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1

IVIVC from Long Acting Olanzapine Microspheres  

PubMed Central

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

Faraj, Jabar A.; DeLuca, Patrick P.

2014-01-01

2

Development of Risperidone PLGA Microspheres  

PubMed Central

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

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

2014-01-01

3

PLGA microspheres encapsulating siRNA.  

PubMed

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

De Rosa, Giuseppe; Salzano, Giuseppina

2015-01-01

4

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

PubMed

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

Yang, Yang; Gao, Yongliang; Mei, Xingguo

2013-01-01

5

Biodegradation and biocompatibility of PLA and PLGA microspheres  

Microsoft Academic Search

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

James M Anderson; Matthew S Shive

1997-01-01

6

RANKL delivery from calcium phosphate containing PLGA microspheres.  

PubMed

Ideally, bone substitute materials would undergo cell-mediated degradation during the remodeling process of the host bone tissue while being replaced by newly formed bone. In an attempt to exploit the capacity of Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) to stimulate osteoclast-like cells formation, this study explored different loading methods for RANKL in injectable calcium phosphate cement (CPC) and the effect on release and biological activity. RANKL was loaded via the liquid phase of CPC by adsorption onto or incorporation into poly(lactic-co-glycolic acid) (PLGA) microspheres with two different morphologies (i.e., hollow and dense), which were subsequently embedded in CPC. As controls nonembedded PLGA-microspheres were used as well as plain CPC scaffolds with RANKL adsorbed onto the surface. RANKL release and activity were evaluated by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) and osteoclast-like cells formation in cell culture experiments. Results indicated that sustained release of active RANKL can be achieved upon RANKL adsorption to PLGA microspheres, whereas inactive RANKL was released from CPC-PLGA formulations with RANKL incorporated within the microspheres or within the liquid phase of the CPC. These results demonstrate that effective loading of RANKL in injectable CPC is only possible via adsorption to PLGA microspheres, which are subsequently embedded within the CPC-matrix. PMID:23529979

Félix Lanao, Rosa P; Bosco, Ruggero; Leeuwenburgh, Sander C G; Kersten-Niessen, Monique J F; Wolke, Joop G C; van den Beucken, Jeroen J J P; Jansen, John A

2013-11-01

7

PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy  

PubMed Central

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.

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

2015-01-01

8

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

E-print Network

Review Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres for controlled release drug delivery applications, and many models have been proposed to describe PLGA Accepted 18 October 2012 Available online 26 October 2012 Keywords: Modeling Controlled release drug

Braatz, Richard D.

9

Stabilization of Tetanus Toxoid Encapsulated in PLGA Microspheres  

PubMed Central

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT) in PLGA microspheres. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: 1) protein aggregation mediated by formaldehyde and 2) acid-induced protein unfolding and epitope damage. Further, we systemically identified excipients which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA. PMID:18710256

Jiang, Wenlei; Schwendeman, Steven P.

2014-01-01

10

A novel trans-lymphatic drug delivery system: Implantable gelatin sponge impregnated with PLGA–paclitaxel microspheres  

Microsoft Academic Search

A translymphatic drug delivery system which incorporates poly-lactide-co-glycolide–paclitaxel (PLGA–PTX) or PLGA–rhodamine microspheres into gelatin sponge matrix is described. The system combines the sustained release properties of PLGA–PTX with the structural advantages of gelatin matrix that can be implanted directly to the lymphatic site for both therapeutic and prophylactic purposes. The PLGA microspheres were prepared using spray drying technique. The particles

Jiang Liu; Dale Meisner; Elizabeth Kwong; Xiao Y. Wu; Michael R. Johnston

2007-01-01

11

Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot  

PubMed Central

Background Radix Ophiopogonis polysaccharide (ROP), a highly hydrophilic macromolecule, has a unique anti-ischemic action in the myocardium. One of the main problems with its use is its relatively short half-life in vivo. To solve this problem, injectable long-acting drug delivery systems, which combine mono-PEGylation (PEG, polyethylene glycol) with the in situ formation of poly(d,l-lactide-co-glycolide) copolymer (PLGA) depots, were tested in this study. Methods Through a moderate coupling reaction between 20 kDa amino-terminated methoxy-PEG and excessive ROP with activated hydroxyls, a long-circulating and bioactive mono-PEGylated ROP was prepared and characterized. A reasonable and applicable range of PLGA formulations loaded with the mono-PEGylated ROP were prepared, characterized, and evaluated in vivo. Results Relative to ROP, the half-life of which was only 0.5 hours, the conjugate alone, following subcutaneous administration, showed markedly prolonged retention in the systemic circulation, with a mean residence time in vivo of approximately 2.76 days. In combination with in situ-forming PLGA depots, the residence time of the conjugate in vivo was prolonged further. In particular, a long-lasting and steady plasma exposure for nearly a month was achieved by the formulation comprising 40% 30 kDa PLGA in N-methyl-2-pyrrolidone. Conclusion Long-lasting and steady drug exposure could be achieved using mono-PEGylation in combination with in situ formation of PLGA depots. Such a combination with ROP would be promising for long-term prophylaxis and/or treatment of myocardial ischemia. For high-dose and highly hydrophilic macromolecular drugs like ROP, more than one preparation technology might be needed to achieve week-long or month-long delivery per dosing. PMID:25489243

Shi, XiaoLi; Lin, Xiao; Zheng, XiangWei; Feng, Yi; Shen, Lan

2014-01-01

12

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

PubMed

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

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

2011-01-01

13

Stromal-Derived Factor1 Alpha-Loaded PLGA Microspheres for Stem Cell Recruitment  

Microsoft Academic Search

Purpose  Stromal-derived factor-1 alpha (SDF-1?) is a chemoattractant that has been investigated for treating various diseases, with\\u000a the goal of recruiting endogenous stem cells to the site of injury. Biodegradable PLGA microspheres were investigated as a\\u000a means to deliver SDF-1? in a sustained-release manner.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We encapsulated SDF-1? into biodegradable poly(lactide-co-glycolide) (PLGA) microspheres using a double-emulsion solvent extraction\\/evaporation technique. We varied several

Daisy P. Cross; Chun Wang

14

Effect of different sintering methods on bioactivity and release of proteins from PLGA microspheres  

PubMed Central

Macromolecule release from poly(d,l-lactide-co-glycolide) (PLGA) microspheres has been well-characterized, and is a popular approach for delivering bioactive signals from tissue-engineered scaffolds. However, the effect of some processing solvents, sterilization, and mineral incorporation (when used in concert) on long-term release and bioactivity has seldom been addressed. Understanding these effects is of significant importance for microsphere-based scaffolds, given that these scaffolds are becoming increasingly more popular, yet growth factor activity following sintering and/or sterilization is heretofore unknown. The current study evaluated the 6-week release of transforming growth factor (TGF)-?3 and bone morphogenetic protein (BMP)-2 from PLGA and PLGA/hydroxyapatite (HAp) microspheres following exposure to ethanol (EtOH), dense phase carbon dioxide (CO2), or ethylene oxide (EtO). EtO was chosen based on its common use in scaffold sterilization, whereas EtOH and CO2 were chosen given their importance in sintering microspheres together to create scaffolds. Release supernatants were then used in an accelerated cell stimulation study with human bone marrow stromal cells (hBMSCs) with monitoring of gene expression for major chondrogenic and osteogenic markers. Results indicated that in microspheres without HAp, EtOH exposure led to the greatest amount of delivery, whilst those treated with CO2 delivered the least growth factor. In contrast, formulations with HAp released almost half as much protein, regardless of EtOH or CO2 exposure. Notably, EtO exposure was not found to significantly affect the amount of protein released. Cell stimulation studies demonstrated that eluted protein samples performed similarly to positive controls in PLGA-only formulations, and ambiguously in PLGA/HAp composites. In conclusion, the use of EtOH, subcritical CO2, and EtO in microsphere-based scaffolds may have only slight adverse effects, and possibly even desirable effects in some cases, on protein availability and bioactivity. PMID:23910352

Dormer, Nathan H.; Gupta, Vineet; Scurto, Aaron M.; Berkland, Cory J.; Detamore, Michael S.

2013-01-01

15

Studies on the preparation, characterization and pharmacological evaluation of tolterodine PLGA microspheres.  

PubMed

In this study, poly(d,l-lactide-co-glycolide) (PLGA) microspheres of tolterodine depot formulation were prepared using oil in water (o/w) method to investigate their potential pharmacokinetic and pharmacodynamic advantages over tolterodine l-tartrate tablets. Morphological studies of the microspheres showed a spherical shape and smooth surface with mean size of 50.69-83.01 microm, and the encapsulation efficiency was improved from 62.55 to 79.10% when the polymer concentration increased from 180 to 230 mg/ml. The addition of stearic or palmitic acids could significantly raise the drug entrapment efficiency but only slightly affected the in vitro release. A low initial burst followed by a proximately constant release of tolterodine was noticed in the in vitro release profiles. The in vivo study was carried out by intramuscular (i.m.) administration of tolterodine-loaded microspheres on beagle dogs, and a sustained release of drug from the PLGA microspheres was achieved until the 18th day with a low initial burst. Since the absence of hepatic first pass metabolism, only a single active compound-tolterodine was detected in the plasma. This avoided the coexistence of two active compounds in plasma in the case of oral administration of tolterodine, which may lead to a difficulty in dose control due to the different metabolic capacity of patients. In the pharmacodynamic study, the influence of tolterodine PLGA microspheres on the inhibition of carbachol-induced rat urinary bladder contraction was more significant than that of tolterodine l-tartrate tablets. There were invisible changes in rat bladder slices between tolterodine-loaded PLGA microspheres group and tolterodine l-tartrate tablets group. These results indicate that the continuous inhibition of muscarinic receptor may offer an alternative therapy of urge incontinence. PMID:20600717

Sun, Fengying; Sui, Cheng; Teng, Lesheng; Liu, Ximing; Teng, Lirong; Meng, Qingfan; Li, Youxin

2010-09-15

16

5-Fluorouracil encapsulated HA/PLGA composite microspheres for cancer therapy.  

PubMed

5-Fluorouracil (5FU) was successfully entrapped within poly(lactide-co-glycolide) (PLGA) and hydroyapatite (HA) composite microspheres using the emulsification/solvent extraction technique. The effects of HA to PLGA ratio, solvent ratio as well as polymer inherent viscosity (IV) on encapsulation efficiency were investigated. The degradation and drug release rates of the microspheres were studied for 5 weeks in vitro in phosphate buffered solution of pH 7.4 at 37 °C. The drug release profile followed a biphasic pattern with a small initial burst followed by a zero-order release for up to 35 days. The initial burst release decreased with increasing HA content. The potential of HA in limiting the initial burst release makes the incorporation of HA into PLGA microspheres advantageous since it reduces the risk of drug overdose from high initial bursts. The linear sustained drug release profile over the course of 5 weeks makes these 5-FU-loaded HA/PLGA composite microparticles a promising delivery system for the controlled release of chemotherapy drugs in the treatment of cancer. PMID:22843166

Lin, Yuting; Li, Yan; Ooi, Chui Ping

2012-10-01

17

Fabrication and characterization of monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells for controlled drug release.  

PubMed

Monodisperse PLGA-alginate core-shell microspheres with controlled size and homogeneous shells were first fabricated using capillary microfluidic devices for the purpose of controlling drug release kinetics. Sizes of PLGA cores were readily controlled by the geometries of microfluidic devices and the fluid flow rates. PLGA microspheres with sizes ranging from 15 to 50?m were fabricated to investigate the influence of the core size on the release kinetics. Rifampicin was loaded into both monodisperse PLGA microspheres and PLGA-alginate core-shell microspheres as a model drug for the release kinetics studies. The in vitro release of rifampicin showed that the PLGA core of all sizes exhibited sigmoid release patterns, although smaller PLGA cores had a higher release rate and a shorter lag phase. The shell could modulate the drug release kinetics as a buffer layer and a near-zero-order release pattern was observed when the drug release rate of the PLGA core was high enough. The biocompatibility of PLGA-alginate core-shell microspheres was assessed by MTT assay on L929 mouse fibroblasts cell line and no obvious cytotoxicity was found. This technique provides a convenient method to control the drug release kinetics of the PLGA microsphere by delicately controlling the microstructures. The obtained monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells could be a promising device for controlled drug release. PMID:23535235

Wu, Jun; Kong, Tiantian; Yeung, Kelvin Wai Kwok; Shum, Ho Cheung; Cheung, Kenneth Man Chee; Wang, Liqiu; To, Michael Kai Tsun

2013-07-01

18

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

PubMed

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

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

2011-10-15

19

Microencapsulation of inorganic nanocrystals into PLGA microsphere vaccines enables their intracellular localization in dendritic cells by electron and fluorescence microscopy.  

PubMed

Biodegradable poly-(D,L-lactide-co-glycolide) microspheres (PLGA-MS) are approved as a drug delivery system in humans and represent a promising antigen delivery device for immunotherapy against cancer. Immune responses following PLGA-MS vaccination require cross-presentation of encapsulated antigen by professional antigen presenting cells (APCs). While the potential of PLGA-MS as vaccine formulations is well established, the intracellular pathway of cross-presentation following phagocytosis of PLGA-MS is still under debate. A part of the controversy stems from the difficulty in unambiguously identifying PLGA-MS within cells. Here we show a novel strategy for the efficient encapsulation of inorganic nanocrystals (NCs) into PLGA-MS as a tool to study their intracellular localization. We microencapsulated NCs as an electron dense marker to study the intracellular localization of PLGA-MS by transmission electron microscopy (TEM) and as fluorescent labels for confocal laser scanning microscopy. Using this method, we found PLGA-MS to be rapidly taken up by dendritic cells and macrophages. Co-localization with the lysosomal marker LAMP1 showed a lysosomal storage of PLGA-MS for over two days after uptake, long after the initiation of cross-presentation had occurred. Our data argue against an escape of PLGA-MS from the endosome as has previously been suggested as a mechanism to facilitate cross-presentation of PLGA-MS encapsulated antigen. PMID:21223984

Schliehe, Christopher; Schliehe, Constanze; Thiry, Marc; Tromsdorf, Ulrich I; Hentschel, Joachim; Weller, Horst; Groettrup, Marcus

2011-05-10

20

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

PubMed

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

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

2015-01-01

21

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

NASA Astrophysics Data System (ADS)

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.

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

2014-08-01

22

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

PubMed

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

Zhang, Zhiyue; Huang, Guihua

2012-01-01

23

Radiosterilisation of indomethacin PLGA/PEG-derivative microspheres: protective effects of low temperature during gamma-irradiation.  

PubMed

Currently, gamma-irradiation seems to be a good method for sterilising drug delivery systems made from biodegradable polymers. The gamma-irradiation of microspheres can cause several physicochemical changes in the polymeric matrix. These modifications are affected by the temperature, irradiation dose and nature of the encapsulated drug and additives. This study has aimed to evaluate the influence of temperature during the sterilisation process by gamma irradiation in indomethacin PLGA microspheres including a PEG-derivative. Microspheres were prepared by the solvent evaporation method from o/w emulsion and were then exposed to gamma-irradiation. A dose of 25 kGy was used to ensure effective sterilisation. Some microspheres were sterilised with dry ice protection that guaranteed a low temperature during the process whilst others were sterilised without such dry ice protection. The effects of gamma-irradiation on the characteristics of non-loaded PLGA/PEG-derivative and indomethacin loaded PLGA/PEG-derivative microspheres with and without protection were studied. Non-protected microspheres showed changes in their morphological surface, polymer glass transition temperature, molecular weight and release rate of indomethacin after sterilisation. However, microspheres sterilised with protection did not show significant differences after gamma-irradiation exposure. The sterilisation method was satisfactory when the indomethacin loaded microspheres including a PEG-derivative were exposed to gamma-irradiation at low temperature. PMID:16495023

Fernández-Carballido, Ana; Puebla, Patricia; Herrero-Vanrell, Rocío; Pastoriza, Pilar

2006-04-26

24

Microencapsulation of PEGylated Adenovirus within PLGA Microspheres for Enhanced Stability and Gene Transfection Efficiency  

Microsoft Academic Search

Purpose  Green fluorescent protein (GFP) encoding adenovirus (ADV) was surface modified with polyethylene glycol (PEG) for microencapsulation\\u000a within poly(lactic-co-glycolic acid) (PLGA) microspheres with the aim of improving stability and gene transfection activity.\\u000a \\u000a \\u000a \\u000a Methods  A series of PEGylated ADV (PEG-ADV) with different PEG seeding densities on the viral surface was prepared and the GFP expression\\u000a efficiency of each PEG-ADV in the series determined.

Hyejung Mok; Ji Won Park; Tae Gwan Park

2007-01-01

25

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

Microsoft Academic Search

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

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

2002-01-01

26

Effect of polymer porosity on aqueous self-healing encapsulation of proteins in PLGA microspheres.  

PubMed

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 to 10% w/w) with increasing ?, with typically ?20 to 25% pores estimated accessible to entry by the enzyme from the external solution. Release kinetics of lysozyme under physiological conditions is continuous over more than two weeks and most strongly influenced by ? and protein loading before reaching a lag phase until 28 d 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

Reinhold, Samuel E; Schwendeman, Steven P

2013-12-01

27

Bone regeneration using a freeze-dried 3D gradient-structured scaffold incorporating OIC-A006-loaded PLGA microspheres based on ?-TCP/PLGA.  

PubMed

To reveal the latent capacity of the growth factor-like low-molecular-weight material OIC-A006 in tissue regeneration, it is essential to design a porous scaffold in order to concurrently accommodate cells and drug release in a controlled manner. Consequently, we fabricated poly (L-lactide-co-glycolide) (PLGA)-based microspheres with an OIC-A006-loaded gradient-structured ?-TCP/PLGA scaffold by freeze-drying which could then be used for drug delivery and bone regeneration. The OIC-A006-loaded ?-TCP/PLGA scaffold consisted of two parts which loaded different doses of OIC-A006 (6.25 ?M, outside; 12.5 ?M, inside). The porosity, compressive strength, SEM, degradation, and cumulative amount of drug release in vitro were characterized. Furthermore, we confirmed the incorporation of OIC-A006 into the PLGA-based microspheres within the scaffolds using UV-spectrophotometry, and the amount of drug remaining in the scaffold was maintained by 10 % for up to 28 days. The drug release was slower in the normal-structured drug-loaded scaffold. The OIC-A006 released action from the OIC-A006-loaded ?-TCP/PLGA scaffold with ideal the rapeutic prospects in tissue regeneration. In vitro cell culture results showed that this gradient-structured composite scaffold can induce the adhesion and proliferation of rat bone marrow stromal cells towards osteoblasts. These results showed that the newly developed OIC-A006-loaded scaffolds with gradient structure can be potentially applied to bone regeneration in clinical applications. PMID:25577209

Lin, Liulan; Gao, Haitao; Dong, Yangyang

2015-01-01

28

Novel preparation method for sustained-release PLGA microspheres using water-in-oil-in-hydrophilic-oil-in-water emulsion  

PubMed Central

An increasing number of drugs are needing improved formulations to optimize patient compliance because of their short half-lives in blood. Sustained-release formulations of drugs are often required for long-term efficacy, and microspheres are among the most popular ones. When drugs are encapsulated into microsphere formulations, different methods of preparation need to be used according to specific clinical requirements and the differing physicochemical characteristics of individual drugs. In this work, we developed a novel method for sustained-release drug delivery using a water-in-oil-in-hydrophilic oil-in-water (w/o/oh/w) emulsion to encapsulate a drug into poly(lactic-co-glycolic acid) (PLGA) microspheres. Different effects were achieved by varying the proportions and concentrations of hydrophilic oil and PLGA. Scanning electron and optical microscopic images showed the surfaces of the microspheres to be smooth and that their morphology was spherical. Microspheres prepared using the w/o/oh/w emulsion were able to load protein efficiently and had sustained-release properties. These results indicate that the above-mentioned method might be useful for developing sustained-release microsphere formulations in the future. PMID:23882140

Hong, Xiaoyun; Wei, Liangming; Ma, Liuqing; Chen, Yinghui; Liu, Zhenguo; Yuan, Weien

2013-01-01

29

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

PubMed

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

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

2014-06-01

30

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

PubMed

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

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

2013-01-01

31

Encapsulation of Exenatide in Poly-(d,l-Lactide-Co-Glycolide) Microspheres Produced an Investigational Long-Acting Once-Weekly Formulation for Type 2 Diabetes  

PubMed Central

Abstract Exenatide once-weekly (EQW [2?mg s.c.]) is under development as monotherapy as an adjunct to diet and exercise or as a combination therapy with an oral antidiabetes drug(s) in adults with type 2 diabetes. This long-acting formulation contains the active ingredient of the original exenatide twice-daily (EBID) formulation encapsulated in 0.06-mm-diameter microspheres of medical-grade poly-(d,l-lactide-co-glycolide) (PLG). After mechanical suspension and subcutaneous injection by the patient, EQW microspheres hydrate in situ and adhere to one another to form an amalgam. A small amount of loosely bound surface exenatide, typically less than 1%, releases in the first few hours, whereas drug located in deeper interstices diffuses out more slowly (time to maximum, ?2 weeks). Fully encapsulated exenatide (i.e., drug initially inaccessible to diffusion) releases over a still longer period (time to maximum, ?7 weeks) as the PLG matrix hydrolyzes into lactic acid and glycolic acid, which are subsequently eliminated as carbon dioxide and water. For EQW, plasma exenatide concentrations reach the therapeutic range by 2 weeks and steady state by 6–7 weeks. This gradual approach to steady state seems to improve tolerability, as nausea is less frequent with EQW than EBID. EQW administrations may be associated with palpable skin nodules that generally resolve without further medical intervention. In comparative trials, EQW improved hemoglobin A1c more than EBID, sitagliptin, pioglitazone, or insulin glargine and reduced fasting plasma glucose more than EBID. Weight loss due to EQW or EBID was similar. EQW is the first glucose-lowering agent that is administered once weekly. PMID:21751887

MacConell, Leigh; Sarin, Viren; Trautmann, Michael; Herbert, Paul

2011-01-01

32

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

PubMed Central

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

Li, Hongli; Yuan, Mingwei; Yuan, Minglong

2014-01-01

33

Sustained release of TGFbeta3 from PLGA microspheres and its effect on early osteogenic differentiation of human mesenchymal stem cells.  

PubMed

Despite the widespread role of transforming growth factor-beta3 (TGFbeta3) in wound healing and tissue regeneration, its long-term controlled release has not been demonstrated. Here, we report microencapsulation of TGFbeta3 in poly-d-l-lactic-co-glycolic acid (PLGA) microspheres and determine its bioactivity. The release profiles of PLGA-encapsulated TGFbeta3 with 50:50 and 75:25 PLA:PGA ratios differed throughout the experimental period. To compare sterilization modalities of microspheres, bFGF was encapsulated in 50:50 PLGA microspheres and subjected to ethylene oxide (EO) gas, radio-frequency glow discharge (RFGD), or ultraviolet (UV) light. The release of bFGF was significantly attenuated by UV light, but not significantly altered by either EO or RFGD. To verify its bioactivity, TGFbeta3 (1.35 ng/mL) was control-released to the culture of human mesenchymal stem cells (hMSC) under induced osteogenic differentiation. Alkaline phosphatase staining intensity was markedly reduced 1 week after exposing hMSC-derived osteogenic cells to TGFbeta3. This was confirmed by lower alkaline phosphatase activity (2.25 +/- 0.57 mU/mL/ng DNA) than controls (TGFbeta3- free) at 5.8 +/- 0.9 mU/mL/ng DNA (p < 0.05). Control-released TGFbeta3 bioactivity was further confirmed by lack of significant differences in alkaline phosphatase upon direct addition of 1.35 ng/mL TGFbeta3 to cell culture (p > 0.05). These findings provide baseline data for potential uses of microencapsulated TGFbeta3 in wound healing and tissue-engineering applications. PMID:16579687

Moioli, Eduardo K; Hong, Liu; Guardado, Jesse; Clark, Paul A; Mao, Jeremy J

2006-03-01

34

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

PubMed

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

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

2013-06-10

35

Sustained release of melatonin from poly (lactic-co-glycolic acid) (PLGA) microspheres to induce osteogenesis of human mesenchymal stem cells in vitro.  

PubMed

Melatonin promotes bone formation and prevents bone degradation via receptor-dependent or receptor-independent actions. The aim of this study is to encapsulate melatonin into poly (lactic-co-glycolic acid) (PLGA) microspheres (PLGA-MEL-MS) and create a melatonin sustained release system, then to evaluate its effect on the osteogenesis of human mesenchymal stem cells (hMSCs) in vitro. PLGA-MEL-MS were prepared by single emulsion solvent evaporation technique. Scanning electron microscopy demonstrated the incorporation of melatonin did not disturb the conventional generation of PLGA microspheres in size and morphology. In vitro drug release assay showed that PLGA-MEL-MS exhibited a biphasic drug release pattern: a low initial burst release effect with approximately 40% drug release at the first 3 days and a relatively retarded and continuous release with about 85% drug release over the 25 days. Cell proliferation assay demonstrated that PLGA-MEL-MS had no apparent effect on proliferation of human MSCs. In an osteogenesis assay, PLGA-MEL-MS obviously enhanced alkaline phosphatase (ALP) mRNA expression and increased ALP activity compared to that in the control group. Meanwhile, several markers of osteoblast differentiation were also significantly upregulated, including runx2, osteopontin, and osteocalcin. Furthermore, quantificational alizarin red-based assay demonstrated that PLGA-MEL-MS significantly enhanced calcium deposit of hMSCs compared to the controls. Therefore, this simple melatonin sustained release system can control released melatonin to generate a microenvironment with a relatively stable concentration of melatonin for a period of time to support osteogenic differentiation of hMSCs in vitro. This suggests that this system may be used as bone growth stimulator in bone healing in vivo. PMID:22712496

Zhang, Liangming; Zhang, Jinling; Ling, You; Chen, Changhua; Liang, Anjing; Peng, Yan; Chang, Hong; Su, Peiqiang; Huang, Dongsheng

2013-01-01

36

PEGylated TNF-related apoptosis-inducing ligand (TRAIL)-loaded sustained release PLGA microspheres for enhanced stability and antitumor activity  

Microsoft Academic Search

The purpose of this work was to develop an effective PEGylated TNF-related apoptosis-inducing ligand (PEG-TRAIL) delivery system for antitumor therapy based on local injection to tumor sites that has a sustained effect without protein aggregation or an initial release burst. The authors designed poly (lactic-co-glycolic) acid (PLGA) microspheres that deliver PEG-TRAIL locally and continuously at tumor sites with sustained biological

Tae Hyung Kim; Hai Hua Jiang; Chan Woong Park; Yu Seok Youn; Seulki Lee; Xiaoyuan Chen; Kang Choon Lee

2011-01-01

37

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

Microsoft Academic Search

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.

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

2001-01-01

38

rhEGF-loaded PLGA-Alginate microspheres enhance the healing of full-thickness excisional wounds in diabetised Wistar rats.  

PubMed

Diabetic foot ulcers (DFUs) represent a major clinical challenge in the ageing population. To address this problem, rhEGF-loaded Poly-Lactic-co-Glycolic-Acid (PLGA)-Alginate microspheres (MS) were prepared by a modified w/o/w-double-emulsion/solvent evaporation method. Different formulations were evaluated with the aim of optimising MSs properties by adding NaCl to the surfactant solution and/or the solvent removal phase and adding alginate as a second polymer. The characterisation of the developed MS showed that alginate incorporation increased the encapsulation efficiency (EE) and NaCl besides increasing the EE also became the particle surface smooth and regular. Once the MS were optimised, the target loading of rhEGF was increased to 1% (PLGA-Alginate MS), and particles were sterilised by gamma radiation to provide the correct dosage for in vivo studies. In vitro cell culture assays demonstrated that neither the microencapsulation nor the sterilisation process affected rhEGF bioactivity or rhEGF wound contraction. Finally, the MS were evaluated in vivo for treatment of the full-thickness wound model in diabetised Wistar rats. rhEGF MS treated animals showed a statistically significant decrease of the wound area by days 7 and 11, a complete re-epithelisation by day 11 and an earlier resolution of the inflammatory process. Overall, these findings demonstrate the promising potential of rhEGF-loaded MS (PLGA-Alginate MS) to promote faster and more effective wound healing, and suggest its possible application in DFU treatment. PMID:23872142

Gainza, Garazi; Aguirre, José Javier; Pedraz, José Luis; Hernández, Rosa María; Igartua, Manoli

2013-11-20

39

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

PubMed

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

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

2014-10-01

40

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)

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.

Azeke, John Imuetinyan-Jesu, Jr.

41

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

PubMed Central

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

Chue, Pierre

2007-01-01

42

Microspheres  

NASA Technical Reports Server (NTRS)

Vital information on a person's physical condition can be obtained by identifying and counting the population of T-cells and B-cells, lymphocytes of the same shape and size that help the immune system protect the body from the invasion of disease. The late Dr. Alan Rembaum developed a method for identifying the cells. The method involved tagging the T-cells and B-cells with microspheres of different fluorescent color. Microspheres, which have fluorescent dye embedded in them, are chemically treated so that they can link with antibodies. With the help of a complex antibody/antigen reaction, the microspheres bind themselves to specific 'targets,' in this case the T-cells or B-cells. Each group of cells can then be analyzed by a photoelectronic instrument at different wavelengths emitted by the fluorescent dyes. Same concept was applied to the separation of cancer cells from normal cells. Microspheres were also used to conduct many other research projects. Under a patent license Magsphere, Inc. is producing a wide spectrum of microspheres on a large scale and selling them worldwide for various applications.

1990-01-01

43

Long-acting reversible contraception.  

PubMed

Although short-acting reversible hormonal contraceptives, such as oral contraceptives and the contraceptive patch and vaginal ring, remain the most commonly used contraceptive methods in the United States, they are also associated with the highest failure rates. Long-acting reversible contraception (LARC) methods, such as intrauterine devices and contraceptive implants, offer high continuation rates and very low failure rates, and are safe for use in most women. The provision of LARC methods to adolescent, young adult and nulliparous women is a relatively new concept that offers an innovative option for these populations. PMID:24138662

Peck, Susan A

2013-10-01

44

Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation.  

PubMed

This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA) to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA) was selected as model compound because of its sensitiveness of ?-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of Mw and Tg of the starting PLGA (Mw PLGA = 26.3 ± 1.3 kDa vs. Mw g-CA-PLGA = 22.8 ± 0.7 kDa; Tg PLGA = 47.7 ± 0.8 °C vs. Tg g-CA-PLGA = 47.4 ± 0.2 °C). By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation efficiency (EE), suggesting that the presence of caffeic residues improved the compatibility between components (EEPLGA = 35.0% ± 0.7% vs. EEg-CA-PLGA = 95.6% ± 2.7%). Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were -25 mV and -15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of Mw and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs. PMID:25569163

Selmin, Francesca; Puoci, Francesco; Parisi, Ortensia I; Franzé, Silvia; Musazzi, Umberto M; Cilurzo, Francesco

2015-01-01

45

Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes.  

