected in the medium and increased with time. The PLGA-TCP-icaritin scaffold facilitated the attachment, proliferation and osteogenic differentiation of BMSCs. In vitro cytotoxicity test and in vivo intramuscular implantation showed that the composite scaffold had no toxicity with good biocompatibility. In conclusion, an osteopromotive phytomolecule, icaritin, was successfully incorporated into PLGA-TCP to form an innovative porous composite scaffold with sustained release of osteopromotive icaritin, and this scaffold had good biocompatibility and osteopromotion, suggesting its potential for orthopaedic applications. Copyright © 2012 John Wiley & Sons, Ltd. PMID:23255530

  3. Redifferentiation of dedifferentiated bovine chondrocytes when cultured in vitro in a PLGA–collagen hybrid mesh

    Microsoft Academic Search

    Guoping Chen; Takashi Sato; Takashi Ushida; Rei Hirochika; Tetsuya Tateishi

    2003-01-01

    Bovine articular chondrocytes dedifferentiated and lost their ability to express articular cartilage-specific extracellular matrices such as type II collagen and aggrecan when cultured in a culture flask during in vitro multiplication. A poly(DL-lactic-co-glycolic acid) (PLGA)–collagen hybrid mesh was prepared and used to redifferentiate the dedifferentiated cells. The two passaged dedifferentiated chondrocytes were seeded in a PLGA–collagen hybrid mesh and cultured

  4. Reduction of surface-induced inflammatory reaction on PLGA\\/MPC polymer blend

    Microsoft Academic Search

    Yasuhiko Iwasaki; Shin-ichi Sawada; Kazuhiko Ishihara; Gilson Khang; Hai Bang Lee

    2002-01-01

    Poly(lactide-co-glycolide) (PLGA) has been believed to be a good biocompatible material for tissue engineering due to its biodegradability and non-toxicity of the monomer. However, the inflammatory reaction of adherent cells on the surface has not been discussed sufficiently. We hypothesized that the inflammatory reaction of adherent cells on PLGA might occur and could be reduced by blending a 2-methacryloyloxyethyl phosphorylcholine

  5. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity

    Microsoft Academic Search

    Cristina Fonseca; Sérgio Simões; Rogério Gaspar

    2002-01-01

    The main objective of this study was to develop a polymeric drug delivery system for paclitaxel, intended to be intravenously administered, capable of improving the therapeutic index of the drug and devoid of the adverse effects of Cremophor® EL. To achieve this goal paclitaxel (Ptx)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-Nps) were prepared by the interfacial deposition method. The influence of

  6. Drug release from biodegradable injectable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymers

    Microsoft Academic Search

    Byeongmoon Jeong; You Han Bae; Sung Wan Kim

    2000-01-01

    An aqueous solution of newly developed low-molecular-weight PEG–PLGA–PEG triblock copolymers with a specific composition is a free flowing sol at room temperature but becomes a gel at body temperature. Two model drugs, ketoprofen and spironolatone, which have different hydrophobicities, were released from the PEG–PLGA–PEG triblock copolymer hydrogel formed in situ by injecting the solutions into a 37°C aqueous environment. Ketoprofen

  7. Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery

    Microsoft Academic Search

    Dong-Hwan Kim; David C. Martin

    2006-01-01

    The release of the anti-inflammatory agent dexamethasone (DEX) from nanoparticles of poly(lactic-co-glycolic acid) (PLGA) embedded in alginate hydrogel (HG) matrices was investigated. DEX-loaded PLGA nanoparticles were prepared using a solvent evaporation technique and were characterized for size, drug loading, and in-vitro release. The crosslinking density of the HG was studied and correlated with drug release kinetics. The amount of DEX

  8. Surface modification of PLGA nanoparticles by carbopol to enhance mucoadhesion and cell internalization.

    PubMed

    Surassmo, Suvimol; Saengkrit, Nattika; Ruktanonchai, Uracha Rungsardthong; Suktham, Kunat; Woramongkolchai, Noppawan; Wutikhun, Tuksadon; Puttipipatkhachorn, Satit

    2015-06-01

    Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90nm), and strong negative surface charge (-25.70mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer. PMID:25937384

  9. Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease: a systematic review of clinical benefit

    PubMed Central

    Ulrik, Charlotte Suppli

    2012-01-01

    Background: Long-acting bronchodilators are central in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). The aim of this systematic review is to provide an overview of the studies evaluating the safety and clinical efficacy of inhaled glycopyrronium bromide, a novel long-acting muscarinic antagonist, in patients with COPD. Methods: This study was performed as a systematic literature review. Results: Inhaled glycopyrronium bromide seems to be a safe and well tolerated long-acting muscarinic antagonist with a fast onset of action. In patients suffering from moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of forced expiratory volume in one second, use of relief medication, percentage of days with no use of rescue medication, daytime dyspnea scores, and probably also on health status. Furthermore, in this group of patients, glycopyrronium bromide has beneficial effects on dynamic hyperinflation and exercise tolerance. Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, but long-term controlled trials with exacerbation rate as the primary outcome variable have not been published yet. Conclusion: Once-daily inhaled glycopyrronium bromide has characteristics important for use in COPD, including a fast onset of action, sustained 24-hour bronchodilatation, and improvement in exercise tolerance, and therefore appears to have the potential for a significant role in the future management of COPD. PMID:23055716

  10. Organic aerogel microspheres and fabrication method therefor

    DOEpatents

    Mayer, Steven T. (San Leandro, CA); Kong, Fung-Ming (Pleasanton, CA); Pekala, Richard W. (Pleasant Hill, CA); Kaschmitter, James L. (Pleasanton, CA)

    1996-01-01

    Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  11. Organic aerogel microspheres and fabrication method therefor

    DOEpatents

    Mayer, S.T.; Kong, F.M.; Pekala, R.W.; Kaschmitter, J.L.

    1996-04-16

    Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  12. 21 CFR 870.1360 - Trace microsphere.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...Identification. A trace microsphere is a radioactively tagged nonbiodegradable particle that is intended to be injected into an artery or vein and trapped in the capillary bed for the purpose of studying blood flow within or to an organ. (b)...

  13. 21 CFR 870.1360 - Trace microsphere.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...Identification. A trace microsphere is a radioactively tagged nonbiodegradable particle that is intended to be injected into an artery or vein and trapped in the capillary bed for the purpose of studying blood flow within or to an organ. (b)...

  14. 21 CFR 870.1360 - Trace microsphere.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...Identification. A trace microsphere is a radioactively tagged nonbiodegradable particle that is intended to be injected into an artery or vein and trapped in the capillary bed for the purpose of studying blood flow within or to an organ. (b)...

  15. 21 CFR 870.1360 - Trace microsphere.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...Identification. A trace microsphere is a radioactively tagged nonbiodegradable particle that is intended to be injected into an artery or vein and trapped in the capillary bed for the purpose of studying blood flow within or to an organ. (b)...

  16. 21 CFR 870.1360 - Trace microsphere.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...Identification. A trace microsphere is a radioactively tagged nonbiodegradable particle that is intended to be injected into an artery or vein and trapped in the capillary bed for the purpose of studying blood flow within or to an organ. (b)...

  17. Design and Optimization of PLGA-Based Diclofenac Loaded Nanoparticles

    PubMed Central

    Cooper, Dustin L.; Harirforoosh, Sam

    2014-01-01

    Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide) (PLGA) based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion-evaporation technique with varying concentrations of poly vinyl alcohol (PVA) (0.1, 0.25, 0.5, or 1%) or didodecyldimethylammonium bromide (DMAB) (0.1, 0.25, 0.5, 0.75, or 1%) stabilizers centrifuged at 8,800 rpm or 12,000 rpm. The resultant nanoparticles were evaluated based on particle size, zeta potential, and entrapment efficacy. DMAB formulated NPs showed the lowest particle size (108±2.1 nm) and highest zeta potential (?27.71±0.6 mV) at 0.1 and 0.25% respectively, after centrifugation at 12,000 rpm. Results of the PVA based NP formulation showed the smallest particle size (92.4±7.6 nm) and highest zeta potential (?11.14±0.5 mV) at 0.25% and 1% w/v, respectively, after centrifugation at 12,000 rpm. Drug entrapment reached 77.3±3.5% and 80.2±1.2% efficiency with DMAB and PVA formulations, respectively. The results of our study indicate the use of DMAB for increased nanoparticle stability during formulation. Our study supports the effective utilization of PLGA based nanoparticle formulation for diclofenac. PMID:24489896

  18. Biomimetic Hybrid Nanofiber Sheets Composed of RGD Peptide-Decorated PLGA as Cell-Adhesive Substrates

    PubMed Central

    Shin, Yong Cheol; Lee, Jong Ho; Kim, Min Jeong; Park, Ji Hoon; Kim, Sung Eun; Kim, Jin Su; Oh, Jin-Woo; Han, Dong-Wook

    2015-01-01

    In biomedical applications, there is a need for tissue engineering scaffolds to promote and control cellular behaviors, including adhesion, proliferation and differentiation. In particular, the initial adhesion of cells has a great influence on those cellular behaviors. In this study, we concentrate on developing cell-adhesive substrates applicable for tissue engineering scaffolds. The hybrid nanofiber sheets were prepared by electrospinning poly(lactic-co-glycolic acid) (PLGA) and M13 phage, which was genetically modified to enhance cell adhesion thru expressing RGD peptides on their surface. The RGD peptide is a specific motif of extracellular matrix (ECM) for integrin receptors of cells. RGD peptide-decorated PLGA (RGD-PLGA) nanofiber sheets were characterized by scanning electron microscopy, immunofluorescence staining, contact angle measurement and differential scanning calorimetry. In addition, the initial adhesion and proliferation of four different types of mammalian cells were determined in order to evaluate the potential of RGD-PLGA nanofiber sheets as cell-adhesive substrates. Our results showed that the hybrid nanofiber sheets have a three-dimensional porous structure comparable to the native ECM. Furthermore, the initial adhesion and proliferation of cells were significantly enhanced on RGD-PLGA sheets. These results suggest that biomimetic RGD-PLGA nanofiber sheets can be promising cell-adhesive substrates for application as tissue engineering scaffolds. PMID:26034884

  19. Biomimetic Hybrid Nanofiber Sheets Composed of RGD Peptide-Decorated PLGA as Cell-Adhesive Substrates.

    PubMed

    Shin, Yong Cheol; Lee, Jong Ho; Kim, Min Jeong; Park, Ji Hoon; Kim, Sung Eun; Kim, Jin Su; Oh, Jin-Woo; Han, Dong-Wook

    2015-01-01

    In biomedical applications, there is a need for tissue engineering scaffolds to promote and control cellular behaviors, including adhesion, proliferation and differentiation. In particular, the initial adhesion of cells has a great influence on those cellular behaviors. In this study, we concentrate on developing cell-adhesive substrates applicable for tissue engineering scaffolds. The hybrid nanofiber sheets were prepared by electrospinning poly(lactic-co-glycolic acid) (PLGA) and M13 phage, which was genetically modified to enhance cell adhesion thru expressing RGD peptides on their surface. The RGD peptide is a specific motif of extracellular matrix (ECM) for integrin receptors of cells. RGD peptide-decorated PLGA (RGD-PLGA) nanofiber sheets were characterized by scanning electron microscopy, immunofluorescence staining, contact angle measurement and differential scanning calorimetry. In addition, the initial adhesion and proliferation of four different types of mammalian cells were determined in order to evaluate the potential of RGD-PLGA nanofiber sheets as cell-adhesive substrates. Our results showed that the hybrid nanofiber sheets have a three-dimensional porous structure comparable to the native ECM. Furthermore, the initial adhesion and proliferation of cells were significantly enhanced on RGD-PLGA sheets. These results suggest that biomimetic RGD-PLGA nanofiber sheets can be promising cell-adhesive substrates for application as tissue engineering scaffolds. PMID:26034884

  20. The fabrication of PLGA microvessel scaffolds with nano-patterned inner walls.

    PubMed

    Wang, Gou-Jen; Lin, Yan-Cheng; Hsu, Shan-Hui

    2010-10-01

    Poly (lactic-co-glycolic acid) (PLGA) is one of the most commonly used biodegradable, biocompatible materials. Nanostructured PLGA has immense potential for application in tissue engineering. In this article we discuss a novel approach for the fabrication of PLGA microvessel scaffolds with nanostructured inner walls. In this novel nano-patterning approach, the thermal reflow technique is first adapted to fabricate a semi-cylindrical photoresist master mold. A thin film of titanium and a thin film of aluminum are sputtered in sequence on the semi-cylindrical microvessel network. Aluminum foil anodization is then executed to transform the aluminum thin film into a porous anodic aluminum oxide (AAO) film. During the casting process a PLGA solution is cast on the AAO film to build up semi-cylindrical PLGA microstructures with nanostructured inner walls after which inductive coupled plasma (ICP) is implemented to assist bonding of the two PLGA structures. The result is the building of a network of microchannels with nano-patterned inner walls. Bovine endothelial cells (BECs) are carefully cultured in the scaffold via semi-dynamic seeding for 7 days. Observations show that the BECs grew more separately in a nano-patterned microvessel scaffold than they did in a smooth surface scaffold. PMID:20532635

  1. In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

    2014-09-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

  2. Carbon microsphere-filled Pyrrone foams.

    NASA Technical Reports Server (NTRS)

    Kimmel, B. G.

    1973-01-01

    Syntactic foam formulations were prepared from mixtures of Pyrrone prepolymers and hollow carbon microspheres. Very low curing shrinkages were obtained for high volume loadings of microspheres. The resulting syntactic foams were found to be remarkably stable over a wide range in temperature. A technique was developed for the emplacement of these foam formulations in polyimide-fiberglass, titanium alloy and stainless steel honeycomb without sacrificing low curing shrinkage or thermal stability.

  3. Method for introduction of gases into microspheres

    DOEpatents

    Hendricks, Charles D. (Livermore, CA); Koo, Jackson C. (San Ramon, CA); Rosencwaig, Allan (Danville, CA)

    1981-01-01

    A method for producing small hollow glass spheres filled with a gas by introduction of the gas during formation of the hollow glass spheres. Hollow glass microspheres having a diameter up to about 500.mu. with both thin walls (0.5 to 4.mu.) and thick walls (5 to 20.mu.) that contain various fill gases, such as Ar, Kr, Xe, Br, DT, H.sub.2, D.sub.2, He, N.sub.2, Ne, CO.sub.2, etc. in the interior thereof, can be produced by the diffusion of the fill gas or gases into the microsphere during the formation thereof from a liquid droplet of glass-forming solution. This is accomplished by filling at least a portion of the multiple-zone drop-furnace used in producing hollow microspheres with the gas or gases of interest, and then taking advantage of the high rate of gaseous diffusion of the fill gas through the wall of the gel membrane before it transforms into a glass microsphere as it is processed in the multiple-zone furnace. Almost any gas can be introduced into the inner cavity of a glass microsphere by this method during the formation of the microsphere provided that the gas is diffused into the gel membrane or microsphere prior to its transformation into glass. The process of this invention provides a significant savings of time and related expense of filling glass microspheres with various gases. For example, the time for filling a glass microballoon with 1 atmosphere of DT is reduced from about two hours to a few seconds.

  4. New functional microspheres with active succinimide groups

    Microsoft Academic Search

    Y. Morital; M. Yoshida; M. Asano; I. Kaetsu

    1987-01-01

    Radiation-induced polymerization of monomers, for example N-methacryl-oxysuccinimide (MASu) and diethylene glycol dimethacrylate (2G), in ethyl propionate, was performed from +25°C to -78°C. The copoly (MASu\\/2G) microspheres were obtained in MASu monomer compositions of 30 wt % or below. The average particle diameter of copoly(MASu\\/2G, 20\\/80 wt %) microspheres obtained at irradiation temperatures of 25°, 0°, and -43 °C were 0.81±0.29,

  5. Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E TPGS nanoparticles for lung cancer therapy.

    PubMed

    Zhang, Jinxie; Tao, Wei; Chen, Yuhan; Chang, Danfeng; Wang, Teng; Zhang, Xudong; Mei, Lin; Zeng, Xiaowei; Huang, Laiqiang

    2015-04-01

    A doxorubicin-loaded mannitol-functionalized poly(lactide-co-glycolide)-b-D-?-tocopheryl polyethylene glycol 1000 succinate nanoparticles (DOX-loaded M-PLGA-b-TPGS NPs) were prepared by a modified nanoprecipitation method. The NPs were characterized by the particle size, surface morphology, particle stability, in vitro drug release and cellular uptake efficiency. The NPs were near-spherical with narrow size distribution. The size of M-PLGA-b-TPGS NPs was ~110.9 nm (much smaller than ~143.7 nm of PLGA NPs) and the zeta potential was -35.8 mV (higher than -42.6 mV of PLGA NPs). The NPs exhibited a good redispersion since the particle size and surface charge hardly changed during 3-month storage period. In the release medium (phosphate buffer solution vs. fetal bovine serum), the cumulative drug release of DOX-loaded M-PLGA-b-TPGS, PLGA-b-TPGS, and PLGA NPs were 76.41 versus 83.11 %, 58.94 versus 73.44 % and 45.14 versus 53.12 %, respectively. Compared with PLGA-b-TPGS NPs and PLGA NPs, the M-PLGA-b-TPGS NPs possessed the highest cellular uptake efficiency in A549 and H1975 cells (lung cancer cells). Ultimately, both in vitro and in vivo antitumor activities were evaluated. The results showed that M-PLGA-b-TPGS NPs could achieve a significantly higher level of cytotoxicity in cancer cells and a better antitumor efficiency on xenograft BALB/c nude mice tumor model than free DOX. In conclusion, the DOX-loaded M-PLGA-b-TPGS could be used as a potential DOX-loaded nanoformulation in lung cancer chemotherapy. PMID:25791459

  6. PLGA nanofiber membranes loaded with epigallocatechin-3-O-gallate are beneficial to prevention of postsurgical adhesions

    PubMed Central

    Shin, Yong Cheol; Yang, Won Jun; Lee, Jong Ho; Oh, Jin-Woo; Kim, Tai Wan; Park, Jong-Chul; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-01-01

    This study concentrates on the development of biodegradable nanofiber membranes with controlled drug release to ensure reduced tissue adhesion and accelerated healing. Nanofibers of poly(lactic-co-glycolic acid) (PLGA) loaded with epigallocatechin-3-O-gallate (EGCG), the most bioactive polyphenolic compound in green tea, were electrospun. The physicochemical and biomechanical properties of EGCG-releasing PLGA (E-PLGA) nanofiber membranes were characterized by atomic force microscopy, EGCG release and degradation profiles, and tensile testing. In vitro antioxidant activity and hemocompatibility were evaluated by measuring scavenged reactive oxygen species levels and activated partial thromboplastin time, respectively. In vivo antiadhesion efficacy was examined on the rat peritonea with a surgical incision. The average fiber diameter of E-PLGA membranes was approximately 300–500 nm, which was almost similar to that of pure PLGA equivalents. E-PLGA membranes showed sustained EGCG release mediated by controlled diffusion and PLGA degradation over 28 days. EGCG did not adversely affect the tensile strength of PLGA membranes, whereas it significantly decreased the elastic modulus and increased the strain at break. E-PLGA membranes were significantly effective in both scavenging reactive oxygen species and extending activated partial thromboplastin time. Macroscopic observation after 1 week of surgical treatment revealed that the antiadhesion efficacy of E-PLGA nanofiber membranes was significantly superior to those of untreated controls and pure PLGA equivalents, which was comparable to that of a commercial tissue-adhesion barrier. In conclusion, the E-PLGA hybrid nanofiber can be exploited to craft strategies for the prevention of postsurgical adhesions. PMID:25187710

  7. In vitro and in vivo anti-tumor activities of nanoparticles based on doxorubicin–PLGA conjugates

    Microsoft Academic Search

    Hyuk Sang Yoo; Keun Hyeung Lee; Jong Eun Oh; Tae Gwan Park

    2000-01-01

    Doxorubicin was chemically conjugated to a terminal end group of poly(d,l-lactic-co-glycolic acid) [PLGA] by an ester linkage and the doxorubicin–PLGA conjugate was formulated into nanoparticles. A carboxylic acid end group of PLGA was conjugated to a primary hydroxyl group of doxorubicin. The primary amine group of doxorubicin was protected during the conjugation process and then deprotected. The nanoparticles containing the

  8. Demonstration of Microsphere Insulation in Cryogenic Vessels

    NASA Astrophysics Data System (ADS)

    Baumgartner, R. G.; Myers, E. A.; Fesmire, J. E.; Morris, D. L.; Sokalski, E. R.

    2006-04-01

    While microspheres have been recognized as a legitimate insulation material for decades, actual use in full-scale cryogenic storage tanks has not been demonstrated until now. The performance and life-cycle-cost advantages previously predicted have now been proven. Most bulk cryogenic storage tanks are insulated with either multilayer insulation (MLI) or perlite. Microsphere insulation, consisting of hollow glass bubbles, combines in a single material the desirable properties that other insulations only have individually. The material has high crush strength, low density, is noncombustible, and performs well in soft vacuum. These properties were proven during recent field testing of two 22,700-L (6,000-gallon) liquid nitrogen tanks, one insulated with microsphere insulation and the other with perlite. Normal evaporation rates (NER) for both tanks were monitored with precision test equipment and insulation levels within the tanks were observed through view ports as an indication of insulation compaction. Specific industrial applications were evaluated based on the test results and beneficial properties of microsphere insulation. Over-the-road trailers previously insulated with perlite will benefit not only from the reduced heat leak, but also the reduced mass of microsphere insulation. Economic assessments for microsphere-insulated cryogenic vessels including life-cycle cost are also presented.

  9. Nonlinear elasticity of microsphere heaps

    NASA Astrophysics Data System (ADS)

    Ortiz, Carlos P.; Daniels, Karen E.; Riehn, Robert

    2014-08-01

    Thermal fluctuations, geometric exclusion, and external driving all govern the mechanical response of dense particulate suspensions. Here, we measure the stress-strain response of quasi-two-dimensional flow-stabilized microsphere heaps in a regime in which all three effects are present using a microfluidic device. We observe that the elastic modulus and the mean interparticle separation of the heaps are tunable via the confining stress provided by the fluid flow. Furthermore, the measured stress-strain curves exhibit a universal nonlinear shape, which can be predicted from a thermal van der Waals equation of state with excluded volume. This analysis indicates that many-body interactions contribute a significant fraction of the stress supported by the heap.

  10. Intervertebral Spinal Fusion Using a RP-based PLGA\\/TCP\\/ bBMP Biomimetic Grafting Material

    Microsoft Academic Search

    Xing Ma; Xiaoming Wu; Yunyu Hu; Zhuo Xiong; Rong Lv; Jun Wang; Dan Li; Yongnian Yan

    2009-01-01

    Three-dimensional highly porous poly(DL-lactic-co-glycolic acid)\\/ tricalcium phosphate (PLGA\\/TCP) scaffolds were synthesized via a rapid prototyping (RP) technique. Bovine bone morphogenetic protein (bBMP) was loaded into the biopolymer scaffolds (PLGA\\/TCP\\/bBMP). Both the PLGA\\/TCP scaffolds and the PLGA\\/TCP\\/bBMP composites were evaluated by scanning electron microscopy. Lumbar intervertebral body fusion at L2?3 and L4?5 levels were performed on 15 goats using one of

  11. Curvature Capillary Migration of Microspheres

    E-print Network

    Nima Sharifi-Mood; Iris B. Liu; Kathleen J. Stebe

    2015-05-11

    We address the question: How does capillarity propel microspheres along curvature gradients? For a particle on a fluid interface, there are two conditions that can apply at the three phase contact line: Either the contact line adopts an equilibrium contact angle, or it can be pinned by kinetic trapping, e.g. at chemical heterogeneities, asperities or other pinning sites on the particle surface. We formulate the curvature capillary energy for both scenarios for particles smaller than the capillary length and far from any pinning boundaries. The scale and range of the distortion made by the particle are set by the particle radius; we use singular perturbation methods to find the distortions and to rigorously evaluate the associated capillary energies. For particles with equilibrium contact angles, contrary to the literature, we find that the capillary energy is negligible, with the first contribution bounded to fourth order in the product of the particle radius and the deviatoric curvature. For pinned contact lines, we find curvature capillary energies that are finite, with a functional form investigated previously by us for disks and microcylinders on curved interfaces. In experiments, we show microsphere migrate along deterministic trajectories toward regions of maximum deviatoric curvature with curvature capillary energies ranging from $6 \\times10^3 - 5 \\times 10^4~k_BT$. These data agree with the curvature capillary energy for the case of pinned contact lines. The underlying physics of this migration is a coupling of the interface deviatoric curvature with the quadrupolar mode of nanometric disturbances in the interface owing to the particle's contact line undulations. This work is an example of the major implications of nanometric roughness and contact line pinning for colloidal dynamics.

  12. Fabrication of core-shell microcapsules using PLGA and alginate for dual growth factor delivery system.

    PubMed

    Choi, Dong Hoon; Park, Chul Ho; Kim, Ik Hwan; Chun, Heung Jae; Park, Kwideok; Han, Dong Keun

    2010-10-15

    To effectively harness the great potential of stem cells, we designed a dual growth factor delivery system for the application toward stem cell differentiation into specific lineages. This system carries a core-shell structure within microcapsules made of poly(L-lactide-co-glycolide) (PLGA) and alginate, which were fabricated using a coaxial electro-dropping method. Both PLGA and alginate were supplied from the inner and outer nozzles, respectively. The size and shape of microcapsules were greatly varying depending on the variables: nozzle size, applied voltage, volumetric feeding ratio (PLGA:alginate), feeding rate, and polymer concentrations. Once proper conditions were met, single or multi PLGA cores were found settled within the microcapsules. From the microscopic images, wrinkled surfaces of microcapsules were observed, along with the PLGA cores inside the alginate domain. When two different microcapsules were made, switching the position of bone morphogenetic protein (BMP)-2 and dexamethasone (Dex) for either core or shell domain, their release profiles were very unique on a temporal basis, based on their location in the microcapsules. An initial burst of biomolecules was highly suppressed when either biomolecule was loaded in the PLGA core. It was clear that the osteogenic biomolecules encapsulated in the microcapsule could be released together and their concentrations were disparate at each time point. Meanwhile as the hydrogel constructs including rat bone marrow stromal cells (BMSCs) and osteogenic factor-loaded microcapsules were cultured for up to 4 weeks, the gene expressions levels of osteopontin, type I collagen, and osteocalcin were significantly upregulated as compared to the control group. The present coaxial system was very effective in manufacturing PLGA core-alginate shell microcapsules and in encapsulating multiple biomolecules essential for stem cell differentiation. PMID:20647022

  13. Bone induction by biomimetic PLGA copolymer loaded with a novel synthetic RADA16-P24 peptide in vivo.

    PubMed

    Pan, Haitao; Hao, Shaofei; Zheng, Qixin; Li, Jingfeng; Zheng, Jin; Hu, Zhilei; Yang, Shuhua; Guo, Xiaodong; Yang, Qin

    2013-08-01

    Bone morphogenetic protein-2 (BMP-2) is a key bone morphogenetic protein, and poly(lactic-co-glycolic acid) (PLGA) has been widely used as scaffold for clinical use to carry treatment protein. In the previous studies, we have synthesized BMP-2-related peptide (P24) and found its capacity of inducing bone regeneration. In this research, we have synthesized a new amphiphilic peptide Ac-RADA RADA RADA RADA S[PO4]KIPKASSVPTELSAISTLYLDDD-CONH2 (RADA16-P24) with an assembly peptide RADA16-Ion the P24 item of BMP2 to form divalent ion-induced gelatin. Two methods of physisorption and chemical cross-linking were used to bind RADA16-P24 onto the surface of the copolymer PLGA to synthesize RADA16-P24-PLGA, and its capacity of attaching bone marrow stromal cells (BMSCs) was evaluated in vitro and inducing ectopic bone formation was examined in vivo. In vitro our results demonstrated that RADA16-P24-PLGA copolymer prepared by physisorbing or prepared by chemical cross-linking had a peptide binding rate of (2.0180±0.5296)% or (10.0820±0.8405)% respectively (P<0.05). In addition the BMSCs proliferated vigorously in the RADA16-P24-PLGA biomaterials. Significantly the percentage of BMSCs attached to RADA16-P24-PLGA composite prepared by chemical cross-linking and physisorbing were (71.4±7.5) % or (46.7±5.8) % (P<0.05). The in vivo study showed that RADA16-P24-PLGA chemical cross-linking could better induce ectopic bone formation compared with RADA16-P24-PLGA physisorbing and PLGA. It is concluded that the PLGA copolymer is a good RADA16-P24 carrier. This novel RADA16-P24-PLGA composite has strong osteogenic capability. PMID:23706219

  14. Deposition of PLGA Nanoparticles on Stents Bull. Korean Chem. Soc. 2009, Vol. 30, No. 5 1085 A Novel Deposition Method of PLGA Nanoparticles on Coronary Stents

    E-print Network

    Park, Jong-Sang

    . We found that the nanoparticles were deposited uniformly and closely packed. The amount of paclitaxel was easily controlled by the drug content of the nanoparticles and the deposition count. Key Words: PLGA) was `Baker Analyzed'HPLC solvent. Distilled water produced by Millipore (Millipore Corporation) was used

  15. Rheological Behavior of an Epoxy Resin with Hollow Glass Microspheres

    NASA Astrophysics Data System (ADS)

    Costa, Cleber C.; Calado, Verônica; Tavares, Frederico W.