PubMed

Inhalable glycol chitosan-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing palmitic acid-modified exendin-4 (Pal-Ex4) (chitosan Pal-Ex4 PLGA NPs) were prepared and characterized. The surface morphology, particle size, and zeta potential of chitosan Pal-Ex4 PLGA NPs were investigated, and the adsorption and cytotoxicity of chitosan Pal-Ex4 PLGA NPs were evaluated in human lung epithelial cells (A549). Finally, the lung deposition characteristics and hypoglycemia caused by chitosan Pal-Ex4 PLGA NPs were evaluated after pulmonary administration in imprinting control region (ICR) and type 2 diabetic db/db mice. Results showed that chitosan Pal-Ex4 PLGA NPs were spherical, compact and had a diameter of ~700 nm and a positive surface charge of +28.5 mV Chitosan-coated PLGA NPs were adsorbed onto A549 cells much more so than non-coated PLGA NPs. Pal-Ex4 release from chitosan-coated PLGA NPs was delayed by as much as 1.5 days as compared with chitosan-coated Ex4 PLGA NPs. In addition, chitosan-coated PLGA NPs remained in the lungs for ~72 hours after pulmonary administration, whereas most non-coated PLGA NPs were lost at 8 hours after administration. Furthermore, the hypoglycemic efficacy of inhaled chitosan Pal-Ex4 PLGA NPs was 3.1-fold greater than that of chitosan Ex4 PLGA NPs in db/db mice. The authors believe chitosan Pal-Ex4 PLGA NPs have considerable potential as a long-acting inhalation delivery system for the treatment of type 2 diabetes. PMID:23976850

Lee, Changkyu; Choi, Ji Su; Kim, Insoo; Oh, Kyung Taek; Lee, Eun Seong; Park, Eun-Seok; Lee, Kang Choon; Youn, Yu Seok

2013-01-01

46

Injectable long-acting in situ forming systems for Radix Ophiopogonis polysaccharide.  

PubMed

In the area of injectable long-acting formulations, the in situ forming system (ISFS) is an attractive alternative for its various superiorities. In this study, both hydrophilic and hydrophobic in situ forming systems, using Poloxamer and sucrose acetate isobutyrate (SAIB) or poly(d,l-lactide-co-glycolide) copolymer (PLGA) as carrier, respectively, were investigated for Radix Ophiopogonis polysaccharide (ROP), a natural anti-myocardial ischemic fructan. A reasonable and applicable range of formulations were selected from each carrier for in vivo study by investigating their rheological property. The results from in vivo evaluation show that relatively promising sustained behaviors were achieved by formulations 24% P407/10% P188, 40% PLGA30k/NMP, and 30% PLGA50k/NMP. Significant differences of drug release kinetics were observed between in situ thermally-induced Poloxamer-based hydrogels and in situ solvent exchange-induced hydrophobic PLGA depots. This suggests that different ISFS could be chosen to provide different application purpose for polysaccharide drugs. In the case of ROP, Poloxamer-based ISFS is promising for short-term acute therapies; however, PLGA-based ISFS might be promising for long-term precaution or/and cure of myocardial ischemia. PMID:25236608

Shi, XiaoLi; Lin, Xiao; Yao, ChunXia; Shen, Lan; Feng, Yi

2015-01-01

47

Stability of proteins within biodegradable microspheres  

E-print Network

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 ...

Fu, Karen, 1967-

2000-01-01

48

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

PubMed

Abstract 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

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

49

Directive counseling on long-acting contraception.  

PubMed Central

National rates of unintended births are a major public health concern. The availability of highly effective long-acting contraceptives has prompted some public officials to promote the coercive use of these methods to reduce such problems as intergenerational poverty and child abuse. Broad-brush public policies that require long-term contraceptive use are unethical. However, persuasion to use these methods can be appropriate. One place for exerting ethically justified influence is in family planning counseling. The dominant nondirective counseling model, which excludes the possibility of vigorous persuasion, is overly rigid. Family planning professionals should develop practice protocols that permit and guide the exercise of directive counseling to use long-acting contraception. PMID:8659650

Moskowitz, E; Jennings, B

1996-01-01

50

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

E-print Network

increases, protrusions start to appear, become more numerous and finally fuse to yield sponge-like capsules (PLA-PEG) led to sponge-like microspheres with faster drug release. Similar sponge morphologies were of size and specific surface area as a function of PLGA-PEG percentage. In addition, interfacial tension

Raphael, Elie

51

Long-acting preparations of exenatide  

PubMed Central

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

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

2013-01-01

52

Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium.  

PubMed

This study aimed to prepare biodegradable microspheres containing flurbiprofen sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery system to the periodontal pocket. Microspheres were prepared from biodegradable copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation method. The effects of the different copolymers and amounts of polyvinyl alcohol (PVA) as a dispersing agent on characteristics of the microspheres were evaluated. Although there was no correlation between microsphere size and amount of PVA, an optimum PVA concentration was essential to achieve narrower size distributions of microspheres. As the concentration of PVA increased, the drug loading of the microspheres increased. The effect of PVA on drug loading was found to be statistically significant for those microspheres prepared from PLGA 50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of microspheres (60-80%) were affected neither by different PVA concentrations nor by copolymer compositions (p > 0.05). According to the first-order release rate constants of the microspheres, the microspheres of PLGA 50:50 released the drug at the highest rate consistently, with the highest hydrophilicity of this copolymer. PMID:16423798

Samati, Yekta; Yüksel, Nilüfer; Tarimci, Nilüfer

2006-01-01

53

Poly(L-glutamic acid)/chitosan polyelectrolyte complex porous microspheres as cell microcarriers for cartilage regeneration.  

PubMed

In this study a novel kind of porous poly(l-glutamic acid) (PLGA)/chitosan polyelectrolyte complex (PEC) microsphere was developed through electrostatic interaction between PLGA and chitosan. By adjusting the formula parameters chitosan microspheres with an average pore size of 47.5 ± 5.4 ?m were first developed at a concentration of 2 wt.% and freeze temperature of -20 °C. For self-assembly of the PEC microspheres porous chitosan microspheres were then incubated in PLGA solution at 37 °C. Due to electrostatic interaction a large amount of PLGA (110.3 ?g mg(-1)) was homogeneously absorbed within the chitosan microspheres. The developed PEC microspheres retained their original size, pore diameters and interconnected porous structure. Fourier transform infrared spectroscopy, thermal gravimetric analysis and zeta potential analysis revealed that the PEC microspheres were successfully prepared through electrostatic interaction. Compared with microspheres fabricated from chitosan, the porous PEC microspheres were shown to efficiently promote chondrocyte attachment and proliferation. After injection subcutaneously for 8 weeks PEC microspheres loaded with chondrocytes were found to produce significant more cartilaginous matrix than chitosan microspheres. These results indicate that these novel fabricated porous PLGA/chitosan PEC microspheres could be used as injectable cell carriers for cartilage tissue engineering. PMID:24025620

Fang, Jianjun; Zhang, Yun; Yan, Shifeng; Liu, Zhiwen; He, Shiming; Cui, Lei; Yin, Jingbo

2014-01-01

54

Cytoplasmic delivery of a macromolecular fluorescent probe by poly(d, l-lactic-co-glycolic acid) microspheres.  

PubMed

A macromolecular fluorescent probe encapsulated in poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres was used as a model for studying cytoplasmic delivery of antigens. We hypothesized that Texas red dextran loaded in PLGA microspheres would be delivered to the cytoplasm and that cytoplasmic delivery would be affected by polymer molecular weight. Cellular localization of the Texas red dextran was investigated at two different molecular weights of PLGA: 6000 and 60,000 g/mol. Intracellular degradation and processing of Texas red dextran-loaded PLGA microspheres by mouse peritoneal macrophages was monitored both in vitro and in vivo for a 7-day period using confocal laser scanning microscopy (CLSM). The results revealed cytoplasmic delivery of the fluorescent probe at both molecular weights of PLGA. Furthermore, the CLSM images showed that both in vitro and in vivo, the kinetics of microsphere degradation and cytoplasmic delivery were more rapid for the 6000 g/mol PLGA microspheres than the 60,000 g/mol PLGA microspheres. Hence, this study provides physical evidence that PLGA microspheres are capable of cytoplasmic delivery and that delivery to the cytosol can be controlled by modifying formulation parameters such as polymer molecular weight. PMID:10756318

Newman, K D; Kwon, G S; Miller, G G; Chlumecky, V; Samuel, J

2000-06-15

55

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

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

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

2014-12-01

56

Controlled delivery of a hydrophilic drug from a biodegradable microsphere system by supercritical anti-solvent precipitation technique  

Microsoft Academic Search

The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA\\/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10mm in geometric mean diameter could be prepared, with high

S. Lee; M. S. Kim; J. S. Kim; H. J. Park; J. S. Woo; B. C. Lee; S. J. Hwang

2006-01-01

57

A biomimetic approach to active self-microencapsulation of proteins in PLGA.  

PubMed

A biomimetic approach to organic solvent-free microencapsulation of proteins based on the self-healing capacity of poly (dl)-lactic-co-glycolic acid (PLGA) microspheres containing glycosaminoglycan-like biopolymers (BPs), was examined. To screen BPs, aqueous solutions of BP [high molecular weight dextran sulfate (HDS), low molecular weight dextran sulfate (LDS), chondroitin sulfate (CS), heparin (HP), hyaluronic acid (HA), chitosan (CH)] and model protein lysozyme (LYZ) were combined in different molar and mass ratios, at 37°C and pH7. The BP-PLGA microspheres (20-63?m) were prepared by a double water-oil-water emulsion method with a range of BP content, and trehalose and MgCO3 to control microclimate pH and to create percolating pores for protein. Biomimetic active self-encapsulation (ASE) of proteins [LYZ, vascular endothelial growth factor165 (VEGF) and fibroblast growth factor (FgF-20)] was accomplished by incubating blank BP-PLGA microspheres in low concentration protein solutions at ~24°C, for 48h. Pore closure was induced at 42.5°C under mild agitation for 42h. Formulation parameters of BP-PLGA microspheres and loading conditions were studied to optimize protein loading and subsequent release. LDS and HP were found to bind >95% LYZ at BP:LYZ>0.125 w/w, whereas HDS and CS bound >80% LYZ at BP:LYZ of 0.25-1 and <0.33, respectively. HA-PLGA microspheres were found to be not ideal for obtaining high protein loading (>2% w/w of LYZ). Sulfated BP-PLGA microspheres were capable of loading LYZ (~2-7% w/w), VEGF (~4% w/w), and FgF-20 (~2% w/w) with high efficiency. Protein loading was found to be dependent on the loading solution concentration, with higher protein loading obtained at higher loading solution concentration within the range investigated. Loading also increased with content of sulfated BP in microspheres. Release kinetics of proteins was evaluated in-vitro with complete release media replacement. Rate and extent of release were found to depend upon volume of release (with non-sink conditions observed <5ml release volume for ~18mg loaded BP-PLGA microspheres), ionic strength of release media and loading solution concentration. HDS-PLGA formulations were identified as having ideal loading and release characteristics. These optimal microspheres released ~73-80% of the encapsulated LYZ over 60days, with >90% of protein being enzymatically active. Nearly 72% of immunoreactive VEGF was similarly released over 42days, without significant losses in heparin binding affinity in the release medium. PMID:25219750

Shah, Ronak B; Schwendeman, Steven P

2014-12-28

58

A short-term (accelerated release) approach to evaluate peptide release from PLGA depot formulations  

Microsoft Academic Search

An accelerated method to evaluate peptide release from poly(dl-lactide-co-glycolide) (PLGA) depot formulations in short time\\u000a is described. Peptide-loaded microspheres were made from hydrophilic 50?50 PLGA by a dispersionsolyent extraction technique,\\u000a and peptide release was studied at 37°C and at higher temperatures in various media. For all accelerated conditions, release\\u000a was faster at temperatures above the glass transition, Tg, of the

Mohammed Shameem; Heeyong Lee; Patrick P. DeLuca

1999-01-01

59

Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics.  

PubMed

There are now long-acting versions of six antipsychotic drugs on the U.S. market, and with them, five unique combinations of molecular form and delivery strategy long-acting-injectable-antipsychotics (LAIAs) show evidence of reduced relapses of schizophrenia, but their introduction has been slow, taking at least nine years after the approval of each oral drug. Oily solutions of lipophilic prodrugs were the first to enter the LAIA market, but they relied on esterification of a hydroxyl handle that was lost with the emergence of the atypical antipsychotics. A review of the literature and patents shows that companies tested many different approaches before reaching the currently marketed versions, including aqueous suspensions of poorly soluble salts, polymeric microspheres, and new approaches to making prodrugs. Yet, very little has been published to support faster development of safe long-acting injectables (LAIs). This review introduces some of the critical considerations in creating an LAI; then it analyzes the existing products and discusses areas where further research is needed. The available literature suggests that lipophilic prodrugs may be inherently safer than poorly soluble salts as LAIs. Other areas needing additional study include (1) the range of physical properties acceptable for LAIs and the effect of prodrug tail length in achieving them, and (2) the role of physiological responses at the injection site in the release of drug from a depot. PMID:24679167

Remenar, Julius F

2014-06-01

60

Subcritical CO2 sintering of microspheres of different polymeric materials to fabricate scaffolds for tissue engineering.  

PubMed

The aim of this study was to use CO2 at sub-critical pressures as a tool to sinter 3D, macroporous, microsphere-based scaffolds for bone and cartilage tissue engineering. Porous scaffolds composed of ~200 ?m microspheres of either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) were prepared using dense phase CO2 sintering, which were seeded with rat bone marrow mesenchymal stromal cells (rBMSCs), and exposed to either osteogenic (PLGA, PCL) or chondrogenic (PLGA) conditions for 6 weeks. Under osteogenic conditions, the PLGA constructs produced over an order of magnitude more calcium than the PCL constructs, whereas the PCL constructs had far superior mechanical and structural integrity (125 times stiffer than PLGA constructs) at week 6, along with twice the cell content of the PLGA constructs. Chondrogenic cell performance was limited in PLGA constructs, perhaps as a result of the polymer degradation rate being too high. The current study represents the first long-term culture of CO2-sintered microsphere-based scaffolds, and has established important thermodynamic differences in sintering between the selected formulations of PLGA and PCL, with the former requiring adjustment of pressure only, and the latter requiring the adjustment of both pressure and temperature. Based on more straightforward sintering conditions and more favorable cell performance, PLGA may be the material of choice for microspheres in a CO2 sintering application, although a different PLGA formulation with the encapsulation of growth factors, extracellular matrix-derived nanoparticles, and/or buffers in the microspheres may be advantageous for achieving a more superior cell performance than observed here. PMID:24094202

Bhamidipati, Manjari; Sridharan, BanuPriya; Scurto, Aaron M; Detamore, Michael S

2013-12-01

61

[Aripiprazole long-acting for the maintenance treatment of schizophrenia.  

PubMed

Antipsychotics are the cornerstone for the maintenance treatment of schizophrenia patients. Their long-acting formulations are helpful for preventing relapses through improvement of adherence to medication and a better pharmacokinetic coverage. However, their use is often reserved for refractory or non-observant clinical forms because of limitations among both clinicians and patients. The development of a new formulation of long-acting injectable aripiprazole administered every 4 weeks is a new option. Two randomized controlled trials vs. placebo and vs. oral aripiprazole respectively show a superiority and non-inferiority in terms of relapse prevention. Meanwhile, a mirror-image study demonstrates fewer hospitalizations. The safety profile is comparable to the oral formulation, particularly in terms of metabolic and neurological side-effects. As mentioned in various professional recommendations, long-acting injectable antipsychotics, so long-acting injectable aripiprazole, are one of the major strategies of the maintenance treatment for patients with schizophrenia. PMID:25453734

Samalin, L; Charpeaud, T; Llorca, P-M

2014-11-13

62

PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis  

Microsoft Academic Search

A novel controlled release formulation has been developed with PEGylated human insulin encapsulated in PLGA microspheres that produces multi-day release in vivo. The insulin is specifically PEGylated at the amino terminus of the B chain with a relatively low molecular weight PEG (5000 Da). Insulin with this modification retains full biological activity, but has a limited serum half-life, making encapsulation

Kenneth D. Hinds; Kathleen M. Campbell; Kathleen M. Holland; Danny H. Lewis; Claude A. Piché; Paul G. Schmidt

2005-01-01

63

PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis.  

PubMed

A novel controlled release formulation has been developed with PEGylated human insulin encapsulated in PLGA microspheres that produces multi-day release in vivo. The insulin is specifically PEGylated at the amino terminus of the B chain with a relatively low molecular weight PEG (5000 Da). Insulin with this modification retains full biological activity, but has a limited serum half-life, making encapsulation necessary for sustained release beyond a few hours. PEGylated insulin can be co-dissolved with PLGA in methylene chloride and microspheres made by a single o/w emulsion process. Insulin conformation and biological activity are preserved after PEGylation and PLGA encapsulation. The monolithic microspheres have inherently low burst release, an important safety feature for an extended release injectable insulin product. In PBS at 37 degrees C, formulations with a drug content of approximately 14% show very low (< 1%) initial release of insulin over one day and near zero order drug release after a lag of 3-4 days. In animal studies, PEG-insulin microspheres administered subcutaneously as a single injection produced < 1% release of insulin in the first day but then lowered the serum glucose levels of diabetic rats to values < 200 mg/dL for approximately 9 days. When doses were given at 7-day intervals, steady state drug levels were achieved after only 2 doses. PEG-insulin PLGA microparticles show promise as a once-weekly dosed, sustained release basal insulin formulation. PMID:15911045

Hinds, Kenneth D; Campbell, Kathleen M; Holland, Kathleen M; Lewis, Danny H; Piché, Claude A; Schmidt, Paul G

2005-06-01

64

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

NASA Astrophysics Data System (ADS)

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.

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

2011-02-01

65

Clinical blood chemistry values and long acting phenothiazines.  

PubMed

Fifty-nine chronic schizophrenic patients received one year of treatment with either fluphenazine enanthate or pipothiazine palmitate IM. Both long acting neuroleptics significantly decreased serum albumin, total protein and creatinine values. Triglycerides were decreased only early in treatment. Pretreatment findings from therapy responders, as compared with those who failed to respond to treatment, included higher albumin values and to a lesser extent, lower lactic dehydrogenase values and greater height. These results were discussed with an eye toward the hepatocellular effects of long acting phenothiazines and the effect of liver function on the pharmacokinetics of these medications. PMID:6114503

Schneider, S J; Kirby, E J; Itil, T M

1981-05-01

66

The discovery of long acting ? 2-adrenoreceptor agonists  

Microsoft Academic Search

The design and profile of a series of saligenin containing long acting ?2-adrenoreceptor agonists is described. Evaluation of these analogues using a guinea-pig tissue model demonstrates that analogues within this series have significantly longer durations of action than salmeterol and have the potential for a once daily profile in human.

Alan D. Brown; Mark E. Bunnage; Paul A. Glossop; Kim James; Rhys Jones; Russell A. Lewthwaite; Simon Mantell; Christelle Perros-Huguet; David A. Price; Mike Trevethick; Rob Webster

2007-01-01

67

The discovery of long acting beta2-adrenoreceptor agonists.  

PubMed

The design and profile of a series of saligenin containing long acting beta(2)-adrenoreceptor agonists is described. Evaluation of these analogues using a guinea-pig tissue model demonstrates that analogues within this series have significantly longer durations of action than salmeterol and have the potential for a once daily profile in human. PMID:17498952

Brown, Alan D; Bunnage, Mark E; Glossop, Paul A; James, Kim; Jones, Rhys; Lane, Charlotte A L; Lewthwaite, Russell A; Mantell, Simon; Perros-Huguet, Christelle; Price, David A; Trevethick, Mike; Webster, Rob

2007-07-15

68

Novel polymeric microspheres containing norcantharidin for chemoembolization  

Microsoft Academic Search

Chemoembolization has been found to be a potentially effective method of treating certain types of cancer. It involves arterial embolization of a tumor, in combination with simultaneous or subsequent local delivery of chemotherapeutic agents. In this study, PLGA-alginate microspheres were evaluated for their potential application in chemoembolization. Norcantharidin, which possesses anti-tumor properties, was used to investigate the application of drug-containing

Xiaohua Liu; Wan Sia Heng; Qi Li; Lai Wah Chan

2006-01-01

69

Emerging role of long acting muscarinic antagonists for asthma  

PubMed Central

Acetlycholine is involved in the control of airway smooth muscle constriction and in recruitment of inflammatory cells via neuronal and paracrine effects on muscarinic type 3 receptors. Long acting muscarinic antagonists (LAMA) are well established in guidelines for COPD but are not currently licensed for use in asthma. There are emerging data from key clinical trials to show that LAMA may confer bronchodilator effects and improved control when used in addition to inhaled corticosteroid (ICS) alone or in conjunction with long acting ?-adrenoceptor agonists (LABA). Further studies in persistent asthmatic patients are required to evaluate ICS sparing effects of LAMA looking particularly at airway hyper-responsiveness and surrogate inflammatory markers, in addition to evaluation of possible synergy between LAMA and LABA when given together. Future possible development of combination inhalers comprising ICS/LAMA or ICS/LAMA/LABA will require long term studies looking at asthma control and exacerbations in both adult and paediatric patients. PMID:23534447

Lipworth, Brian J

2014-01-01

70

Long-acting medications for the hyperkinetic disorders  

Microsoft Academic Search

A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder\\u000a is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A\\u000a panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice,\\u000a and conclusions are reported: (1)

Tobias Banaschewski; David Coghill; Paramala Santosh; Alessandro Zuddas; Philip Asherson; Jan Buitelaar; Marina Danckaerts; Manfred Döpfner; Stephen V. Faraone; Aribert Rothenberger; Joseph Sergeant; Hans-Christoph Steinhausen; Edmund J. S. Sonuga-Barke; Eric Taylor

2006-01-01

71

Novel long-acting bronchodilators for COPD and asthma.  

PubMed

An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once-daily beta2-agonists or ultra long-acting beta2-agonists (LABAs) such as carmoterol, indacaterol, GSK-159797, GSK-597901, GSK-159802, GSK-642444 and GSK-678007 are under development for the treatment of asthma and COPD. Also some new long-acting antimuscarinic agents (LAMAs) such as aclidinium, LAS-35201, GSK656398, GSK233705, NVA-237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once-daily dual-action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M3 antagonist-beta2 agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products. PMID:18604231

Cazzola, M; Matera, M G

2008-10-01

72

Novel long-acting bronchodilators for COPD and asthma  

PubMed Central

An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once-daily ?2-agonists or ultra long-acting ?2-agonists (LABAs) such as carmoterol, indacaterol, GSK-159797, GSK-597901, GSK-159802, GSK-642444 and GSK-678007 are under development for the treatment of asthma and COPD. Also some new long-acting antimuscarinic agents (LAMAs) such as aclidinium, LAS-35201, GSK656398, GSK233705, NVA-237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once-daily dual-action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M3 antagonist-?2 agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products. PMID:18604231

Cazzola, M; Matera, M G

2008-01-01

73

In vitro drug release behavior, mechanism and antimicrobial activity of rifampicin loaded low molecular weight PLGA-PEG-PLGA triblock copolymeric nanospheres.  

PubMed

Poly (lactic-co-glycolic acid) (PLGA (92:8)) and a series of PLGA-PEG-PLGA tri block copolymers were synthesized by direct melt polycondensation. The copolymers were characterized by FTIR, and 1HNMR spectroscopic techniques, viscosity, gel permeation chromatography (GPC) and powder x-ray diffraction (XRD). The rifampicin (RIF) loaded polymeric nanospheres (NPs) were prepared by ultrasonication-W/O emulsification technique. The NPs have been characterized by field emission scanning electron microscopy (FESEM), TEM, powder X-ray diffraction (XRD), UVvisible spectroscopy and DLS measurements. The drug loaded triblock copolymeric NPs have five folds higher drug content and drug loading efficiency than that of PLGA microspheres (MPs). The in vitro drug release study shows that the drug loaded NPs showed an initial burst release after that sustained release up to 72 h. All the triblock copolymeric NPs follow anomalous drug diffusion mechanism while the PLGA MPs follow non-Fickian super case-II mechanism up to 12 h. The overall in-vitro release follows second order polynomial kinetics up to 72 h. The antimicrobial activity of the RIF loaded polymer NPs was compared with that of pure RIF and tetracycline (TA). The RIF loaded triblock copolymeric NPs inhibited the bacterial growth more effectively than the pure RIF and TA. PMID:23701139

Gajendiran, M; Divakar, S; Raaman, N; Balasubramanian, S

2013-12-01

74

Intra-articular treatment of arthritis with microsphere formulations of paclitaxel: biocompatibility and efficacy determinations in rabbits  

Microsoft Academic Search

Objectives:To assess the biocompatibility of controlled release microspheres prepared from different polymeric biomaterials in various size ranges in rabbit synovial joints and based on these data, design and evaluate the efficacy of an intra-articular, paclitaxel-loaded microspheres formulation in rabbit models of arthritis. Methods:Paclitaxel-loaded microspheres of poly(lactide-co-glycolide) (PLGA), poly(L-lactic acid) (PLA) and poly(caprolactone) (PCL) were prepared in different size ranges and

R. T. Liggins; T. Cruz; W. Min; L. Liang; W. L. Hunter; H. M. Burt

2004-01-01

75

Effects of 10-hydroxycamptothecin, delivered from locally injectable poly(lactide-co-glycolide) microspheres, in a murine human oral squamous cell carcinoma regression model.  

PubMed

This study investigated whether local delivery of 10-hydroxycamptothecin provides effective inductive chemotherapy as assessed by significant tumor reduction. Established tumorigenic human oral squamous cell carcinoma cells were used for these experiments. The experimental groups were comprised of: control (blank (no drug) poly(lactide-co-glycolide) (PLGA) microspheres), intraperitoneal 10-hydroxycamptothecin delivery + blank microspheres, local bolus 10-hydroxycamptothecin + blank microspheres, and PLGA controlled-release microspheres. The 10-hydroxycamptothecin dose administered was 12 mg/kg (bolus-intraperitoneal, local) or controlled-release over 10 days. Regardless of delivery route, 10-hydroxycamptothecin significantly reduces tumor volume. However, PLGA microspheres provide significantly higher intratumor-drug concentrations (approximately 10 and 100 fold higher) relative to local bolus and intraperitoneal routes, respectively. Also, only the PLGA microspheres significantly reduced tumor weights. Camptothecin clinical applications are limited by drug inactivation at physiological pH and the need for sustained infusions. However, due to their acidic, camptothecin-stabilizing microclimate, PLGA microspheres could provide a novel delivery system for camptothecin-based induction chemotherapy. PMID:11497251

Mallery, S R; Shenderova, A; Pei, P; Begum, S; Ciminieri, J R; Wilson, R F; Casto, B C; Schuller, D E; Morse, M A

2001-01-01

76

Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes.  

PubMed

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.-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

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

2014-12-01

77

A Qualitative Analysis of Long-Acting Reversible Contraception.  

PubMed

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

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

2014-11-26

78

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

PubMed

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

Michie, L; Cameron, S T

2013-06-01

79

Dual release of dexamethasone and TGF-?3 from polymeric microspheres for stem cell matrix accumulation in a rat disc degeneration model.  

PubMed

Low back pain is frequently caused by nucleus pulposus (NP) degeneration. Tissue engineering is a powerful therapeutic strategy which could restore the normal biomechanical motion of the human spine. Previously we reported that a new nanostructured three-dimensional poly(lactide-co-glycolide) (PLGA) microsphere, which is loaded with dexamethasone and growth factor embedded heparin/poly(l-lysine) nanoparticles via a layer-by-layer system, was an effective cell carrier in vitro for NP tissue engineering. This study aimed to investigate whether the implantation of adipose-derived stem cell (ADSC)-seeded PLGA microspheres into the rat intervertebral disc could regenerate the degenerated disc. Changes in disc height by plain radiograph, T2-weighted signal intensity in magnetic resonance imaging (MRI), histology, immunohistochemistry and matrix-associated gene expression were evaluated in normal controls (NCs) (without operations), a degeneration control (DC) group (with needle puncture, injected only with Dulbecco's modified Eagle's medium), a PLGA microspheres (PMs) treatment group (with needle puncture, PLGA microspheres only injection), and PLGA microspheres loaded with ADSCs treatment (PMA) group (with needle puncture, PLGA microspheres loaded with ADSC injection) for a 24-week period. The results showed that at 24 weeks post-transplantation, the PM and PMA groups regained disc height values of ?63% and 76% and MRI signal intensities of ?47% and 76%, respectively, compared to the NC group. Biochemistry, immunohistochemistry and gene expression analysis also indicated the restoration of proteoglycan accumulation in the discs of the PM and PMA groups. However, there was almost no restoration of proteoglycan accumulation in the discs of the DC group compared with the PM and PMA groups. Taken together, these data suggest that ADSC-seeded PLGA microspheres could partly regenerate the degenerated disc in vivo after implantation into the rat degenerative intervertebral disc. PMID:23973308

Liang, Cheng-zhen; Li, Hao; Tao, Yi-qing; Peng, Li-hua; Gao, Jian-qing; Wu, Jing-jun; Li, Fang-cai; Hua, Jian-ming; Chen, Qi-xin

2013-12-01

80

Polyacrolein microspheres  

NASA Technical Reports Server (NTRS)

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.

Rembaum, Alan (Inventor)

1987-01-01

81

Polyacrolein microspheres  

NASA Technical Reports Server (NTRS)

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.

Rembaum, Alan (Inventor)

1986-01-01

82

Polyacrolein microspheres  

NASA Technical Reports Server (NTRS)

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.

Rembaum, Alan (Inventor)

1983-01-01

83

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

PubMed Central

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

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

2014-01-01

84

Preparation of microspheres containing low solubility drug compound by electrohydrodynamic spraying.  

PubMed

Micro- and nanoparticle formulations are widely used to improve the bioavailability of low solubility drugs. In this study, electrospraying is introduced as a method for producing drug-loaded microspheres at ambient conditions. PLGA microspheres containing celecoxib, a low solubility drug, were prepared with the objective of producing near-monodisperse microspheres with the drug in a stable amorphous form. We found that it is possible to produce near-monodisperse celecoxib-loaded PLGA microspheres at different polymer:drug ratios. The microspheres produced were in the size range 1-5 ?m depending on the polymer:drug ratio and had smooth surfaces. Thermal analysis further indicates that celecoxib is present in an amorphous form inside the microspheres. Drug dissolution studies showed an initial burst release followed by a period of sustained release with the dissolution curve depending on the polymer:drug ratio. Electrospraying is thus a promising method for producing amorphous microspheres of low solubility drugs such as celecoxib. The microsphere properties may be further optimized to achieve an appropriate dissolution profile with the aim of increasing oral bioavailability of low solubility drugs. PMID:21511018

Bohr, Adam; Kristensen, Jakob; Stride, Eleanor; Dyas, Mark; Edirisinghe, Mohan

2011-06-30

85

Pharmacokinetics of olanzapine long-acting injection: the clinical perspective  

PubMed Central

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

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

2014-01-01

86

Possible interaction between letrozole and long-acting injectable zuclopenthixol.  

PubMed

Abstract 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

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

2015-01-01

87

Long-acting olanzapine versus long-acting risperidone for schizophrenia in Spain ¿ a cost-effectiveness comparison.  

PubMed

BackgroundIn schizophrenia, medication adherence is critical to achieve better patient outcomes and to avoid relapses, which are responsible for a significant proportion of total healthcare costs for this chronic illness. The aim of this study was to assess the cost-effectiveness of olanzapine long-acting injection (OLAI) compared with risperidone long-acting injection (RLAI) in patients with schizophrenia in Spain.MethodsA discrete event simulation (DES) model was developed from a Spanish healthcare system perspective to estimate clinical and economic outcomes for patients with schizophrenia over a five-year period. Patients who had earlier responded to oral medication and have a history of relapse due to adherence problems were considered. Identical model populations were treated with either OLAI or RLAI. In the absence of a head-to-head clinical trial, discontinuation and relapse rates were obtained from open-label studies. The model accounted for age, gender, risks of relapse and discontinuation, relapse management, hospitalization, treatment switching and adverse events. Direct medical costs for the year 2011 and outcomes including relapse avoided, life years (LYs), and quality-adjusted life years (QALYs) were discounted at a rate of 3%.ResultsWhen comparing RLAI and OLAI, the model predicts that OLAI would decrease 5-year costs by ¿2,940 (Standard Deviation between replications 300.83), and result in a QALY and LY gains of 0.07 (SD 0.019) and 0.04 (SD 0.025), respectively. Patients on OLAI had fewer relapses compared to RLAI (1.392 [SD 0.035] vs. 1.815 [SD 0.035]) and fewer discontinuations (1.222 [SD 0.031] vs. 1.710 [SD 0.039]). Sensitivity analysis indicated that the study was robust and conclusions were largely unaffected by changes in a wide range of parameters.ConclusionsThe present evaluation results in OLAI being dominant over RLAI, meaning that OLAI represents a more effective and less costly alternative compared to RLAI in the treatment of patients with schizophrenia in the Spanish setting. PMID:25438678

Dilla, Tatiana; Möller, Jörgen; O Donohoe, Paul; Alvarez, María; Sacristán, José A; Happich, Michael; Tockhorn, Antje

2014-12-01

88

Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide vaccine.  