    2008-07-01

    An investigation was carried out on the rheological behavior of a TET/DGEBA epoxy formulations with hollow glass microspheres using different types and different volume fractions of microspheres to manufacture composites. It was proposed an equation to describe viscosity as a function of microsphere volume fracion. The fit to the experimental data was excellent.

  16. Patterning of silica microsphere monolayers with focused femtosecond laser pulses

    Microsoft Academic Search

    Wenjian Cai; Rafael Piestun

    2006-01-01

    We demonstrate the patterning of monolayer silica microsphere lattices with tightly focused femtosecond laser pulses. We selectively removed microspheres from a lattice and characterized the effect on the lattice and the substrate. The proposed physical mechanism for the patterning process is laser-induced breakdown followed by ablation of material. We show that a microsphere focuses radiation in its interior and in

  17. Preparation of monodisperse, reactive hydrogel microspheres and their amphoterization

    Microsoft Academic Search

    M. Kashiwabara; K. Fujimoto; H. Kawaguchi

    1995-01-01

    Monodisperse, reactive hydrogel microspheres were prepared by precipitation polymerization ofp-nitrophenyl acrylate (NPA) with acrylamide, methacrylic acid, and methylenebisacrylamide in ethanol. The size of microspheres was controlled by the monomer ratio. Some fraction of reactive ester decomposed during the polymerization. The reactive hydrogel microspheres were converted to amphoteric ones by the reaction of NPA units with diamine. The isoelectric point of

  18. Comparison of the Peak-to-trough Fluctuation in Plasma Concentration of Long-acting Injectable Antipsychotics and Their Oral Equivalents

    PubMed Central

    Sheehan, John J.; Reilly, Kristin R.; Fu, Dong-Jing

    2012-01-01

    Background: Small peak-to-trough drug levels have been suggested to be related to improved tolerability. The aim of this study is to review the steady-state, peak-to-trough, plasma-concentration fluctuation of long-acting injectable antipsychotics and equivalent oral formulations. Methods: A review of published literature and clinical study reports identified references that reported, depicted, or permitted derivation of the steady-state, peak-to-trough, plasma-concentration fluctuation of antipsychotics (the ratio of maximum concentration to minimum concentration following administration according to the recommended dosing interval) over the dosing interval. Suitable references were identified for haloperidol decanoate, olanzapine pamoate, paliperidone palmitate, risperidone long-acting injectable, and zuclopenthixol decanoate and their oral equivalents except zuclopenthixol. The single-dose time to maximum plasma concentration (Tmax) and half-life (t1/2) were also identified. Results: The steady-state, peak-to-trough, plasma-concentration ratios of oral antipsychotics varied from 1.47 (paliperidone extended-release, once daily) to 3.30 (active-moiety risperidone, once daily). Among long-acting injectable antipsychotics, the ratios varied from 1.56 (paliperidone palmitate, once monthly) to approximately 4 (olanzapine pamoate, once every four weeks). Among drugs with similar dosing intervals, longer Tmax and/or t1/2 generally correlated with less peak-to-trough fluctuation. Conclusion: Peak-to-trough fluctuations in plasma concentrations vary widely and may be affected by differences in dosing, pharmacokinetic sampling, subjects’ phenotypes, concomitant medications, comorbid diseases, and formulation. These fluctuations may affect clinical response and tolerability. Along with other patient-specific and drug-specific factors, these fluctuations warrant consideration when selecting an antipsychotic and antipsychotic formulation. Further study is needed with more robust and generalizable peak-to-trough fluctuation data. PMID:22984648

  19. Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

    PubMed Central

    Lee, Ji Woo; Kim, Hyung Jin; Choe, Yun Mee; Kang, Hee Suk; Kim, Soon Ki; Jun, Yong Hoon

    2014-01-01

    Purpose Long-acting gonadotropin-releasing hormone agonists (GnRHa) are commonly used to treat central precocious puberty (CPP) in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects. Methods This retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate) at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate. Results Six serious side effects (0.9%) were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621). Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE) in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy. Conclusion Sterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP. PMID:25346917

  20. A Prospective Study Comparing the Long-term Effectiveness of Injectable Risperidone Long-acting Therapy and Oral Aripiprazole in Patients with Schizophrenia

    PubMed Central

    Macfadden, Wayne; Ma, Yi-Wen; Thomas Haskins, J.; Bossie, Cynthia A.

    2010-01-01

    Objective: To test the hypothesis that long-term maintenance with injectable risperidone long-acting therapy is superior to oral daily aripiprazole in stable patients with schizophrenia. Design: This two-year, rater-blinded, open-label, multicenter study (NCT00299702) randomized subjects to injectable risperidone long-acting therapy (25–50mg, injected every 2 weeks) or oral aripiprazole (5–30mg/day), with study visits every two weeks. Subjects who met relapse criteria or discontinued study drug could remain in the study. Setting: Clinical trial. Participants: Stable subjects with schizophrenia not adequately benefiting from current treatment who experienced two or more relapses in the past two years. If recently relapsed, subjects were stabilized (per clinician judgment) for two or more months before entry. Measurements: Primary endpoints: time to relapse and time in remission. Safety assessments included adverse event reporting. Results: Of 355 subjects randomized, 349 were in the intent-to-treat analysis set. Data inspection revealed that 53 (14.9%) randomized subjects deviated from inclusion/exclusion criteria, most commonly not meeting stability requirements. At baseline, mean (standard deviation [SD]) Positive and Negative Syndrome Scale total score was 68.9 (14.6); 115 (33.0%) intent-to-treat subjects met remission criteria. Approximately 29 percent in each group discontinued the study before completing two years. No significant between-group differences were noted in time to relapse or time in remission. No new tolerability issues were identified. Conclusion: Results failed to demonstrate superiority with injectable risperidone long-acting therapy versus oral aripiprazole. The study design did not allow for valid conclusions of equivalence or noninferiority. Although this study attempted to mimic a real-world treatment setting for stable patients, the broad study population, the lack of patient selection for nonadherence, biweekly visits, regular assessments, and other design issues limited generalizability and interpretation relative to the study hypothesis. PMID:21191530

  1. Reducing Prescriptions of Long-Acting Benzodiazepine Drugs in Denmark: A Descriptive Analysis of Nationwide Prescriptions during a 10-Year Period.

    PubMed

    Eriksen, Sophie Isabel; Bjerrum, Lars

    2015-06-01

    Prolonged consumption of benzodiazepine drugs (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone; altogether Z drugs) is related to potential physiological and psychological dependence along with other adverse effects. This study aimed to analyse the prescribing of long-acting BZD (half-life >10 hr), compared to short-acting BZD in Denmark during a 10-year period. Descriptive analysis of total sales data from the Danish Register of Medicinal Product Statistics, to individuals in the primary healthcare sector, of all BZD and Z drugs in the period of 2003-2013. Prescription data derive from all community and hospital pharmacies in Denmark. The prescribing of long-acting BZD was reduced from 25.8 defined daily doses (DDD)/1000 inhabitants/day in 2003 to 8.8 DDD/1000 inhabitants/day in 2013, a relative reduction of 66%. The prescribing of short-acting BZD was reduced from 26.1 DDD/1000 inhabitants/day in 2003 to 16.4 DDD/1000 inhabitants/day in 2013, a relative reduction of 37%. Prescription data in this study did not include information about indications for initiating treatments. In addition, due to compliance problems, some of the prescribed drugs may not have been consumed according to the prescription. The observed reduction in BZD use was correlated to the introduction of new national guidelines on prescription of addictive drugs, but this study was not designed to detect a causal relationship. The prescribing of long-acting BZD decreased considerably more than the prescribing of short-acting BZD in the 10-year period. PMID:25382355

  2. Nano-functionalization of protein microspheres

    NASA Astrophysics Data System (ADS)

    Yoon, Sungkwon; Nichols, William T.

    2014-08-01

    Protein microspheres are promising building blocks for the assembly of complex functional materials. Here we demonstrate a set of three techniques that add functionality to the surface of protein microspheres. In the first technique, a positive surface charge on the protein spheres is deposited by electrostatic adsorption. Negatively charged silica and gold nanoparticle colloids can then electrostatically bind reversibly to the microsphere surface. In the second technique, nanoparticles are covalently anchored to the protein shell using a simple one-pot process. The strong covalent bond between sulfur groups in cysteine in the protein shell irreversibly binds to the gold nanoparticles. In the third technique, surface morphology of the protein microsphere is tuned through hydrodynamic instability at the water-oil interface. This is accomplished through the degree of solubility of the oil phase in water. Taken together these three techniques form a platform to create nano-functionalized protein microspheres, which can then be used as building blocks for the assembly of more complex macroscopic materials.

  3. Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis

    PubMed Central

    Tricco, Andrea C; Ashoor, Huda M; Antony, Jesmin; Beyene, Joseph; Veroniki, Areti Angeliki; Isaranuwatchai, Wanrudee; Harrington, Alana; Wilson, Charlotte; Tsouros, Sophia; Soobiah, Charlene; Yu, Catherine H; Hutton, Brian; Hoch, Jeffrey S; Hemmelgarn, Brenda R; Moher, David; Majumdar, Sumit R

    2014-01-01

    Objective To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. Design Systematic review and network meta-analysis. Data sources Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013. Study selection Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included. Results 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference ?0.39%, 95% confidence interval ?0.59% to ?0.19%; ?0.26%, ?0.48% to ?0.03%; and ?0.36%, ?0.65% to ?0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: ?5.51 kg, ?6.56 to ?4.46 kg; glargine once daily versus NPH once daily: ?5.14 kg, ?6.07 to ?4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses. Conclusions Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility. Systematic review registration PROSPERO CRD42013003610. PMID:25274009

  4. Development of Drug-Loaded PLGA Microparticles Bull. Korean Chem. Soc. 2011, Vol. 32, No. 3 867 DOI 10.5012/bkcs.2011.32.3.867

    E-print Network

    Park, Jong-Sang

    Development of Drug-Loaded PLGA Microparticles Bull. Korean Chem. Soc. 2011, Vol. 32, No. 3 867 DOI 10.5012/bkcs.2011.32.3.867 Development of Drug-Loaded PLGA Microparticles with Different Release and sustained release rates of low molecular weight drugs, poly(lactic-co-glycolic acid) (PLGA) microparticles

  5. Thermal Process to Strengthen PLGA Nanoparticle Layers Bull. Korean Chem. Soc. 2009, Vol. 30, No. 9 1985 Thermal Process for Enhancing Mechanical Strength

    E-print Network

    Park, Jong-Sang

    Thermal Process to Strengthen PLGA Nanoparticle Layers Bull. Korean Chem. Soc. 2009, Vol. 30, No. 9 1985 Thermal Process for Enhancing Mechanical Strength of PLGA Nanoparticle Layers on Coronary Stents@plaza.snu.ac.kr Received June 5, 2009, Accepted July 14, 2009 Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loading

  6. In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

    NASA Astrophysics Data System (ADS)

    Zhang, Jiang; Liu, Yang; Luo, Rifang; Chen, Si; Li, Xin; Yuan, Shuheng; Wang, Jin; Huang, Nan

    2015-02-01

    Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

  7. Drug release from irradiated PLGA and PLLA multi-layered films.

    PubMed

    Loo, Say Chye Joachim; Tan, Zhi Ying Serlin; Chow, Yi Jun; Lin, Siew Ling Ivy

    2010-07-01

    Poly(lactide-co-glycolic acid) (PLGA) and poly(L-lactide) (PLLA) films are widely studied for various biomedical applications. Because of their use for drug delivery, achieving controlled release from these biodegradable films has become an area of intense research. The objective of this study is therefore to investigate how PLGA and PLLA films fabricated through an irradiated-multi-layer approach can be a viable technique to achieve controlled drug delivery. In this study, lidocaine base (lido-base) and lidocaine salt (lido-salt) were used as model hydrophobic and hydrophilic drugs, respectively. Results show that multi-layer PLGA underwent pseudo surface degradation, while multi-layer PLLA degraded to a lesser extent over the same study period. Triphasic release was observed for lido-base, whereas lido-salt was released through a biphasic profile, from both polymer systems. The two dominating release phases for both drugs were diffusion and zero-order release, where the latter is characterized by the onset of mass loss. It was shown that PLGA had a shorter diffusion phase and a longer zero-order phase, while the contrary was true for PLLA. This difference was due to the faster degradation for PLGA. In conclusion, the hydrophilic gradient induced from an irradiated-multi-layer film system shows potential for controlled and sustained release of drugs. PMID:20112427

  8. Surface Entrapment of Fibronectin on Electrospun PLGA Scaffolds for Periodontal Tissue Engineering

    PubMed Central

    Gritsch, Kerstin; Salles, Vincent; Attik, Ghania N.; Grosgogeat, Brigitte

    2014-01-01

    Abstract Nowadays, the challenge in the tissue engineering field consists in the development of biomaterials designed to regenerate ad integrum damaged tissues. Despite the current use of bioresorbable polyesters such as poly(l-lactide) (PLA), poly(d,l-lactide-co-glycolide) (PLGA), and poly-?-caprolactone in soft tissue regeneration researches, their hydrophobic properties negatively influence the cell adhesion. Here, to overcome it, we have developed a fibronectin (FN)-functionalized electrospun PLGA scaffold for periodontal ligament regeneration. Functionalization of electrospun PLGA scaffolds was performed by alkaline hydrolysis (0.1 or 0.01?M NaOH). Then, hydrolyzed scaffolds were coated by simple deposition of an FN layer (10??g/mL). FN coating was evidenced by X-ray photoelectron analysis. A decrease of contact angle and greater cell adhesion to hydrolyzed, FN-coated PLGA scaffolds were noticed. Suitable degradation behavior without pH variations was observed for all samples up to 28 days. All treated materials presented strong shrinkage, fiber orientation loss, and collapsed fibers. However, functionalization process using 0.01?M NaOH concentration resulted in unchanged scaffold porosity, preserved chemical composition, and similar mechanical properties compared with untreated scaffolds. The proposed simplified method to functionalize electrospun PLGA fibers is an efficient route to make polyester scaffolds more biocompatible and shows potential for tissue engineering. PMID:24940563

  9. Experimental research on ectopic osteogenesis of BMP2-derived peptide P24 combined with PLGA copolymers.

    PubMed

    Duan, Zhixia; Zheng, Qixin; Guo, Xiaodong; Yuan, Quan; Chen, Shunguang

    2007-04-01

    To experimentally evaluate the ectopic osteogenetic capacity of synthesized BMP2-derived peptide P24 combined with poly lactic-co-glycolic acid (PLGA), Wistar rats were divided into two groups: group A, in which BMP2-derived peptide P24/PLGA complex was implanted, and group B which received simple PLGA implant. The complex was respectively implanted into the back muscles of rats. Samples were taken the 1st, 4th, 8th, and the 12th week after the implantation. Their bone formation was detected by X-ray examination, and tissue response was histologically observed. Western blotting was used for the detection of the expression of collagen I (Col-I) and osteopontin (OPN). There was acute inflammation in the tissue around both types of implants at early stage. The cartilage was found around implant areas 4 weeks after the implantation of BMP2-derived peptide p24/PLGA complex, 8 weeks after the implantation, osteoblasts were found, and 12 weeks after the implantation, typical trabecular bone structure was observed. In group B, after 12 weeks, no osteoblasts were found. It is concluded that PLGA is an ideal scaffold material for bone tissue engineering. BMP2-derived peptide can start endochondral ossification and is more effective in inducing ectopic osteogenesis. PMID:17497291