PubMed

Advanced contraceptive peptide vaccines suffer from the unavailability of adjuvants capable of enhancing the antibody response with acceptable safety. We sought to overcome this limitation by employing two novel poly(lactic-co-glycolic acid) (PLGA) microsphere formulations to deliver a synthetic human chorionic gonadotropin (hCG) peptide antigen co-synthesized with a T-cell epitope from tetanus toxoid (TT), C-TT2-CTP35: surface-conjugated immunogen to induce phagocytosis; and encapsulated peptide to provide a depot effect, with MgCO(3) co-encapsulated in the polymer to neutralize acidity from the biodegrading PLGA polyester. A single immunization of encapsulated peptide in rabbits elicited a stronger antibody response with equivalent duration relative to a positive control--three injections of the peptide administered in a squalene-based water-in-oil emulsion. Surface-conjugated peptide was less effective but enhanced antibody levels at 1/5 the dose, relative to soluble antigen. Most remarkable and unexpected was the finding that co-encapsulation of base was essential to attain the powerful adjuvant effect of the PLGA-MgCO(3) system, as the MgCO(3)-free microspheres were completely ineffective. A promising contraceptive hCG peptide vaccine with acceptable side effects (i.e., local tissue reactions) was achieved by minimizing PLGA and MgCO(3) doses, without significantly affecting antibody response. PMID:16996662

Cui, Chengji; Stevens, Vernon C; Schwendeman, Steven P

2007-01-01

89

Long-acting reversible contraception: a review in special populations.  

PubMed

Almost half of the pregnancies in the United States are unintended. Currently available contraceptive methods are highly efficacious, but the most commonly used methods rely on patients for appropriate use. There has been a push to advocate for long-acting reversible contraceptives (LARCs) as first-line methods because they are placed by medical professionals and are the most effective form of reversible contraception available. There are four LARCs currently available in the United States: the Copper T intrauterine device, two forms of the levonorgestrel intrauterine system, and the etonogestrel subdermal implant. Once inserted, they can be left in place for 3-10 years, depending on the device. Some of these devices have been available for a number of years, but their use is limited in the United States due to controversies and misconceptions. A MEDLINE search from 1990-2012 was conducted to identify articles describing the use of LARCs in populations with limited data, including postpartum women, adolescents and nulliparous women, and women with sexually transmitted infections, including human immunodeficiency virus (HIV). Health care provider safety concerns surrounding intrauterine device (IUD) expulsions and infection are issues for use in adolescents and nulliparous women. Concern regarding IUD expulsion in the postpartum population questions the benefit of immediate versus delayed insertion, and the progestin effect in the levonorgestrel IUD and etonogestrel implant is of theoretic concern for breastfeeding women. In women with HIV, concerns have been raised about increased viral shedding with the IUD and drug interactions with the progestin methods. Many misconceptions surrounding LARCs are unfounded, but individual risk factors may leave LARC users at risk of unintended pregnancy if not addressed properly. PMID:24130075

Prescott, Gina M; Matthews, Christina M

2014-01-01

90

Original article Effect of a single injection of a long-acting  

E-print Network

Original article Effect of a single injection of a long-acting gonadotropin-releasing hormone of a long-acting form of gonadotropin-releasing hormone (GnRH) agonist on the reproductive systems of male of the carcass charasteristics such as meat ratio (49.1 vs 50.2% in TM and IM; P

Paris-Sud XI, Université de

91

Fluorescent microspheres  

NASA Technical Reports Server (NTRS)

Latex particles with attached antibodies have potential biochemical and environmental applications. Human red blood cells and lymphocytes have been labeled with fluorescent microspheres by either direct or indirect immunological technique. Immunolatex spheres can also be used for detecting and localizing specific cell surface receptors. Hormones and toxins may also be bondable.

Rembaum, A.

1978-01-01

92

Coaxial electrohydrodynamic atomization process for production of polymeric composite microspheres  

PubMed Central

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

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

2013-01-01

93

Glass microspheres  

SciTech Connect

This patent describes a glass microsphere having a diameter of about 54 micrometers or less and adapted for radiation therapy of a mammal. The glass consists of essentially an yttrium oxide-aluminosilicate glass composition lying substantially within a quadrilateral region of the ternary composition diagram of the yttria-alumina-silica system, the quadrilateral region being defined by its four corners having the following combination of weight proportions of the components: 20% silica, 10% alumina, 70% yttria; 70% silica, 10% alumina, 20% yttria; 70% silica, 20% alumina, 10% yttria; and 20% silica, 45% alumina, 35% yttria, the glass having a chemical durability such that subsequent to irradiation and administration of the microsphere to the mammal, the mircosphere will not release a significant amount of yttrium-90 into the mammal's system.

Day, D.E.; Ehrhardt, G.J.

1988-12-06

94

Evaluation of PEGylated Exendin-4 Released from Poly (Lactic-co-Glycolic Acid) Microspheres for Antidiabetic Therapy.  

PubMed

Peptide-based therapies have the potential to induce antibody formation if the molecules differ from a native human peptide. Several reports have disclosed the occurrence of antibody generation in a patient treated with exenatide. The immune response can be problematic from a clinical stand point, particularly if the antibodies neutralize the efficacy of the biotherapeutic agent or cause a general immune reaction. To overcome this limit, PEGylated exendin-4 analogs were designed and examined for metabolic stability and biological activity. To develop an extended release delivery system for exendin-4 for the safe and effective delivery of bioactive exendin-4 without peptide acylation and immunogenicity, PEGylated exendin-4 was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres by w/o/w double emulsion solvent evaporation method. Peptide-loaded microspheres were characterized in terms of morphology, particle diameter, and peptide encapsulation efficiency. Then, the release profile of the peptide from PLGA microspheres and the acylated products from PLGA polymer degradation was determined. The results obtained showed that the stability of exendin-4 was greatly improved by PEGylation. Moreover, eliminated acylation during PLGA polymer degradation in vitro and reduced immunogenicity in vivo were observed. The findings demonstrate that PEGylated exendin-4-loaded microspheres may be a safe and biocompatible system for clinical development. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:72-80, 2015. PMID:25407390

Lim, Sung Mook; Eom, Ha Na; Jiang, Hai Hua; Sohn, Minji; Lee, Kang Choon

2015-01-01

95

?-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release.  

PubMed

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with ?-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of ?-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. ?-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, ?-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion. PMID:22295954

Song, Xia; Song, San-Kong; Zhao, Pei; Wei, Li-Ming; Jiao, Hai-Sheng

2013-01-01

96

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

E-print Network

Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone Mineralization Poly(D, L-lactide-co-glycolide) Gelatin Calcium phosphate Surface mineralization is an effective. In this study, we prepared mineralized poly(D,L-lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun

Zheng, Yufeng

97

Ovalbumin peptide encapsulated in poly(d,l lactic-co-glycolic acid) microspheres is capable of inducing a T helper type 1 immune response.  

PubMed

An ovalbumin (OVA) peptide, consisting of residues 323-339, was incorporated into poly(d,l lactic-co-glycolic acid) (PLGA) microspheres and administered to mice. It was hypothesized that microencapsulation of the peptide in PLGA microspheres would avoid the need for traditional adjuvants and bias the immune response towards a type 1 T helper (Th1) response. An immunomodulator, monophosphoryl lipid A (MPLA), was incorporated into the microspheres to determine its efficacy in enhancing a Th1 response. The specificity of the immune response was determined using a T cell proliferation assay. The type of T helper response was determined by analysis of the cytokine secretion profiles of the proliferating T cells. Following s.c. immunization, the results revealed a T cell-specific immune response for the encapsulated OVA peptide both with and without MPLA. The cytokine profiles revealed high levels of IFN-gamma with very low levels of IL-4 and IL-10, suggesting a Th1 response. Furthermore, incorporation of MPLA in the peptide loaded PLGA microspheres resulted in an increase in the production of IFN-gamma. Hence, peptide-loaded PLGA microspheres are capable of eliciting a specific Th1 immune response, which may be further enhanced in the presence MPLA. PMID:9741903

Newman, K D; Samuel, J; Kwon, G

1998-06-01

98

Effect of water on exenatide acylation in poly(lactide-co-glycolide) microspheres.  

PubMed

Peptide or protein degradation often occurs when water flows into the dosage form. The aim of this study was to investigate the effect of water on exenatide acylation in poly(lactide-co-glycolide) (PLGA) microspheres. Exenatide-loaded PLGA microspheres were incubated at different relative humidities (RH) as well as in solutions of different pH for 20 days. The stability of exenatide was monitored using HPLC and HPLC-MS analysis. The alteration of exenatide conformation caused by water was investigated by FT-IR spectroscopy. Exenatide and glycolide were incubated in DMSO-water solutions to verify the effect of exenatide conformation state on the peptide acylation. Exenatide was relatively stable in microspheres at lower RH, and the absorbed water could act as a plasticizer and thus promote the peptide acylation by PLGA. However, when the microspheres were incubated at 100% RH, the excessively absorbed water could cause conformation recovery of exenatide and play an inhibitory effect on acylation. The formation of acylated exenatide incubated in acetate buffer saline of pH 6.0 was more than that of pH 4.5 and 3.0. Stability studies of exenatide in glycolide solutions showed that exenatide in nonnative monomer state was easier to be acylated by eletrophiles than that in aggregation state. PMID:23872225

Liang, Rongcai; Li, Xiang; Shi, Yanan; Wang, Aiping; Sun, Kaoxiang; Liu, Wanhui; Li, Youxin

2013-09-15

99

Microradiographic microsphere manipulator  

DOEpatents

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.

Singleton, Russell M. (Livermore, CA)

1980-01-01

100

Hybrid microspheres  

NASA Technical Reports Server (NTRS)

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.

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

1985-01-01

101

Lappaconitine-loaded microspheres for parenteral sustained release: effects of formulation variables and in vitro characterization.  

PubMed

Lappaconitine instead of its hydrobromide salts has been encapsulated in poly (lactide-co-glycolide) acid (PLGA) microspheres by the simple o/w emulsion solvent evaporation technique. The effects of several variables including emulsifier (polyvinyl alcohol, PVA) concentration, stirring speed, PLGA concentration and drug/polymer mass ratios on quality of microspheres have been investigated. The particle size and size distribution can be controlled by PVA concentration, stirring speed and PLGA concentration. The entrapment efficiency and the burst release of lappaconitine from drug-loaded microspheres were dominantly affected by the drug/polymer mass ratio and PVA concentration. The best parameters of formulation were 1.5% PVA, the PLGA concentration of 50 g/L, and the stirring speed of 800 rpm and drug/polymer of 1:5. The optimized formulation has a mean particle size of 19.3 +/- 0.93 microm, mean entrapment efficiency of 70.77 +/- 3.23% and mean drug loading of 11.45 +/- 0.47%. Based on the optimized parameters of formulation, the effects of oil/aqueous solubility partition ratio of drug on entrapment efficiency of drug-loaded microspheres prepared by o/w emulsion solvent evaporation were further studied. A good linear relation existed between the partition ratio and entrapment efficiency. The optimized microspheres were characterized by SEM, FT-IR, DSC and XRD. SEM shows spherical and smooth surface and uniform size distribution. The results of DSC, FT-IR study reveal no interaction between drug and polymer. The results of the XRD study indicate lappaconitine trapped in microsphere exists in form of an amorphous or disordered crystalline status in polymer matrix. The in vitro release models were evaluated with two different groups of drug-loaded microspheres including microspheres washed with distilled water and 0.01N HCL, respectively. The drug release profile of lappaconitine-loaded microspheres washed with distilled water agreed with zero order equation and that of the latter better agreed with first order equation. PMID:22026119

Xu, HeLin; Zhong, HaiJun; Liu, MinMin; Xu, ChunLian; Gao, Yuan

2011-09-01

102

A Review of Long-Acting Medications for ADHD in Canada  

PubMed Central

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

Hosenbocus, Sheik; Chahal, Raj

2009-01-01

103

Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons.  

PubMed

Neurotrophic factors therapy requires their precise delivery to the targeted neuronal population. For this purpose, a wide range of strategies have been developed, and among them the stereotaxic implantation of biodegradable microparticles. To assess the in vivo activity of NGF-releasing PLGA microspheres, unloaded and NGF-loaded microparticles were implanted in the rat brain, near the septal cholinergic neurons, axotomized by an unilateral transection of the fornix-fimbria. Histological analysis at two and six weeks after implantation revealed a non-specific astro- and micro-glial reaction around the microspheres, identical for both unloaded and NGF-loaded microspheres. No neuronal toxicity was noticed, and healthy looking neurons were observed in contact with the microspheres. In the non-treated animals, the percentage of axotomized surviving neurons, when compared to the contralateral intact side, was 31 +/- 2 and 27 +/- 1% at two and six weeks, respectively. Unloaded microspheres caused no protective nor neurotoxic effects (40 +/- 9 and 39 +/- 6% of surviving cholinergic neurons at two and six weeks, respectively). In contrast, NGF-loaded microspheres showed a significant effect on the survival of axotomized cholinergic neurons at two and six weeks after implantation (66 +/- 9 and 61 +/- 5% when compared to the contralateral intact side, respectively). These results show that PLGA microparticles present no neurotoxicity and release sufficient amounts of bioactive NGF to significantly limit the lesion-induced disappearance of cholinergic neurons in the septum during at least six weeks. PLGA microparticles can be used in the future to administer neurotrophic factors in central nervous system disorders. PMID:10966020

Péan, J M; Menei, P; Morel, O; Montero-Menei, C N; Benoit, J P

2000-10-01

104

Cellular uptake, antioxidant and antiproliferative activity of entrapped ?-tocopherol and ?-tocotrienol in poly (lactic-co-glycolic) acid (PLGA) and chitosan covered PLGA nanoparticles (PLGA-Chi).  

PubMed

The aim of this study was to formulate and characterize ?-tocopherol (?-T) and tocotrienol-rich fraction (TRF) entrapped in poly (lactide-co-glycolide) (PLGA) and chitosan covered PLGA (PLGA-Chi) based nanoparticles. The resultant nanoparticles were characterized and the effect of nanoparticles entrapment on the cellular uptake, antioxidant, and antiproliferative activity of ?-T and TRF were tested. In vitro uptake studies in Caco2 cells showed that PLGA and PLGA-Chi nanoparticles displayed a greater enhancement in the cellular uptake of ?-T and TRF when compared with the control without causing toxicity to the cells (p<0.0001). Furthermore, the cellular internalization of both PLGA and PLGA-Chi nanoparticles labeled with FITC was investigated by fluorescence microscopy; both types of nanoparticles were able to get internalized into the cells with reasonable amounts. However, PLGA-Chi nanoparticles showed significantly higher (3.5-fold) cellular uptake compared to PLGA nanoparticles. The antioxidant activity studies demonstrated that entrapment of ?-T and TRF in PLGA and PLGA-Chi nanoparticles exhibited greater ability in inhibiting cholesterol oxidation at 48h compared to the control. In vitro antiproliferative studies confirmed marked cytotoxicity of TRF on MCF-7 and MDA-MB-231 cell lines when delivered by PLGA and PLGA-Chi nanoparticles after 48h incubation compared to control. In summary, PLGA and PLGA-Chi nanoparticles may be considered as an attractive and promising approach to enhance the bioavailability and activity of poorly water soluble compounds such as ?-tocopherol and tocotrienols. PMID:25622049

Alqahtani, Saeed; Simon, Lacey; Astete, Carlos E; Alayoubi, Alaadin; Sylvester, Paul W; Nazzal, Sami; Shen, Yixiao; Xu, Zhimin; Kaddoumi, Amal; Sabliov, Cristina M

2015-05-01

105

Amyloid as a Depot for the Formulation of Long-Acting Drugs  

PubMed Central

Amyloids are highly organized protein aggregates that are associated with both neurodegenerative diseases such as Alzheimer disease and benign functions like skin pigmentation. Amyloids self-polymerize in a nucleation-dependent manner by recruiting their soluble protein/peptide counterpart and are stable against harsh physical, chemical, and biochemical conditions. These extraordinary properties make amyloids attractive for applications in nanotechnology. Here, we suggest the use of amyloids in the formulation of long-acting drugs. It is our rationale that amyloids have the properties required of a long-acting drug because they are stable depots that guarantee a controlled release of the active peptide drug from the amyloid termini. This concept is tested with a family of short- and long-acting analogs of gonadotropin-releasing hormone (GnRH), and it is shown that amyloids thereof can act as a source for the sustained release of biologically active peptides. PMID:18254658

Maji, Samir K; Schubert, David; Rivier, Catherine; Lee, Soon; Rivier, Jean E; Riek, Roland

2008-01-01

106

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

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

107

Microfluidic fabrication of polymeric core-shell microspheres for controlled release applications  

PubMed Central

We report a facile and robust microfluidic method to fabricate polymeric core-shell microspheres as delivery vehicles for biomedical applications. The characteristics of core-shell microspheres can be precisely and easily tuned by manipulating the microfluidic double emulsion templates. The addition of a shell can significantly improve the versatility as well as functionality of these microspheres as delivery vehicles. We demonstrate that the nature of the shell material plays an important role in the properties of the core-shell delivery vehicles. The release kinetics is significantly influenced by the material of the shell and other characteristics such as the thickness. For example, by adding a poly(lactic-co-glycolic acid) (PLGA) shell to an alginate core, the encapsulation efficiency is enhanced and undesired leakage of hydrophilic actives is prevented. By contrast, adding an alginate shell to PLGA core can lead to a reduction of the initial release rate, thus extending the release period of hydrophobic actives. Microfluidic fabrication enables the generation of precisely controlled core-shell microspheres with a narrow size distribution, which enables the investigation of the relationship between the release kinetics of these microspheres and their characteristics. The approach of using core-shell particles as delivery vehicles creates new opportunities to customize the release kinetics of active ingredients. PMID:24404061

Kong, Tiantian; Wu, Jun; Yeung, Kelvin Wai Kwok; To, Michael Kai Tsun; Shum, Ho Cheung; Wang, Liqiu

2013-01-01

108

Long-acting Preparations in Substance Abuse Management: A Review and Update  

PubMed Central

Many pharmacological approaches have been used in managing substance use disorders. Conventional pharmacological agents have relatively short durations of action which make them vulnerable to non-adherence and relapse to substance use disorder. To overcome this problem, long-acting preparations have been developed with the aim of reducing the frequency of use and hence improving adherence. This review takes a broad overview of the long-acting preparations available for the management of substance use disorders. The pharmacology, advantages and disadvantages of these preparations are discussed. Many of these preparations hold promise for improving patient outcomes. PMID:23833336

Hegde, Aditya; Singh, Shubh Mohan; Sarkar, Siddharth

2013-01-01

109

One and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate  

Microsoft Academic Search

The biodegradable polymers poly(lactic\\/glycolic acid) (PLGA) and poly(lactic acid) (PLA) were used as wall materials in the preparation of microspheres (msp) containing the LH-RH superagonist leuprorelin (leuprolide) acetate. A novel W\\/O\\/W emulsion-solvent evaporation method was devised for the preparation of msp containing this water-soluble peptide. This method achieved high entrapment efficiency and sustained drug release over a long period predominantly

Hiroaki Okada

1997-01-01

110

Fabrication of a Layered Microstructured Polymeric Microspheres as a Cell Carrier for Nucleus Pulposus Regeneration  

Microsoft Academic Search

This study aimed to investigate the feasibility of nanostructured 3D poly(lactide-co-glycolide) (PLGA) constructs, which are loaded with dexamethasone (DEX) and growth factor embedded hepaiin\\/poly(L-lysine) nanoparticles by a layer-by-layer system, to serve as an effective scaffold for nucleus pulposus (NP) tissue engineering. Our results demonstrated that the microsphere constructs were capable of simultaneously releasing basic fibroblast growth factor and DEX with

Chengzhen Liang; Hao Li; Chan Li; Zhiru Yang; Xiaopeng Zhou; Yiqing Tao; Yuxiang Xiao; Fangcai Li; Qixin Chen

2012-01-01

111

Delivery of MUC1 mucin peptide by Poly(d,l-lactic-co-glycolic acid) microspheres induces type 1 T helper immune responses.  

PubMed

Synthetic peptides corresponding to the variable tandem repeat domain of the cancer-associated antigen MUC1 mucin are candidates for cancer vaccines. In our investigation mice were immunized via subcutaneous injection with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres containing a MUC1 mucin peptide. It was hypothesized that microencapsulation of the MUC1 mucin peptide would prime for antigen-specific Th1 responses while avoiding the need for traditional adjuvants and carrier proteins. Furthermore, an immunomodulator, monophosphoryl lipid A (MPLA), was incorporated into the peptide-loaded PLGA microspheres based on its ability to enhance Th1 responses. The results revealed T cell specific immune responses. The cytokine secretion profiles of the T cells consisted of high levels of interferon-gamma with undetectable levels of interleukin-4 and interleukin-10. Moreover, incorporation of MPLA in the MUC1 peptide-loaded PLGA microspheres resulted in an increase in interferon-gamma production. The antibody response was negative for IgM and IgG in the absence of MPLA; however, in the presence of MPLA antibody production was negative for IgM with a minimal IgG response consisting of IgG2a, IgG2b, and IgG3. Based on the antibody and cytokine profiles, it was concluded that MUC1 mucin peptide-loaded PLGA microspheres are capable of eliciting specific Th1 responses, which may be enhanced through the use of MPLA. PMID:9811500

Newman, K D; Sosnowski, D L; Kwon, G S; Samuel, J

1998-11-01

112

Microsphere size influences the foreign body reaction.  

PubMed

Biodegradable poly-(DL-lactide-co-glycolide) (PLGA) microspheres (MSP) are attractive candidate vehicles for site-specific or systemic sustained release of therapeutic compounds. This release may be altered by the host's foreign body reaction (FBR), which is dependent on the characteristics of the implant, e.g. chemistry, shape or size. In this study, we focused on the characterisation of the influence of MSP size on the FBR. To this end we injected monodisperse MSP of defined size (small 5.8 µm, coefficient of variance (CV) 14 % and large 29.8 µm, CV 4 %) and polydisperse MSP (average diameter 34.1 µm, CV 51 %) under the skin of rats. MSP implants were retrieved at day 7, 14 and 28 after transplantation. The FBR was studied in terms of macrophage infiltration, implant encapsulation, vascularisation and extracellular matrix deposition. Although PLGA MSP of all different sizes demonstrated excellent in vitro and in vivo biocompatibility, significant differences were found in the characteristics of the FBR. Small MSP were phagocytosed, while large MSP were not. Large MSP occasionally elicited giant cell formation, which was not observed after implantation of small MSP. Cellular and macrophage influx and collagen deposition were increased in small MSP implants compared to large MSP. We conclude that the MSP size influences the FBR and thus might influence clinical outcome when using MSP as a drug delivery device. We propose that a rational choice of MSP size can aid in optimising the therapeutic efficacy of microsphere-based therapies in vivo. PMID:25350249

Zandstra, J; Hiemstra, C; Petersen, A H; Zuidema, J; van Beuge, M M; Rodriguez, S; Lathuile, A A; Veldhuis, G J; Steendam, R; Bank, R A; Popa, E R

2014-01-01

113

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

PubMed Central

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

Catalán, Rosa; Penadés, Rafael

2011-01-01

114

RESEARCH Open Access Long acting b2-agonist and corticosteroid restore  

E-print Network

was to determine whether a long-acting b2 adrenergic receptor agonist (salmeterol hydroxynaphthoate, Sal) combined-acting b2 adrenergic receptor agonist after bacterial infection restores the airway glandular cell function with a combination of b2 adrenergic receptor agonist and glucocorticoid. Background The epithelial lining

Paris-Sud XI, Université de

115

The discovery of adamantyl-derived, inhaled, long acting ? 2-adrenoreceptor agonists  

Microsoft Academic Search

The design and profile of a series of adamantyl-containing long acting ?2-adrenoreceptor agonists are described. An optimal pharmacokinetic profile of low oral bioavailability was combined with a strong pharmacology profile when assessed using a guinea pig trachea tissue model. A focus was then placed on developing a robust synthetic route to ensure rapid delivery of material for clinical trials.

Alan D. Brown; Mark E. Bunnage; Paul A. Glossop; Kim James; Rhys Jones; Russell A. Lewthwaite; Simon Mantell; Christelle Perros-Huguet; David A. Price; Mike Trevethick; Rob Webster

2008-01-01

116

Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?  

ERIC Educational Resources Information Center

Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

2006-01-01

117

microsphere assemblies  

NASA Astrophysics Data System (ADS)

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.

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

2014-09-01

118

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

Microsoft Academic Search

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

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

2011-01-01

119

Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?  

PubMed

Despite current guidelines and the range of available treatments, over a half of patients with asthma continue to suffer from poor symptomatic control and remain at risk of future worsening. Although a number of non-pharmacological measures are crucial for good clinical management of asthma, new therapeutic controller medications will have a role in the future management of the disease. Several long-acting anticholinergic bronchodilators are under investigation or are available for the treatment of respiratory diseases, including tiotropium bromide, aclidinium bromide, glycopyrronium bromide, glycopyrrolate and umeclidinium bromide, although none is yet licensed for the treatment of asthma. A recent Phase III investigation demonstrated that the once-daily long-acting anticholinergic bronchodilator tiotropium bromide improves lung function and reduces the risk of exacerbation in patients with symptomatic asthma, despite the use of inhaled corticosteroids (ICS) and long-acting ?2-agonists (LABAs). This has prompted the question of what the rationale is for long-acting anticholinergic bronchodilators in asthma. Bronchial smooth muscle contraction is the primary cause of reversible airway narrowing in asthma, and the baseline level of contraction is predominantly set by the level of 'cholinergic tone'. Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce. Further, anticholinergic compounds may also have anti-inflammatory properties. Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations. PMID:25030457

Price, David; Fromer, Leonard; Kaplan, Alan; van der Molen, Thys; Román-Rodríguez, Miguel

2014-01-01

120

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

PubMed Central

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

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

2014-01-01

121

Solubility of Ketoprofen in colloidal PLGA.  

PubMed

The successful design and development of pharmaceutical drug-polymer composites requires detailed information about the phase behavior of the drug-polymer binary system. This study presents an extended investigation of the phase equilibrium established between the chiral anti-inflammatory drug Ketoprofen (KET) and the bio-compatible and biodegradable polymer poly(lactic-co-glycolic) acid 5050 (PLGA). Equilibration experiments were carried out in aqueous suspensions of KET crystals together with PLGA in the form of spherical amorphous nanoparticles obtained by supercritical fluid extraction of emulsions (SFEE). The influence of temperature was studied in the range between 0°C and 50°C, while the effect of KET chirality was investigated by using two different crystalline forms of KET, namely enantiopure S-KET and a racemic compound, RS-KET, in equilibration experiments. It was found that the level of KET established in PLGA at equilibrium increases with temperature, e.g. from 6.9 wt.% at 20°C to 25.8 wt.% at 40°C for the case of S-KET. At each temperature level, the solubility of KET in PLGA was lower for equilibration with RS-KET, significantly higher for equilibration with S-KET, and the highest for simultaneous equilibration with both crystalline species. Experimental solubility data of KET in PLGA were also described in a model based on the Sanchez-Lacombe equation of state. For experiments carried out at 10°C or below, an equilibrium state could not be reached even after a prolonged equilibration period, presumably because the polymer phase had undergone a transition into the glassy state. For this temperature range, where an experimental equilibration is not any more possible, the model may be used to estimate the solubility of KET in PLGA by extrapolation. PMID:20728513

Kluge, Johannes; Mazzotti, Marco; Muhrer, Gerhard

2010-10-31

122

Biodegradable microspheres as carriers for native superoxide dismutase and catalase delivery.  

PubMed

The purpose of this research was to encapsulate superoxide dismutase (SOD) and catalase (CAT) in biodegradable microspheres (MS) to obtain suitable sustained protein delivery. A modified water/oil/water double emulsion method was used for poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) PLA MS preparation co-encapsulating mannitol, trehalose, and PEG400 for protein stabilization. Size, morphology, porosity, mass loss, mass balance, in vitro release and in vitro activity were assessed by using BCA protein assay, scanning electron microscopy, BET surface area, and particle-sizing techniques. In vitro activity retention within MS was evaluated by nicotinammide adenine dinucleotide oxidation and H2O2 consumption assays. SOD encapsulation efficiency resulted in 30% to 34% for PLA MS and up to 51% for PLGA MS, whereas CAT encapsulation was 34% and 45% for PLGA and PLA MS, respectively. All MS were spherical with a smooth surface and low porosity. Particle mean diameters ranged from 10 to 17 mum. CAT release was prolonged, but the results were incomplete for both PLA and PLGA MS, whereas SOD was completely released from PLGA MS in a sustained manner after 2 months. CAT results were less stable and showed a stronger interaction than SOD with the polymers. Mass loss and mass balance correlated well with the release profiles. SOD and CAT in vitro activity was preserved in all the preparations, and SOD was better stabilized in PLGA MS. PLGA MS can be useful for SOD delivery in its native form and is promising as a new depot system. PMID:15760048

Giovagnoli, Stefano; Blasi, Paolo; Ricci, Maurizio; Rossi, Carlo

2004-01-01

123

Emerging treatments in the management of bipolar disorder – focus on risperidone long acting injection  

PubMed Central

Bipolar disorder is a life-long psychiatric illness characterized by a high frequency of relapses and substantial societal costs. Almost half of the patients are prescribed second generation antipsychotics for treatment of manic states, or as the maintenance therapy. Risperidone long acting injection (RLAI) as a monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder was approved by Food and Drug Administration (FDA) in United States in May 2009. In this review we will consider the aspects of pharmacology, pharmacokinetics, metabolism, safety and tolerability, and clinical trials focusing on the efficacy of RLAI in bipolar disorder. The patients’ perspective and attitudes to long-acting injections will also be discussed. PMID:20856609

El-Hage, Wissam; Surguladze, Simon A

2010-01-01

124

Efficacy of parvaquone and long-acting oxytetracycline in Theileria annulata infection.  

PubMed

Therapeutic and prophylactic efficacies of parvaquone and long-acting oxytetracycline were tested against Theileria annulata infection, induced by injecting a suspension of infected ground tick tissues (GUTS) into groups of 4 or 5 calves. This infection killed two of four control calves, while all the animals given a single intramuscular dose of 20 mg kg-1 parvaquone or long-acting oxytetracycline on the day of infection underwent mild reactions and recovered. Two separate doses of parvaquone of 10 mg kg-1 administered on the first and second days of fever protected four out of five calves. All the recovered animals from both treated and control groups resisted a homologous challenge with GUTS on Day 45 post-infection which killed three out of four susceptible unimmunized control calves. PMID:3750805

Bansal, G C; Sharma, S P

1986-08-01

125

An open trial of octreotide long-acting release in the management of short bowel syndrome  

Microsoft Academic Search

OBJECTIVES:The aim of this study was to assess the effects of the long-acting release (LAR) depot octreotide preparation Sandostatin LAR Depot on stool water and electrolyte losses, fecal fat excretion, and GI transit in patients with short bowel syndrome.METHODS:We performed a 15-wk, prospective, open-label study of intramuscular (i.m.) Sandostatin LAR Depot, 20 mg, at 0, 3, 7, and 11 wk.

Vandana Nehra; Michael Camilleri; Duane Burton; LaVonne Oenning; Darlene G. Kelly

2001-01-01

126

Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease  

Microsoft Academic Search

Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease.BackgroundThe fluid filling renal cysts in human polycystic kidneys is secreted chiefly by the tubular epithelium lining the cysts via secondary chloride transport. Inhibiting this process by somatostatin therapy should induce shrinking of renal cysts.MethodsIn this randomized, cross-over, placebo-controlled trial we compared the risk\\/benefit profile of 6-month treatment with

PIERO RUGGENENTI; ANDREA REMUZZI; PATRIZIA ONDEI; GIORGIO FASOLINI; LUCA ANTIGA; BOGDAN ENE-IORDACHE; GIUSEPPE REMUZZI; FRANKLIN H EPSTEIN

2005-01-01

127

The discovery of adamantyl-derived, inhaled, long acting beta(2)-adrenoreceptor agonists.  

PubMed

The design and profile of a series of adamantyl-containing long acting beta(2)-adrenoreceptor agonists are described. An optimal pharmacokinetic profile of low oral bioavailability was combined with a strong pharmacology profile when assessed using a guinea pig trachea tissue model. A focus was then placed on developing a robust synthetic route to ensure rapid delivery of material for clinical trials. PMID:18226900

Brown, Alan D; Bunnage, Mark E; Glossop, Paul A; James, Kim; Jones, Rhys; Lane, Charlotte A L; Lewthwaite, Russell A; Mantell, Simon; Perros-Huguet, Christelle; Price, David A; Trevethick, Mike; Webster, Rob

2008-02-15

128

Plasma Disposition of Conventional and Long-Acting Moxifloxacin in Sheep after Intravenous Administration  

PubMed Central

This study describes disposition of long-acting moxifloxacin and conventional formulations of moxifloxacin in sheep after intravenous administration in five male sheep. Long acting moxifloxacin solution (10% moxifloxacin in solution with L-arginine, N-butyl alcohol, and benzyl alcohol) and conventional moxifloxacin (10%) were injected in jugular vein. Blood samples were collected from contralateral jugular vein in test tubes containing 30–50?IU heparin (anticoagulant) periodically from 0.083 to 72?h of drug administration. Drug concentrations in plasma were determined using High-Performance Liquid Chromatography (HPLC) with fluorescence detector. The mobile phase consisted of a mixture of buffer (10?gm of tetrabutyl ammonium hydrogen sulphate per liter-deionised water) and acetonitrile (80?:?20). The buffer was 0.067M of disodium hydrogen phosphate with pH of 7.5. The flow rate was 1?mL·min?1 at ambient temperature. The effluent was monitored at 296?nm excitation and 504?nm emissions wavelength. HPLC with fluorescence detector method for plasma moxifloxacin assay was standardized with specific modification for plasma of sheep in the present study. After single-dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001??g·mL?1 was maintained for up to 72?h. Conventional formulation of moxifloxacin remained in body for up to 24?h of drug administration with the level of 0.015 ± 0.005 ?g·mL?1. PMID:23738134

Modi, C. M.; Mody, S. K.; Modi, F. D.; Patel, H. B.

2012-01-01

129

Long-acting nifedipine in the management of the hypertensive patient  

PubMed Central

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

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

2008-01-01

130

Evaluation of Orntide microspheres in a rat animal model and correlation to in vitro release profiles.  

PubMed

Orntide acetate, a novel luteinizing hormone-releasing hormone (LHRH) antagonist, was prepared and evaluated in vivo in 30-day and 120-day sustained delivery formulations using a rat animal model. Orntide poly(d,l-lactide-co-glycolide) (PLGA) and poly(d,l- lactide) (PLA) microspheres were prepared by a dispersion method and administered subcutaneously in a liquid vehicle to rats at 2.2 mg Orntide/kg of body weight (30-day forms) or 8.8 mg Orntide/kg (120-day forms). Serum levels of Orntide and testosterone were monitored by radioimmunoassays, and a dose-response study at 4 doses (3, 2.25, 1.5, and 1.75 mg Orntide/kg) was conducted to determine the effective dose of Orntide. Microspheres with diameters between 3.9 and 14 micron were prepared. The onset and duration of testosterone suppression varied for different microsphere formulations and were influenced both by polymer properties and by microsphere characteristics. Microspheres prepared with 50:50 and 75:25 copolymers effectively sustained peptide release for 14 to 28 days, whereas an 85:15 copolymer and the PLA microspheres extended the pharmacological response for more than 120 days. Increase in drug load generally accelerated peptide release from the microspheres, resulting in higher initial serum levels of Orntide and shorter duration of the release. In general, apparent release was faster in vivo than under in vitro conditions. Orntide microspheres effectively suppressed testosterone in rats, providing rapid onset of release and extended periods of chemical castration. Testosterone suppression occurred immediately after microsphere administration without the initial elevation seen with LHRH superagonists. PMID:14727892

Kostanski, J W; Dani, B A; Reynolds, G A; Bowers, C Y; DeLuca, P P

2000-01-01

131

Making Polymeric Microspheres  

NASA Technical Reports Server (NTRS)

Combination of advanced techniques yields uniform particles for biomedical applications. Process combines ink-jet and irradiation/freeze-polymerization techniques to make polymeric microspheres of uniform size in diameters from 100 to 400 micrometer. Microspheres used in chromatography, cell sorting, cell labeling, and manufacture of pharmaceutical materials.

Rhim, Won-Kyu; Hyson, Michael T.; Chung, Sang-Kun; Colvin, Michael S.; Chang, Manchium

1989-01-01

132

Production of hollow aerogel microspheres  

DOEpatents

A method is described for making hollow aerogel microspheres of 800-1200 .mu. diameter and 100-300 .mu. wall thickness by forming hollow alcogel microspheres during the sol/gel process in a catalytic atmosphere and capturing them on a foam surface containing catalyst. Supercritical drying of the formed hollow alcogel microspheres yields hollow aerogel microspheres which are suitable for ICF targets.

Upadhye, Ravindra S. (Pleasanton, CA); Henning, Sten A. (Dalby, SE)

1993-01-01

133

Metabolism of proteinoid microspheres  

NASA Technical Reports Server (NTRS)

The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolysis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres; these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature.

Nakashima, T.; Fox, S. W. (Principal Investigator)

1987-01-01

134

Metabolism of proteinoid microspheres  

NASA Technical Reports Server (NTRS)

The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolyis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres; these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature.

Nakashima, T.; Fox, S. W. (Principal Investigator)

1987-01-01

135

The role of inhaled long-acting beta-2 agonists in the management of asthma.  

PubMed Central

The role of inhaled beta-2 agonists in the management of asthma has changed significantly over the last several years. This review outlines the most recent understanding of the pathophysiology of asthma and the studies that define the roles that both short- and long-acting beta-2 agonists play in therapy for this disease. A concentration on the clinical pharmacology and genetic implications for clinical use of this class of drugs in accordance with the national and international guidelines are described. PMID:16532973

Kelly, H. William; Harkins, Michelle S.; Boushey, Homer

2006-01-01

136

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

PubMed

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

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

2014-06-01

137

Comparing Microspheres with Different Internal Phase of Polyelectrolyte as Local Drug Delivery System for Bone Tuberculosis Therapy  

PubMed Central

We use hydrophobic poly(lactic-co-glycolic) acid (PLGA) to encapsulate hydrophilic ofloxacin to form drug loading microspheres. Hyaluronic acid (HA) and polylysine (Pls) were used as internal phase additives to see their influences on the drug loading and releasing. Double emulsion (water-in-oil-in-water) solvent extraction/evaporation method was used for the purpose. Particle size analysis display that the polyelectrolytes have low impact on the microsphere average size and distribution. Scanning electron microscope (SEM) pictures show the wrinkled surface resulted by the internal microcavity of the microspheres. Microspheres with HA inside have higher drug loading amounts than microspheres with Pls inside. The loading drug amounts of the microspheres increase with the HA amounts inside, while decreasing with the Pls amounts inside. All the polyelectrolytes adding groups have burst release observed in experiments. The microspheres with Pls internal phase have faster release rate than the HA groups. Among the same polyelectrolyte internal phase groups, the release rate increases with the amounts increasing when Pls is inside, while it decreases with the amounts increasing when HA is inside. PMID:24707480

Chen, Long; Li, Hong; Deng, Chun-Ling; Chen, Xiao-Feng

2014-01-01

138

Comparing microspheres with different internal phase of polyelectrolyte as local drug delivery system for bone tuberculosis therapy.  

PubMed

We use hydrophobic poly(lactic-co-glycolic) acid (PLGA) to encapsulate hydrophilic ofloxacin to form drug loading microspheres. Hyaluronic acid (HA) and polylysine (Pls) were used as internal phase additives to see their influences on the drug loading and releasing. Double emulsion (water-in-oil-in-water) solvent extraction/evaporation method was used for the purpose. Particle size analysis display that the polyelectrolytes have low impact on the microsphere average size and distribution. Scanning electron microscope (SEM) pictures show the wrinkled surface resulted by the internal microcavity of the microspheres. Microspheres with HA inside have higher drug loading amounts than microspheres with Pls inside. The loading drug amounts of the microspheres increase with the HA amounts inside, while decreasing with the Pls amounts inside. All the polyelectrolytes adding groups have burst release observed in experiments. The microspheres with Pls internal phase have faster release rate than the HA groups. Among the same polyelectrolyte internal phase groups, the release rate increases with the amounts increasing when Pls is inside, while it decreases with the amounts increasing when HA is inside. PMID:24707480

Wu, Gang; Chen, Long; Li, Hong; Deng, Chun-Ling; Chen, Xiao-Feng

2014-01-01

139

Flow-through ultrasonic emulsification combined with static micromixing for aseptic production of microspheres by solvent extraction.  

PubMed

Final sterilisation of drug-loaded polymeric microspheres is problematic as dry heat or steam sterilisation are not applicable, and gamma-irradiation may result in radiolytic scission of the polymer chains, and potentially damage the bioactive compound. Therefore, aseptic production is the method of choice to obtain a sterile product. A novel process for the production of microspheres is introduced based on the principle of double emulsion-solvent extraction. The process uses a flow-through ultrasonic cell for the preparation of the primary emulsion, in combination with a static micromixer for the production of the double emulsion. Because of its small scale, the equipment is readily accommodated in a laminar air-flow cabinet or an isolator. Thanks to the low technical complexity and easy handling of the process, only minimal manual interventions is required. Finally, the possibility for in-place cleaning and sterilisation makes the equipment and process well suited for aseptic microsphere preparation. Microspheres were prepared from poly(lactic-co-glycolic acid) (PLGA), and bovine serum albumin (BSA) served as model protein for microencapsulation. The BSA-in-PLGA (w/o) emulsions produced by the ultrasonic flow-through cell exhibited mean droplet sizes of <700 nm. Further processing into microspheres of 15-40 microm mean diameter resulted in approx. 70% BSA encapsulation efficiency. Batch-to-batch reproducibility was excellent. Microsphere batches produced under aseptic conditions to assure product sterility exhibited no microbial contamination when examined by a simplified sterility test. The presented technology offers great potential for aseptic microsphere production for batch-sizes suitable, e.g. for clinical investigations. Complete validation of product sterility would, however, demand more extended tests. PMID:16009542

Freitas, Sergio; Rudolf, Beat; Merkle, Hans P; Gander, Bruno

2005-10-01

140

Long-acting anticoagulant overdose: brodifacoum kinetics and optimal vitamin K dosing.  

PubMed

Ingestion of long-acting anticoagulant rodenticides such as brodifacoum can lead to prolonged and life-threatening coagulopathy. A paucity of conflicting information is available on brodifacoum's half-life and elimination pharmacokinetics. In addition, the optimal dose, duration, and route of administration of vitamin K(1) therapy are unknown. We report the case of a 52-year-old man who ingested eight 43-g boxes of a rodenticide (d-Con Mouse-Prufe II; 0.005% brodifacoum; Reckitt & Colman, Wayne, NJ). This case demonstrates that after stabilization with fresh frozen plasma, high-dose oral vitamin K(1) therapy ( congruent with 7 mg/kg per 24 hours divided every 6 hours) was effective in treating brodifacoum-induced coagulopathy. The concentration of vitamin K(1) required for normal coagulation in this case was less than the accepted value of 1 microg/mL, which is derived from a rabbit model. In this case, brodifacoum appears to follow zero-order elimination pharmacokinetics. In future cases of patients with ingestions of long-acting anticoagulants who present with coagulopathy, it may be useful to obtain serial brodifacoum concentrations to determine elimination curves to help predict the duration of oral vitamin K(1) therapy. PMID:10969235

Bruno, G R; Howland, M A; McMeeking, A; Hoffman, R S

2000-09-01

141

Microsphere Insulation Panels  

NASA Technical Reports Server (NTRS)

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.

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

2006-01-01

142

Preparation and characterization of poly(lactic-co-glycolic acid) microspheres loaded with a labile antiparkinson prodrug.  

PubMed

L-dopa-?-lipoic acid (LD-LA) is a new multifunctional prodrug for the treatment of Parkinson's disease. In human plasma, LD-LA catechol esters and amide bonds are chemically and enzymatically cleaved, respectively, resulting in a half-life time of about fifty minutes. In the present work, the unstable LD-LA was entrapped into biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres designed as depot systems to protect this prodrug against degradation and to obtain a sustained release of the intact compound. The microspheres were prepared by an oil-in-water emulsion/solvent evaporation technique and the effect of formulation and processing parameters (polymer concentration in the organic solvent, volumes ratio of the phases, rate of the organic solvent evaporation) on microspheres characteristics (size, loading, morphology, release) was investigated. Also emphasis was given on the stability of the drug before and after release as well as on the underlying mass transport mechanisms controlling LD-LA release. Interestingly, when encapsulated in appropriate conditions into PLGA microspheres, the labile prodrug was stabilized and released via Fickian diffusion up to more than one week. PMID:21356295

D'Aurizio, E; van Nostrum, C F; van Steenbergen, M J; Sozio, P; Siepmann, F; Siepmann, J; Hennink, W E; Di Stefano, A

2011-05-16

143

Organic aerogel microspheres  

DOEpatents

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.

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

144

Organic aerogel microspheres  

DOEpatents

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.

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

1999-06-01

145

Compartmentalization in proteinoid microspheres  

NASA Technical Reports Server (NTRS)

Proteinoid microspheres with stable internal compartments and internal structure are made from acidic proteinoid and basic proteinoid with calcium. The populations of microspheres are characterized by a wide diversity of structure. A model of primitive intracellular communication is suggested by the observed movement of internal particles between compartments of a multicompartmentalized unit. Differential response to pH change and to temperature change has been demonstrated within one population and suggests one mode of adaptive selection among primordial cell populations.

Brooke, S.; Fox, S. W.

1977-01-01

146

Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain  

Microsoft Academic Search

Trimethylated chitosan (TMC) surface-modified poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (TMC\\/PLGA–NP) were synthesized as a drug carrier for brain delivery. TMC was covalently coupled to the surface of PLGA nanoparticles (PLGA–NP) via a carbodiimide-mediated link. The zeta potential of TMC\\/PLGA–NP was about 20mV with a mean diameter around 150nm. 6-coumarin loaded PLGA–NP and TMC\\/PLGA–NP were injected into the caudal vein of mice, and

Zhao H. Wang; Zhan Y. Wang; Chang S. Sun; Chun Y. Wang; Tong Y. Jiang; Si L. Wang

2010-01-01

147

Multivalent design of long-acting ?(2)-adrenoceptor agonists incorporating biarylamines.  

PubMed

A series of potent ?2-adrenoceptor agonists incorporating a biarylamine secondary binding group was identified. The previously reported milveterol (5), identified by a multivalent approach and containing a typical ?2-agonist primary binding group linked via a phenethylamine linker to a hydrophilic secondary binding group, served as an initiation point. A more hydrophobic set of secondary binding groups was explored, prepared rapidly from a common intermediate by Buchwald-Hartwig amination. TD-5471 (25), a potent and selective full agonist of the human ?2-adrenoceptor, was identified as the most promising agent. It is potent, with slow onset in an in vitro guinea pig trachea model and shows a dose-dependent and long duration of action in an in vivo guinea pig model of bronchoprotection. TD-5471 is structurally differentiated from milveterol and its long duration of action is consistent with a correlation with hydrophobicity observed in other long-acting ?2-agonist discovery programs. PMID:24813741

Jacobsen, John R; Aggen, James B; Church, Timothy J; Klein, Uwe; Pfeiffer, Juergen W; Pulido-Rios, Teresa M; Thomas, G Roger; Yu, Cecile; Moran, Edmund J

2014-06-15

148

Reversible Contraception Update: The Importance of Long-Acting Reversible Contraception  

PubMed Central

The past several years have seen an expansion in contraception options. Emerging data support the use of long-acting reversible contraception (LARC) such as the intrauterine device and subdermal implant as the most effective methods of contraception with the highest continuation rates and very high levels of patient satisfaction. In addition, the appropriate target population for the use of the intrauterine device now includes nulliparous women and adolescents. When a patient considers initiating a new contraceptive method, it is important to consider the characteristics of each method, including the side effects, effectiveness, and patient acceptability. Additionally, medical comorbidities must also be evaluated prior to choosing a method. In this article, we provide a brief overview of available reversible contraceptive methods, with an emphasis on LARC. PMID:19641264

Mestad, Renee E.; Kenerson, Jessica; Peipert, Jeffrey F.

2011-01-01

149

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal  

PubMed Central

Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper’s blending of experimental trials with observational research is particularly appropriate and effective. PMID:25360245

Veguilla, Miguel Ruiz; Taylor, David; Balanzá-Martinez, Vicent

2014-01-01

150

Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus  

PubMed Central

GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP). PMID:24594934

Andrews, Chasity D.; Spreen, William R.; Mohri, Hiroshi; Moss, Lee; Ford, Susan; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Bohm, Rudolf P.; Cheng-Mayer, Cecilia; Hong, Zhi; Markowitz, Martin; Ho, David D.

2015-01-01

151

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

PubMed

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

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

2014-08-01

152

Long-acting muscarinic receptor antagonists for the treatment of respiratory disease.  

PubMed

The use of muscarinic receptor antagonists in the treatment of chronic obstructive pulmonary disease (COPD) is well established. More recently, the potential for long-acting muscarinic receptor antagonists (LAMAs) in the treatment of asthma has also been investigated. While LAMAs offer advantages over short-acting muscarinic receptor antagonists, in terms of a reduced dosing frequency, there remains a need for therapies that improve symptom control throughout both the day and night, provide better management of exacerbations and deliver improved health-related quality of life. Furthermore, the potential for unwanted anticholinergic side effects, particularly cardiovascular effects, remains a concern for this class of compounds. Novel LAMAs in clinical development for the treatment of respiratory disease include: aclidinium bromide, NVA237 (glycopyrronium bromide), GP-MDI, EP-101, CHF-5259, umeclidinium bromide, CHF-5407, TD-4208, AZD8683 and V-0162. These compounds offer potential advantages in terms of onset of action, symptom control and safety. In addition, a number of LAMAs are also being developed as combination treatments with long-acting ?2-agonists (LABAs) or inhaled glucocorticosteroids, potentially important treatment options for patients who require combination therapy to achieve an optimal therapeutic response as their disease progresses. More recently, compounds such as GSK961081 and THRX-198321 have been identified that combine LAMA and LABA activity in the same molecule, and have the potential to offer the benefits of combination therapy in a single compound. Here, we review novel LAMAs and dual action compounds in clinical development, with a particular focus on how they may address the current unmet clinical needs in the treatment of respiratory disease, particularly COPD. PMID:23274274

Cazzola, Mario; Page, Clive; Matera, Maria Gabriella

2013-06-01

153

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

PubMed

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

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

2015-01-01

154

Controlled release of vascular endothelial growth factor using poly-lactic-co-glycolic acid microspheres: In vitro characterization and application in polycaprolactone fumarate nerve conduits  

PubMed Central

Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator. Controlled release of such stimulators may enhance and guide the vascularization process, and when applied in a nerve conduit may play a role in nerve regeneration. We report the fabrication and in vitro characterization of VEGF encapsulating poly-lactic-co-glycolic acid (PLGA) microspheres and the in vivo application of nerve conduits supplemented with VEGF-containing microspheres. PLGA microspheres containing VEGF were prepared by the double emulsion-solvent evaporation technique. This yielded 83.16% of the microspheres with a diameter < 53 µm. VEGF content measured by ELISA indicated 93.79 ±10.64% encapsulation efficiency. Release kinetics were characterized by an initial burst release of 67.6±8.25% within the first 24 hours, followed by consistent release of approximately 0.34% per day for 4 weeks. Bioactivity of the released VEGF was tested by human umbilical vein endothelial cell (HUVEC) proliferation assay. VEGF released at all time points enhanced HUVEC proliferation confirming that VEGF retained its bioactivity through the 4-week time period. When the microsphere delivery system was placed in a biosynthetic nerve scaffold, robust nerve regeneration was observed. This study established a novel system for controlled release of growth factors and enables in vivo studies of nerve conduits conditioned with this system. PMID:22019759

Rui, Jing; Dadsetan, Mahrokh; Runge, M. Brett; Spinner, Robert J.; Yaszemski, Michael J.; Windebank, Anthony J.; Wang, Huan

2014-01-01

155

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

E-print Network

polymers and hydroxyapatite: Relevance to synthetic bone-like materials and tissue engineering scaffolds. Acta Biomaterialia 2008, 4(5), 1288–1296. 18. Boccaccini, A. R.; Torres, F. G.; Nazhat, S. N.; Fadzullah, S. H. S. M.; Maquet, V. Mechanical... properties and bioactivity of porous PLGA/TiO 2 nanoparticle-filled composites for tissue engineering scaffolds. Composites Science and Technology 2007, 67(6), 1139–1147. 19. Maquet, V.; Boccaccini, A. R.; Pravata, L.; Notingher, I.; Jerome, R...

Ege, Duygu; Best, Serena; Cameron, Ruth

2014-01-11

156

Doppler cooling a microsphere  

E-print Network

Doppler cooling the center-of-mass motion of an optically levitated microsphere via the velocity dependent scattering force from narrow whispering gallery mode (WGM) resonances is described. Light that is red detuned from the WGM resonance can be used to damp the center-of-mass motion in a process analogous to the Doppler cooling of atoms. Leakage of photons out of the microsphere when the incident field is near resonant with the narrow WGM resonance acts to damp the motion of the sphere. The scattering force is not limited by saturation, but can be controlled by the incident power. Cooling times on the order of seconds are calculated for a 20 micron diameter silica microsphere trapped within optical tweezers, with a Doppler temperature limit in the microKelvin regime.

P. F. Barker

2010-04-08

157

Doppler cooling a microsphere  

E-print Network

Doppler cooling the center-of-mass motion of an optically levitated microsphere via the velocity dependent scattering force from narrow whispering gallery mode (WGM) resonances is described. Light that is red detuned from the WGM resonance can be used to damp the center-of-mass motion in a process analogous to the Doppler cooling of atoms. Leakage of photons out of the microsphere when the incident field is near resonant with the narrow WGM resonance acts to damp the motion of the sphere. The scattering force is not limited by saturation, but can be controlled by the incident power. Cooling times on the order of seconds are calculated for a 20 micron diameter silica microsphere trapped within optical tweezers, with a Doppler temperature limit in the microKelvin regime.

Barker, P F

2010-01-01

158

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs  

PubMed Central

Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

2014-01-01

159

Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma  

PubMed Central

The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID:25114786

Xia, Ying; Kelton, Christina M. L.; Xue, Liang; Bian, Boyang; Wigle, Patricia R.

2013-01-01

160

Demand for long-acting and permanent contraceptive methods among Kurdish women in Mahabad, Iran.  

PubMed

It is anticipated that the demand for contraceptives in Iran will increase in the near future as the number of women of reproductive age increases and with women wanting smaller families. The aim of this paper was to study the demand for long-acting and permanent contraceptive methods (LAPCMs), and its determinants, among Kurdish women in Mahabad city, Iran. Data were taken from the Mahabad Fertility Survey (MFS) conducted on a sample of over 700 households in April 2012. The results show that the demand for LAPCMs was 71.35% at the time of survey, although only 27.7% of women were using these methods. Thus, the number of unintended pregnancies is likely to increase in the future if this gap is not reduced. The multivariate analysis showed significant impacts on the dependent variables of the number of children ever born, perceived contraceptive costs and childbearing intentions. Moreover, women at the end of their reproductive lives and those with higher education were more likely to desire LAPCMs. It is concluded that despite a growing use of contraceptive methods in Iran in recent decades, the development of reproductive health services and promotion of the quality of family planning services remains a necessity. PMID:24406051

Hosseini, Hatam; Torabi, Fatemeh; Bagi, Balal

2014-11-01

161

Rethinking the role of long-acting atypical antipsychotics in the community setting.  

PubMed

Schizophrenia is a relapsing and evolving condition, which requires treatment continuity. Increasing evidence shows that antipsychotic discontinuation is associated with relapse in most patients, and that early interventions have a positive impact on long-term outcomes. Poor adherence to antipsychotics is a major factor in the treatment of schizophrenia and a relevant risk factor for relapse. Considerable effort has been made toward improving adherence, including the development of long-acting injectable (LAI) antipsychotics. LAIs have traditionally been reserved for patients with repeated nonadherence; currently, several misconceptions prevent their more widespread use. The recent introduction of LAI formulations of atypical antipsychotics and the encouraging results in terms of the reduction in relapse rates and avoidance of hospitalization warrant a reassessment of the role of LAIs in the management of schizophrenia. This paper presents the position of a panel of nine Italian schizophrenia experts on the use of novel LAI medications, with a focus on community-based services, the prevailing setting of schizophrenia treatment in Italy. The need to change the attitude toward LAIs--no longer a treatment of last resort, but a component of multimodal strategies leading patients to remission and rehabilitation--is emphasized. The paper also presents recommendations for LAI atypical antipsychotic use in the community setting. PMID:22859065

Altamura, Alfredo Carlo; Aguglia, Eugenio; Bassi, Mariano; Bogetto, Filippo; Cappellari, Lodovico; De Giorgi, Serafino; Fagiolini, Andrea; Ferrannini, Luigi; Girardi, Paolo

2012-11-01

162

The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.  

PubMed

Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women. PMID:25589631

Radzio, Jessica; Spreen, William; Yueh, Yun Lan; Mitchell, James; Jenkins, Leecresia; García-Lerma, J Gerardo; Heneine, Walid

2015-01-14

163

Thienorphine is a potent long-acting partial opioid agonist: a comparative study with buprenorphine.  

PubMed

A strategy in the development of new treatment for opioid addiction is to find partial opioid agonists with properties of long duration of action and high oral bioavailability. In a search for such compounds, thienorphine, a novel analog of buprenorphine, was synthesized. Here, we reported that, like buprenorphine, thienorphine bound potently and nonselectively to mu-, delta-, and kappa-opioid receptors stably expressed in CHO (Chinese hamster ovary) cells and behaved as a partial agonist at mu-opioid receptor. However, some differences were observed between the pharmacological profiles of thienorphine and buprenorphine. In vitro, thienorphine was more potent than buprenorphine in inhibiting [3H]diprenorphine and stimulating guanosine 5'-O-(3-[35S]thio)triphosphate binding to rat mu-opioid receptor stably expressed in CHO cells. In vivo, thienorphine exhibited a less potent but more efficacious antinociceptive effect with an ED50 value of 0.25 mg/kg s.c. and more potent antimorphine effect with an ED50 value of 0.64 mg/kg intragastric, compared with buprenorphine. Additionally, the bioavailability of thienorphine was greatly higher than that of buprenorphine after oral administration. Moreover, compared with buprenorphine, thienorphine showed a similar long-lasting antinociceptive effect but a much longer antagonism of morphine-induced lethality (more than 15 days). These results indicate that thienorphine is a potent, long-acting partial opioid agonist with high oral bioavailability and may have possible application in treating addiction. PMID:16569757

Yu, Gang; Yue, Yong-Juan; Cui, Meng-Xun; Gong, Ze-Hui

2006-07-01

164

Indacaterol: a new once daily long-acting beta2 adrenoceptor agonist  

PubMed Central

Introduction: Indacaterol is a novel once daily long-acting beta agonist (LABA) developed for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. Aims: This review summarizes preclinical and clinical data of indacaterol, including all data generated during the phase II trial program, and further discusses the outlook and potential of the drug in the future treatment of COPD and asthma. Evidence review: Clinical studies suggest that indacaterol produces rapid and sustained bronchodilation in COPD patients and asthmatics of different severities. Until now, clinical studies of up to 28 days’ duration have been published that have confirmed the suitability of indacaterol for once daily dosing, along with a favorable overall safety and tolerability profile. Outcomes summary: Indacaterol monotherapy has potential in COPD, where antiinflammatory treatment is not fully established and issues about a potential risk of LABA use causing excess mortality have not been raised. In addition, indacaterol represents an option for future combination therapies in both asthma and COPD. However, more data are required, particularly in COPD, to fully assess the therapeutic potential of indacaterol in improving symptoms, quality of life, exacerbation rates, disease progression, exercise capacity, and hyperinflation. The currently ongoing phase III clinical trial program will add knowledge in respect to many long-term efficacy outcomes and gather further safety and tolerability data in both asthma and COPD. PMID:20694063

Beeh, Kai M; Beier, Jutta

2010-01-01

165

Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.  

PubMed

Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-? and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases. PMID:24587893

Alagha, Khuder; Palot, Alain; Sofalvi, Tunde; Pahus, Laurie; Gouitaa, Marion; Tummino, Celine; Martinez, Stephanie; Charpin, Denis; Bourdin, Arnaud; Chanez, Pascal

2014-03-01

166

Aclidinium bromide, a novel long-acting muscarinic M3 antagonist for the treatment of COPD.  

PubMed

Aclidinium bromide is a novel, inhaled, long-acting antimuscarinic agent being developed by Almirall Prodesfarma SA and Forest Laboratories Inc as a once-daily treatment for COPD. In preclinical studies, aclidinium bromide demonstrated a comparable profile to tiotropium bromide, with a slightly quicker onset of action but shorter duration of action. Clinical trials have demonstrated an unquestionably interesting pharmacological profile characterized by a faster rate of onset of the smooth muscle relaxing activity than tiotropium bromide and a rapid plasma hydrolysis in human plasma to inactive metabolites that may account for its favorable cardiovascular safety profile. However, the disappointing efficacy results of the recent phase III trials have cast doubt on the real advantage of introducing this drug on the market. Discussions with the FDA concluded that more trials are needed to assess selected dosing regimens, including higher and/or more frequent doses. At the time of publication, further phase III trials with aclidinium bromide were ongoing, and the developing companies were also extending development to combinations of aclidinium bromide with formoterol or an undisclosed inhaled corticosteroid. PMID:19431081

Cazzola, Mario

2009-05-01

167

Aclidinium bromide, a long-acting antimuscarinic, does not affect QT interval in healthy subjects.  