  10. The construction and investigation of PLGA artificial bone by biomimetic mineralization.

    PubMed

    Zhao, Ming; Zheng, Qixin; Wang, Jinguang; Wang, Yuntao; Hao, Jie

    2005-01-01

    To modify the surface property of poly lactide-co-glycolide (PLGA) by biomimetic mineralization to construct a new kind of artificial bone. PLGA films and 3-diamensional (3-D) porous scaffolds hydrolyzed in alkaline solution were minerilized in SBF for 14 days. The morphology and composition of the mineral grown on PLGA were analyzed with SEM, FTIR and XRD. The porosity of the scaffolds was detected by using the liquid displacement method. The compressive strength of the scaffolds was detected by using a Shimadzu universal mechanic tester. An obvious mineral coating was detected on the surface of films and scaffolds. The main component of the mineral was carbonated hydroxyapatite (HA) similar to the major mineral component of bone tissues. The porosity of the un-mineralized and mineralized porous scaffolds was (84.86 +/- 8.52) % and (79.70 +/- 7.70) % respectively. The compressive strength was 0.784 +/- 0.156 N/mm2 in un-mineralized 3-D porous PLGA and 0.858 +/- 0.145 N/mm2 in mineralized 3-D porous PLGA. There were no significant differences between the mineralized and un-mineralized scaffolds (P > 0.05) in porosity and biomechanics. Biomimetic mineralization is a suitable method to construct artificial bone. PMID:16696326

  11. Development of a porous PLGA-based scaffold for mastoid air cell regeneration

    PubMed Central

    Gould, Toby W. A.; Birchall, John P.; Mallick, Ali S.; Alliston, Tamara; Lustig, Lawrence R.; Shakesheff, Kevin M.

    2015-01-01

    Objective To develop a porous, biodegradable scaffold for mastoid air cell regeneration. Study Design In vitro development of a temperature-sensitive poly(DL-lactic acid-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) scaffold tailored for this application. Methods Human mastoid bone microstructure and porosity was investigated using micro-computed tomography. PLGA/PEG-alginate scaffolds were developed and scaffold porosity was assessed. Human bone marrow mesenchymal stem cells (hBM-MSCs) were cultured on the scaffolds in vitro. Scaffolds were loaded with ciprofloxacin and release of ciprofloxacin over time in vitro was assessed. Results Porosity of human mastoid bone was measured at 83% with an average pore size of 1.3mm. PLGA/PEG-alginate scaffold porosity ranged from 43–78% depending on the alginate bead content. hBM-MSCs proliferate on the scaffolds in vitro, and release of ciprofloxacin from the scaffolds was demonstrated over 7–10 weeks. Conclusion The PLGA/PEG-alginate scaffolds developed in this study demonstrate similar structural features to human mastoid bone, support cell growth and display sustained antibiotic release. These scaffolds may be of potential clinical use in mastoid air cell regeneration. Further in vivo studies to assess the suitability of PLGA/PEG-alginate scaffolds for this application are required. PMID:23670365

  12. Adrenomedullin delivery in microsphere-scaffold composite for remodeling of the alveolar bone following tooth extraction: an experimental study in the rat

    PubMed Central

    2013-01-01

    Background Alveolar ridge resorption, as a significant problem in implant and restorative dentistry, has long been considered as an inevitable outcome following tooth extraction. Recently, adrenomedullin (ADM) is reported to be able to stimulate the proliferation and migration of various cells including osteoblasts. The purpose of this study was to investigate the influence of local ADM application in the tooth extraction socket in vivo. Methods Chitosan micropheres were developed by an emulsion-ionic cross-linking method for ADM delivery. Poly (L -lactic-co-glycolic) acid (PLGA) and nano-hydroxyapatite (nHA) were used to prepare scaffolds to contain the micrspheres with ADM. In vivo experiment was evaluated by transplanting the composite into the rat socket right after the incisor extraction. After 4, 8, 12 weeks implantation, radiographic and histological tests were carried out to evaluate the effect of released ADM on the alveolar bone. Results The microspheres had a spherical structure and a relative rough and uniform surface, and the particle size was under a normal distribution, with the average diameter of 38.59 ?m. The scaffolds had open and interconnected pores. In addition, the high porosity of the composite was 88.93%. Radiographic and histological examination revealed that the PLGA/nHA/CMs/ADM composite could accelerate the alveolar bone remodeling and reduce the residual ridge resorption compared with the PLGA/nHA/CMs scaffold. Conclusions The results of this study suggest that local application of ADM has the potential to preserve the residual alveolar ridge and accelerate the alveolar bone remodeling. PMID:24099554

  13. Endocytosis of Nanomedicines: The Case of Glycopeptide Engineered PLGA Nanoparticles

    PubMed Central

    Vilella, Antonietta; Ruozi, Barbara; Belletti, Daniela; Pederzoli, Francesca; Galliani, Marianna; Semeghini, Valentina; Forni, Flavio; Zoli, Michele; Vandelli, Maria Angela; Tosi, Giovanni

    2015-01-01

    The success of nanomedicine as a new strategy for drug delivery and targeting prompted the interest in developing approaches toward basic and clinical neuroscience. Despite enormous advances on brain research, central nervous system (CNS) disorders remain the world’s leading cause of disability, in part due to the inability of the majority of drugs to reach the brain parenchyma. Many attempts to use nanomedicines as CNS drug delivery systems (DDS) were made; among the various non-invasive approaches, nanoparticulate carriers and, particularly, polymeric nanoparticles (NPs) seem to be the most interesting strategies. In particular, the ability of poly-lactide-co-glycolide NPs (PLGA-NPs) specifically engineered with a glycopeptide (g7), conferring to NPs’ ability to cross the blood brain barrier (BBB) in rodents at a concentration of up to 10% of the injected dose, was demonstrated in previous studies using different routes of administrations. Most of the evidence on NP uptake mechanisms reported in the literature about intracellular pathways and processes of cell entry is based on in vitro studies. Therefore, beside the particular attention devoted to increasing the knowledge of the rate of in vivo BBB crossing of nanocarriers, the subsequent exocytosis in the brain compartments, their fate and trafficking in the brain surely represent major topics in this field. PMID:26102358

  14. Endocytosis of Nanomedicines: The Case of Glycopeptide Engineered PLGA Nanoparticles.

    PubMed

    Vilella, Antonietta; Ruozi, Barbara; Belletti, Daniela; Pederzoli, Francesca; Galliani, Marianna; Semeghini, Valentina; Forni, Flavio; Zoli, Michele; Vandelli, Maria Angela; Tosi, Giovanni

    2015-01-01

    The success of nanomedicine as a new strategy for drug delivery and targeting prompted the interest in developing approaches toward basic and clinical neuroscience. Despite enormous advances on brain research, central nervous system (CNS) disorders remain the world's leading cause of disability, in part due to the inability of the majority of drugs to reach the brain parenchyma. Many attempts to use nanomedicines as CNS drug delivery systems (DDS) were made; among the various non-invasive approaches, nanoparticulate carriers and, particularly, polymeric nanoparticles (NPs) seem to be the most interesting strategies. In particular, the ability of poly-lactide-co-glycolide NPs (PLGA-NPs) specifically engineered with a glycopeptide (g7), conferring to NPs' ability to cross the blood brain barrier (BBB) in rodents at a concentration of up to 10% of the injected dose, was demonstrated in previous studies using different routes of administrations. Most of the evidence on NP uptake mechanisms reported in the literature about intracellular pathways and processes of cell entry is based on in vitro studies. Therefore, beside the particular attention devoted to increasing the knowledge of the rate of in vivo BBB crossing of nanocarriers, the subsequent exocytosis in the brain compartments, their fate and trafficking in the brain surely represent major topics in this field. PMID:26102358

  15. Spectral and Spatial Characterization of Protein Loaded PLGA Nanoparticles

    PubMed Central

    Zidan, Ahmed S.; Rahman, Ziyaur; Habib, Muhammad J.; Khan, Mansoor A.

    2011-01-01

    The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess drug contents in poly(dl-lactide-co-glycolide) (PLGA) based nanoparticles of a model protein, cyclosporine A (CyA). A 6-factors 12-runs designed set of experiments with Plackett–Burman (PB) screening was applied in order to examine the effects of drug loading (X1), polymer loading (X2), emulsifier concentration (X3), stirring rate (X4), type of organic solvent (X5), and ratio of organic to aqueous phases' volumes (X6), on drug entrapment efficiency (EFF). After omitting the factors with nonsignificant influences on EFF, a reduced mathematical relationship, EFF = 48.34 + 7.3X1 ? 29.95X3, was obtained to explain the effect of the significant factors on EFF. Using two different sets for calibration and validation, the developed NIR calibration model was able to assess CyA contents within the 12 PB formulations. NIR spectral imaging was capable of clearly distinguishing the 12 formulations, both qualitatively and quantitatively. A good correlation with a coefficient of 0.9727 was obtained for constructing a quantile-quantile plot for the actual drug loading percentage and the % standard deviation obtained for the drug loading prediction using the hyperspectral images. PMID:19774658

  16. Localized drugs delivery hydroxyapatite microspheres for osteoporosis therapy

    NASA Astrophysics Data System (ADS)

    Lee, J. H.; Ko, I. H.; Jeon, S.-H.; Chae, J. H.; Lee, E. J.; Chang, J. H.

    2011-10-01

    This study describes the preparation of hydroxyapatite microspheres for local drugs delivery. The formation of the hydroxyapatite microspheres was initiated by enzymatic decomposition of urea and accomplished by emulsification process (water-in-oil). The microspheres obtained were sintered at 500°C. Scanning electron microscope (SEM) indicated that the microspheres have various porous with random size, which maximizes the surface area. Cytotoxicity was not observed after sintering. Osteoporosis drugs, alendronate and BMP-2, were loaded into HAp microspheres and the releases of both molecules showed sustained releasing profiles.

  17. Microspheres for controlled release drug delivery.

    PubMed

    Varde, Neelesh K; Pack, Daniel W

    2004-01-01

    Controlled release drug delivery employs drug-encapsulating devices from which therapeutic agents may be released at controlled rates for long periods of time, ranging from days to months. Such systems offer numerous advantages over traditional methods of drug delivery, including tailoring of drug release rates, protection of fragile drugs and increased patient comfort and compliance. Polymeric microspheres are ideal vehicles for many controlled delivery applications due to their ability to encapsulate a variety of drugs, biocompatibility, high bioavailability and sustained drug release characteristics. Research discussed in this review is focused on improving large-scale manufacturing, maintaining drug stability and enhancing control of drug release rates. This paper describes methods of microparticle fabrication and the major factors controlling the release rates of encapsulated drugs. Furthermore, recent advances in the use of polymer microsphere-based systems for delivery of single-shot vaccines, plasmid DNA and therapeutic proteins are discussed, as well as some future directions of microsphere research. PMID:14680467

  18. Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    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 ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-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 NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX 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.

  19. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    PubMed Central

    2014-01-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC. PMID:25232295

  20. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters.

    PubMed

    Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming

    2014-01-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC. PMID:25232295

  1. Polymeric Microspheres as Protein Transduction Reagents*

    PubMed Central

    Nagel, David; Behrendt, Jonathan M.; Chimonides, Gwen F.; Torr, Elizabeth E.; Devitt, Andrew; Sutherland, Andrew J.; Hine, Anna V.

    2014-01-01

    Discovering the function of an unknown protein, particularly one with neither structural nor functional correlates, is a daunting task. Interaction analyses determine binding partners, whereas DNA transfection, either transient or stable, leads to intracellular expression, though not necessarily at physiologically relevant levels. In theory, direct intracellular protein delivery (protein transduction) provides a conceptually simpler alternative, but in practice the approach is problematic. Domains such as HIV TAT protein are valuable, but their effectiveness is protein specific. Similarly, the delivery of intact proteins via endocytic pathways (e.g. using liposomes) is problematic for functional analysis because of the potential for protein degradation in the endosomes/lysosomes. Consequently, recent reports that microspheres can deliver bio-cargoes into cells via a non-endocytic, energy-independent pathway offer an exciting and promising alternative for in vitro delivery of functional protein. In order for such promise to be fully exploited, microspheres are required that (i) are stably linked to proteins, (ii) can deliver those proteins with good efficiency, (iii) release functional protein once inside the cells, and (iv) permit concomitant tracking. Herein, we report the application of microspheres to successfully address all of these criteria simultaneously, for the first time. After cellular uptake, protein release was autocatalyzed by the reducing cytoplasmic environment. Outside of cells, the covalent microsphere–protein linkage was stable for ?90 h at 37 °C. Using conservative methods of estimation, 74.3% ± 5.6% of cells were shown to take up these microspheres after 24 h of incubation, with the whole process of delivery and intracellular protein release occurring within 36 h. Intended for in vitro functional protein research, this approach will enable study of the consequences of protein delivery at physiologically relevant levels, without recourse to nucleic acids, and offers a useful alternative to commercial protein transfection reagents such as Chariot™. We also provide clear immunostaining evidence to resolve residual controversy surrounding FACS-based assessment of microsphere uptake. PMID:24692642

  2. Number needed to treat and number needed to harm with paliperidone palmitate relative to long-acting haloperidol, bromperidol, and fluphenazine decanoate for treatment of patients with schizophrenia

    PubMed Central

    Gopal, Srihari; Berwaerts, Joris; Nuamah, Isaac; Akhras, Kasem; Coppola, Danielle; Daly, Ella; Hough, David; Palumbo, Joseph

    2011-01-01

    Background: We analyzed data retrieved through a PubMed search of randomized, placebo-controlled trials of first-generation antipsychotic long-acting injectables (haloperidol decanoate, bromperidol decanoate, and fluphenazine decanoate), and a company database of paliperidone palmitate, to compare the benefit-risk ratio in patients with schizophrenia. Methods: From the eight studies that met our selection criteria, two efficacy and six safety parameters were selected for calculation of number needed to treat (NNT), number needed to harm (NNH), and the likelihood of being helped or harmed (LHH) using comparisons of active drug relative to placebo. NNTs for prevention of relapse ranged from 2 to 5 for paliperidone palmitate, haloperidol decanoate, and fluphenazine decanoate, indicating a moderate to large effect size. Results: Among the selected maintenance studies, NNH varied considerably, but indicated a lower likelihood of encountering extrapyramidal side effects, such as akathisia, tremor, and tardive dyskinesia, with paliperidone palmitate versus placebo than with first-generation antipsychotic depot agents versus placebo. This was further supported by an overall higher NNH for paliperidone palmitate versus placebo with respect to anticholinergic use and Abnormal Involuntary Movement Scale positive score. LHH for preventing relapse versus use of anticholinergics was 15 for paliperidone palmitate and 3 for fluphenazine decanoate, favoring paliperidone palmitate. Conclusion: Overall, paliperidone palmitate had a similar NNT and a more favorable NNH compared with the first-generation long-acting injectables assessed. PMID:21552311

  3. Association of dose escalation of octreotide long-acting release on clinical symptoms and tumor markers and response among patients with neuroendocrine tumors.