PubMed

In this phase I trial, the effect of aclidinium, a novel, inhaled long-acting muscarinic antagonist, on QT interval was evaluated, and its cardiovascular safety was assessed in 272 healthy subjects. Aclidinium 200 µg, aclidinium 800 µg, matching placebo, or open-label moxifloxacin 400 mg was administered daily for 3 days. The primary outcome was mean change in individual heart rate-corrected QT interval (QTcI). Secondary measures included Bazett-corrected QT interval (QTcB), Fridericia-corrected (QTcF) intervals, 12-lead electrocardiogram (ECG) readings, and 24-hour 12-lead Holter ECG parameters. Adverse events, vital signs, and laboratory and pharmacokinetic parameters were also assessed. Maximum mean QTcI change from time-matched baseline on day 3 was -1.0 milliseconds at 2 hours for aclidinium 200 µg, -1.8 milliseconds at 5 minutes for 800 µg, +11.0 milliseconds at 4 hours for moxifloxacin, and -1.2 milliseconds at 23.5 hours for placebo. Aclidinium had no significant effects on secondary ECG measures. Aclidinium plasma concentrations were generally below the lower limit of quantitation (0.05 ng/mL) after 200 µg and were detected only up to 1 hour after the 800-µg dose in the majority of cases. It is concluded that aclidinium bromide, at doses up to 800 µg, has a favorable cardiovascular safety profile with no effect on QT interval. PMID:20959525

Lasseter, Kenneth C; Aubets, Jordi; Chuecos, Ferran; Gil, Esther Garcia

2011-06-01

168

Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases  

PubMed Central

Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-? and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases. PMID:24587893

Palot, Alain; Sofalvi, Tunde; Pahus, Laurie; Gouitaa, Marion; Tummino, Celine; Martinez, Stephanie; Charpin, Denis; Bourdin, Arnaud; Chanez, Pascal

2014-01-01

169

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

PubMed

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

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

2010-02-01

170

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

PubMed Central

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

Di Lorenzo, Rosaria; Brogli, Alice

2010-01-01

171

Tissue damage caused by the intramuscular injection of long-acting penicillin.  

PubMed

In order to elucidate whether tissue damage produced on occasion by intramuscular injection of long-acting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits. In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol. In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femoral artery as control. The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations. None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations. None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities. These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug. PMID:3982907

Schanzer, H; Jacobson, J H

1985-04-01

172

Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir-boosted atazanavir nanoformulations.  

PubMed

Long-acting nanoformulated antiretroviral therapy (nanoART) that targets monocyte-macrophages could improve the drug's half-life and protein-binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly increased drug bioavailability and PD by five and 100 times, respectively. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice and infected with HIV-1ADA led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitates drug carriage and antiretroviral responses. PMID:25522973

Puligujja, Pavan; Balkundi, Shantanu S; Kendrick, Lindsey M; Baldridge, Hannah M; Hilaire, James R; Bade, Aditya N; Dash, Prasanta K; Zhang, Gang; Poluektova, Larisa Y; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S; McMillan, JoEllyn M; Gendelman, Howard E

2015-02-01

173

Emulsified Chitosan-plga Scaffolds for Tissue Engineering.  

E-print Network

??This study evaluated the formation of chitosan-50:50 poly-lactic-co-glycolic acid (PLGA) blend matrices using controlled rate freezing and lyophilization technique. An emulsion system was used in… (more)

Moshffeghian, Aliakbar

2005-01-01

174

Doppler cooling a microsphere.  

PubMed

Doppler cooling the center-of-mass motion of an optically levitated microsphere via the velocity-dependent scattering force from narrow whispering gallery mode resonances is described. Light that is red detuned from the whispering gallery mode resonance can be used to damp the center-of-mass motion in a process analogous to the Doppler cooling of atoms. The scattering force is not limited by saturation but can be controlled by the incident power. Cooling times on the order of seconds are calculated for a 20 ?m diameter silica microsphere trapped within optical tweezers. PMID:20868038

Barker, P F

2010-08-13

175

PEGylated PLGA nanoparticles for the improved delivery of doxorubicin  

Microsoft Academic Search

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

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

2009-01-01

176

Use of long-acting neuroleptics to reduce the stress response to management practices in red deer  

Microsoft Academic Search

Three groups of six adult red deer hinds were used to determine whether long-acting neuroleptic (LAN) tranquillisers were able to modify the behavioural and physiological responses of the deer to a range of routine management stressors: such drugs may eventually prove useful in capture procedures for wild animals. While the stressors increased moving activity and decreased inactive lying and inter-animal

Silvana Diverio; Pete J. Goddard; Iain J. Gordon

1996-01-01

177

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

PubMed Central

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

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

2013-01-01

178

A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma  

Microsoft Academic Search

Although various types of treatment of hepatocellular carcinoma (HCC) have been tried, the prognosis remains dismal, especially in patients with advanced stage of the disease. Somatostatin analogues exert antitumor effects. HCC have been shown to exhibit somatostatin receptors. The present randomized placebo-controlled study aimed at examining the efficacy of long-acting octreotide (Sandostatin LAR) for the treatment of advanced HCC. Seventy

Man-Fung Yuen; Ronnie Tung-Ping Poon; Ching-Lung Lai; Sheung-Tat Fan; Chung-Mau Lo; Ka-Wah Wong; Wai Man Wong; Benjamin Chun-Yu Wong

2002-01-01

179

Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility.  

PubMed

Efforts to develop long circulating polymeric nanoparticles have propelled many strategies in nanoparticle surface modification to bypass immune surveillance and systemic clearance. In this context, our present study reports on the preparation and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA) nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery system. Amino groups of mucin were conjugated to the terminal carboxylic acid groups on PLGA to be followed by nanoparticle synthesis via standard solvent evaporation technique. Detailed in vitro experiments were performed to illustrate the significance of alternating copolymer structured mucin modified PLGA nanoparticles in terms of enhanced hemocompatibility and cellular uptake. Mucylation proved promising in controlling PLGA nanoparticle- interaction with plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity and complement activation. Besides hemocompatibility, the modified and unmodified nanoparticles were also found to be cytocompatible with L929 and C6 cell lines. The fluorescent and confocal image analysis evaluated the extent of cellular uptake of nanoparticles into C6 cells. Specifically the combination of stealth properties and cellular internalization capacity of mucin modified PLGA nanoparticle (PLGA-Mucin) lead us to propose it as a safe, efficient and multifunctional nanoplatform for disease specific intravenous drug delivery applications as far as in vitro experiments are concerned. PMID:23978287

Thasneem, Y M; Rekha, M R; Sajeesh, S; Sharma, Chandra P

2013-11-01

180

Meta-analysis of the efficacy and safety of long-acting non-ergot dopamine agonists in Parkinson's disease.  

PubMed

A meta-analysis of randomized controlled trials (RCT) was performed to evaluate the efficacy and safety of long-acting non-ergot dopamine agonists (NEDA) versus placebo in Parkinson's disease (PD). A comprehensive literature search up to February 2013 was performed, and the weighted mean differences (WMD) and relative risks (RR) with 95% confidence intervals (CI) were calculated. Nine RCT (n=2857) which assessed the rotigotine transdermal patch, extended-release pramipexole, and ropinirole prolonged-release, were included. Compared with placebo, long-acting NEDA achieved greater improvements in Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score (WMD -1.77, 95% CI -2.13 to -1.41), motor score (WMD -4.18, 95% CI -4.94 to -3.43) and the ADL and motor subtotal score (WMD -5.12, 95% CI -6.16 to -4.07), as well as a reduction in "off" time (WMD -1.29, 95% CI -1.64 to -0.93) and an increase in "on" time without troublesome dyskinesia (WMD 1.55, 95% CI 1.06 to 2.04). Compared with placebo, long-acting NEDA were associated with a higher risk of nausea, but no difference was found in headache incidence. Higher risks of dizziness, somnolence, constipation, vomiting, and insomnia were only found in early PD while higher risks of dyskinesia and hallucination were only found in advanced PD. The results of our meta-analysis showed that the use of long-acting NEDA can reduce the symptoms of PD patients. However, long-acting NEDA were also associated with a higher incidence of adverse events, especially in early PD patients, compared with placebo. PMID:24786715

Zhou, Chang-Qing; Zhang, Jiang-Wei; Wang, Min; Peng, Guo-Guang

2014-07-01

181

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

PubMed Central

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

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

2013-01-01

182

Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors.  

PubMed

Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotide in vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60?mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60?mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5 expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5 expression is a potentially predictive biomarker for response. PMID:25376618

Cives, M; Kunz, P L; Morse, B; Coppola, D; Schell, M J; Campos, T; Nguyen, P T; Nandoskar, P; Khandelwal, V; Strosberg, J R

2015-02-01

183

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

PubMed Central

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

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

184

Who Is Using Long-Acting Reversible Contraceptive Methods? Findings from Nine Low-Fertility Countries  

PubMed Central

CONTEXT Long-acting reversible contraceptive (LARC) methods—IUDs and implants—are more effective than other reversible methods, yet are little used in the United States. Examining which U.S. women use LARC methods and how they differ from users in other low-fertility countries may help point the way toward increasing use. METHODS Data from married or cohabiting women participating in the National Survey of Family Growth (2008–2010) and in eight countries’ Generations and Gender Programme surveys (2004–2010) were used in bivariate and multinomial logistic regression analyses examining LARC use within each setting. RESULTS The proportion of contraceptive use accounted for by LARC methods was generally greater in Europe (10–32%) than in the United States (10%) and Australia (7%). Compared with LARC use among comparable groups in other countries, use was particularly low among U.S. women who were married, were aged 40–44 or had had three or more children, yet was comparatively high among 18–24-year-olds. Among U.S. women, those aged 35–39 or 40–44 were more likely than 18–29-year-olds to rely on sterilization rather than on LARC methods (odds ratios, 3.0 and 10.7, respectively), those who had had three or more children were more likely to do so than were those who had had none or one (4.9), and women who had completed college were less likely than those who had not finished high school to do so (0.4). CONCLUSIONS Certain subgroups of U.S. women may benefit from the reversibility and effectiveness of LARC methods. PMID:25040454

Eeckhaut, Mieke C. W.; Sweeney, Megan M.; Gipson, Jessica D.

2014-01-01

185

?? long-acting and anticholinergic drugs control TGF-?1-mediated neutrophilic inflammation in COPD.  

PubMed

We quantified TGF-?1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-?1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled ?(2)-adrenoceptor agonist) and Tiotropium Spiriva®, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-?1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and TGF-?1 in HS is higher than in HC; 2) ISSs from COPD and HS caused increased neutrophil adhesion to 16-HBE when compared to ISSs from HC. The effect of ISSs from COPD was significantly reduced by TGF-?1 depletion or by the pretreatment with Olodaterol or Tiotropium alone or in combination, while the effect of ISSs from HS was significantly reduced by the pretreatment with Olodaterol alone; 3) mAChR2, mAChR3 and ChAT expression was increased in 16-HBE stimulated with ISSs from COPD and TGF-?1 depletion significantly reduced this effect on mAChR3 and ChAT expression; 4) rhTGF-?1 increased mAChR2, mAChR3 and ChAT expression in 16-HBE; 5) Olodaterol did not affect the expression of mAChRs and ChAT in 16-HBE. Our findings support the use of ?? long-acting and anticholinergic drugs to control the bronchoconstriction and TGF-?1-mediated neutrophilic inflammation in COPD. PMID:22440430

Profita, Mirella; Bonanno, Anna; Montalbano, Angela Marina; Albano, Giusy Daniela; Riccobono, Loredana; Siena, Liboria; Ferraro, Maria; Casarosa, Paola; Pieper, Michael Paul; Gjomarkaj, Mark

2012-07-01

186

The knowledge and attitudes of psychiatrists towards antipsychotic long-acting injections in Nigeria  

PubMed Central

Background: Antipsychotic long-acting injections (LAIs) reduce covert nonadherence with medication in the clinical management of psychotic disorders. However, they are variably utilised by clinicians, especially in the long term. Factors including poor knowledge, stigma and perceived coercion can all adversely influence LAI utilisation. Previous research has emanated almost exclusively from developed countries. This study explores the knowledge and attitudes of psychiatrists and trainees in Nigeria towards LAIs. Methods: A cross-sectional study was undertaken among mental health professionals in Nigeria using a pre-existing questionnaire. Results: Participant psychiatrists (n = 128) expressed positive attitudes towards LAIs. Their knowledge concerning LAIs and its side effects was fair. The participants reported that nearly half (41.7%) of their patients with a psychotic illness were on LAIs. Those who reported a high prescribing rate for LAIs (>40%) were more likely to endorse more positive ‘patient-centred attitudes’ (p < 0.04). In contrast to previous reports, psychiatrists reported that patients were less likely to feel ashamed when on LAIs, though most endorsed the statement that force was required during LAI administration. Conclusion: The desirability of treatment by injections differs in Africa in comparison to Western cultures, possibly due to the increased potency that injections are perceived to have. This is perhaps evidenced by high rates reported for use of LAIs. Nigerian psychiatrists had positive attitudes to LAIs but their knowledge, particularly regarding side effects, was fair and needs to be improved. Providing information to patients prior to antipsychotic treatment may enhance informed consent in a country where medical paternalism is still relatively strong. PMID:23983972

Omoaregba, Joyce O.; Okonoda, Kingsley M.; Otefe, Edebi U.; Patel, Maxine X.

2012-01-01

187

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

PubMed

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

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

2014-10-15

188

Onset of effect of aclidinium, a novel, long-acting muscarinic antagonist, in patients with COPD.  

PubMed

ABSTRACT Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). The aim of this study was to assess the rate of onset of bronchodilation with aclidinium compared with placebo and tiotropium. This was a double-blind, double-dummy, multicenter, crossover study in COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV(1)) ?30% and <60% predicted. On study days, patients received single doses of aclidinium 200 ?g, tiotropium 18 ?g, or placebo. Serial spirometry was conducted from 10 minutes to 3 hours post-dose. The primary variable was the percentage of patients with an increase in FEV(1) of ?10% above baseline at 30 minutes post-dose. Other assessments included change from baseline in FEV(1) and dyspnea over 3 hours post-dose. A total of 115 patients entered the study. Significantly more patients had an increase in FEV(1) of ?10% above baseline at 30 minutes with aclidinium and tiotropium versus placebo (49.5% and 51.8% versus 13.8%; p < 0.0001). At 30 minutes, the relative increase from baseline in FEV(1) was significantly higher for aclidinium and tiotropium versus placebo (12% and 11% versus 3%; p < 0.0001). Aclidinium and tiotropium also significantly increased FEV(1) (p < 0.01) and improved the perception of dyspnea compared with placebo at all measured time points from 10 minutes to 3 hours post-dose. In conclusion, aclidinium provided effective bronchodilation, similar to that seen with tiotropium, with significant improvements compared with placebo observed from 10 minutes post-dose. PMID:20854047

Vestbo, Jørgen; Vogelmeier, Claus; Creemers, Jacques; Falques, Meritxell; Ribera, Anna; Gil, Esther Garcia

2010-10-01

189

Preclinical evaluation of long-acting muscarinic antagonists: comparison of tiotropium and investigational drugs.  

PubMed

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation caused by persistent inflammatory processes in the airways. An increased cholinergic tone mediates different pathophysiological features of COPD, such as bronchoconstriction and mucus hypersecretion, mostly through activation of the human muscarinic M(3) receptor (hM(3)) subtype. Tiotropium bromide (Spiriva) is a well established muscarinic antagonist in the pharmacological management of COPD with a once-daily posology. The rationale behind the sustained bronchodilation obtained with tiotropium consists in its slow dissociation from hM(3) receptors. In this study, we performed a comprehensive preclinical comparison of tiotropium with other long-acting muscarinic antagonists (LAMAs) currently in clinical development, namely aclidinium bromide and glycopyrrolate. The different muscarinic antagonists were characterized for their 1) affinity toward the different human muscarinic receptor subtypes expressed in Chinese hamster ovary cells and kinetics of receptor dissociation, 2) potency in inhibiting the agonist-induced activation of muscarinic receptors through measurement of second messengers, and 3) efficacy and duration of bronchoprotection, as tested in a model of acetylcholine-induced bronchoconstriction in anesthetized dogs over a period of 24 h. All of the tested LAMAs showed high affinity and potency toward the hM(3) receptor (tiotropium, pA(2) = 10.4; aclidinium, pA(2) = 9.6; and glycopyrrolate, pA(2) = 9.7). However, dissociation half-lives of the LAMAs from the hM(3) receptor differed significantly (tiotropium, t((1/2)) = 27 h; aclidinium, t((1/2)) = 10.7 h; and glycopyrrolate, t((1/2)) = 6.1 h). In line with their kinetic properties at the hM(3), the tested LAMAs provided different levels of bronchoprotection in the in vivo setting 24 h after administration (tiotropium = 35%, aclidinium = 21%, and glycopyrrolate = 0% at 24 h) when applied at equieffective doses. PMID:19478135

Casarosa, Paola; Bouyssou, Thierry; Germeyer, Sabine; Schnapp, Andreas; Gantner, Florian; Pieper, Michael

2009-08-01

190

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

PubMed

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

Secura, G

2013-06-01

191

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

PubMed Central

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

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

2014-01-01

192

Doped zinc oxide microspheres  

DOEpatents

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.

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

1993-01-01

193

Doped zinc oxide microspheres  

DOEpatents

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.

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

1993-12-14

194

Microsphere insulation systems  

NASA Technical Reports Server (NTRS)

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.

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

2005-01-01

195

Polyvinyl pyridine microspheres  

NASA Technical Reports Server (NTRS)

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.

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

1980-01-01

196

Poly(DL-lactide-co-glycolide) microporous microsphere-based depot formulation of a peptide-like antineoplastic agent.  

PubMed

In the present investigation, a poly(DL-co-glycolide) (PLGA)-based, microspheric depot system for bleomycin (BLM) has been formulated, and the same has been evaluated in-vivo in C57BL/6J mice bearing transplantable melanoma B16F1 murine solid tumour. The microparticulate delivery systems were formulated employing a water-in-oil-in-water (W/O/W) emulsion-solvent evaporation technique and characterized in-vitro. The microspheres were injected subcutaneously to form a drug depot at the site of injection in mice bearing experimental tumours and the drug was continuously infused into the systemic circulation with progressive biodegradation. The drug-loaded microspheres exhibited improved pharmacodynamic efficacy, as evidenced by retarded tumour growth kinetics. Preliminary pharmacokinetic studies illustrated controlled release of the drug into the systemic circulation over the study period to exert an anti-neoplastic action. These studies demonstrated the feasibility of employing a PLGA-based microparticulate system as an effective biodegradable, injectable, depot-forming therapeutic system for long-term administration of anti-neoplastic agents. PMID:12396388

Shenoy, D B; D'Souza, R J; Udupa, N

2002-01-01

197

Covalent immobilization of bioactive poly(amidoamine)s onto plasma-functionalized PLGA surfaces  

NASA Astrophysics Data System (ADS)

An approach to the surface modification of poly(lactic-co-glycolic acid) (PLGA) to render it adhesive to poly(amidoamine) (PAA) hydrogels, thus allowing fabrication of entirely biodegradable and biomimetic multilayered composite biomaterials with the PLGA film playing the role of reinforcing material, for instance imparting resistance to stitching, is N2/H2 plasma treatment of PLGA surfaces aimed at introducing amine groups and covalently immobilizing PAAs. Grafting of linear PAAs, demonstrated by XPS analysis, is reported first. Coherent PAA/PLGA composite hydrogels with embedded PLGA films can be obtained likewise. They are soft, elastic and resistant to osmotic shock. In contrast, hydrogels prepared from untreated PLGA films delaminate on swelling. Accessible hybrid PAA/PLGA materials may expand PLGA’s biomedical applications.

Zanini, Stefano; Riccardi, Claudia; Natalello, Antonino; Cappelletti, Graziella; Cartelli, Daniele; Fenili, Fabio; Manfredi, Amedea; Ranucci, Elisabetta

2014-09-01

198

Pharmacokinetic and technical comparison of Sandostatin® LAR® and other formulations of long-acting octreotide  

PubMed Central

Background Sandostatin® LAR® (Novartis Pharma AG) is a long-acting repeatable formulation of the somatostatin analogue octreotide, the safety and efficacy of which has been established through 15 years of clinical experience. Recently, other formulations of octreotide using polymer poly(lactic-co-glycolic acid) technology have been developed. This study compares the composition and pharmacokinetic (PK) profile of Sandostatin LAR with three other versions of the depot delivery system (formulations A, B and C, available in selected countries). Findings Sandostatin LAR exhibited a characteristic concentration-time profile with a limited initial release of octreotide ('burst'), an erosion phase from weeks 3-5, and a slowly declining concentration to day 52. The PK profiles of formulations A and B were characterized by a large initial burst during days 0-2, with up to 41% of the overall area under the plasma-concentration time curve achieved. Low and variable octreotide concentrations were observed during the microparticle erosion phase (days 2-62 [day 82 formulation C]) for formulations A, B and C. Sandostatin LAR microparticles are spherical in shape with an average diameter of approximately 50 ?m, determined by scanning electron microscopy evaluation. Formulation A had smaller, irregular microparticles, and formulations B and C exhibited a large range of particle diameters (< 20 to > 100 ?m). Inductively coupled plasma-optical emission spectroscopy detected a high tin content of 104 mg/kg in formulation B, the presence of which may suggest inadequate purification following polymer synthesis using tin(II)-octoate as catalyst. PK profiles for formulations A, B and C after a single intramuscular injection of 4 mg/kg in male New Zealand rabbits differed markedly from the PK profile of Sandostatin LAR. Conclusions Clear differences were seen between Sandostatin LAR and formulations A, B and C, including variations in microparticle size, shape and impurity content. Considering the significant differences in the octreotide release profile between Sandostatin LAR and the other formulations, the safety and efficacy of the other formulations cannot be inferred from the Sandostatin LAR efficacy and safety profile; each of these other formulations should be assessed accordingly. PMID:21906300

2011-01-01

199

Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses  

PubMed Central

Background Discontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare professionals (HCPs) towards LAI antipsychotics may influence their prescribing decisions and may influence medication choices offered to patients. We therefore conducted a survey to investigate factors driving LAI use as well as physician and nurse attitudes to LAI antipsychotics and to different injection sites. Methods An independent market research agency conducted the survey of HCPs across Europe. Participants were recruited by telephone and completed the survey online. Using conjoint analyses (a multivariate statistical technique analysing preferences on the basis of ranking a limited number of attributes which are presented repetitively), attitudes to oral versus LAI medication and gluteal versus deltoid injection routes were assessed. Results A total of 891 HCPs across Europe were surveyed. Of these, 40% would choose LAI antipsychotics for first episode patients whereas 90% would select LAI antipsychotics for chronic patients with two to five psychotic episodes. Dominant elements in antipsychotic choice were low sedation but no tardive dyskinesia, no or mild pain at injection and low risk of embarrassment or impact upon therapeutic alliance. Eighty-six per cent of respondents considered that having the choice of a deltoid as well as gluteal administration site was beneficial over not having that choice. Two thirds of respondents said they agreed that medication administration via the deltoid muscle may reduce social embarrassment associated with LAI antipsychotics and most respondents (61%) believed that administration of LAI antipsychotics into the deltoid muscle as opposed to the gluteal muscle may be more respectful to the patient. Conclusions In this survey of physicians and nurses, attitudes towards LAI antipsychotics compared with oral medication were generally positive. Respondents considered that the availability of a deltoid administration route would offer increased choice in LAI antipsychotic administration and may be perceived as more respectful and less socially embarrassing. PMID:23414331

2013-01-01

200

Activity of aclidinium bromide, a new long-acting muscarinic antagonist: a phase I study  

PubMed Central

AIM Aclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine-induced bronchoconstriction. METHODS This double-blind, partial-crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 µg) or placebo. Drug activity was assessed for 24 h after administration by specific airway conductance (sGaw), airways resistance (Raw) and bronchial responsiveness (PC35 sGaw methacholine). RESULTS Aclidinium significantly increased sGaw compared with placebo at all assessments and doses (sGaw mean ± SD AUC (l kPa?1 h) for placebo 24.4 ± 4.37, for 50 µg 29.0 ± 7.08, for 300 µg 31.2 ± 6.68 and for 600 µg 32.7 ± 7.95) (P < 0.009), except 50 µg at 1 and 24 h. Significant decreases in Raw were observed with aclidinium 300 and 600 µg compared with placebo at all assessments (Raw mean ± SD AUC (kPa s?1 l?1 h) for placebo 7.7 ± 3.46, for 300 µg 5.8 ± 2.33, for 600 µg 6.3 ± 3.11) (P < 0.04) except 600 µg at 24 h. Differences between aclidinium 300 and 600 µg vs. placebo in PC35 doubling concentration were significant at all assessments (mean ± SD AUC (mg ml?1 h) for placebo 100.0 ± 30.27, for 50 µg 117.2 ± 33.33, for 300 µg 168.9 ± 28.66 and for 600 µg 179.1 ± 15.73 (P < 0.0001). For all endpoints, there was a significant difference between aclidinium 50 µg and the higher doses (P < 0.0001). Aclidinium was not detected in plasma and was well tolerated. CONCLUSION Aclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long-acting efficacy and providing a rationale for future studies in patients with COPD. PMID:20573081

Schelfhout, Vanessa J; Ferrer, Pau; Jansat, Josep Maria; Peris, Francesc; Gil, Esther Garcia; Pauwels, Romain A; Joos, Guy F

2010-01-01

201

Achieving cost-neutrality with long-acting reversible contraceptive methods?  

PubMed Central

Objectives This analysis aimed to estimate the average annual cost of available reversible contraceptive methods in the United States. In line with literature suggesting long-acting reversible contraceptive (LARC) methods become increasingly cost-saving with extended duration of use, it aimed to also quantify minimum duration of use required for LARC methods to achieve cost-neutrality relative to other reversible contraceptive methods while taking into consideration discontinuation. Study design A three-state economic model was developed to estimate relative costs of no method (chance), four short-acting reversible (SARC) methods (oral contraceptive, ring, patch and injection) and three LARC methods [implant, copper intrauterine device (IUD) and levonorgestrel intrauterine system (LNG-IUS) 20 mcg/24 h (total content 52 mg)]. The analysis was conducted over a 5-year time horizon in 1000 women aged 20–29 years. Method-specific failure and discontinuation rates were based on published literature. Costs associated with drug acquisition, administration and failure (defined as an unintended pregnancy) were considered. Key model outputs were annual average cost per method and minimum duration of LARC method usage to achieve cost-savings compared to SARC methods. Results The two least expensive methods were copper IUD ($304 per women, per year) and LNG-IUS 20 mcg/24 h ($308). Cost of SARC methods ranged between $432 (injection) and $730 (patch), per women, per year. A minimum of 2.1 years of LARC usage would result in cost-savings compared to SARC usage. Conclusions This analysis finds that even if LARC methods are not used for their full durations of efficacy, they become cost-saving relative to SARC methods within 3 years of use. Implications Previous economic arguments in support of using LARC methods have been criticized for not considering that LARC methods are not always used for their full duration of efficacy. This study calculated that cost-savings from LARC methods relative to SARC methods, with discontinuation rates considered, can be realized within 3 years. PMID:25282161

Trussell, James; Hassan, Fareen; Lowin, Julia; Law, Amy; Filonenko, Anna

2014-01-01

202

Janus nanogels of PEGylated Taxol and PLGA-PEG-PLGA copolymer for cancer therapy  

NASA Astrophysics Data System (ADS)

Nanogels are promising carriers for the delivery of anti-cancer drugs for cancer therapy. We report in this study on a Janus nanogel system formed by mixing a prodrug of Taxol (PEGylated Taxol) and a copolymer of PLGA-PEG-PLGA. The Janus nanogels have good stability over months in aqueous solutions and the freeze-dried powder of nanogels can be re-dispersed instantly in aqueous solutions. The Janus nanogels show an enhanced inhibition effect on tumor growth in a mice breast cancer model probably due to the enhanced uptake of the nano-sized materials by the EPR effect. What is more, the nanogels can also serve as physical carriers to co-deliver other anti-cancer drugs such as doxorubicin to further improve the anti-cancer efficacy. The results obtained from H&E staining and TUNEL assay also support the observation of tumor growth inhibition. These results suggest the potential of this novel delivery system for cancer therapy.Nanogels are promising carriers for the delivery of anti-cancer drugs for cancer therapy. We report in this study on a Janus nanogel system formed by mixing a prodrug of Taxol (PEGylated Taxol) and a copolymer of PLGA-PEG-PLGA. The Janus nanogels have good stability over months in aqueous solutions and the freeze-dried powder of nanogels can be re-dispersed instantly in aqueous solutions. The Janus nanogels show an enhanced inhibition effect on tumor growth in a mice breast cancer model probably due to the enhanced uptake of the nano-sized materials by the EPR effect. What is more, the nanogels can also serve as physical carriers to co-deliver other anti-cancer drugs such as doxorubicin to further improve the anti-cancer efficacy. The results obtained from H&E staining and TUNEL assay also support the observation of tumor growth inhibition. These results suggest the potential of this novel delivery system for cancer therapy. Electronic supplementary information (ESI) available: Synthesis and characterization of compounds, dynamic time sweep, H&E result and body weight change of mice. See DOI: 10.1039/c3nr02937a

Wei, Jun; Wang, Huaimin; Zhu, Meifeng; Ding, Dan; Li, Dongxia; Yin, Zhinan; Wang, Lianyong; Yang, Zhimou

2013-09-01

203

Porous microsphere and its applications  

PubMed Central

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

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

2013-01-01

204

Modulation of transcriptional responses by poly(I:C) and human rhinovirus: effect of long-acting ??-adrenoceptor agonists.  

PubMed

Exacerbations of asthma, a chronic inflammatory respiratory disease, are associated with viral upper respiratory tract infections involving human rhinovirus. Although glucocorticoids (corticosteroids) effectively control airways inflammation in many asthmatics, human rhinovirus-associated exacerbations show reduced glucocorticoid responsiveness. Using human bronchial epithelial BEAS-2B cells, we show that human rhinovirus reduced glucocorticoid-inducible activation of glucocorticoid response element (GRE) reporter systems in a time- and concentration-dependent manner. The synthetic double-stranded viral RNA mimetic, polyinosinic:polycytidylic acid (poly(I:C)), also reduced activation of GRE reporter systems in BEAS-2B and pulmonary A549 cells. In addition, poly(I:C) decreased transcription from cAMP response element (CRE)-, TATA-, simian virus 40- and nuclear factor-kappa B (NF-?B)-dependent reporter systems. The effects of poly(I:C) on GRE-reporter activation were countered by the long-acting ?2-adrenoceptor agonists, formoterol and salmeterol. Likewise, increased expression of the gene cyclin-dependent kinase inhibitor 1C (CDKN1C; p57(KIP2)) by dexamethasone was reduced by poly(I:C), but was substantially enhanced by the addition of formoterol. Poly(I:C) induced the expression of interleukin-8 (IL8; CXCL8) and this was significantly decreased by dexamethasone, formoterol or their combination. This confirms that not all transcriptional responses were attenuated by poly(I:C) and that decreased glucocorticoid-dependent transcription can be counteracted by the addition of long-acting ?2-adrenoceptor agonists. These data show how human rhinovirus may attenuate glucocorticoid-induced transcription to reduce anti-inflammatory activity. However, addition of long-acting ?2-adrenoceptor agonist to the glucocorticoid functionally restored this response and shows how glucocorticoid plus long-acting ?2-adrenoceptor agonist combinations may prove beneficial during virus-induced exacerbations of asthma. PMID:23523474

Rider, Christopher F; Miller-Larsson, Anna; Proud, David; Giembycz, Mark A; Newton, Robert

2013-05-15

205

Long acting ?2 agonists for stable chronic obstructive pulmonary disease with poor reversibility: a systematic review of randomised controlled trials  

Microsoft Academic Search

BACKGROUND: The long acting ?2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD). We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD. METHODS: After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed,

Don Husereau; Vijay Shukla; Michel Boucher; Shaila Mensinkai; Robert Dales

2004-01-01

206

A retrospective observational study comparing rescue medication use in children on combined versus separate long-acting ?-agonists and corticosteroids  

Microsoft Academic Search

BackgroundData on the efficacy and safety of long-acting ?2-agonists (LABA) in children are limited, and current guidelines recommend that LABA always be used with inhaled corticosteroids (ICS).ObjectiveTo compare asthma control, assessed by rescue medications use, in children prescribed LABA and ICS as a fixed-dose combination (LABA\\/ICS) or concurrently via separate inhalers (LABA+ICS).MethodsRetrospective observational study of asthma medication prescribed to children

H. Elkout; J. S. McLay; C. R. Simpson; P. J. Helms

2010-01-01

207

Comparison of long acting oxytetracycline and parvaquone in immunisation against East Coast fever by infection and treatment.  