    PubMed

    Al-Efraij, Khalid; Aljama, Mohammed A; Kennecke, Hagen Fritz

    2015-06-01

    Patients with nonresectable metastatic neuroendocrine tumors (NETs) experience symptoms of hormone hypersecretion including diarrhea, flushing, and bronchoconstriction, which can interfere with quality of life [Anthony and Vinik (2011) Pancreas, 40:987]. Treatment with a long-acting release formulation of octreotide, a somatostatin analog, can help to alleviate these symptoms. Although high doses of octreotide are often required for adequate symptom control, the relationship between octreotide dose escalation and symptom control in the NET context is not well quantified in the literature. A retrospective chart review was conducted of nonresectable metastatic NET patients who received a dose greater than 30 mg intramuscular octreotide long-acting formulation (O-LAR) at any time between January 2005 and December 2011 at the British Columbia Cancer Agency (BCCA). The association between dose escalation of O-LAR, chromogranin A (CGA), 24-h urine 5-hydoxyindoacetate (5-HIAA), symptom control, and radiological progression was explored. Dose escalation of O-LAR was associated with improved symptom control in NET patients who were refractory to the standard dose levels. Reduction of serum CGA & 5-HIAA levels by at least 10% was observed in 31% and 23% respectively. Retrospective review of imaging did not document any reductions in tumor volume. Higher doses of O-LAR are associated with improved symptom control in NET patients. The variability in tumor marker levels in response to O-LAR dose escalation may indicate that tumor marker levels may not be an accurate assessment of therapeutic efficacy. PMID:25727756

  4. Association of dose escalation of octreotide long-acting release on clinical symptoms and tumor markers and response among patients with neuroendocrine tumors

    PubMed Central

    Al-Efraij, Khalid; Aljama, Mohammed A; Kennecke, Hagen Fritz

    2015-01-01

    Patients with nonresectable metastatic neuroendocrine tumors (NETs) experience symptoms of hormone hypersecretion including diarrhea, flushing, and bronchoconstriction, which can interfere with quality of life [Anthony and Vinik (2011) Pancreas, 40:987]. Treatment with a long-acting release formulation of octreotide, a somatostatin analog, can help to alleviate these symptoms. Although high doses of octreotide are often required for adequate symptom control, the relationship between octreotide dose escalation and symptom control in the NET context is not well quantified in the literature. A retrospective chart review was conducted of nonresectable metastatic NET patients who received a dose greater than 30 mg intramuscular octreotide long-acting formulation (O-LAR) at any time between January 2005 and December 2011 at the British Columbia Cancer Agency (BCCA). The association between dose escalation of O-LAR, chromogranin A (CGA), 24-h urine 5-hydoxyindoacetate (5-HIAA), symptom control, and radiological progression was explored. Dose escalation of O-LAR was associated with improved symptom control in NET patients who were refractory to the standard dose levels. Reduction of serum CGA & 5-HIAA levels by at least 10% was observed in 31% and 23% respectively. Retrospective review of imaging did not document any reductions in tumor volume. Higher doses of O-LAR are associated with improved symptom control in NET patients. The variability in tumor marker levels in response to O-LAR dose escalation may indicate that tumor marker levels may not be an accurate assessment of therapeutic efficacy. PMID:25727756

  5. Formulation and evaluation of nasal mucoadhesive microspheres of sumatriptan succinate.

    PubMed

    Jain, Snehal A; Chauk, Dheeraj S; Mahajan, Hitendra S; Tekade, Avinash R; Gattani, Surendra G

    2009-12-01

    The purpose of present research work was to develop mucoadhesive microspheres for nasal delivery with the aim to avoid hepatic first-pass metabolism, improve therapeutic efficacy and enhance residence time. For the treatment of migraine, hydroxypropyl methylcellulose (HPMC) K4M and K15M based microspheres containing sumatriptan succinate (SS) were prepared by spray-drying technique. The microspheres were evaluated with respect to the yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, in vitro drug release, histological study and stability. Microspheres were characterized by differential scanning calorimetry, scanning electron microscopy and X-ray diffraction study. It was found that the particle size, swelling ability and incorporation efficiency of microspheres increases with increasing drug-to-polymer ratio. HPMC-based microspheres show adequate mucoadhesion and do not have any destructive effect on nasal mucosa. On the basis of these results, SS microspheres based on HPMC may be considered as a promising nasal delivery system. PMID:19888880

  6. Cell specific, variable density, polymer microspheres

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Molday, Robert S. (Inventor)

    1977-01-01

    Biocompatible polymeric microspheres having an average diameter below about 3 microns and having density at least 15% greater or lesser than organic cells and having covalent binding sites are provided in accordance with this invention. The microspheres are obtained by copolymerizing a hydroxy or amine substituted acrylic monomer such as hydroxyethylmethacrylate with a light or dense comonomer such as a fluoromonomer. A lectin or antibody is bound to the hydroxy or amine site of the bead to provide cell specificity. When added to a cell suspension the marked bead will specifically label the cell membrane by binding to specific receptor sites thereon. The labelled membrane can then be separated by density gradient centrifugation.

  7. Quantum Magnetomechanics with Levitating Superconducting Microspheres

    E-print Network

    O. Romero-Isart; L. Clemente; C. Navau; A. Sanchez; J. I. Cirac

    2012-03-07

    We show that by magnetically trapping a superconducting microsphere close to a quantum circuit, it is experimentally feasible to perform ground-state cooling and to prepare quantum superpositions of the center-of-mass motion of the microsphere. Due to the absence of clamping losses and time dependent electromagnetic fields, the mechanical motion of micrometer-sized metallic spheres in the Meissner state is predicted to be very well isolated from the environment. Hence, we propose to combine the technology of magnetic microtraps and superconducting qubits to bring relatively large objects to the quantum regime.

  8. Quantum Magnetomechanics with Levitating Superconducting Microspheres

    E-print Network

    Romero-Isart, O; Navau, C; Sanchez, A; Cirac, J I

    2011-01-01

    We show that by magnetically trapping a superconducting microsphere close to a quantum circuit, it is experimentally feasible to perform ground state cooling and to prepare quantum superpositions of the center-of-mass motion of the microsphere. Due to the absence of clamping losses and time dependent electromagnetic fields, the mechanical motion of micrometer-sized metallic spheres in the Meissner state is predicted to be extremely well isolated from the environment. Hence, we propose to combine the technology of magnetic mictrotraps and superconducting qubits to bring relatively large objects to the quantum regime.

  9. Quantum Magnetomechanics with Levitating Superconducting Microspheres

    NASA Astrophysics Data System (ADS)

    Romero-Isart, O.; Clemente, L.; Navau, C.; Sanchez, A.; Cirac, J. I.

    2012-10-01

    We show that by magnetically trapping a superconducting microsphere close to a quantum circuit, it is possible to perform ground-state cooling and prepare quantum superpositions of the center-of-mass motion of the microsphere. Due to the absence of clamping losses and time-dependent electromagnetic fields, the mechanical motion of micrometer-sized metallic spheres in the Meissner state is predicted to be very well isolated from the environment. Hence, we propose to combine the technology of magnetic microtraps and superconducting qubits to bring relatively large objects to the quantum regime.

  10. Effects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma

    PubMed Central

    Xiao, Xiaojun; Zeng, Xiaowei; Zhang, Xinxin; Ma, Li; Liu, Xiaoyu; Yu, Haiqiong; Mei, Lin; Liu, Zhigang

    2013-01-01

    Background Pollen allergy is the most common allergic disease. However, tropical pollens, such as those of Palmae, have seldom been investigated compared with the specific immunotherapy studies done on hyperallergenic birch, olive, and ragweed pollens. Although poly(lactic-co-glycolic acid) (PLGA) has been extensively applied as a biodegradable polymer in medical devices, it has rarely been utilized as a vaccine adjuvant to prevent and treat allergic disease. In this study, we investigated the immunotherapeutic effects of recombinant Caryota mitis profilin (rCmP)-loaded PLGA nanoparticles and the underlying mechanisms involved. Methods A mouse model of allergenic asthma was established for specific immunotherapy using rCmP-loaded PLGA nanoparticles as the adjuvant. The model was evaluated by determining airway hyperresponsiveness and levels of serum-specific antibodies (IgE, IgG, and IgG2a) and cytokines, and observing histologic sections of lung tissue. Results The rCmP-loaded PLGA nanoparticles effectively inhibited generation of specific IgE and secretion of the Th2 cytokine interleukin-4, facilitated generation of specific IgG2a and secretion of the Th1 cytokine interferon-gamma, converted the Th2 response to Th1, and evidently alleviated allergic symptoms. Conclusion PLGA functions more appropriately as a specific immunotherapy adjuvant for allergen vaccines than does conventional Al(OH)3 due to its superior efficacy, longer potency, and markedly fewer side effects. The rCmP-loaded PLGA nanoparticles developed herein offer a promising avenue for specific immunotherapy in allergic asthma. PMID:24376349

  11. Electrospun PLGA Fibers Incorporated with Functionalized Biomolecules for Cardiac Tissue Engineering

    PubMed Central

    Yu, Jiashing; Lee, An-Rei; Lin, Wei-Han; Lin, Che-Wei; Wu, Yuan-Kun

    2014-01-01

    Structural similarity of electrospun fibers (ESFs) to the native extracellular matrix provides great potential for the application of biofunctional ESFs in tissue engineering. This study aimed to synthesize biofunctionalized poly (L-lactide-co-glycolide) (PLGA) ESFs for investigating the potential for cardiac tissue engineering application. We developed a simple but novel strategy to incorporate adhesive peptides in PLGA ESFs. Two adhesive peptides derived from laminin, YIGSR, and RGD, were covalently conjugated to poly-L-lysine, and then mingled with PLGA solution for electrospinning. Peptides were uniformly distributed on the surface and in the interior of ESFs. PLGA ESFs incorporated with YIGSR or RGD or adsorbed with laminin significantly enhanced the adhesion of cardiomyocytes isolated from neonatal rats. Furthermore, the cells were found to adhere better on ESFs compared with flat substrates after 7 days of culture. Immunofluorescent staining of F-actin, vinculin, a-actinin, and N-cadherin indicated that cardiomyocytes adhered and formed striated ?-actinin better on the laminin-coated ESFs and the YIGSR-incorporated ESFs compared with the RGD-incorporated ESFs. The expression of ?-myosin heavy chain and ?-tubulin on the YIGSR-incorporated ESFs was significantly higher compared with the expression level on PLGA and RGD-incorporated samples. Furthermore, the contraction of cardiomyocytes was faster and lasted longer on the laminin-coated ESFs and YIGSR-incorporated ESFs. The results suggest that aligned YIGSR-incorporated PLGA ESFs is a better candidate for the formation of cardiac patches. This study demonstrated the potential of using peptide-incorporated ESFs as designable-scaffold platform for tissue engineering. PMID:24471778

  12. Sustained release properties of alginate microspheres and tabletted microspheres of diclofenac sodium.

    PubMed

    Gürsoy, A; Cevik, S

    2000-01-01

    This study focused on the properties of diclofenac sodium (DNa) alginate (alg) microspheres and tabletted DNa alg microspheres using different polymers as additives. DNa alginate microspheres were prepared by the emulsification method and different polymers such as Eudragit (Eud) NE 30 D, Eudragit (Eud) RS 30 D and Aquacoat, which were incorporated into alg gel to control the release rate of drug. The release properties of DNa alg microspheres (1:1) were affected by the size, drug load of microspheres and also by the incorporated polymers, pH and ionic strength of dissolution medium. Tabletting of alg microspheres using carrageenan (carr), alg, pectin, NaCMC, tragacanth (trgh) and HPMC as additives in a (50:50) ratio produced tablets with good physical properties and also better controlled release of DNa. Dissolution studies were carried out in pH 7.2 phosphate buffer and phosphate buffers whose pH values were gradually changed from pH 3 to 7.4. The rank order of DNa release from tablets was carr < alg < pectin < NaCMC < trgh < HPMC which relates to the viscosity and swelling properties of polymers. The drug release was very slow from trgh and HPMC based tablets, but addition of carr or alg in different ratios could adjust the release rate of drug. PMID:11038116

  13. Structural and degradation characteristics of an innovative porous PLGA/TCP scaffold incorporated with bioactive molecular icaritin.

    PubMed

    Xie, Xin-Hui; Wang, Xin-Luan; Zhang, Ge; He, Yi-Xin; Wang, Xiao-Hong; Liu, Zhong; He, Kai; Peng, Jiang; Leng, Yang; Qin, Ling

    2010-10-01

    Phytomolecules may chemically bind to scaffold materials for medical applications. The present study used an osteoconductive porous poly(l-lactide-co-glycolide)/tricalcium phosphate (PLGA/TCP) to incorporate an exogenous phytoestrogenic molecule icaritin to form a PLGA/TCP/icaritin composite scaffold material with potential slow release of icaritin during scaffold degradation. Accordingly, the present study was designed to investigate its in vitro degradation characteristics and the release pattern of icaritin at three different doses (74 mg, 7.4 mg and 0.74 mg per 100 g PLGA/TCP, i.e. in the PLGA/TCP/icaritin-H, -M and -L groups, respectively). A PLGA/TCP/icaritin porous composite scaffold was fabricated using a computer-controlled printing machine. The PLGA/TCP/icaritin scaffolds were incubated in saline at 37 °C for 12 weeks and the pure PLGA/TCP scaffold served as a control. During the 12 weeks in vitro degradation, the scaffolds in all four groups showed changes, including a decrease in weight, volume and pore size of the composite scaffold, while there was a decrease in acidity and an increase in Ca and lactic acid concentrations in the degradation medium, especially after 7 weeks. The rate of degradation was explained by the relationship with the content of icaritin incorporated into the scaffolds. The higher the icaritin content in the scaffolds, the slower the degradation could be observed during 12 weeks. After 12 weeks, the SEM showed that the surface of the PLGA/TCP and PLGA/TCP/icaritin-L groups was relatively smooth with a gradual decrease in number and size of the micropores, while the porous morphology on the surface of the PLGA/TCP/icaritin-M and PLGA/TCP/icaritin-H groups was partly maintained, accompanied by a decrease in phosphate (P) and calcium (Ca) contents at the surface. Though the mechanical property of the PLGA/TCP/icaritin scaffold decreased after degradation, its porous structure was maintained, which was essential for cell migration and ingrowth of newly regenerated tissues in vivo. The controlled release of icaritin from the composite scaffold reached about 70% of the incorporated icaritin into the degradation medium after 12 weeks. The above findings suggested that the structural and degradation properties of the porous composite PLGA/TCP/icaritin scaffold were dependent on icaritin concentrations. This innovative composite porous scaffold material developed in the present study may be used as a good scaffold material for enhancing bone repair, especially at high concentrations of icaritin. In vivo confirmation is, however, needed to substantiate our in vitro findings. PMID:20876954

  14. Beat-Frequency/Microsphere Medical Ultrasonic Imaging

    NASA Technical Reports Server (NTRS)

    Yost, William T.; Cantrell, John H.; Pretlow, Robert A., III

    1995-01-01

    Medical ultrasonic imaging system designed to provide quantitative data on various flows of blood in chambers, blood vessels, muscles, and tissues of heart. Sensitive enough to yield readings on flows of blood in heart even when microspheres used as ultrasonic contrast agents injected far from heart and diluted by circulation of blood elsewhere in body.