PubMed

Two groups of five cattle were immunised with a field isolate of Theileria parva as stabilate and simultaneously treated with long acting oxytetracycline or parvaquone in early clinical disease. The oxytetracycline group suffered a marked fall in leucocyte count and one animal died during immunisation. The parvaquone group suffered a less severe fall in leucocyte count and all survived. The surviving immunised cattle were immune to homologous challenge but susceptible to subsequent challenge with T p lawrencei. PMID:6438743

Dolan, T T; Linyonyi, A; Mbogo, S K; Young, A S

1984-09-01

208

Attitudes of women in Scotland to contraception: a qualitative study to explore the acceptability of long-acting methods  

Microsoft Academic Search

Background and methodologyLong-acting reversible contraception (LARC) (i.e. injections, implants and intrauterine methods) has the potential to reduce unintended pregnancies but in the UK these methods are under-used. To inform a campaign planned to increase awareness of LARC, eight focus discussion groups were held with 55 women in two cities in Scotland, UK. Trained interviewers sought spontaneous views of unintended pregnancy

Anna Glasier; Jane Scorer; Alison Bigrigg

2008-01-01

209

Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty  

Microsoft Academic Search

Summary OBJECTIVE Following a successful clinical trial in 1996, the long-acting GnRH analogue goserelin (Zoladex LA 10·8 mg; Astra Zeneca) has been our preferred treatment for central early (CEP) or precocious puberty (CPP). However, some female patients have expressed concern about perceived weight gain during therapy and delay in the onset or resumption of menses on completion of therapy. The

W. F. Paterson; E. McNeill; D. Young; M. D. C. Donaldson

2004-01-01

210

Amelioration of the Cardiovascular Effects of Cocaine in Rhesus Monkeys by a Long-Acting Mutant Form of Cocaine Esterase  

Microsoft Academic Search

A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R\\/G173Q CocE; double mutant CocE (DM CocE)) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at

Gregory T Collins; Kathy A Carey; Diwahar Narasimhan; Joseph Nichols; Aaron A Berlin; Nicholas W Lukacs; Roger K Sunahara; James H Woods; Mei-Chuan Ko; M-C Ko

2011-01-01

211

Potentiation of Local Anesthetic Activity of Neosaxitoxin with Bupivacaine or Epinephrine: Development of a Long-Acting Pain Blocker  

Microsoft Academic Search

Local anesthetics effectively block and relieve pain, but with a relatively short duration of action, limiting its analgesic\\u000a effectiveness. Therefore, a long-acting local anesthetic would improve the management of pain, but no such agent is yet available\\u000a for clinical use. The aim of this study is to evaluate the potentiation of the anesthetic effect of neosaxitoxin, with bupivacaine\\u000a or epinephrine

Alberto J. Rodriguez-Navarro; Marcelo Lagos; Cristian Figueroa; Carlos Garcia; Pedro Recabal; Pamela Silva; Veronica Iglesias; Nestor Lagos

2009-01-01

212

Protein micropatterns by PEG grafting on Dewetted PLGA films.  

PubMed

The ability to control protein and cell positioning on a microscopic scale is crucial in many biomedical applications, such as single cell studies. We have developed and investigated the grafting of poly(ethylene glycol) (PEG) brushes onto poly(d,l-lactide-co-glycolide) (PLGA) thin films, which can be micropatterned by exploiting their spontaneous dewetting on top of polystyrene (PS) films. Dense PEG brushes with excellent protein repellence were achieved on PLGA by using cloud point grafting conditions, and selective adsorption of proteins on the micropatterned substrates was achieved by exploiting the different affinity protein adsorption onto the PEG brushes and the PS holes. PEG-grafted PLGA films showed better resistance against spontaneous degradation in buffer than bare PLGA films, due to passivation by the thin PEG coating. The simplicity of dewetting and subsequent grafting approaches, coupled with the ability to coat and pattern nonplanar substrates give rise to possible applications of PEG-grafted PLGA films in single cell studies and cell cultures for tissue engineering. PMID:25195610

Ghezzi, Manuel; Thickett, Stuart C; Telford, Andrew M; Easton, Christopher D; Meagher, Laurence; Neto, Chiara

2014-10-01

213

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

PubMed Central

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

Addissie, Adamu

2014-01-01

214

Fabrication of pillared PLGA microvessel scaffold using femtosecond laser ablation  

PubMed Central

One of the persistent challenges confronting tissue engineering is the lack of intrinsic microvessels for the transportation of nutrients and metabolites. An artificial microvascular system could be a feasible solution to this problem. In this study, the femtosecond laser ablation technique was implemented for the fabrication of pillared microvessel scaffolds of polylactic-co-glycolic acid (PLGA). This novel scaffold facilitates implementation of the conventional cell seeding process. The progress of cell growth can be observed in vitro by optical microscopy. The problems of becoming milky or completely opaque with the conventional PLGA scaffold after cell seeding can be resolved. In this study, PLGA microvessel scaffolds consisting of 47 ?m × 80 ?m pillared branches were produced. Results of cell culturing of bovine endothelial cells demonstrate that the cells adhere well and grow to surround each branch of the proposed pillared microvessel networks. PMID:22605935

Wang, Hsiao-Wei; Cheng, Chung-Wei; Li, Ching-Wen; Chang, Han-Wei; Wu, Ping-Han; Wang, Gou-Jen

2012-01-01

215

Microencapsulation of curcumin in PLGA microcapsules by coaxial flow focusing  

NASA Astrophysics Data System (ADS)

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.

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

2014-03-01

216

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles  

PubMed Central

Background Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells. Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry. Results PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility. Conclusion PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity. PMID:24410831

2014-01-01

217

Dextran-based microspheres as controlled delivery systems for proteins.  

E-print Network

??Dextran-based microspheres as controlled delivery systems for proteins Dextran based microspheres are investigated as controlled delivery system for proteins. Microspheres were prepared by polymerization of… (more)

Vlugt-Wensink, K.D.F.

2007-01-01

218

Metal containing polymeric functional microspheres  

NASA Technical Reports Server (NTRS)

Polymeric functional microspheres containing metal or metal compounds are formed by addition polymerization of a covalently bondable olefinic monomer such as hydroxyethylmethacrylate in the presence of finely divided metal or metal oxide particles, such as iron, gold, platinum or magnetite, which are embedded in the resulting microspheres. The microspheres can be covalently bonded to chemotherapeutic agents, antibodies, or other proteins providing a means for labeling or separating labeled cells. Labeled cells or microspheres can be concentrated at a specific body location such as in the vicinity of a malignant tumor by applying a magnetic field to the location and then introducing the magnetically attractable microspheres or cells into the circulatory system of the subject. Labeled cells can be separated from a cell mixture by applying a predetermined magnetic field to a tube in which the mixture is flowing. After collection of the labeled cells, the magnetic field is discontinued and the labeled sub-cell population recovered.

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

1979-01-01

219

Immunofluorescence detection methods using microspheres  

NASA Astrophysics Data System (ADS)

Microsphere-based immunoassays were devised for compounds of agricultural and biomedical interest (e.g., digoxin, theophylline, and zearalenone). Commercially available microspheres with surface functional groups for chemical derivatization were used as solid carriers. After immobilizing the target substances, the surface of the haptenized microspheres was blocked by a protein to reduce aspecific binding. Competitive immunoassays were performed using the functionalized microspheres and antibodies labeled with horseradish peroxidase. Immunofluorescence signal amplification was achieved by enzyme-catalyzed reporter deposition (CARD). An epifluorescence microscope, a CCD camera interfaced with a computer, and microscopy image analysis software were employed for quantitative detection of fluorescent light emitted from individual microspheres. Integration of several such immunoassays and application of an optical encoding method enabled multianalyte determination. These immunoassays can also be utilized in an immunosensor array format. This immunoarray format could facilitate miniaturization and automation of multianalyte immunoassays.

Szurdoki, Ferenc; Michael, Karri L.; Agrawal, Divya; Taylor, Laura C.; Schultz, Sandra L.; Walt, David R.

1999-01-01

220

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

PubMed Central

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

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

2014-01-01

221

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

NASA Astrophysics Data System (ADS)

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.

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

2010-12-01

222

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

NASA Astrophysics Data System (ADS)

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.

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

223

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

PubMed Central

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.

2011-01-01

224

PEG-PLGA copolymers: their structure and structure-influenced drug delivery applications.  

PubMed

In the paper, we begin by describing polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA) which was chosen as a typical model copolymer for the construction of nano-sized drug delivery systems and also the types of PEG-PLGA copolymers that were eluted. Following this we examine the structure-influenced drug delivery applications including nanoparticles, micelles and hydrogels. After that, the preparation methods for nano-sized delivery systems are presented. In addition, the drug loading mode of PEG-PLGA micelles is divided into three aspects. Finally, the drug release profiles of PEG-PLGA micelles, both in terms of their in vitro and in vivo characteristics, are represented. PEG-PLGA copolymers are very suitable for the construction of micelles as carriers for insoluble drugs. This article reviews the structure and the different structure-influenced applications of PEG-PLGA copolymers, concentrating on the application of PEG-PLGA micelles. PMID:24675377

Zhang, Keru; Tang, Xing; Zhang, Juan; Lu, Wei; Lin, Xia; Zhang, Yu; Tian, Bin; Yang, Hua; He, Haibing

2014-06-10

225

Soil and Water Lab, DNA Microsphere Procedure Page 1 Protocol for Making DNA Microspheres Large Batch  

E-print Network

Soil and Water Lab, DNA Microsphere Procedure Page 1 Protocol for Making DNA Microspheres ­ Large Batch Last Updated 24 June 2014 Goal: Incorporate DNA into PLA microspheres. DNA serves as identification of specific tracer

Walter, M.Todd

226

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

PubMed Central

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

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

2014-01-01

227

A 12-week subchronic intramuscular toxicity study of risperidone-loaded microspheres in rats.  

PubMed

Long-acting injectable formulations of antipsychotics have been an important treatment option to increase the compliance of the patient with schizophrenia by monitoring drug administration and identifying medication noncompliance and to improve the long-term management of schizophrenia. Risperidone, a serotoninergic 5-HT2 and dopaminergic D2 receptor antagonist, was developed to be a long-acting sustained-release formulation for the treatment of schizophrenia. In this study, 12-week subchronic toxicity study of risperidone-loaded microspheres (RMs) in rats by intramuscular injection with an 8-week recovery phase was carried out to investigate the potential subchronic toxicity of a novel long-acting sustained-release formulation. The results indicated that the dosage of 10-90 mg/kg of RM for 2 weeks did not cause treatment-related mortality. The main drug-related findings were contributed to the dopamine D2 receptor and ?1-adrenoceptor antagonism of risperidone such as elevation of serum and pituitary prolactin levels and ptosis and changes in reproductive system (uterus, ovary, vagina, mammary gland, testis, seminal vesicle, epididymis, and prostate). In addition, foreign body granuloma in muscle at injection sites caused by poly-lactide-co-glycolide was observed. At the end of the recovery phase, these changes mostly returned to normal. The results indicated that RM had a good safety profile in rats. PMID:24812153

Zhang, J; Ye, L; Wang, W; Du, G; Yu, X; Zhu, X; Dong, Q; Cen, X; Guan, X; Fu, F; Tian, J

2015-02-01

228

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

PubMed Central

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

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

2014-01-01

229

Towards Monodispersed Polymer Microspheres  

NASA Astrophysics Data System (ADS)

Uniform polymer microspheres prepared by Spinning Disk Atomization Our spinning disk atomization (SDA) can, relative to other existing techniques, produce micron-sized particles of very narrow size distribution. Around the edge of the disk, small teeth channel the flow into identical droplets that are flung off over the disk rim. These solidify during flight to form spherical particles. Applications for spheres produced by SDA can be found in areas such as adhesives, powder coatings, food, biomedical use, drug delivery systems, etc. We have atomized polyethyleneglycol into very narrowly dispersed microspheres ranging from 50 to 500 =B5m. The aim of this work is to model the droplet formation occurring at the rim of the spinning disk in order to better understand the experimental results. The viscosity contribution in the fluid breakup is qualitatively analyzed and is adapted to the theoretical model to show how it affects the droplet size. We have used the pendant drop model (Ramesh Babu, S. Journal of Colloid and Interface Science 116, 350-372 (1987).) for spinning disk atomization to describe the drop-shape evolution during growth.

Senuma, Yoshinori; Hilborn, Jons

1998-03-01

230

Development of Sulfadiazine-Decorated PLGA Nanoparticles Loaded with 5-Fluorouracil and Cell Viability.  

PubMed

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

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

231

The control of skin-permeating rate of bisoprolol by ion-pair strategy for long-acting transdermal patches.  

PubMed

A moderate drug permeating rate (flux) is desirable for long-acting transdermal patches. In this work, a novel simple method of controlling bisoprolol (BSP) flux by ion-pair strategy was initiated. Different ion-pair complexes including bisoprolol maleate (BSP-M), bisoprolol tartarate, bisoprolol besilate, and bisoprolol fumarate were prepared and their fluxes through rabbit abdominal skin were determined separately in vitro. Furthermore, permeation behavior from isopropyl myristate, solubility index in pressure-sensitive adhesives, determined by DSC, and n-octanol/water partition coefficient (log P) were investigated to illustrate the mechanism of drug permeation rate controlling. The results showed that compared to free BSP (J = 25.98 ± 2.34 ?g/cm(2)/h), all BSP ion-pair complexes displayed lower and controllable flux in the range of 0.11 to 4.19 ?g/cm(2)/h. After forming ion-pair complexes, the capability of BSP to penetrate through skin was weakened due to the lowered log P and increased molecule weight. Accordingly, this study has demonstrated that the flux of BSP could be controlled by ion-pair strategy, and among all complexes investigated, BSP-M was the most promising candidate for long-acting transdermal patches. PMID:22639239

Song, Wenting; Cun, Dongmei; Xi, Honglei; Fang, Liang

2012-09-01

232

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

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

Park, Jong-Sang

233

CCMR: Characterization of Microsphere Lasers  

NSDL National Science Digital Library

Silica microspheres use total internal reflection to stimulate emission and so there is very little loss and an ultrahigh Q. Because of their size (5-10 ?m in radius, their mode volume is incredibly small, and can thus achieve great optical circulating powers. This combination of high Q and small mode volume is condcive to creating microlasers with ultralow threshold power. Unfortunately, these same characteristics make coupling light incredibly difficult. The modes are quite thin, and with a standard laser’s optical frequency at 1015 and a 109 precision, stabilizing the laser’s frequency to be within the microsphere’s mode is tricky. Furthermore, the microspheres are susceptible to noise and thermal fluctuations Our goal is to build an electronic circuit to stabilize the pump laser’s frequency within such a small range.

Tsai, Tracy

2005-08-17

234

Glass microsphere lubrication  

NASA Technical Reports Server (NTRS)

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.

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

1991-01-01

235

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

PubMed Central

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

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

2013-01-01

236

Electrospun PLGA\\/collagen nanofibrous membrane as early-stage wound dressing  

Microsoft Academic Search

Electrospinning of polylactide–polyglycolide (PLGA)\\/collagen in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) to fabricate a biomimetic nanofibrous extracellular membranes for wound dressing and tissue engineering was investigated. The morphology of as-spun PLGA\\/collagen nanofibers was examined by scanning electron microscopy. The average diameter of electrospun nanofibers was 250nm (range of 150–650nm). Degradation rate of PLGA\\/collagen nanofibrous membranes, cytocompatibility and cellular responses to membranes, cell and nanofibers

Shih-Jung Liu; Yi-Chuan Kau; Chi-Yin Chou; Jan-Kan Chen; Ren-Chin Wu; Wen-Ling Yeh

2010-01-01

237

Nobilamides A-H, long-acting transient receptor potential vanilloid-1 (TRPV1) antagonists from mollusk-associated bacteria.  

PubMed

New compounds nobilamides A-H and related known compounds A-3302-A and A-3302-B were isolated based upon their suppression of capsaicin-induced calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, nobilamide B and A-3302-A, were shown to be long-acting antagonists of mouse and human TRPV1 channels, abolishing activity for >1 h after removal of drug presumably via a covalent attachment. Other derivatives also inhibited the TRPV1 channel, albeit with low potency, affording a structure-activity profile to support the proposed mechanism of action. While the activities were modest, we propose a new mechanism of action and a new site of binding for these inhibitors that may spur development of related analogues for treatment of pain. PMID:21524089

Lin, Zhenjian; Reilly, Christopher A; Antemano, Rowena; Hughen, Ronald W; Marett, Lenny; Concepcion, Gisela P; Haygood, Margo G; Olivera, Baldomero M; Light, Alan; Schmidt, Eric W

2011-06-01

238

Nobilamides A-H, Long-Acting Transient Receptor Potential Vanilloid-1 (TRPV1) Antagonists from Mollusk-Associated Bacteria  

PubMed Central

New compounds nobilamides A-H and related known compounds A-3302-A and A-3302-B were isolated based upon their suppression of capsaicin-induced calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, nobilamide B and A-3302-A, were shown to be long-acting antagonists of mouse and human TRPV1 channels, abolishing activity for >1 h after removal of drug presumably via a covalent attachment. Other derivatives also inhibited the TRPV1 channel, albeit with low potency, affording a structure-activity profile to support the proposed mechanism of action. While the activities were modest, we propose a new mechanism of action and a new site of binding for these inhibitors that may spur development of related analogs for treatment of pain. PMID:21524089

Lin, Zhenjian; Reilly, Christopher A.; Antemano, Rowena; Hughen, Ronald W.; Marett, Lenny; Concepcion, Gisela P.; Haygood, Margo G.; Olivera, Baldomero M.; Light, Alan; Schmidt, Eric W.

2011-01-01

239

Real-world perceptions of inhaled corticosteroid/long-acting ?2-agonist combinations in the treatment of asthma.  

PubMed

Prescribing data for Europe show a shift from inhaled corticosteroids (ICSs) prescribed alone or in free combination with long-acting ?(2)-agonists (LABAs) to fixed-dose single-inhaler combinations of these agents. However, existing guidelines provide little advice on selecting a specific ICS/LABA combination therapy for the treatment of asthma. European survey data indicate that the factors physicians take into account when making prescribing decisions are broadly in line with those considered to be important by experts in a Delphi process: the availability of a range of doses, the efficacy of the combination, the long-term safety and tolerability of the ICS and LABA components, the potency of the ICS and the speed of onset of the LABA. Further research is needed to help inform physician choice of ICS/LABA combinations for patients with asthma. PMID:23273164

Price, David; Bousquet, Jean

2012-12-01

240

Comparative double-blind trial of intra-articular injections of two long-acting forms of betamethasone.  

PubMed

Two injectable betamethasone preparations, betamethasone dipropionate/betamethasone phosphate and betamethasone acetate/betamethasone phosphate were compared in a controlled trial on 22 "matched patient pairs" with rheumatic diseases. The two preparations were injected intra-articularly in knee joints affected by active synovitis. The time until onset of action and the duration of clinically adequate anti-inflammatory effect were recorded. All injections produced clinically significant effects. The interval before recurrence of symptoms varied from 2 days to more than 3 months. The dipropionate form showed statistically significantly longer duration of action. No difference was noted in the time until onset of action. Local side effects were not observed. The double-blind method of clinical evaluation proved useful in comparing duration of action between long-acting corticosteroids. PMID:1101375

Husby, G; Kåss, E; Spongsveen, K L

1975-01-01

241

Formulations for modulation of protein release from large-size PLGA microparticles for tissue engineering.  

PubMed

In this study we present an approach to pre-program lysozyme release from large size (100-300?m) poly(dl-lactic acid-co-glycolic acid) (PLGA) microparticles. This approach involved blending in-house synthesized triblock copolymers with a PLGA 85:15. In this work it is demonstrated that the lysozyme release rate and the total release are related to the mass of triblock copolymer present in polymer formulation. Two triblock copolymers (PLGA-PEG1500-PLGA and PLGA-PEG1000-PLGA) were synthesized and used in this study. In a like-for-like comparison, these two triblock copolymers appeared to have similar effects on the release of lysozyme. It was shown that blending resulted in the increase of the total lysozyme release and shortened the release period (70% release within 30days). These results demonstrated that blending PLGA-PEG-PLGA triblock copolymer with PLGA 85:15 can be used as a method to pre-program protein release from microparticles. These microparticles with modulated protein release properties may be used to create microparticle-based tissue engineering constructs with pre-programmed release properties. PMID:25492193

Qodratnama, Roozbeh; Serino, Lorenzo Pio; Cox, Helen C; Qutachi, Omar; White, Lisa J

2015-02-01

242

In vitro evaluation of 5-aminolevulinic acid (ALA) loaded PLGA nanoparticles  

PubMed Central

Background 5-Aminolevulinic acid (ALA) is a prodrug for topical photodynamic therapy. The effectiveness of topical ALA can be limited by its bioavailability. The aim of this study was to develop a novel ALA delivery approach using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Methods A modified double emulsion solvent evaporation method was used to prepare ALA loaded PLGA NPs (ALA PLGA NPs). The characteristics, uptake, protoporphyrin IX fluorescence kinetics, and cytotoxicity of ALA PLGA NPs toward a human skin squamous cell carcinoma cell line were examined. Results The mean particle size of spherical ALA PLGA NPs was 65.6 nm ± 26 nm with a polydispersity index of 0.62. The encapsulation efficiency was 65.8% ± 7.2% and ALA loading capacity was 0.62% ± 0.27%. When ALA was dispersed in PLGA NPs, it turned into an amorphous phase. ALA PLGA NPs could be taken up by squamous cell carcinoma cells and localized in the cytoplasm. The protoporphyrin IX fluorescence kinetics and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay showed that ALA PLGA NPs were more effective than free ALA of the same concentration. Conclusion PLGA NPs provide a promising ALA delivery strategy for topical ALA-photodynamic therapy of skin squamous cell carcinoma. PMID:23926429

Shi, Lei; Wang, Xiuli; Zhao, Feng; Luan, Hansen; Tu, Qingfeng; Huang, Zheng; Wang, Hao; Wang, Hongwei

2013-01-01

243

Characterization of nickel-decorated PLGA particles anchored with a his-tagged polycation.  

PubMed

The pharmacological impact of oligodeoxynucleotides (ODN) as transcription factors decoys (anti-sense) depends on the efficiency of cellular uptake. In this study, we sought to generate nickel-decorated particles to facilitate the entry of ODN into dendritic cells (DCs), the primary instigators of immune responses. Nickel ions were incorporated into the matrix of poly(D,L-lactide-co-glycolide) (PLGA) particles using the metal chelating lipid DOGS-NTA-Ni. Submicrometer-sized PLGA particles containing nickel ions (PLGA-Ni) were formed using a double-emulsion solvent evaporation method. Infrared spectroscopy provided chemical proofs of nickel incorporation into the PLGA matrix. Binding of the polycation O10H6 raised the surface potential of PLGA-Ni from -17 mV to +13 mV. This change was partially reserved by the presence of free imidazole, suggesting the binding was mediated by nickel-histidine coordination. When compared to PLGA particles without nickel, ODN bound to O10H6-coated PLGA-Ni particles exhibited enhanced capacity to accumulate in DCs cultured in vitro. DCs exhibited cellular stress after exposure to PLGA-Ni complexed with O10H6 and DNA, but this effect can be prevented by serum and was reversed overnight. These data suggest PLGA-Ni should be further explored as a nucleic acid carrier in the context of anti-sense gene down-regulation. PMID:19520014

Kovacs, Jeffrey R; Tidball, Jenny; Ross, Anthony; Jia, Liang; Zheng, Ying; Gawalt, Ellen S; Meng, Wilson S

2009-01-01

244

The reassertion profiles of long acting ?2-adrenoceptor agonists in the guinea pig isolated trachea and human recombinant ?2-adrenoceptor.  

PubMed

Long acting ?(2)-adrenoceptor agonists as exemplified by salmeterol and formoterol, exhibit reassertion behaviour in isolated airway preparations. This phenomenon is the inhibition of relaxation by a ?(2)-antagonist (e.g. sotalol), followed by the re-establishment of the relaxation when all drugs have been washed out and in the absence of any further agonist addition to the bathing solution. In this study we have compared the reassertion behaviour of salmeterol and formoterol with the new long acting ?(2)-adrenoceptor agonists indacaterol, carmoterol and three Pfizer agonists (PF610,355, PF613,322, UK503590) in the guinea pig isolated trachea and in a novel assay developed in CHO cells expressing the recombinant human ?(2)-adrenoceptor. The results obtained can be divided into two groups: salmeterol-like (persistent duration of action following agonist removal--coupled with reassertion behaviour), as exemplified by indacaterol, PF610,355, PF613,322 and UK503,590 and, formoterol-like (short duration of agonist action and little reassertion behaviour unless supramaximal concentrations are used), as exemplified by carmoterol. Results are discussed in the context of the two theories proposed to explain the long duration of action of salmeterol (binding to a specific 'exosite' of the ?(2)-adrenoceptor) and formoterol (membrane deposition: micro-kinetic theory). Our data suggest that the micro-kinetic theory is an adequate explanation to explain the long duration of action of the ?(2)-adrenoceptor agonists studied in these two assays, although with the current data set we cannot definitively exclude the 'exosite' theory. PMID:21134482

Patel, S; Summerhill, S; Stanley, M; Perros-Huguet, C; Trevethick, M A

2011-04-01

245

Fabrication of glass microspheres with conducting surfaces  

DOEpatents

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.

Elsholz, William E. (Acampo, CA)

1984-01-01

246

Fabrication of glass microspheres with conducting surfaces  

DOEpatents

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.

Elsholz, W.E.

1982-09-30

247

Optimization of maghemite-loaded PLGA nanospheres for biomedical applications.  

PubMed

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

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

248

Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition  

Microsoft Academic Search

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,

Giovanni Vozzi; Christopher Flaim; Arti Ahluwalia; Sangeeta Bhatia

2003-01-01

249

RESEARCH/RESEARCHERS Microspheres Function as  

E-print Network

RESEARCH/RESEARCHERS Microspheres Function as Microlenses for Projection Photolithography Arrays transparent polystyrene microspheres as microlenses. George M. Whitesides and Ming-Hsien Wu, both of Harvard starting from a pattern on a transparency with millimeter-size features. Polystyrene microspheres (with

250

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

PubMed Central

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

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

2013-01-01

251

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

PubMed

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

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

2015-01-01

252

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

PubMed Central

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.

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

2015-01-01

253

?-Irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: I. Effect of Irradiation Doses  

Microsoft Academic Search

To evaluate the effects of different gamma irradiation doses on PEGd,lPLA and PEG-PLGA multiblock copolymers. The behaviour\\u000a of the multiblock copolymers to irradiation was compared to that of PLA, PLGA polymers. PEGd,lPLA, PEG-PLGA, PLA and PLGA\\u000a polymers were irradiated by using a 60Co irradiation source at 5, 15, 25 and 50 kGy total dose. Characterization was performed on all samples before

R. Dorati; C. Colonna; M. Serra; I. Genta; T. Modena; F. Pavanetto; P. Perugini; B. Conti

2008-01-01

254

Modeling the Formation of Polyimide Microspheres  

NASA Technical Reports Server (NTRS)

High temperature polyimide microspheres have been developed from polyimide solid residuum by a simple inflation process. Microspheres have been fabricated from several polyimide precursors through the use of a circulating air oven. Microsphere formation and final physical property characterization have been limited to simple mechanical and thermal testing. The present paper focuses on developing an understanding of microsphere formation through simple geometric rules for an incompressible polymeric material and microscopic observations of precursor residuum inflation. Inflation kinematics of the hollow polyimide microspheres as a function of time and temperature is discussed.

Pipes, R. B.; Weiser, E. S.; Gonsoulin, B.; Hubert, P.

2002-01-01

255

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

PubMed Central

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

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

2013-01-01

256

Preparation and Characterization of Novel PBAE/PLGA Polymer Blend Microparticles for DNA Vaccine Delivery  

PubMed Central

Context. Poly(beta-amino ester) (PBAE) with its pH sensitiveness and Poly(lactic-co-glycolic acid) (PLGA) with huge DNA cargo capacity in combination prove to be highly efficient as DNA delivery system. Objective. To study the effectiveness of novel synthesized PBAE polymer with PLGA blend at different ratios in DNA vaccine delivery. Methods. In the present study, multifunctional polymer blend microparticles using a combination of PLGA and novel PBAE polymers A1 (bis(3-(propionyloxy)propyl)3,3?-(propane-1,3-diyl-bis(methylazanediyl))dipropanoate) and A2 (bis(4-(propionyloxy)butyl)3,3?-(ethane-1,2-diyl-bis(isopropylazanediyl))dipropanoate) at different ratios (85?:?15, 75?:?25, and 50?:?50) were prepared by double emulsion solvent removal method. The microparticles were characterized for cytotoxicity, transfection efficiency, and DNA encapsulation efficiency. Result. It was evident from results that among the microparticles prepared with PLGA/PBAE blend the PLGA?:?PBAE at 85?:?15 ratio was found to be more effective combination than the microparticles prepared with PLGA alone in terms of transfection efficiency and better DNA integrity. Microparticles made of PLGA and PBAE A1 at 85?:?15 ratio, respectively, were found to be less toxic when compared with microparticles prepared with A2 polymer. Conclusion. The results encourage the use of the synthesized PBAE polymer in combination with PLGA as an effective gene delivery system. PMID:25401137

Balashanmugam, Meenashi Vanathi; Nagarethinam, Sivagurunathan; Jagani, Hitesh; Josyula, Venkata Rao; Alrohaimi, Abdulmohsen; Udupa, Nayanabhirama

2014-01-01

257

Pulmonary Delivery of Deslorelin: Large-Porous PLGA Particles and HP?CD Complexes  

Microsoft Academic Search

Purpose. To compare the systemic delivery of deslorelin following intratracheal administration of different deslorelin formulations. The formulations included dry powders of deslorelin, large-porous deslorelin-poly(lactide-co-glycolide) (PLGA) particles, and small conventional deslorelin-PLGA particles. Also, solution formulations of deslorelin and deslorelin-hydroxy-propyl-beta-cyclodextrin (HPßCD) complexes were tested.

Kavitha Koushik; Devender S. Dhanda; Narayan P. S. Cheruvu; Uday B. Kompella

2004-01-01

258

Rivastigmine-loaded PLGA and PBCA nanoparticles: Preparation, optimization, characterization, in vitro and pharmacodynamic studies  

Microsoft Academic Search

Sustained release nanoparticulate formulations of Rivastigmine tartrate (RT) were prepared, optimized (using factorial design) and characterized using the biodegradable polymers, PLGA and PBCA as carriers. The pharmacodynamic performances of the nanoparticles (NPs) were evaluated for brain targeting and memory improvement in scopolamine-induced amnesic mice using Morris Water Maze Test. PLGA NPs were prepared by nanoprecipitation technique, while PBCA NPs were

Shrinidh A. Joshi; Sandip S. Chavhan; Krutika K. Sawant

2010-01-01

259

PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.  

PubMed

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles. PMID:25173841

Chereddy, Kiran Kumar; Her, Charles-Henry; Comune, Michela; Moia, Claudia; Lopes, Alessandra; Porporato, Paolo E; Vanacker, Julie; Lam, Martin C; Steinstraesser, Lars; Sonveaux, Pierre; Zhu, Huijun; Ferreira, Lino S; Vandermeulen, Gaëlle; Préat, Véronique

2014-11-28

260

The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting ?2-adrenoceptor agonist.  