  15. Preparation of small bio-compatible microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping S. (Inventor); Dreyer, William J. (Inventor)

    1979-01-01

    Small, round, bio-compatible microspheres capable of covalently bonding proteins and having a uniform diameter below about 3500 A are prepared by substantially instantaneously initiating polymerization of an aqueous emulsion containing no more than 35% total monomer including an acrylic monomer substituted with a covalently bondable group such a hydroxyl, amino or carboxyl and a minor amount of a cross-linking agent.

  16. PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration

    PubMed Central

    2014-01-01

    The development of tissue engineering in the field of orthopedic surgery is booming. Two fields of research in particular have emerged: approaches for tailoring the surface properties of implantable materials with osteoinductive factors as well as evaluation of the response of osteogenic cells to these fabricated implanted materials (hybrid material). In the present study, we chemically grafted insulin onto the surface of hydroxyapatite nanorods (nHA). The insulin-grafted nHAs (nHA-I) were dispersed into poly(lactide-co-glycolide) (PLGA) polymer solution, which was electrospun to prepare PLGA/nHA-I composite nanofiber scaffolds. The morphology of the electrospun nanofiber scaffolds was assessed by field emission scanning electron microscopy (FESEM). After extensive characterization of the PLGA/nHA-I and PLGA/nHA composite nanofiber scaffolds by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDS), and transmission electron microscopy (TEM), the PLGA/nHA-I and PLGA/nHA (used as control) composite nanofiber scaffolds were subjected to cell studies. The results obtained from cell adhesion, alizarin red staining, and Von Kossa assay suggested that the PLGA/nHA-I composite nanofiber scaffold has enhanced osteoblastic cell growth, as more cells were proliferated and differentiated. The fact that insulin enhanced osteoblastic cell proliferation will open new possibilities for the development of artificial scaffolds for bone tissue regeneration. PMID:25024679

  17. PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration

    NASA Astrophysics Data System (ADS)

    Haider, Adnan; Gupta, Kailash Chandra; Kang, Inn-Kyu

    2014-06-01

    The development of tissue engineering in the field of orthopedic surgery is booming. Two fields of research in particular have emerged: approaches for tailoring the surface properties of implantable materials with osteoinductive factors as well as evaluation of the response of osteogenic cells to these fabricated implanted materials (hybrid material). In the present study, we chemically grafted insulin onto the surface of hydroxyapatite nanorods (nHA). The insulin-grafted nHAs (nHA-I) were dispersed into poly(lactide-co-glycolide) (PLGA) polymer solution, which was electrospun to prepare PLGA/nHA-I composite nanofiber scaffolds. The morphology of the electrospun nanofiber scaffolds was assessed by field emission scanning electron microscopy (FESEM). After extensive characterization of the PLGA/nHA-I and PLGA/nHA composite nanofiber scaffolds by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDS), and transmission electron microscopy (TEM), the PLGA/nHA-I and PLGA/nHA (used as control) composite nanofiber scaffolds were subjected to cell studies. The results obtained from cell adhesion, alizarin red staining, and Von Kossa assay suggested that the PLGA/nHA-I composite nanofiber scaffold has enhanced osteoblastic cell growth, as more cells were proliferated and differentiated. The fact that insulin enhanced osteoblastic cell proliferation will open new possibilities for the development of artificial scaffolds for bone tissue regeneration.

  18. Fabrication of long-acting drug release property of hierarchical porous bioglasses/polylactic acid fibre scaffolds for bone tissue engineering.

    PubMed

    Wang, Dan; Lin, Huiming; Jiang, Jingjie; Jin, Qumei; Li, Lei; Dong, Yan; Qu, Fengyu

    2015-04-01

    Hierarchical porous fibre scaffolds with mesoporous bioglasses (MBGs) and polylactic acid (PLA) were successfully fabricated by the electrospinning method. These compound scaffolds possess macropores with sizes of about 100 nm because of the solvent evaporation from the fibre and the mesoporous structure ( ?4.0 nm) originated from MBGs. The biomineralisation ability was investigated in simulated body fluid. The fibre structure is beneficial for inducing the growth of hydroxyapatite. In addition, compared with pure MBGs, the materials (MP-1 and MP-2) exhibit a long-acting drug release process up to 140 h and the drug release process corresponds with the Fickian diffusion mechanism. With the special fibre morphology and the hierarchical porous structure, the MBGs/PLA fibre scaffolds are expected to have potential application for bone tissue repair and regeneration. PMID:25829170

  19. Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

    PubMed

    Muñoz Torres, Manuel

    2014-03-01

    Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens. PMID:23890782

  20. Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold

    PubMed Central

    Xin, Xuejun; Hussain, Mohammad; Mao, Jeremy J.

    2010-01-01

    Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(D,L-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760±210 nm. The average Young’s modulus of electrospun PLGA nanofibers was 42±26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1–4 weeks at a density of 2×106 cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells. PMID:17010425

  1. PLGA/TCP composite scaffold incorporating bioactive phytomolecule icaritin for enhancement of bone defect repair in rabbits.

    PubMed

    Chen, S-H; Lei, M; Xie, X-H; Zheng, L-Z; Yao, D; Wang, X-L; Li, W; Zhao, Z; Kong, A; Xiao, D-M; Wang, D-P; Pan, X-H; Wang, Y-X; Qin, L

    2013-05-01

    Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides support to enhance biological bone repair. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12 mm ulnar bone defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications. PMID:23376238

  2. Long-acting neuroleptic use for reproductive management of non-domestic ungulates using the domestic goat (Capra hircus) as a model.

    PubMed

    Weiss, Rachael B; Schook, Mandi W; Wolfe, Barbara A

    2014-01-01

    Fluphenazine decanoate is a long-acting phenothiazine neuroleptic that attenuates the stress response and may be useful during intensive handling for reproductive procedures in non-domestic ungulates. However, phenothiazines are also associated with elevated serum prolactin, which can suppress fertility in some species. For this study, 10 female domestic goats were used as a model for non-domestic caprids to test effects of fluphenazine decanoate on serum cortisol and reproductive cyclicity following estrus synchronization. Two identical trials were conducted during the breeding season, employing a random crossover design. First, females underwent estrus synchronization using a 14-day treatment with progesterone (330 mg; CIDR). After 7 days of CIDR exposure, the treatment group (n = 5) received fluphenazine decanoate (1.0 mg/kg IM) and controls (n = 5) received an equivalent volume of 0.9% saline IM. At CIDR withdrawal (Day 14), animals received 125 mg cloprostenol sodium to lyse any luteal tissue and synchronize estrus. Blood was collected every 2 hr from 36 hr after CIDR withdrawal until 24 hr after standing estrus, or up to 5 days to monitor stress and reproductive hormones. Serum cortisol, prolactin, luteinizing hormone (LH) and progesterone concentrations were determined by enzyme immunoassay. While treatment with fluphenazine was associated with lower cortisol concentrations compared to controls (P = 0.001), 4 of the 10 treated animals experienced elevated serum prolactin, suppression of the LH surge and inhibition of ovulation. These findings suggest that long-acting neuroleptic drugs reduce the adrenal stress response, but may interfere with reproductive responses and negatively influence breeding success. PMID:24644127

  3. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases

    PubMed Central

    2010-01-01

    Background An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI. Methods Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors. Results Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness). However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified. Conclusions Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post-injection observation period. Trial Registration ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489. PMID:20537128

  4. A prospective trial of customized adherence enhancement plus long-acting injectable antipsychotic medication in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder

    PubMed Central

    Sajatovic, Martha; Levin, Jennifer; Ramirez, Luis F.; Hahn, David Y.; Tatsuoka, Curtis; Bialko, Christopher S.; Cassidy, Kristin A.; Fuentes-Casiano, Edna; Williams, Tiffany D.

    2014-01-01

    Background Treatment non-adherence in people with schizophrenia is associated with relapse and homelessness. Building upon the usefulness of long-acting medication, and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with schizophrenia and schizoaffective disorder. Methods Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence as measured by the Tablets Routine Questionnaire (TRQ) and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. Results Mean age of participants was 41.8 years (SD 8.6), mainly minorities (90% African-American) and mainly single/never married (70%). Most (97%) had past or current substance abuse, and had been incarcerated (97%). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (76% at 6 months) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (p = 0.03). There were significant improvements in psychiatric symptoms (p<.001) and functioning (p<.001). Akathisia was a major side effect with LAI. Conclusion While interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness. PMID:24434094

  5. Profile of paliperidone palmitate once-monthly long-acting injectable in the management of schizophrenia: long-term safety, efficacy, and patient acceptability – a review

    PubMed Central

    González-Rodríguez, Alexandre; Catalán, Rosa; Penadés, Rafael; Garcia-Rizo, Clemente; Bioque, Miquel; Parellada, Eduard; Bernardo, Miquel

    2015-01-01

    Background and objectives Short-term studies focused on once-monthly paliperidone palmitate (PP) at doses of 25 mg eq, 50 mg eq, 75 mg eq, 100 mg eq, or 150 mg eq have shown its efficacy and tolerability in the treatment of schizophrenia patients. However, few open-label and long-term studies are available regarding this new pharmacological formulation. Thus, our main aim was to review the scientific evidence on efficacy, safety, tolerability, and preference of PP in these populations. Method Electronic searches were conducted by using PubMed and ISI Web of Knowledge databases. All relevant studies published from 2009 until January 2015 were included without any language restriction if patients met diagnostic criteria for schizophrenia, and adequate information on efficacy, safety, and tolerability of once-monthly PP was available. Results Nineteen studies were identified irrespective of the study design and duration of the follow-up period. Randomized, double-blind, placebo-controlled trials found that schizophrenia patients receiving PP showed a significant improvement in psychotic symptoms and similar adverse events compared to placebo and suggested that all doses of PP were efficacious and well tolerated. Other studies demonstrated noninferiority of PP compared to risperidone long-acting injectable in recently diagnosed schizophrenia patients, chronically ill patients, as well as in acute and nonacute symptomatic schizophrenia patients, and a similar proportion of treatment-emergent adverse events between both groups were also noted. Conclusion Several studies have demonstrated that schizophrenia patients treated with PP show higher rates of improvement of psychotic symptoms compared to placebo, and similar efficacy and tolerability outcomes were noted when comparing PP to risperidone long-acting injectable or oral, paliperidone extended release.

  6. A noncytolytic antibody-like extendin-4-IgG4 fusion protein as a long-acting potential anti-diabetic agent

    PubMed Central

    Li, Xiaoxia; Hu, Pinliang; Yang, Rungong; Bai, Jie; Wang, Xingheng; Fu, Shuhong; Yang, Siyi; Ma, Jinwei; Gong, Meiliang; Chen, Hong; Zhou, Feng; Chen, Yanbing; Zhou, Qian

    2015-01-01

    Background: GLP-1 and its analogs have a variety of anti-diabetic effects. However, short half-life and rapid degraded by DPP-IV limits the therapeutic potential of the native GLP-1. So, many DPP-IV-resistant and long-acting GLP-1 analogs were developed. In this study, an antibody-like extendin-4-IgG4 fusion protein was developed. Methods: The ?4 constant region contains two amino acid substitutions relative to native ?4 (S228P and L235E) lead to affinity for Fc?RI to be low and stability of the IgG4 molecular. The fusion protein was expressed in CHO cells and assembled into an immunoglobulin-like structure with molecular weight of approximately 130 kDa. Results: The Exendin-4-IgG4 fusion protein was found to affinity bind GLP-1R in vitro. In vivo when compared the potency and duration of glucose-lowering effects in diabetic (db/db) mice at the same dose, exendin-4 resulted in a glucose-lowering effect that persisted only for 6 hours, but the extendin-4-IgG4 fusion protein for more than 168 hours. Injecting subcutaneously with a high dose of the fusion protein led normal BALB/c mice to the lower blood glucose level but did not cause serious hypoglycemia. Especially, the half-life time of the fusion protein in cynomolgus monkeys was about 180 hours, almost the longest half-life time among the developed GPL-1 analogues, which suggested a longer half-life time in human. Conclusions: The intact antibody-like fusion protein has more advantages than the Fc fusion protein including the intent of prolonging the half-life. These results also suggested the fusion protein was a safe and long-acting potential anti-diabetic agent.

  7. Evaluation of a combined drug-delivery system for proteins assembled with polymeric nanoparticles and porous microspheres; characterization and protein integrity studies.

    PubMed

    Alcalá-Alcalá, Sergio; Benítez-Cardoza, Claudia G; Lima-Muñoz, Enrique J; Piñón-Segundo, Elizabeth; Quintanar-Guerrero, David

    2015-07-15

    This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, ?-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(d,l-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of ?-amylase activity using 2-chloro-4-nitrophenyl-?-d-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release. PMID:25936624

  8. Glycolic Acid-Catalyzed Deamidation of Asparagine Residues in Degrading PLGA Matrices: A Computational Study

    PubMed Central

    Manabe, Noriyoshi; Kirikoshi, Ryota; Takahashi, Ohgi

    2015-01-01

    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. PMID:25837471

  9. AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery.

    PubMed

    Aravind, Athulya; Jeyamohan, Prashanti; Nair, Remya; Veeranarayanan, Srivani; Nagaoka, Yutaka; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D Sakthi

    2012-11-01

    Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110?nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery. PMID:22615073

  10. Fabrication and characterization of PLGA\\/HAp composite scaffolds for delivery of BMP2 plasmid DNA

    Microsoft Academic Search

    Hemin Nie; Chi-Hwa Wang

    2007-01-01

    The objective of this study is to construct complex of DNA and PLGA\\/HAp composite scaffold for bone tissue engineering. Naked DNA has low transfection efficiency so DNA loaded chitosan particles are used nowadays in gene delivery due to their high transfection efficiency, but unfortunately this is accompanied by strong immunological reaction of cells. In order to preserve the advantage of

  11. Preparation of Biodegradable, Surface Engineered PLGA Nanospheres with Enhanced Lymphatic Drainage and Lymph Node Uptake

    Microsoft Academic Search

    Ann E. Hawley; Lisbeth Illum; Stanley S. Davis

    1997-01-01

    Purpose. Nanospheres can be utilised for the targeting of drugs and diagnostic agents to the regional lymph nodes. The surface modification of model polystyrene, (PS), and poly(lactide-co-glycolide),(PLGA), nanospheres by poly(lactide)-poly(ethylene glycol), (PLA:PEG), copolymers has been assessed by in vitro characterisation and in vivobiodistribution studies following subcutaneous administration of the nanospheres to the rat.

  12. Adipose tissue engineering using mesenchymal stem cells attached to injectable PLGA spheres

    Microsoft Academic Search

    Yu Suk Choi; Si-Nae Park; Hwal Suh

    2005-01-01

    The reconstruction of soft tissue defects remains a challenge in plastic and reconstructive surgery, and a real clinical need exists for an adequate solution. This study was undertaken in order to differentiate mesenchymal stem cells (MSCs) into adipocytes, and to then assess the possibility of constructing adipose tissue via the attachment of MSCs to injectable PLGA spheres. We also designed

  13. In vitro and in vivo release of ciprofloxacin from PLGA 50:50 implants

    Microsoft Academic Search

    M. Ramchandani; D. Robinson

    1998-01-01

    Poly(lactides-co-glycolides) [PLGA] are widely investigated biodegradable polymers and are extensively used in several biomaterials applications as well as drug delivery systems. These polymers degrade by bulk hydrolysis of ester bonds and break down into their constituent monomers, lactic and glycolic acids which are excreted from the body. The purpose of this investigation was to develop and characterize a biodegradable, implantable

  14. Miscibility of choline-substituted polyphosphazenes with PLGA and osteoblast activity on resulting blends.

    PubMed

    Weikel, Arlin L; Owens, Steven G; Morozowich, Nicole L; Deng, Meng; Nair, Lakshmi S; Laurencin, Cato T; Allcock, Harry R

    2010-11-01

    The preparation of phosphazene tissue engineering scaffolds with bioactive side groups has been accomplished using the biological buffer, choline chloride. Mixed-substituent phosphazene cyclic trimers (as model systems) and polymers with choline chloride and glycine ethyl ester, alanine ethyl ester, valine ethyl ester, or phenylalanine ethyl ester were synthesized. Two different synthetic protocols were examined. A sodium hydride mediated route resulted in polyphosphazenes with a low choline content, while a cesium carbonate mediated process produced polyphosphazenes with higher choline content. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media revealed that the polymer blends hydrolyzed to near-neutral pH media (?5.8 to 6.8). The effect of different molecular structures on cellular adhesion showed osteoblast proliferation with an elevated osteoblast phenotype expression compared to PLGA over a 21-day culture period. PMID:20800277

  15. Molecular beam levitator for sputter coating of microspheres

    NASA Astrophysics Data System (ADS)

    Varon, J.; Goldstein, I. S.

    1981-07-01

    A molecular beam levitation system is described which is presently being used to sputter deposit coatings on hollow glass microspheres for use as laser fusion targets. Stable levitation of the microspheres has been achieved down to 1×10-4 Torr and levitated microspheres have been coated successfully using both dc and rf magnetron sputter guns in a pressure range from 1 to 10 ?m. The system has proven to be highly dependable in both levitation and recovery of the coated microspheres. The levitating gas flow does not appear to interfere with the deposition process, and the rotation of the microsphere, which is produced by the gas flow, ensures that uniform coatings are obtained. Microradiography has shown the coatings to have a high degree of uniformity and the SEM reveals local surface finishes, under specific deposition conditions, of better than 250 Å. Due to the excellent stability of the levitated microspheres, simultaneous deposition using multiple heads may be possible.

  16. Beat frequency ultrasonic microsphere contrast agent detection system

    NASA Technical Reports Server (NTRS)

    Pretlow, III, Robert A. (Inventor); Yost, William T. (Inventor); Cantrell, Jr., John H. (Inventor)

    1997-01-01

    A system for and method of detecting and measuring concentrations of an ultrasonically-reflective microsphere contrast agent involving detecting non-linear sum and difference beat frequencies produced by the microspheres when two impinging signals with non-identical frequencies are combined by mixing. These beat frequencies can be used for a variety of applications such as detecting the presence of and measuring the flow rates of biological fluids and industrial liquids, including determining the concentration level of microspheres in the myocardium.

  17. In vivo uptake and acute immune response to orally administered chitosan and PEG coated PLGA nanoparticles

    SciTech Connect

    Semete, B., E-mail: Bsemete@csir.co.z [Council for Scientific and Industrial Research, Polymers and Composites, P O Box 395 Pretoria, 0001 (South Africa); Booysen, L.I.J. [Council for Scientific and Industrial Research, Polymers and Composites, P O Box 395 Pretoria, 0001 (South Africa); Department of Pharmaceutics, North-West University, Potchefstroom Campus, Potchefstroom, 2520 (South Africa); Kalombo, L. [Council for Scientific and Industrial Research, Polymers and Composites, P O Box 395 Pretoria, 0001 (South Africa); Venter, J.D. [South African Medical Research Council, TB laboratory, Pretoria, 0001 (South Africa); Katata, L.; Ramalapa, B. [Council for Scientific and Industrial Research, Polymers and Composites, P O Box 395 Pretoria, 0001 (South Africa); Verschoor, J.A. [Department of Biochemistry, University of Pretoria, Pretoria, 0001 (South Africa); Swai, H. [Council for Scientific and Industrial Research, Polymers and Composites, P O Box 395 Pretoria, 0001 (South Africa)

    2010-12-01

    Nanoparticulate drug delivery systems offer great promise in addressing challenges of drug toxicity, poor bioavailability and non-specificity for a number of drugs. Much progress has been reported for nano drug delivery systems for intravenous administration, however very little is known about the effects of orally administered nanoparticles. Furthermore, the development of nanoparticulate systems necessitates a thorough understanding of the biological response post exposure. This study aimed to elucidate the in vivo uptake of chitosan and polyethylene glycol (PEG) coated Poly, DL, lactic-co-glycolic Acid (PLGA) nanoparticles and the immunological response within 24 h of oral and peritoneal administration. These PLGA nanoparticles were administered orally and peritoneally to female Balb/C mice, they were taken up by macrophages of the peritoneum. When these particles were fluorescently labelled, intracellular localisation was observed. The expression of pro-inflammatory cytokines IL-2, IL-6, IL-12p70 and TNF-{alpha} in plasma and peritoneal lavage was found to remain at low concentration in PLGA nanoparticles treated mice as well as ZnO nanoparticles during the 24 hour period. However, these were significantly increased in lipopolysaccharide (LPS) treated mice. Of these pro-inflammatory cytokines, IL-6 and IL-12p70 were produced at the highest concentration in the positive control group. The anti-inflammatory cytokines IL-10 and chemokines INF-{gamma}, IL-4, IL-5 remained at normal levels in PLGA treated mice. IL-10 and INF-{gamma} were significantly increased in LPS treated mice. MCP-1 was found to be significantly produced in all groups in the first hours, except the saline treated mice. These results provide the first report to detail the induction of cytokine production by PLGA nanoparticles engineered for oral applications.

  18. Preparation of uniform magnetic recoverable catalyst microspheres with hierarchically mesoporous structure by using porous polymer microsphere template.

    PubMed

    Ren, Lianbing; Teng, Chao; Zhu, Lili; He, Jie; Wang, You; Zuo, Xinbing; Hong, Mei; Wang, Yong; Jiang, Biwang; Zhao, Jing

    2014-01-01

    Merging nanoparticles with different functions into a single microsphere can exhibit profound impact on various applications. However, retaining the unique properties of each component after integration has proven to be a significant challenge. Our previous research demonstrated a facile method to incorporate magnetic nanoparticles into porous silica microspheres. Here, we report the fabrication of porous silica microspheres embedded with magnetic and gold nanoparticles as magnetic recoverable catalysts. The as-prepared multifunctional composite microspheres exhibit excellent magnetic and catalytic properties and a well-defined structure such as uniform size, high surface area, and large pore volume. As a result, the very little composite microspheres show high performance in catalytic reduction of 4-nitrophenol, special convenient magnetic separability, long life, and good reusability. The unique nanostructure makes the microspheres a novel stable and highly efficient catalyst system for various catalytic industry processes. PMID:24708885

  19. Preparation of porous zirconia microspheres by internal gelation method

    SciTech Connect

    Pathak, Sachin S. [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Pius, I.C. [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)], E-mail: icpius@lycos.com; Bhanushali, R.D.; Rao, T.V. Vittal; Mukerjee, S.K. [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2008-11-03

    A modified internal gelation process for the preparation of porous zirconia microspheres has been developed. The conventional method has been modified by adding a surfactant in the feed broth. The effects of variation of surfactant concentration, washing techniques and temperature of calcination on the pore volume and the surface area of the microspheres have been studied. The conditions were optimized to obtain porous stable microspheres suitable for various applications. The microspheres were characterized by surface area analysis, pore volume analysis, thermogravimetric analysis and X-ray diffraction. The ion exchange behavior was studied using pH titration.

  20. Patterning of silica microsphere monolayers with focused femtosecond laser pulses

    SciTech Connect

    Cai Wenjian; Piestun, Rafael [Department of Physics, University of Colorado, Boulder, Colorado 80309-0390 (United States); Department of Electrical and Computer Engineering, University of Colorado, Boulder, Colorado 80309-0425 (United States)

    2006-03-13

    We demonstrate the patterning of monolayer silica microsphere lattices with tightly focused femtosecond laser pulses. We selectively removed microspheres from a lattice and characterized the effect on the lattice and the substrate. The proposed physical mechanism for the patterning process is laser-induced breakdown followed by ablation of material. We show that a microsphere focuses radiation in its interior and in the near field. This effect plays an important role in the patterning process by enhancing resolution and accuracy and by reducing the pulse energy threshold for damage. Microsphere patterning could create controlled defects within self-assembled opal photonic crystals.

  1. Effect of the covalent modification of horseradish peroxidase with poly(ethylene glycol) on the activity and stability upon encapsulation in polyester microspheres.

    PubMed

    Al-Azzam, Wasfi; Pastrana, Emil A; King, Brian; Méndez, Jessica; Griebenow, Kai

    2005-08-01

    Encapsulation of proteins in polyester microspheres by coacervation methods frequently causes protein inactivation and aggregation. Furthermore, an often-substantial amount of the encapsulated proteins is released within the first 24 h from the microspheres. To overcome these problems poly(ethylene glycol) (PEG) was employed as excipient and protein-modifying agent. The model protein horseradish peroxidase (HRP) was chemically modified or co-lyophilized with PEG of differing molecular weights, namely PEG(5000), PEG(20000), and PEG(40000). The lyophilized preparations were encapsulated in poly(D,L-lactide-co-glycolic) acid (PLGA) microspheres by a coacervation method. Covalent modification of HRP with PEG increased the encapsulation efficiency (EE) from 83% to about 100% while PEG when used as an excipient reduced the EE. Encapsulation caused aggregation of ca. 5% of non-modified HRP and the residual specific activity was only 57%. Covalent modification with PEG reduced HRP aggregation to less than 1% and improved its residual activity to more than 95%. When PEG was used as excipient similar results were found with respect to a reduction in encapsulation-induced aggregation, but no more than 80% of residual activity was obtained even for the best formulation after encapsulation. It was also found that covalent modification of HRP with PEG substantially reduced the unwanted initial "burst" release observed during the initial 24 h of in vitro release from about 70% to 23%. Furthermore, HRP activity and stability were also improved during in vitro release for HRP-PEG conjugates. The data show that covalent modification of proteins with PEG might be useful to improve protein stability during coacervation encapsulation and subsequent release as well as to increase EE and reduce the burst release. PMID:15986459

  2. Neutron transmission measurements on hydrogen filled microspheres

    NASA Astrophysics Data System (ADS)

    Dyrnjaja, Eva; Hummel, Stefan; Keding, Marcus; Smolle, Marie-Theres; Gerger, Joachim; Zawisky, Michael

    2014-01-01

    Hollow microspheres are promising candidates for future hydrogen storage technologies. Although the physical process for hydrogen diffusion through glass is well understood, measurements of static quantities (e.q. hydrogen pressure inside the spheres) as well as dynamic properties (e.g. diffusion rate of hydrogen through glass) are still difficult to handle due to the small size of the spheres (d?15?m). For diffusion rate measurements, the long-term stability of the experiment is also mandatory due to the relatively slow diffusion rate. In this work, we present an accurate and long-term stable measurement technique for static and dynamic properties, using neutron radiography. Furthermore, possible applications for hydrogen filled microspheres within the scope of radiation issues are discussed.

  3. Cell specific, variable density, polymer microspheres

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Molday, Robert S. (Inventor)

    1978-01-01

    Biocompatible polymeric microspheres having an average diameter below about 3 microns and having a density at least 15% greater or lesser than organic cells and having covalent binding sites are provided in accordance with this invention. The microspheres are obtained by copolymerizing a hydroxy or amine substituted acrylic monomer such as hydroxyethylmethacrylate with a light or dense comonomer such as a fluoromonomer. A lectin or antibody is bound to the hydroxy or amine site of the bead to provide cell specificity. When added to a cell suspension the marked bead will specifically label the cell membrane by binding to specific receptor sites thereon. The labelled membrane can then be separated by density gradient centrifugation.

  4. Optical Microspherical Resonators for Biomedical Sensing

    PubMed Central

    Soria, Silvia; Berneschi, Simone; Brenci, Massimo; Cosi, Franco; Conti, Gualtiero Nunzi; Pelli, Stefano; Righini, Giancarlo C.

    2011-01-01

    Optical resonators play an ubiquitous role in modern optics. A particular class of optical resonators is constituted by spherical dielectric structures, where optical rays are total internal reflected. Due to minimal reflection losses and to potentially very low material absorption, these guided modes, known as whispering gallery modes, can confer the resonator an exceptionally high quality factor Q, leading to high energy density, narrow resonant-wavelength lines and a lengthy cavity ringdown. These attractive characteristics make these miniaturized optical resonators especially suited as laser cavities and resonant filters, but also as very sensitive sensors. First, a brief analysis is presented of the characteristics of microspherical resonators, of their fabrication methods, and of the light coupling techniques. Then, we attempt to overview some of the recent advances in the development of microspherical biosensors, underlining a number of important applications in the biomedical field. PMID:22346603

  5. Fluorescence dynamics of microsphere-adsorbed sunscreens

    NASA Astrophysics Data System (ADS)

    Krishnan, R.