PubMed

The optimisation of two series of 4-hydroxybenzothiazolone derived ?2-adrenoceptor agonists, bearing ?-substituted cyclopentyl and ?-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the ?-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting ?2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project. PMID:25065493

Arnold, Nicola; Beattie, David; Bradley, Michelle; Brearley, Andrew; Brown, Lyndon; Charlton, Steven J; Fairhurst, Robin A; Farr, David; Fozard, John; Fullerton, Joe; Gosling, Martin; Hatto, Julia; Janus, Diana; Jones, Darryl; Jordan, Lynne; Lewis, Christine; Maas, Janet; McCarthy, Clive; Mercer, Mark; Oakman, Helen; Press, Neil; Profit, Rachel; Schuerch, Friedrich; Sykes, David; Taylor, Roger J; Trifilieff, Alexandre; Tuffnell, Andrew

2014-09-01

261

In vitro biocompatibility of polypyrrole/PLGA conductive nanofiber scaffold with cultured rat hepatocytes  

NASA Astrophysics Data System (ADS)

To intruduce conductive biomaterial into liver tissue engineering, a conductive nanofiber scaffold, polypyrrole/poly(lactic-co-glycolic)acid(PLGA), was designed and prepared via electro-spinning and oxidative polymerization. Effects of the scaffold on hepatocyte adhesion, viability and function were then investigated. SEM revealed pseudopodium formation and abundant extracellular matrix on the surface of PLGA membrane and polypyrrole/PLGA membrane. The adhesion rate, cellular activity, urea synthesis and albumin secretion of the hepatocytes cultured on polypyrrole/PLGA group were similar to those on the PLGA group, but were significantly higher than those on the control group. There were no significant differences in concentrations of LDH and TNF-? among three groups. These results suggested the potential application of this conductive nanofiber scaffold as a suitable substratum for hepatocyte culturing in liver tissue engineering.

Chu, Xue-Hui; Xu, Qian; Feng, Zhang-Qi; Xiao, Jiang-Qiang; Li, Qiang; Sun, Xi-Tai; Cao, Yang; Ding, Yi-Tao

2014-09-01

262

Insulin Degludec, a Long-Acting Once-Daily Basal Analogue for Type 1 and Type 2 Diabetes Mellitus.  

PubMed

Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes. PMID:25065475

Berard, Lori; MacNeill, Gail

2014-07-21

263

Characteristics of signalling properties mediated by long-acting insulin analogue glargine and detemir in target cells of insulin.  

PubMed

Glargine and detemir are long-acting human insulin analogues with a smooth peakless profile of action. Although their binding affinities to the insulin receptor have been studied, little is known about the subsequent signalling properties activated after the binding. We directly compared intracellular signalling properties of them in various cultured cells. Regarding the metabolic signalling, glargine and insulin-induced comparable dose-dependent phosphorylation of insulin receptor, IRS-1, Akt, and GSK3, whereas detemir-induced kinetics were markedly lower in 3T3-L1 adipocytes and L6 myocytes. A similar pattern of phosphorylation induction was observed in primary hepatocytes and vascular smooth muscle cells (VSMCs). Because of the binding of detemir to albumin with high affinity, the phosphorylation kinetics and glucose uptake of detemir, but not glargine, decreased with increasing concentrations of BSA. Concerning the mitogenic properties, glargine and insulin-induced comparable dose-dependent phosphorylation of MAP kinase (MAPK) and 5-bromo-2'-deoxyuridine (BrdU) incorporation. Detemir-induced phosphorylation of MAPK was apparently reduced, whereas it stimulated BrdU incorporation with relatively similar dose-dependent manner in VSMCs. These results indicate that glargine has comparable properties to human insulin in metabolic and mitogenic signalling and action. In contrast, detemir-induced metabolic signaling is less potent in all cell types studied, and is reduced further by increasing concentrations of albumin. PMID:18585815

Wada, Tsutomu; Azegami, Mari; Sugiyama, Maine; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

2008-09-01

264

Within-drug benefit-risk evaluation of olanzapine long-acting injection at one and two years of treatment  

PubMed Central

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

Detke, Holland C; Lauriello, John; Landry, John; McDonnell, David P

2014-01-01

265

Biology of a novel class of potent long-acting angiotensin converting enzyme inhibitors: the acyl lysinamido phosphonates.  

PubMed

The acyl lysinamido phosphonates represent a novel class of angiotensin I converting enzyme (ACE) inhibitors. Representatives of this class produce 50% inhibition of purified rabbit lung ACE at concentrations less than 8 nmol/l. After intravenous and oral administration to normotensive rats the phosphonates inhibited an angiotensin I pressor response by 50% at doses less than or equal to enalapril (oral studies) or its free acid, MK-422 (intravenous studies); however, the duration of effect was much longer after the phosphonates. In conscious cynomolgus monkeys, representatives of the phosphonate class showed greater inhibition of an angiotensin I pressor response and for a much longer period of time than enalapril, fosinopril and lisinopril. Similarly, in sodium-depleted monkeys the blood pressure lowering effects of enalapril, lisinopril and fosinopril were of short duration compared with those of the phosphonates. It is concluded that the acyl lysinamido phosphonates represent a potent and long-acting class of ACE inhibitors in vitro and in vivo. PMID:3241238

DeForrest, J M; Waldron, T L; Scalese, R J; Harvey, C M

1988-12-01

266

11 fertility response in suckled beef cows supplemented with long-acting progesterone after timed artificial insemination.  

PubMed

Corpus luteum (CL) and progesterone (P4) secretion are affected by preovulatory follicle (POF) size. Increased circulating P4 during early diestrus has a positive effect on embryo development in beef cattle. However, the combined effects of the POF size and P4 supplementation during early diestrus on fertility of beef cows are not known. The objective was to evaluate the effects of POF size and supplementation of long-acting P4 after timed-AI on pregnancy rates (P/AI). Suckled Nelore cows (n=596) were evaluated twice by transrectal Doppler ultrasonography (US) 10 days apart to detect the cyclic status. In Study 1, anestrous cows (absence of CL on both exams) received an intravaginal P4 device and an oestradiol benzoate (EB) injection on Day -10 (day of the second US). Devices were removed and sodium cloprostenol [prostaglandin F2? (PGF2?)], oestradiol cypionate, and eCG were given on Day -2. Cows were timed-AI on Day 0 and assigned to receive placebo (control group, n=187) or 150mg of long-acting P4 on Day 4 (P4 group, n=189). In Study 2, cyclic cows (presence of CL) received a PGF2? injection on Day -20 (first US). Cows with a new CL on Day -10 received an intravaginal P4 device and an injection of EB and were split to receive an injection of PGF2? [large follicle (LF); n=109] or not [small follicle (SF); n=111]. Devices were removed and PGF2? was injected on Day -2. Ovulation was induced with buserelin acetate, and cows were timed-AI on Day 0 and split to receive placebo (LF/control group, n=55, and SF/control group, n=55) or 150mg of long-acting P4 on Day 4 (LF/P4 group, n=56, and SF/P4 group, n=54). Ultrasonographic scanning was done on Days 0, 4, and between 35 and 40 to detect the POF and CL sizes and P/AI, respectively. Data were analysed using PROC GLIMMIX (SAS Institute Inc., Cary, NC). In anestrous cows, P/AI was reduced in POF with <11mm. The P/AI was greater in the P4-treated group than in the control group for all cows (55.6% v. 46.0%; P=0.05) and for ovulated cows (59%, 105/178 v. 49%, 86/173; P=0.08). For cyclic cows, POF size (mm) on Day 0 (13.5±0.3 v. 11.2±0.2), ovulation rate (90% v. 77%), and CL area (cm(2)) on Day 4 (1.46±0.05 v. 1.25±0.05) were greater (P<0.007) in the LF group than in the SF group. There was a main effect of follicle group on P/AI (54%, LF group v. 38%, SF group; P<0.01). Moreover, P/AI were greater (P<0.05) in the LF/control (56%) and LF/P4 (52%) groups than in the SF/control group (31%), whereas no difference was detected between the SF/P4 group (45%) and the other groups. Among cows that ovulated, P/AI was lower (P=0.05) in the SF/control group (41%, 17/41) compared with the LF/control group (62%, 31/50) and were similar for the SF/P4 group (56%, 25/45) and LF/P4 group (57%, 28/49) compared with others. We suggest that P4-stimulated embryotrophic effects improved fertility in anestrous beef cows supplemented with long-acting P4 on Day 4 after timed-AI. Also, the presence of a functional CL during follicle growth results in smaller POF and CL and reduces the ovulatory and P/AI rates in cyclic cows. Post-AI P4 supplementation may attenuate the negative effects of small POF/CL. PMID:25472060

Pugliesi, G; Santos, F B; Lopes, E; Nogueira, E; Maio, J R G; Binelli, M

2014-12-01

267

Radioimmunoassay for octapeptide analogs of somatostatin: Measurement of serum levels after administration of long-acting microcapsule formulations  

SciTech Connect

The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH{sub 2} (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 conjugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra- and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy.

Mason-Garcia, M.; Vaccarella, M.; Horvath, J.; Redding, T.W.; Groot, K.; Orsolini, P.; Schally, A.V. (Endocrine, Polypeptide and Cancer Institute, New Orleans, LA (USA))

1988-08-01

268

Counseling and provision of long-acting reversible contraception in the US: National survey of nurse practitioners  

PubMed Central

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

Harper, Cynthia C.; Stratton, Laura; Raine, Tina R.; Thompson, Kirsten; Henderson, Jillian T.; Blum, Maya; Postlethwaite, Debbie; Speidel, J Joseph

2013-01-01

269

Study of long-acting reversible contraceptive use in a UK primary care database: validation of methodology.  

PubMed

OBJECTIVES To develop and validate algorithms to identify new users of long-acting reversible contraceptives (LARCs) in a primary care database, The Health Improvement Network (THIN). METHODS Women in THIN aged 12 to 49 years in 2005 were studied. THIN was searched using Read and MULTILEX codes to identify new users of copper intrauterine devices (Cu-IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS) and progestogen-only implants. Validation was undertaken for a randomly selected sample of 398 LARC users, in which their primary care physicians were asked to complete a questionnaire detailing LARC use. RESULTS Questionnaires were received for 379 patients (95%), confirming 316 (83%) as new LARC users. Confirmation rates for Cu-IUDs, the LNG-IUS and progestogen-only implants were 64%, 94% and 89%, respectively. The use of Read codes alone had the lowest confirmation rate, particularly for Cu-IUD users. Confirmation rates increased by using MULTILEX codes when available, or by examination of computerised medical records. CONCLUSIONS Computer algorithms were used to identify new LARC users. While THIN is a useful resource for studying LARC uptake, steps to gather additional information are necessary to ensure the validity of LARC classification. PMID:24229345

Cea Soriano, Lucía; Wallander, Mari-Ann; Andersson, Susan W; Requena, Gema; García-Rodríguez, Luis A

2014-02-01

270

Introduction of postabortion contraception, prioritizing long-acting reversible contraceptives, in the principal maternity hospital of Gabon.  

PubMed

A prospective, descriptive, analytic study was conducted at the Centre Hospitalier de Libreville in Gabon between February and September 2013 to evaluate acceptance of long-acting reversible contraceptives (LARC) and depot-medroxyprogesterone acetate (DMPA) following abortion. Women received counseling on the combined oral pill, DMPA, copper intrauterine devices (IUDs), and implants. The association between sociodemographic and clinical characteristics, knowledge of contraceptives, and acceptance was analyzed. Of the 383 women admitted with abortion complications, 206 (53.7%) knew of no systemic contraceptives. The best-known method was the oral pill (42.0%). Only 14 women (3.6%) knew of a LARC method (IUD or implants) and only 2 (0.5%) said the injectable was their best-known method. Over 90% accepted a modern contraceptive method after abortion. Two-thirds (66.8%) chose the pill, 14.6% DMPA, and 9.3% a LARC method. Only 9.1% of the women refused to initiate use of any method. PMID:24745694

Mayi-Tsonga, Sosthène; Obiang, Pamphile Assoumou; Minkobame, Ulysse; Ngouafo, Doris; Ambounda, Nathalie; de Souza, Maria Helena

2014-07-01

271

Poly(alkyl cyanoacrylate) nanocapsules as a delivery system in the rat for octreotide, a long-acting somatostatin analogue.  

PubMed

Poly(alkyl cyanoacrylate) nanocapsules have been used as biodegradable polymeric drug carriers for subcutaneous and peroral delivery of octreotide, a long-acting somatostatin analogue; their ability to reduce insulin secretion or prolactin secretion in response to oestrogens has been studied in adult male rats. The nanocapsules, prepared by interfacial emulsion polymerization of isobutyl cyanoacrylate, were 260 nm in diameter and incorporated 60% of octreotide. Administered subcutaneously, the octreotide-loaded (20 micrograms kg-1) nanocapsules suppressed the insulinaemia peak induced by intravenous glucose overload and depressed insulin secretion over 48 h, preventing the secretory rebound; however, glycaemia was unaffected. In parallel, the plasma octreotide concentration increased 2.7 times. Administered perorally to oestrogen-treated rats, octreotide-loaded nanocapsules (200 and 1000 micrograms kg-1) significantly improved the reduction of prolactin secretion (by 72 and 88%, respectively, compared with 32 and 54% with free octreotide) and slightly increased plasma octreotide level. Thus nanocapsules could be of interest as a biodegradable drug carrier for the administration of octreotide. PMID:9364401

Damgé, C; Vonderscher, J; Marbach, P; Pinget, M

1997-10-01

272

A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis.  

PubMed

Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with plasma and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in plasma and rectum. Ex vivo antiviral activity of cervicovaginal lavage (CVL) was also assessed. After a single dose, RPV concentrations peaked at days 6-8 and were present in plasma and genital-tract fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma. At the 1,200 mg dose, CVL showed greater antiviral activity, above baseline, at days 28 and 56. All doses were well tolerated. All doses gave prolonged plasma and genital-tract rilpivirine exposure. PK and viral inhibition of repeated doses will be important in further dose selection. PMID:24862215

Jackson, A G A; Else, L J; Mesquita, P M M; Egan, D; Back, D J; Karolia, Z; Ringner-Nackter, L; Higgs, C J; Herold, B C; Gazzard, B G; Boffito, M

2014-09-01

273

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

PubMed

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

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

2014-01-01

274

PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses.  

PubMed

The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-? ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96(®) Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund's adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of -15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund's adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL responses in vivo. PMID:22619507

Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

2012-01-01

275

Microspheres and nanoparticles from ultrasound  

NASA Astrophysics Data System (ADS)

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.

Suh, Won Hyuk

276

21 CFR 522.1451 - Moxidectin microspheres for injection.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Moxidectin microspheres for injection. 522.1451 Section...ANIMAL DRUGS § 522.1451 Moxidectin microspheres for injection. (a) Specifications...One contains 10 percent moxidectin microspheres, and the other contains a...

2014-04-01

277

Composite Tectocapsules Containing Porous Polymer Microspheres as Release Gates  

E-print Network

Composite Tectocapsules Containing Porous Polymer Microspheres as Release Gates Lisa M. Croll: Porous and amphiphilic polymer microspheres were incorporated into polyurea capsules in order to control) microspheres were simply encapsulated along with the xylene core solvent, the amphiphilic poly

Hitchcock, Adam P.

278

Long-acting beta2-agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid  

Microsoft Academic Search

Background: Asthma is a common respiratory disease among both adults and children and short acting inhaled beta-2 agonists are used widely for 'reliever' bronchodilator therapy. Long acting beta-2 agonists (LABA) were introduced as prospective 'symptom controllers' in addition to inhaled corticosteroid 'preventer' therapy (ICS). In this updated review we have included studies in which patients were either not on ICS

E Haydn Walters; Peter G Gibson; Toby J Lasserson; Julia AE Walters

2007-01-01

279

The combined use of risperidone long-acting injection and clozapine in patients with schizophrenia non-adherent to clozapine: a case series  

Microsoft Academic Search

Poor adherence to clozapine treatment represents an important problem in clinical practice because additional useful treatment options are unavailable. Although switching to risperidone long-acting injection (RLAI) has been recommended for those with compliance problems, this medication has been found to be less suitable for patients who previously received clozapine. Based on the suggested beneficial effects of RLAI, such as higher

Se Hyun Kim; Dong Chung Jung; Yong Min Ahn; Yong Sik Kim

2010-01-01

280

Medicaid reimbursement for immediate post-abortion provision of long-acting reversible contraception reduces both unintended pregnancies and health care expenditures.  

PubMed

Medicaid reimbursement for the full cost of long-acting reversible contraception (LARC) provision immediately post-abortion is likely to reduce both unintended pregnancies and health care expenditures. There is a compelling case for states to ensure full reimbursement for LARC insertion immediately post-abortion through both Medicaid fee-for-service programs and managed care plans. PMID:25108581

Tsao, Tsu-Yu; Yunzal-Butler, Cristina; Sackoff, Judith; Kaplan, Deborah

2014-12-01

281

Therapeutic and persistent efficacy of a long-acting (LA) formulation of ivermectin against Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) and sera concentration through time in treated cattle  

Technology Transfer Automated Retrieval System (TEKTRAN)

Concentration-time profile, therapeutic, and persistent efficacy of a single subcutaneous injection of cattle with a long-acting (LA) formulation of ivermectin at a concentration of 630 µg per kg of body weight was determined against Rhipicephalus (Boophilus) microplus. Ivermectin sera concentratio...

282

Long-acting versus short-acting methylphenidate for paediatric ADHD: a systematic review and meta-analysis of comparative efficacy  

PubMed Central

Objective To synthesise existing knowledge of the efficacy and safety of long-acting versus short-acting methylphenidate for paediatric attention deficit hyperactivity disorder (ADHD). Design Systematic review and meta-analysis. Data sources Electronic literature search of CENTRAL, MEDLINE, PreMEDLINE, CINAHL, EMBASE, PsychINFO, Scopus and Web of Science for articles published in the English language between 1950 and 2012. Reference lists of included studies were checked for additional studies. Study selection Randomised controlled trials of paediatric ADHD patients (<18?years), comparing a long-acting methylphenidate form to a short-acting methylphenidate form. Data extraction Two authors independently selected trials, extracted data and assessed risk of bias. Continuous outcomes were compared using standardised mean differences (SMDs) between treatment groups. Adverse events were compared using risk differences between treatment groups. Heterogeneity was explored by subgroup analysis based on the type of long-acting formulation used. Results Thirteen RCTs were included; data from 882 participants contributed to the analysis. Meta-analysis of three studies which used parent ratings to report on hyperactivity/impulsivity had an SMD of ?0.30 (95% CI ?0.51 to ?0.08) favouring the long-acting forms. In contrast, three studies used teacher ratings to report on hyperactivity and had an SMD of 0.29 (95% CI 0.05 to 0.52) favouring the short-acting methylphenidate. In addition, subgroup analysis of three studies which used parent ratings to report on inattention/overactivity indicate that the osmotic release oral system generation long-acting formulation was favoured with an SMD of ?0.35 (95% CI ?0.52 to ?0.17), while the second generation showed less efficacy than the short-acting formulation with an SMD of 0.42 (95% CI 0.17 to 0.68). The long-acting formulations presented with slightly more total reported adverse events (n=578) as compared with the short-acting formulation (n=566). Conclusions The findings from this systematic review indicate that the long-acting forms have a modest effect on the severity of inattention/overactivity and hyperactivity/impulsivity according to parent reports, whereas the short-acting methylphenidate was preferred according to teacher reports for hyperactivity. PMID:23503579

Punja, Salima; Zorzela, Liliane; Hartling, Lisa; Urichuk, Liana; Vohra, Sunita

2013-01-01

283

Preparation of protein-loaded sustained-release microspheres via 'solid-in-oil-in-hydrophilic oil-in-ethanol (S/O/hO/E)' emulsification.  

PubMed

While formulating proteins into solid particles prior to microsphere preparation is regarded as an effective way to stabilize such macromolecules, the protein particles may still contact the aqueous continuous phase and be re-dissolved. Dissolved proteins may not only leak into the aqueous continuous phase (resulting in reduced loading efficiency), but also contact water-oil (the hydrophobic polymer solution) interfaces, factors known to denature proteins. To avoid dissolution of solidified protein particles, we developed a microencapsulation procedure involving a hydrophilic "oil" (hO) continuous phase to which the hydrophobic solution of the controlled-release polymer was dispersed. The hydrophilic "oil" phase was a glycerol-based liquid mixed with ethylene glycol and polyvinyl alcohol solution to adjust viscosity and surface tension. This non-water hydrophilic continuous phase is immiscible with the hydrophobic polymer solution yet unable to dissolve pre-formulated protein particles. After the embryonic microspheres loaded with the protein particles were formed in this hydrophilic "oil" phase, the formulation was transferred into a cold ethanol bath where the microspheres were immediately hardened due to extracting the organic solution by ethanol. This method was examined by microencapsulating bovine serum albumin (BSA) and beta-galactosidase (beta-gal) into polylactide-co-glycolide (PLGA) microspheres for encapsulation efficiency, release kinetics and bioactivity preservation. As measured using size exclusion chromatography (SEC-HPLC), up to 90% added BSA was encapsulated in microspheres, and the release kinetics of the protein was adjusted by selecting surfactants used in microencapsulation emulsification. The assay of enzymatic activity of beta-galactosidase in hydrolysis of o-nitrophenyl-beta-d-galactopyranoside (ONPG) indicated that over 90% of the protein recovered from the microspheres was active. PMID:20483570

Yuan, Weien; Zhang, Yulong; Wu, Fei; Li, Hui; Cai, Yunpeng; Zhang, Yuankuei; Han, Mingjia; Jin, Tuo

2010-09-01

284

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

PubMed

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

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

2013-07-01

285

Quantitative distribution assessment of HoAcAc microspheres and HoPLLA microspheres after direct injection.  

E-print Network

??This experimental study on interstitial brachytherapy describes the distribution of HoAcAc microspheres and HoPLLA microspheres after direct injection in tissue. The microspheres were injected in… (more)

Steenbeek, I.D.

2014-01-01

286

Pharmacoeconomic evaluation of schizophrenia in Taiwan: model comparison of long-acting risperidone versus olanzapine versus depot haloperidol based on estimated costs.  

PubMed

Antipsychotics are the keystone in schizophrenia treatment. Although the benefits of the new generation of antipsychotics has been demonstrated over the last decade, the issues of patient compliance and higher purchasing price of atypical antipsychotics remain unresolved. Risperidone is the only atypical antipsychotic agent with long-acting formulation. Long-acting risperidone is a water-based injection and it has been associated with a low level of pain. The aim of the present study was to test whether an improvement in compliance with the use of a long-acting risperidone, compared with olanzapine and depot haloperidol, can increase the effectiveness and the cost-effectiveness indexes. An economic comparison model with decision tree, rather than a prospective design with real clinical drug trial, was applied. The unit cost for each medical procedure was obtained from the claimed-database of the Bureau of National Health Insurance in Taiwan. An executive committee simulated the incidence of extrapyramidal side-effects and proposed a therapeutic model for each strategy based on a literature review. The probabilities of treatment response of different agents and those of different mental health states were estimated by the executive committee and 10 senior psychiatrists who were randomly selected. Sensitivity analysis was performed for drug cost-effectiveness and compliance improvement for using long-acting risperidone. The results showed that long-acting risperidone is more cost-effective than either olanzapine or depot haloperidol for treating schizophrenia patients whose conditions are stable and whose illness duration ranges from 1 to 5 years. The comparison model with the Kaplan-Meier decision tree may serve as an alternative to prospectively designed studies for cost-effectiveness of atypical antipsychotics. PMID:16048443

Yang, Yen Kuang; Tarn, Yen-Huei; Tarn, Yeng Hui; Wang, Ting Ying; Liu, Chia-Yih; Laio, Yi-Cheng; Chou, Yuan-Hwa; Lee, Shin-Min; Chen, Chun-Chih

2005-08-01

287

Actively Targeted Low-Dose Camptothecin as a Safe, Long-Acting, Disease-Modifying Nanomedicine for Rheumatoid Arthritis  

PubMed Central

Purpose Camptothecin (CPT), a potent topoisomerase I inhibitor, was originally discovered as an anticancer agent to induce programmed cell death of cancer cells. Recent evidence suggests that, similar to cancer, alterations in apoptosis and over-proliferation of key effector cells in the arthritic joint result in rheumatoid arthritis (RA) pathogenesis. Initial in vitro studies have suggested that camptothecin inhibits synoviocyte proliferation, matrix metalloproteinases expression in chrondrocytes and angiogenesis. This study is one of the first to test, in vivo, RA as a new indication for CPT. Methods To circumvent insolubility, instability and toxicity of CPT, we used biocompatible, biodegradable and targeted sterically stabilized micelles (SSM) as nanocarriers for CPT (CPT-SSM). We also surface-modified CPT-SSM with vasoactive intestinal peptide (VIP) for active targeting. We then determined whether this nanomedicine abrogated collagen-induced arthritis (CIA) in mice. Results Based on our findings, this is the first study to report that CPT was found to be efficacious against CIA at concentrations significantly lower than usual anti-cancer dose. Furthermore, a single subcutaneous injection of CPT-SSM-VIP (0.1 mg/kg) administered to CIA mice mitigated joint inflammation for at least 32 days thereafter without systemic toxicity. CPT alone needed at least 10-fold higher dose to achieve the same effect, albeit with some vacuolization in liver histology. Conclusion We propose that CPT-SSM-VIP is a promising targeted nanomedicine and should be further developed as a safe, long-acting, disease-modifying pharmaceutical product for RA. PMID:21132352

Koo, Otilia May Yue; Rubinstein, Israel

2013-01-01

288

Assessment of effectiveness measures in patients with schizophrenia initiated on risperidone long-acting therapy: the SOURCE study results  

PubMed Central

Background To evaluate effectiveness outcomes in a real-world setting in patients with schizophrenia initiating risperidone long-acting therapy (RLAT). Methods This was a 24-month, multicenter, prospective, longitudinal, observational study in patients with schizophrenia who were initiated on RLAT. Physicians could change treatment during the study as clinically warranted. Data were collected at baseline and subsequently every 3 months up to 24 months. Effectiveness outcomes included changes in illness severity as measured by Clinical Global Impression-Severity (CGI-S) scale; functional scores as measured by Personal and Social Performance (PSP) scale, Global Assessment of Functioning (GAF), and Strauss-Carpenter Levels of Functioning (LOF); and health status (Medical Outcomes Survey Short Form-36 [SF-36]). Life-table methodology was used to estimate the cumulative probability of relapse over time. Adverse events were evaluated for safety. Results 532 patients were enrolled in the study; 209 (39.3%) completed the 24-month study and 305 (57.3%) had at least 12 months of follow-up data. The mean (SD) age of patients was 42.3 (12.8) years. Most patients were male (66.4%) and either Caucasian (60.3%) or African American (23.7%). All changes in CGI-S from baseline at each subsequent 3-month follow-up visit were statistically significant (p < .0001), indicating improvement in disease severity. Improvements were also noted for the PSP, GAF, and total LOF, indicating improvement in daily functioning and health outcome. Conclusions Patients with schizophrenia who were initiated on RLAT demonstrated improvements in measures of effectiveness within 3 months, which persisted over 24 months. Trial Registration ClinicalTrials.gov: NCT00246194 PMID:21999346

2011-01-01

289

Darbepoetin alfa, a long-acting erythropoietin analog, offers novel and delayed cardioprotection for the ischemic heart.  

PubMed

Recent studies from our lab and others have shown that the hematopoietic cytokine erythropoietin (EPO) can protect the heart from ischemic damage in a red blood cell-independent manner. Here we examined any protective effects of the long-acting EPO analog darbepoetin alfa (DA) in a rat model of ischemia-reperfusion (I/R) injury. Rats were subjected to 30-min ischemia followed by 72-h reperfusion. In a dose-response study, DA (2, 7, 11, and 30 mug/kg) or vehicle was administered as a single bolus at the start of ischemia. To determine the time window of potential cardioprotection, a single high dose of DA (30 mug/kg) was given at either the initiation or the end of ischemia or at 1 or 24 h after reperfusion. After 3 days, cardiac function and infarct size were assessed. Acute myocyte apoptosis was quantified by TUNEL staining on myocardial sections and by caspase-3 activity assays. DA significantly reduced infarct size from 32.8 +/- 3.5% (vehicle) to 11.0 +/- 3.3% in a dose-dependent manner, while there was no difference in ischemic area between groups. Treatment with DA as late as 24 h after the beginning of reperfusion still demonstrated a significant reduction in infarct size (17.0 +/- 1.6%). Consistent with infarction data, DA improved in vivo cardiac reserve compared with vehicle. Finally, DA significantly decreased myocyte apoptosis and caspase-3 activity after I/R. These data indicate that DA protects the heart against I/R injury and improves cardiac function, apparently through a reduction of myocyte apoptosis. Of clinical importance pointing toward a relevant therapeutic utility, we report that even if given 24 h after I/R injury, DA can significantly protect the myocardium. PMID:17384131

Gao, Erhe; Boucher, Matthieu; Chuprun, J Kurt; Zhou, Rui-Hai; Eckhart, Andrea D; Koch, Walter J

2007-07-01

290

Characteristics Associated With Discontinuation of Long-Acting Reversible Contraception Within the First 6 Months of Use  

PubMed Central

Objective To measure discontinuation within 6 months among users of the levonorgestrel intrauterine system, copper intrauterine device (IUD), and etonogestrel implant, and identify baseline characteristics associated with early discontinuation. Methods This was an analysis of the Contraceptive CHOICE Project, a cohort study of 9,256 participants provided with no-cost contraception and followed with telephone interviews at 3 and 6 months. We used logistic regression to investigate characteristics associated with early discontinuation of the two IUDs and implant and described reasons for discontinuation. Results A total of 6,167 participants were eligible for this analysis. Follow-up data were available for 5,928 participants; 5,495 (93%) were using their method at 6 months and 433 (7%) had discontinued. Discontinuation rates were 7.3%, 8.0%, and 6.9% for the levonorgestrel intrauterine system, copper IUD, and implant, respectively. After adjusting for age, race, marital status, low socioeconomic status, and history of sexually transmitted infection, we found that single and divorced,/separated and widowed women were slightly more likely to discontinue compared to married women (ORadj 1.26, 95% CI 1.01, 1.59, and ORadj 1.62, 95% CI 1.11, 2.37, respectively). No other baseline characteristics, including younger age (14-19 years), were associated with early discontinuation. The most common reason given for discontinuation was cramping among IUD users and irregular or frequent bleeding among implant users. Conclusion Rates of discontinuation of long-acting reversible contraception at 6 months is low and not increased in adolescents and young women. IUDs and the implant should be considered as first-line contraceptive options among all women to reduce unintended pregnancy. PMID:24201685

S, Danielle; Casner, Teya; Secura, Gina M.; Peipert, Jeffrey F.; Madden, Tessa

2014-01-01

291

Molecular Characterisation of Long-Acting Insulin Analogues in Comparison with Human Insulin, IGF-1 and Insulin X10  

PubMed Central

Aims/Hypothesis There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. Methods We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. Results Detemir and glargine each displayed a balanced affinity for insulin receptor (IR) isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ?1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs. Conclusions Detailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir. PMID:22590494

Hansen, Bo F.; Glendorf, Tine; Hegelund, Anne C.; Lundby, Anders; Lützen, Anne; Slaaby, Rita; Stidsen, Carsten Enggaard

2012-01-01

292

Increased corticosteroid sensitivity by a long acting ?2 agonist formoterol via ?2 adrenoceptor independent protein phosphatase 2A activation.  