    2005-03-01

    Sunscreens are generally oily substances which are prepared in organic solvents, emulsions or dispersions with micro- or nanoparticles. These molecules adsorb to and integrate into skin cells. In order to understand the photophysical properties of the sunscreen, we compare steady-state and time-resolved fluorescence in organic solvent of varying dielectric constant ? and adsorbed to polystyrene microspheres and dispersed in water. Steady-state fluorescence is highest and average fluorescence lifetime longest in toluene, the solvent of lowest ?. However, there is no uniform dependence on ?. Sunscreens PABA and padimate-O show complex emission spectra. Microsphere-adsorbed sunscreens exhibit highly non-exponential decay, illustrative of multiple environments of the adsorbed molecule. The heterogeneous fluorescence dynamics likely characterizes sunscreen adsorbed to cells.

  6. Magnetic microsphere-based mixers for microdroplets

    Microsoft Academic Search

    Tamal Roy; Ashok Sinha; Sayan Chakraborty; Ranjan Ganguly; Ishwar K. Puri

    2009-01-01

    While droplet-based microfluidic systems have several advantages over traditional flow-through devices, achieving adequate mixing between reagents inside droplet-based reactors remains challenging. We describe an active mixing approach based on the magnetic stirring of self-assembled chains of magnetic microspheres within the droplet as these stirrers experience a rotating magnetic field. We measure the mixing of a water-soluble dye in the droplet

  7. Functional microspheres of graphene quantum dots

    Microsoft Academic Search

    Yi Ding; Huhu Cheng; Ce Zhou; Yueqiong Fan; Jia Zhu; Huibo Shao; Liangti Qu

    2012-01-01

    Graphene-quantum-dot microspheres (GQDSs) have been prepared by assembly of graphene quantum dots (GQDs) via a water-in-oil (W\\/O) emulsion technique without the addition of any surfactants. Although made of quantum-sized graphene dots, the as-formed GQDSs are solid and remain intact after slight ultrasonication. The versatile W\\/O emulsion method allows the in situ intercalation of functional nanocomponents into the GQDSs for specific

  8. Detection of single molecules in microspheres

    SciTech Connect

    Barnes, M.D.; Whitten, W.B.; Ramsey, J.M. [Oak Ridge National Lab., TN (United States); Ng, K.C. [California State Univ., Fresno, CA (United States). Dept. of Chemistry; Arnold, S. [Polytechnic Inst. of Brooklyn, NY (United States). Microparticle Photophysics Lab.

    1993-07-01

    We have investigated the use of micron-sized liquid droplets as sample medium to detect single fluorescent molecules in solution. The use of microdroplets (5--15 {mu}m diameter) offers several powerful advantages over single-molecule detection schemes involving measurements on bulk liquids where the probe volume is defined by the laser beam. In addition, cavity-quantum electrodynamical (QED) effects have been observed which influence both spontaneous emission rates and fluorescence yields of dye molecules in these microspheres.

  9. Electrospun Nanofibrous PLGA\\/Fullerene-C60 Coated Quartz Crystal Microbalance for Real-Time Gluconic Acid Monitoring

    Microsoft Academic Search

    S. S?eker; Yavuz Emre Arslan

    2010-01-01

    In this paper, a piezoelectric (PZ) sensor based on quartz crystal microbalance (QCM) for the determination of gluconic acid is described. PZ quartz crystals were coated with a 550-700 nm-thick layer of nanoflbers comprising of poly(DL-lactide-co-glycolide) (PLGA) and fullerene-C60 by electrospinning. Glucose oxidase (GOx) was immobilized on coverslips electrospun with nanofibrous PLGA for the interaction of the PZ sensor with

  10. Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold

    Microsoft Academic Search

    Kota Uematsu; Koji Hattori; Yoshiyuki Ishimoto; Jun Yamauchi; Takashi Habata; Yoshinori Takakura; Hajime Ohgushi; Takeshi Fukuchi; Masao Sato

    2005-01-01

    Cartilage engineered from mesenchymal stem cells (MSCs) requires a scaffold to keep the cells in the cartilage defect and to act as a support for inducing hyaline cartilage formation. We developed a novel three-dimensional special poly-lactic-glycolic acid (PLGA) scaffold that provided structural support and stimulated repair. Three-dimensional PLGA scaffolds seeded with cultured MSCs were transplanted into large defects in rabbit

  11. Degradation of poly(lactide- co-glycolide) (PLGA) and poly( l-lactide) (PLLA) by electron beam radiation

    Microsoft Academic Search

    J. S. C. Loo; C. P. Ooi; F. Y. C. Boey

    2005-01-01

    This paper seeks to examine the effects of electron beam (e-beam) radiation on biodegradable polymers (PLGA and PLLA), and to understand their radiation-induced degradation mechanisms. PLGA (80:20) and PLLA polymer films were e-beam irradiated at doses from 2.5 to 50Mrad and the degradation of these films were studied by measuring the changes in their molecular weights, FTIR spectra, thermal and

  12. Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide

    PubMed Central

    Price, David; Kaplan, Alan; Jones, Rupert; Freeman, Daryl; Burden, Anne; Gould, Shuna; von Ziegenweidt, Julie; Ali, Muzammil; King, Christine; Thomas, Mike

    2015-01-01

    Background Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care. Methods Medical records of adults with asthma (aged ?18 years) prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001–2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline) and the year after (outcome) addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course) and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation). Secondary outcomes included lung function test results and short-acting ?2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices. Results Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting ?2 agonist during the baseline year; 67% were prescribed both. Comparing baseline and outcome years, the percentage of patients having at least one exacerbation decreased from 37% to 27% (P<0.001) and the percentage having at least one acute respiratory event decreased from 58% to 47% (P<0.001). There were no significant changes in lung function, and usage of short-acting ?2 agonists (in salbutamol/albuterol equivalents) increased from a median (interquartile range) of 274 (110, 548) to 329 (110, 603) ?g/day (P=0.01). Conclusion In this real-life asthma population, addition of LAMA therapy was associated with significant decreases in the incidence of exacerbations and antibiotic prescriptions for lower respiratory tract infections in the following year. PMID:25609985

  13. Combination of long-acting microcapsules of the D-tryptophan-6 analog of luteinizing hormone-releasing hormone with chemotherapy: investigation in the rat prostate cancer model.

    PubMed Central

    Schally, A V; Redding, T W

    1985-01-01

    The effect of combining hormonal treatment consisting of long-acting microcapsules of the agonist [D-Trp6]LH-RH (the D-tryptophan-6 analog of luteinizing hormone-releasing hormone) with the chemotherapeutic agent cyclophosphamide was investigated in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH formulated from poly(DL-lactide-co-glycolide) and calculated to release a controlled dose of 25 micrograms/day were injected intramuscularly once a month. Cyclophosphamide (Cytoxan) (5 mg/kg of body weight) was injected intraperitoneally twice a week. When the therapy was started 90 days after tumor transplantation--at the time that the cancers were well developed-and was continued for 2 months, tumor volume was significantly reduced by the microcapsules or Cytoxan given alone. The combination of these two agents similarly inhibited tumor growth but did not show a synergistic effect. In another study, the treatment was started 2 months after transplantation, when the developing tumors measured 60-70 mm3. Throughout the treatment period of 100 days, the microcapsules of [D-Trp6]LH-RH reduced tumor volume more than Cytoxan did, and the combination of the two drugs appeared to completely arrest tumor growth. Tumor weights also were diminished significantly in all experimental groups, the decrease in weight being smaller in the Cytoxan-treated group than in rats that received the microcapsules. The combination of Cytoxan plus the microcapsules was 10-100 times more effective than the single agents in reducing tumor weights. In both experiments, testes and ventral prostate weights were significantly diminished, serum testosterone was suppressed to undetectable levels, and prolactin values were reduced by administration of microcapsules of [D-Trp6]LH-RH alone or in combination with Cytoxan. These results in rats suggest that combined administration of long acting microcapsules of [D-Trp6]LH-RH with a chemotherapeutic agent, started soon after the diagnosis of prostate cancer is made, might inhibit the proliferation of androgen-dependent and -independent cells, improve further the therapeutic response, and increase the survival rate. PMID:3157990

  14. Poly D,L-lactide-co-glycolic acid (PLGA)-encapsulated vaccine on immune system in Epinephelus bruneus against Uronema marinum.

    PubMed

    Harikrishnan, Ramasamy; Balasundaram, Chellam; Heo, Moon-Soo

    2012-07-01

    We investigate the efficacy of poly D,L-lactide-co-glycolic acid (PLGA)-encapsulated vaccine on innate and adaptive immune response in kelp grouper (Epinephelus bruneus) against Uronema marinum at weeks 1, 2, and 4. The respiratory burst (RB) activity, complement activity, and ?2-macroglobulin were significantly enhanced in fish immunization with vaccine on week 4 whereas vaccine and PLGA-encapsulated vaccine from weeks 1 to 4. The serum lysozyme activity, antiprotease activity, and antibody level were significantly enhanced in fish immunized with vaccine and PLGA-encapsulated vaccine on weeks 2 and 4. The cumulative mortality was low in PLGA-encapsulated vaccine with 20% whereas high in PLGA and vaccine with 40% and 30%. The results from the present study suggest that PLGA-encapsulated vaccine is useful for further design of immunoprophylatic nano formulation against scuticociliatosis. PMID:22580022

  15. Formulation, characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment.

    PubMed

    Gidwani, Bina; Vyas, Amber

    2014-11-13

    Abstract PLGA nanospheres are considered to be promising drug carrier in the treatment of cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study revealed formation of AL type complex with stability constant (Ks?=?645?M(-1)). This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil-in-water (S/O/W) technique. The particle size and zeta potential of PLGA nanospheres loaded with cyclodextrin-complexed BM were about 151.4?±?2.53?nm and?-?31.9?±?(-3.08)?mV. In-vitro release study represented biphasic release pattern with 20% burst effect and sustained slow release. DSC studies indicated that inclusion complex incorporated in PLGA nanospheres was not in a crystalline state but existed in an amorphous or molecular state. The cytotoxicity experiment was studied in Z-138 cells and IC50 value was found to be 4.3?±?0.11?µM. Cell viability studies revealed that the PLGA nanospheres loaded with complex exerts a more pronounced effect on the cancer cells as compared to the free drug. In conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained drug delivery. The nanospheres were stable after 3 months of storage conditions with slight change in their particle size, zeta potential and entrapment efficiency. PMID:25391288

  16. Degradation of poly(lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by electron beam radiation.

    PubMed

    Loo, J S C; Ooi, C P; Boey, F Y C

    2005-04-01

    This paper seeks to examine the effects of electron beam (e-beam) radiation on biodegradable polymers (PLGA and PLLA), and to understand their radiation-induced degradation mechanisms. PLGA (80:20) and PLLA polymer films were e-beam irradiated at doses from 2.5 to 50 Mrad and the degradation of these films were studied by measuring the changes in their molecular weights, FTIR spectra, thermal and morphological properties. The dominant effect of e-beam irradiation on both PLGA and PLLA is chain scission. Chain scission occurs first through scission of the polymer main chain, followed by hydrogen abstraction. Chain scission, though responsible for the reduction in the average molecular weight, Tc, Tg and Tm of both polymers, encourages crystallization in PLGA. PLLA also undergoes chain scission upon irradiation but to a lesser degree compared to PLGA. The higher crystallinity of PLLA is the key factor in its greater stability to e-beam radiation compared to PLGA. A linear relationship is also established between the decrease in molecular weight with respect to radiation dose. PMID:15482823

  17. Influence of electron-beam radiation on the hydrolytic degradation behaviour of poly(lactide-co-glycolide) (PLGA).

    PubMed

    Loo, Say Chye Joachim; Ooi, Chui Ping; Boey, Yin Chiang Freddy

    2005-06-01

    The purpose of this study is to examine the effect of electron-beam (e-beam) radiation on the hydrolytic degradation of poly(lactide-co-glycolide) (PLGA) films. PLGA films were irradiated and observed to undergo radiation-induced degradation through chain scission, as observed from a drop in its average molecular weight with radiation dose. Irradiated (5, 10 and 20 Mrad) and non-irradiated (0 Mrad) samples of PLGA were subsequently hydrolytically degraded in phosphate-buffered saline solution at 37.0 degrees C over a span of 12 weeks. It was observed that the natural logarithmic molecular weight (lnMn) of PLGA decreases linearly with hydrolytic degradation time. The rate of water uptake is higher for samples irradiated at higher radiation dose (e.g. 20 Mrad) and subsequently causing an earlier onset of mass loss. It is postulated that the increase in water uptake is due to the presence of more hydrophilic end groups, which results in the formation of microcavities because of an increase in osmotic pressure. A relationship between radiation dose and the rate of hydrolytic degradation of PLGA films, through its molecular weight was also established. This relationship allows a more accurate and precise control of the life span of PLGA through the use of e-beam radiation. PMID:15626429

  18. Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells.

    PubMed

    Verderio, Paolo; Bonetti, Paolo; Colombo, Miriam; Pandolfi, Laura; Prosperi, Davide

    2013-03-11

    PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented "enhanced permeation and retention" (EPR) effect. In this paper, we have developed uniform curcumin-bearing PLGA nanoparticles by a single-emulsion process, which exhibited a curcumin release following a Fickian-law diffusion over 10 days in vitro. PLGA nanoparticles were about 120 nm in size, as determined by dynamic light scattering, with a surface negative charge of -30 mV. The loading ratio of encapsulated drug in our PLGA nanoformulation was 8 wt%. PLGA encapsulation provided efficient protection of curcumin from environment, as determined by fluorescence emission experiments. Next, we have investigated the possibility to study the intracellular degradation of nanoparticles associated with a specific G2/M blocking effect on MCF7 breast cancer cells caused by curcumin release in the cytoplasm, which provided direct evidence on the mechanism of action of our nanocomplex. This study was carried out using Annexin V-based cell death analysis, MTT assessment of proliferation, flow cytometry, and confocal laser scanning microscopy. PLGA nanoparticles proved to be completely safe, suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer. PMID:23350530

  19. Novel PLGA-based nanoparticles for the oral delivery of insulin

    PubMed Central

    Malathi, Sampath; Nandhakumar, Perumal; Pandiyan, Velayudham; Webster, Thomas J; Balasubramanian, Sengottuvelan

    2015-01-01

    Background Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-?-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS). Objective To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin. Methods A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration. Results The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects. Conclusion ISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin. PMID:25848248

  20. Composite Tectocapsules Containing Porous Polymer Microspheres as Release Gates

    E-print Network

    Hitchcock, Adam P.

    of amphiphilic porous microspheres, with the release rates scaling with microsphere loading. Scanning micro- spheres that could assemble at the oil-water interface and become embedded in the forming at high temperature to form a capsule wall. Microcap- sules prepared by the assembly of particles