PubMed

Long-acting ?2-adrenoceptor agonists (LABAs) are reported to enhance anti-inflammatory effects of corticosteroids in vitro and in vivo, although the molecular mechanisms have not yet been elucidated. We investigated the role of serine/threonine protein phosphatase 2A (PP2A) on regulation of corticosteroid sensitivity via inhibition of glucocorticoid receptor (GR) phosphorylation as the target of formoterol, an LABA. Corticosteroid sensitivity was determined as IC50 to dexamethasone (Dex) on TNF?-induced IL-8 release in a U937 monocytic cell line (Dex-IC50). Phosphorylation levels of GR-Ser226 and c-Jun N-terminal kinase (JNK) were determined by western-blotting. Phosphatase activity of immunopurified PP2A was measured by fluorescence-based assay. Exposure to IL-2/IL-4 for 48 h decreased Dex sensitivity with a concomitant increase of GR phosphorylation at Ser226 with JNK1 activation. Formoterol restored Dex sensitivity by inhibiting phosphorylation of GR-Ser226 and JNK1. PP2A inhibition by okadaic acid, a phosphatase inhibitor, abrogated formoterol-mediated effects. In addition, formoterol enhanced PP2A activity in intact or IL-2/IL-4 treated U937 cells and human peripheral blood mononuclear cells. In addition, PP2A activation by formoterol was not antagonized by ICI-118551, and formoterol could activate PP2A directly in cell free system. Taken together, formoterol increases corticosteroid sensitivity via activation of PP2A in receptor independent manner, explaining its benefits as add-on therapy for the treatment of corticosteroid-insensitive diseases, such as severe asthma. PMID:22401993

Kobayashi, Yoshiki; Mercado, Nicolas; Miller-Larsson, Anna; Barnes, Peter J; Ito, Kazuhiro

2012-06-01

293

Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.  

PubMed

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

McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

2014-07-01

294

Incidence of tardive dyskinesia: a comparison of long-acting injectable and oral paliperidone clinical trial databases  

PubMed Central

Background To assess the tardive dyskinesia (TD) rate in studies of once-monthly long-acting injectable (LAI) paliperidone palmitate (PP) and once-daily oral paliperidone extended release (Pali ER). Methods Completed schizophrenia and bipolar studies for PP and Pali ER (? 6 month duration with retrievable patient-level data) were included in this post hoc analysis. Schooler–Kane research criteria were applied using Abnormal Involuntary Movement Scale (AIMS) scores to categorise probable (qualifying AIMS scores persisting for ? 3 months) and persistent TD (score persisting ? 6 months). Spontaneously reported TD adverse events (AEs) were also summarised. Impact of exposure duration on dyskinesia (defined as AIMS total score ? 3) was assessed by summarising the monthly dyskinesia rate. Results In the schizophrenia studies, TD rates for PP (four studies, N = 1689) vs. Pali ER (five studies, N = 2054), were: spontaneously reported AE, 0.18% (PP) vs. 0.10% (Pali ER); probable TD, 0.12% (PP) vs. 0.19% (Pali ER) and persistent TD, 0.12% (PP) vs. 0.05% (Pali ER). In the only bipolar study identified [Pali ER (N = 614)], TD rate was zero (spontaneously reported AE reporting, probable and persistent TD assessments). Dyskinesia rate was higher within the first month of treatment with both PP (13.1%) and Pali ER (11.7%) and steadily decreased over time (months 6–7: PP: 5.4%; Pali ER: 6.4%). Mean exposure: PP, 279.6 days; Pali ER, 187.2 days. Conclusions Risk of TD with paliperidone was low (< 0.2%), regardless of the formulation (oral or LAI), in this clinical trial dataset. Longer cumulative exposure does not appear to increase the risk of dyskinesias. PMID:25358867

Gopal, S; Xu, H; Bossie, C; Burón, J A; Fu, D J; Savitz, A; Nuamah, I; Hough, D

2014-01-01

295

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

PubMed Central

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 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50?mg equiv., p=0.02; 100?mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p?0.006) and PANSS negative and positive symptom Marder factor scores (p?0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5–6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia. PMID:20555312

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

2010-01-01

296

In vitro pharmacological characterization of vilanterol, a novel long-acting ?2-adrenoceptor agonist with 24-hour duration of action.  

PubMed

Vilanterol trifenatate (vilanterol) is a novel, long-acting ?(2)-adrenoceptor (?(2)-AR) agonist with 24 h activity. In this study, we describe the preclinical pharmacological profile of vilanterol using radioligand binding and cAMP studies in recombinant assays as well as human and guinea pig tissue systems to characterize ?(2)-AR binding and functional properties. Vilanterol displayed a subnanomolar affinity for the ?(2)-AR that was comparable with that of salmeterol but higher than olodaterol, formoterol, and indacaterol. In cAMP functional activity studies, vilanterol demonstrated similar selectivity as salmeterol for ?(2)- over ?(1)-AR and ?(3)-AR, but a significantly improved selectivity profile than formoterol and indacaterol. Vilanterol also showed a level of intrinsic efficacy that was comparable to indacaterol but significantly greater than that of salmeterol. In cellular cAMP production and tissue-based studies measuring persistence and reassertion, vilanterol had a persistence of action comparable with indacaterol and longer than formoterol. In addition, vilanterol demonstrated reassertion activity in both cell and tissue systems that was comparable with salmeterol and indacaterol but longer than formoterol. In human airways, vilanterol was shown to have a faster onset and longer duration of action than salmeterol, exhibiting a significant level of bronchodilation 22 h after treatment. From these investigations, the data for vilanterol are consistent, showing that it is a novel, potent, and selective ?(2)-AR receptor agonist with a long duration of action. This pharmacological profile combined with clinical data is consistent with once a day dosing of vilanterol in the treatment of both asthma and chronic obstructive pulmonary disease (COPD). PMID:23131596

Slack, Robert J; Barrett, Victoria J; Morrison, Valerie S; Sturton, Richard G; Emmons, Amanda J; Ford, Alison J; Knowles, Richard G

2013-01-01

297

Effect of HIV status on fertility desire and knowledge of long-acting reversible contraception of postpartum Malawian women.  

PubMed

The objectives of this study were to describe the most recent pregnancy intentions and family planning preferences of HIV-infected and HIV-uninfected postpartum Malawian women, and to assess whether HIV status is associated with fertility desire and knowledge of intrauterine contraception (IUC) and the subdermal contraceptive implant. We conducted a cross-sectional analysis of the baseline characteristics of Malawian women enrolled in a prospective cohort study assessing postpartum contraceptive uptake and continuation. Women at a government hospital completed a baseline survey assessing reproductive history, family planning preferences, and knowledge of IUC and the implant. We used Pearson's chi-square tests to compare these parameters between HIV-infected and HIV-uninfected women. Modified Poisson regression was performed to assess the association between HIV status and fertility desire and knowledge about IUC and the implant. Of 634 postpartum women surveyed, HIV-infected women were more likely to report their most recent pregnancy was unintended (49% vs. 37%, p = 0.004). Nearly all women (97%) did not want a child in the next 2 years, but HIV-infected women were more likely to desire no more children (adjusted prevalence ratio [PR]: 1.59; 95% confidence interval [CI]: 1.33, 1.89). HIV-infected women were also less likely to know that IUC (adjusted PR: 0.72; 95% CI: 0.61, 0.84) and the implant (adjusted PR: 0.83; 95% CI: 0.75, 0.92) are safe during breast-feeding. Postpartum women strongly desire family spacing and many HIV-infected postpartum women desire no more children, suggesting an important role for these long-acting methods. Education about the efficacy and safety of IUC and the implant particularly during breast-feeding may facilitate postpartum use. PMID:25367269

O'Shea, Michele S; Rosenberg, Nora E; Hosseinipour, Mina C; Stuart, Gretchen S; Miller, William C; Kaliti, Stephen M; Mwale, Mwawi; Bonongwe, Phylos P; Tang, Jennifer H

2015-04-01

298

Comparison of two long-acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing.  

PubMed Central

1 Eight healthy men received two long-acting formulations of metoprolol 200 mg (SA Astra, SR Geigy), conventional metoprolol 200 mg and atenolol 100 mg once daily for 1 week each in balanced, crossover fashion. There was a washout period of at least a week between each phase. 2 On the last day of each phase, post-exercise heart rate was recorded at intervals and compared to pretreatment values. Plasma metoprolol concentrations were measured. 3 The mean AUC was similar after each of the three formulations of metoprolol (relative bioavailability of SA and SR v conventional was 97%) but with SA and SR metoprolol the time to peak was significantly delayed by about 2 h. 4 In comparison to conventional metoprolol only metoprolol SA was associated with significantly higher plasma metoprolol concentrations at the end of a dosing interval (mean values: conventional, 25 ng/ml, SR 37 ng/ml, SA 51 ng/ml). 5 Mean (+/- s.d.) reduction in exercise tachycardia at the end of a dosing interval was significantly greater with atenolol (14.8 +/- 4.5%) and metoprolol SA (13.7 +/- 10.3%) than with metoprolol SR (10 +/- 8.4%) and conventional metoprolol (8.2 +/- 7.1%). 6 The variability in beta-adrenoceptor blockade at 24 h was much greater with each of the three metoprolol formulations than that with atenolol. This was explained by the variability in metoprolol metabolism. 7 Oxidation phenotype testing with debrisoquine showed there were six extensive metabolisers and two poor metabolisers. The AUC, half-life and response to metoprolol at 24 h were much greater in poor metabolisers. Response to atenolol was not influenced by phenotype. PMID:7138751

Freestone, S; Silas, J H; Lennard, M S; Ramsay, L E

1982-01-01

299

Pharmacokinetics of a long-acting ceftiofur formulation (ceftiofur crystalline free acid) in the ball python (Python regius).  

PubMed

The objective of this study was to determine the pharmacokinetics of a long-acting formulation of ceftiofur crystalline-free acid (CCFA) following intramuscular injection in ball pythons (Python regius). Six adult ball pythons received an injection of CCFA (15 mg/kg) in the epaxial muscles. Blood samples were collected by cardiocentesis immediately prior to and at 0.5, 1, 2, 4, 8, 12, 18, 24, 48, 72, 96, 144, 192, 240, 288, 384, 480, 576, 720, and 864 hr after CCFA administration. Plasma ceftiofur concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was applied to the data. Maximum plasma concentration (Cmax) was 7.096 +/- 1.95 microg/ml and occurred at (Tmax) 2.17 +/- 0.98 hr. The area under the curve (0 to infinity) for ceftiofur was 74.59 +/- 13.05 microg x h/ml and the elimination half-life associated with the terminal slope of the concentration-time curve was 64.31 +/- 14.2 hr. Mean residence time (0 to infinity) was 46.85 +/- 13.53 hr. CCFA at 15 mg/kg was well tolerated in all the pythons. Minimum inhibitory concentration (MIC) data for bacterial isolates from snakes are not well established. For MIC values of < or =0.1 microg/ml, a single dose of CCFA (15 mg/kg) provides adequate plasma concentrations for at least 5 days in the ball python. For MICs > or =0.5 microg/ml, more frequent dosing or a higher dosage may be required. PMID:22950317

Adkesson, Michael J; Fernandez-Varon, Emilio; Cox, Sherry; Martín-Jiménez, Tomás

2011-09-01

300

A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.  

PubMed

Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. 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 (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in 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 six of eight 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 PrEP. PMID:25589630

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

2015-01-14

301

Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein  

PubMed Central

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

McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

2014-01-01

302

Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection  

PubMed Central

Background Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI), and whether observed changes differ from those seen with oral olanzapine. Methods This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264) with daily oral olanzapine (10 mg/day; n=260). Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score) from 64.0–70.8 (P<0.001). Patients on oral olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001). At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05). The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001). Results did not significantly differ between olanzapine-LAI and oral olanzapine. Conclusion In this 2-year, open-label, randomized study of olanzapine-LAI, outpatients with schizophrenia maintained or improved their favorable baseline level of functioning over time. Results did not significantly differ between olanzapine-LAI and oral olanzapine. PMID:25018631

Ascher-Svanum, Haya; Novick, Diego; Haro, Josep Maria; Bertsch, Jordan; McDonnell, David; Detke, Holland

2014-01-01

303

Hydrogels composed of cyclodextrin inclusion complexes with PLGA-PEG-PLGA triblock copolymers as drug delivery systems.  

PubMed

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

Khodaverdi, Elham; Mirzazadeh Tekie, Farnaz Sadat; Hadizadeh, Farzin; Esmaeel, Haydar; Mohajeri, Seyed Ahmad; Sajadi Tabassi, Sayyed A; Zohuri, Gholamhossein

2014-02-01

304

Increased healthy osteoblast to osteosarcoma density ratios on specific PLGA nanopatterns  

PubMed Central

Poly(lactic-co-glycolic acid) ([PLGA] 50:50 wt% PLA:PGA) films with a flat surface and with 27 nm, 190 nm, 300 nm, 400 nm, and 520 nm nanopatterns were fabricated using a cast-mold process. The nanopatterns were transferred from self-assembled polystyrene (PS) beads to PLGA films through polydimethylsiloxane (PDMS) molds. The surface features, root-mean- square (RMS) roughness, and wettability of these PLGA surface features were studied by atomic force microscope (AFM) height scans, AFM z-sensor scans, and water contact angles, respectively. In order to evaluate the influence of the material topography alone (without changes in chemistry) for bone-cancer applications, both human healthy osteoblasts and human cancerous osteosarcoma cells were cultured on these PLGA surface features, and their densities were determined. Most importantly, compared to all other substrates, it was found that the 27 nm PLGA nanopatterns significantly increased the healthy osteoblast-to-osteosarcoma cell-density ratio. For these reasons, and since previous studies have highlighted that similar nanometer PLGA surface features decreased functions of other types of cancerous cells (specifically lung and breast), this study suggests that 27 nm PLGA nanopatterns should be further studied for a wide range of bone-cancer applications, particularly where healthy bone-cell functions need to be promoted over cancerous bone-cell functions. PMID:23326191

Wang, Yongchen; Zhang, Lijuan; Sun, Linlin; Webster, Thomas J

2013-01-01

305

Effects of chemically modified nanostructured PLGA on functioning of lung and breast cancer cells  

PubMed Central

Background The aim of this study was to investigate the effects of poly-lactic-co-glycolic acid (PLGA) nanotopographies with alginate or chitosan protein preadsorption on the functioning of healthy and cancerous lung and breast cells, including adhesion, proliferation, apoptosis, and release of vascular endothelial growth factor (VEGF), which promotes tumor angiogenesis and secretion. Methods We used a well established cast-mold technique to create nanoscale surface features on PLGA. Some of the nanomodified PLGA films were then exposed to alginate and chitosan. Surface roughness and the presence of protein was confirmed by atomic force microscopy. Surface energy was quantified by contact angle measurement. Results Nanostructured PLGA surfaces with 23 nm features decreased synthesis of VEGF in both lung and breast cancer cells compared with conventional PLGA. Preadsorbing alginate further decreased cancer cell function, with nanostructured PLGA preadsorbed with alginate achieving the greatest decrease in synthesis of VEGF in both lung and breast cancer cells. In contrast, compared with nonmodified smooth PLGA, healthy cell functions were either not altered (ie, breast) or were enhanced (ie, lung) by use of nanostructured features and alginate or chitosan protein preadsorption. Conclusion Using this technique, we developed surface nanometric roughness and modification of surface chemistry that could selectively decrease breast and lung cancer cell functioning without the need for chemotherapeutics. This technique requires further study in a wide range of anticancer and regenerative medicine applications. PMID:23696702

Zhang, Lijuan; Webster, Thomas J

2013-01-01

306

Microsphere coated substrate containing reactive aldehyde groups  

NASA Technical Reports Server (NTRS)

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.

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

1984-01-01

307

Filling Porous Microspheres With Magnetic Material  

NASA Technical Reports Server (NTRS)

New process produces magnetic microspheres with controllable sizes, compositions, and properties for use in medical diagnostic tests, biological research, and chemical processes. Paramagnetic microspheres also made with process. Porous plastic microspheres prepared by polymerization of monomer in diluent by cross-linking agent. When diluent removed, it leaves tiny pores throughout polymerized spheres. Size and distribution of pores determined by amount and type of diluent and cross-linking agent.

Chang, Manchium; Colvin, Michael S.

1990-01-01

308

Microencapsulation of a synbiotic into PLGA/alginate multiparticulate gels.  

PubMed

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

Cook, Michael T; Tzortzis, George; Charalampopoulos, Dimitris; Khutoryanskiy, Vitaliy V

2014-05-15

309

Glass microspheres for medical applications  

NASA Astrophysics Data System (ADS)

Radioactive dysprosium lithium borate glass microspheres have been developed as biodegradable radiation delivery vehicles for the radiation synovectomy treatment of rheumatoid arthritis. Once injected into a diseased joint, the microspheres deliver a potent dose of radiation to the diseased tissue, while a non-uniform chemical reaction converts the glass into an amorphous, porous, hydrated dysprosium phosphate reaction product. The non-radioactive, lithium-borate component is dissolved from the glass (up to 94% weight loss), while the radioactive 165Dy reacts with phosphate anions in the body fluids, and becomes "chemically" trapped in a solid, dysprosium phosphate reaction product that has the same size as the un-reacted glass microsphere. Ethylene diamine tetraacetate (EDTA) chelation therapy can be used to dissolve the dysprosium phosphate reaction product after the radiation delivery has subsided. The dysprosium phosphate reaction product, which formed in vivo in the joint of a Sprague-Dawley rat, was dissolved by EDTA chelation therapy in <1 week, without causing any detectable joint damage. The combination of dysprosium lithium borate glass microspheres and EDTA chelation therapy provides an unique "tool" for the medical community, which can deliver a large dose (>100 Gy) of localized beta radiation to a treatment site within the body, followed by complete biodegradability. The non-uniform reaction process is a desirable characteristic for a biodegradable radiation delivery vehicle, but it is also a novel material synthesis technique that can convert a glass to a highly porous materials with widely varying chemical composition by simple, low-temperature, glass/solution reaction. The reaction product formed by nonuniform reaction occupies the same volume as the un-reacted glass, and after drying for 1 h at 300°C, has a specific surface area of ?200 m2/g, a pore size of ?30 nm, and a nominal crushing strength of ?10 MPa. Finally, rhenium glass microspheres, composed of micron-sized, metallic rhenium particles dispersed within a magnesium alumino borate glass matrix were produced by sintering ReO2 powder and glass frit at 1050°C. A 50 mg injection of radioactive rhenium glass microspheres containing 3.7 GBq of 186Re and 8.5 GBq of 188Re could be used to deliver a 100 Gy dose to a cancerous tumor, while limiting the total body dose caused by rhenium dissolution to approximately 1 mGy.

Conzone, Samuel David

310

Osteointegration of PLGA implants with nanostructured or microsized ?-TCP particles in a minipig model.  

PubMed

Bioresorbable suture anchors and interference screws have certain benefits over equivalent titanium-alloy implants. However, there is a need for compositional improvement of currently used bioresorbable implants. We hypothesized that implants made of poly(l-lactide-co-glycolide) (PLGA) compounded with nanostructured particles of beta-tricalcium phosphate (?-TCP) would induce stronger osteointegration than implants made of PLGA compounded with microsized ?-TCP particles. The experimental nanostructured self-reinforced PLGA (85L:15G)/?-TCP composite was made by high-energy ball-milling. Self-reinforced microsized PLGA (95L:5G)/?-TCP composite was prepared by melt-compounding. The composites were characterized by gas chromatography, Ubbelohde viscometry, scanning electron microscopy, laser diffractometry, and standard mechanical tests. Four groups of implants were prepared for the controlled laboratory study employing a minipig animal model. Implants in the first two groups were prepared from nanostructured and microsized PLGA/?-TCP composites respectively. Microroughened titanium-alloy (Ti6Al4V) implants served as positive intra-animal control, and pure PLGA implants as negative control. Cone-shaped implants were inserted in a random order unilaterally in the anterior cortex of the femoral shaft. Eight weeks after surgery, the mechanical strength of osteointegration of the implants was measured by a push-out test. The quality of new bone surrounding the implant was assessed by microcomputed tomography and histology. Implants made of nanostructured PLGA/?-TCP composite did not show improved mechanical osteointegration compared with the implants made of microsized PLGA/?-TCP composite. In the intra-animal comparison, the push-out force of two PLGA/?-TCP composites was 35-60% of that obtained with Ti6Al4V implants. The implant materials did not result in distinct differences in quality of new bone surrounding the implant. PMID:25241283

Kulkova, Julia; Moritz, Niko; Suokas, Esa O; Strandberg, Niko; Leino, Kari A; Laitio, Timo T; Aro, Hannu T

2014-12-01

311

The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability  

PubMed Central

The aim of this research was to increase the oral bioavailability of daidzein by the formulations of poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with daidzein. Amongst the various traditional and novel techniques of preparing daidzein-loaded PLGA nanoparticles, daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were selected. The average drug entrapment efficiency, particle size, and zeta potential of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were 81.9% ± 5%, 309.2 ± 14.0 nm, ?32.14 ± 2.53 mV and 83.2% ± 7.2%, 323.2 ± 4.8 nm, ?18.73 ± 1.68 mV, respectively. The morphological characterization of nanoparticles was observed with scanning electron microscopy by stereological method and the physicochemical state of nanoparticles was valued by differential scanning calorimetry. The in vitro drug-release profile of both nanoparticle formulations fitted the Weibull dynamic equation. Pharmacokinetic studies demonstrated that after oral administration of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 5.57- and 8.85-fold, respectively, compared to daidzein suspension as control. These results describe an effective strategy for oral delivery of daidzein-loaded PLGA nanoparticles and might provide a fresh approach to enhancing the bioavailability of drugs with poor lipophilic and poor hydrophilic properties. PMID:22346351

Ma, Yiran; Zhao, Xinyi; Li, Jian; Shen, Qi

2012-01-01

312

Preparation and Efficacy of Newcastle Disease Virus DNA Vaccine Encapsulated in PLGA Nanoparticles  

PubMed Central

Background Although the Newcastle disease virus (NDV) inactivated vaccines and attenuated live vaccines have been used to prevent and control Newcastle disease (ND) for years, there are some disadvantages. Recently, newly developed DNA vaccines have the potential to overcome these disadvantages. The low delivery efficiency, however, hindered the application of DNA vaccines for ND in practice. Methodology/Principal Findings The eukaryotic expression plasmid pVAX1-F (o) DNA that expressed the F gene of NDV encapsulated in PLGA nanoparticles (pFNDV-PLGA-NPs) were prepared by a double emulsion-solvent evaporation method and optimal preparation conditions of the pFNDV-PLGA-NPs were determined. Under the optimal conditions, the pFNDV-PLGA-NPs were produced in good morphology and had high stability with a mean diameter of 433.5±7.5 nm, with encapsulation efficiency of 91.8±0.3% and a Zeta potential of +2.7 mV. Release assay in vitro showed that the fusion gene plasmid DNA could be sustainably released from the pFNDV-PLGA-NPs up to 93.14% of the total amount. Cell transfection test indicated that the vaccine expressed and maintained its bioactivity. Immunization results showed that better immune responses of SPF chickens immunized with the pFNDV-PLGA-NPs were induced compared to the chickens immunized with the DNA vaccine alone. In addition, the safety of mucosal immunity delivery system of the pFNDV-PLGA-NPs was also tested in an in vitro cytotoxicity assay. Conclusions/Significance The pFNDV-PLGA-NPs could induce stronger cellular, humoral, and mucosal immune responses and reached the sustained release effect. These results laid a foundation for further development of vaccines and drugs in PLGA nanoparticles. PMID:24386106

Luo, Xiaomei; Chen, Gang; Zhang, Yang; Guo, Chen; Dai, Chunxiao; Jin, Zheng; Zhao, Yan; Cui, Hongyu; Wang, Yunfeng

2013-01-01

313

Coupling system to a microsphere cavity  

NASA Technical Reports Server (NTRS)

A system of coupling optical energy in a waveguide mode, into a resonator that operates in a whispering gallery mode. A first part of the operation uses a fiber in its waveguide mode to couple information into a resonator e.g. a microsphere. The fiber is cleaved at an angle .PHI. which causes total internal reflection within the fiber. The energy in the fiber then forms an evanescent field and a microsphere is placed in the area of the evanescent field. If the microsphere resonance is resonant with energy in the fiber, then the information in the fiber is effectively transferred to the microsphere.

Iltchenko, Vladimir (Inventor); Maleki, Lute (Inventor); Yao, Steve (Inventor); Wu, Chi (Inventor)

2002-01-01

314

21 CFR 870.1360 - Trace microsphere.  

Code of Federal Regulations, 2013 CFR

...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1360 Trace microsphere. (a) Identification. A trace...

2013-04-01

315

21 CFR 870.1360 - Trace microsphere.  

Code of Federal Regulations, 2011 CFR

...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1360 Trace microsphere. (a) Identification. A trace...

2011-04-01

316

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

PubMed Central

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

Makadia, Hirenkumar K.; Siegel, Steven J.

2011-01-01

317

Effects of ball-milling on PLGA polymer and its implication on lansoprazole-loaded nanoparticles  

PubMed Central

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

Shabir, Anjumn; Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R.

2011-01-01

318

Compression molding of aerogel microspheres  

DOEpatents

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.

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

1998-03-24

319

Compression molding of aerogel microspheres  

DOEpatents

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.

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

1998-03-24

320

Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies  

PubMed Central

Background The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed. The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection. Methods A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included. Results Of 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study. Conclusions Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation. No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment. For patients achieving suboptimal symptom control, switching long-acting MPH formulations may be beneficial. When switching formulations, it is usually appropriate to titrate the immediate-release component of the formulation; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components. Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response. PMID:24074240

2013-01-01

321

Microspheres in Plasma Display Panels  

NASA Technical Reports Server (NTRS)

Filling small bubbles of molten glass with gases is just as difficult as it sounds, but the technical staff at NASA is not known to shy away from a difficult task. When Microsphere Systems, Inc. (MSI), of Ypsilanti, Michigan, and Imaging Systems Technology, Inc. (IST), of Toledo, Ohio, were trying to push the limits of plasma displays but were having difficulty with the designs, NASA s Glenn Garrett Morgan Commercialization Initiative (GMCI) assembled key personnel at Glenn Research Center and Ohio State University for a brainstorming session to come up with a solution for the companies. They needed a system that could produce hollow, glass micro-sized spheres (microspheres) that could be filled with a variety of gasses. But the extremely high temperature required to force the micro-sized glass bubbles to form at the tip of a metal nozzle resulted in severe discoloration of the microspheres. After countless experiments on various glass-metal combinations, they had turned to the GMCI for help. NASA experts in advanced metals, ceramics, and glass concluded that a new design approach was necessary. The team determined that what was needed was a phosphate glass composition that would remain transparent, and they went to work on a solution. Six weeks later, using the design tips from the NASA team, Tim Henderson, president of MSI, had designed a new system in which all surfaces in contact with the molten glass would be ceramic instead of metal. Meanwhile, IST was able to complete a Phase I Small Business Innovation Research (SBIR) grant supported by the National Science Foundation (NSF) and supply a potential customer with samples of the microspheres for evaluation as filler materials for high-performance insulations.

2006-01-01

322

Nonaggregating Microspheres Containing Aldehyde Groups  

NASA Technical Reports Server (NTRS)

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.

Rembaum, Alan

1989-01-01

323

Making Latex Microspheres in Space  

NASA Technical Reports Server (NTRS)

Equipment yields larger, more uniform particles. Two NASA reports describe first commercial product to be manufactured in space. Product monodisperse latex, suspension of spherical particles of essentially same diameter. Carried aboard Space Shuttle on its orbital missions, monodisperse latex reactor (MLR) produces spheres of much larger size than possible on Earth. Mircospheres 30 micrometers in diameter produced, whereas 5 micrometers is limit for Earthbound reactors. Microspheres as large as 100 micrometers scheduled for production in MLR.

Kornfeld, D. M.; Vanderhoff, J. W.; El-Aasser, M. S.; Micale, F. J.; Sudol, E. D.; Tseng, C. M.; Silwanowicz, A.

1986-01-01

324

Co-delivery of docetaxel and Poloxamer 235 by PLGA-TPGS nanoparticles for breast cancer treatment.  

PubMed

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

Tang, Xiaolong; Liang, Yong; Feng, Xiaojun; Zhang, Rongbo; Jin, Xu; Sun, Leilei

2015-04-01

325

The in vitro pharmacology of GS-5759, a novel bifunctional phosphodiesterase 4 inhibitor and long acting ?2-adrenoceptor agonist.  

PubMed

Inhaled long-acting ?(2)-adrenoceptor agonists (LABA) that act as bronchodilators and the oral anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor roflumilast are both approved therapies for chronic obstructive pulmonary disease (COPD). Here we describe the activity of a novel, inhaled, bifunctional, small molecule (R)-6-[(3-{[4-(5-{[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}pent-1-yn-1-yl)phenyl]carbamoyl}phenyl)sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide (GS-5759), which has specific ?(2) agonist and PDE4 inhibitory activity. GS-5759 demonstrated potent and full agonist activity at ?(2) adrenoceptors (EC(50) = 8 ± 4 nM) and is a potent inhibitor of the PDE4 enzyme (IC(50) = 5 ± 3 nM). In cell assays, GS-5759 inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor ? (TNF?) production in human peripheral mononuclear cells (PBMC) with an IC(50) = 0.3 nM [confidence interval (CI) 0.1-0.6] and in human neutrophils formyl-methionyl-leucyl-phenylalanine (fMLP)-induced super oxide anion production with an IC(50) = 3 nM (CI 0.8-8). The addition of the ?(2) antagonist ICI 118551 shifted the IC(50) in these cell assays to 4 and 38 nM, respectively, demonstrating the contribution of both ?(2) agonist and PDE4 inhibitory activity to GS-5759. GS-5759 was also a potent inhibitor of profibrotic and proinflammatory mediator release from human lung fibroblasts. GS-5759 relaxed guinea pig airway smooth muscle strips precontracted with carbachol in a concentration-dependent manner with an EC(50) = 0.5 µM (CI 0.2-2) and had slow dissociation kinetics with an Off T(1/2) > 720 minutes at an EC(80) concentration of 3 µM. GS-5759 is a novel bifunctional molecule with both potent ?(2) agonist and PDE4 inhibitor activity that could provide inhaled bronchodilator and anti-inflammatory therapy for COPD. PMID:24513870

Tannheimer, Stacey L; Sorensen, Eric A; Cui, Zhi-Hua; Kim, Musong; Patel, Leena; Baker, William R; Phillips, Gary B; Wright, Clifford D; Salmon, Michael

2014-04-01

326

Long-acting bronchodilator use after hospitalization for COPD: an observational study of health insurance claims data  

PubMed Central

Background Treatment of stable chronic obstructive pulmonary disease (COPD) with long-acting bronchodilator (LABD) medications is recommended by the 2014 Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines. The primary objective of this study was to examine LABD prescription fills after a COPD-related hospitalization. Methods This retrospective observational study used claims from Truven Health MarketScan® Commercial and Medicare Supplemental databases. Patients (age ?40, commercial; age ?65, Medicare supplemental) had a first hospitalization with a primary COPD diagnosis between April 1, 2009 and June 30, 2011 (index hospitalization) and were continuously enrolled for 1 year before and 9 months after hospitalization. Patients were categorized according to pre-index and/or post-index pharmacy claims. Results A total of 27,738 patients had an index hospitalization and met inclusion/exclusion criteria. Of those, 19,783 patients had COPD as a primary or secondary diagnosis during the year before index hospitalization and were included in the analysis. Approximately one quarter of the patients (26.32%) did not fill a prescription for an LABD or short-acting bronchodilator both 90 days before and 90 days after hospitalization. During the 90-day pre-index period, 40.57% of patients filled an LABD (with or without a short-acting bronchodilator) prescription. Over half of the patients (56.88%) filled an LABD prescription at some point during the 180-day post-index period, but, of those, a significantly greater proportion of patients filled an LABD prescription in the 1- to 90-day post-index period than in the 91- to 180-day post-index period (51.27% versus 43.66%; P<0.0001). Conclusion A significant proportion of COPD patients in this study did not fill an LABD prescription before hospitalization for COPD. Moreover, hospitalization did not appear to greatly impact LABD initiation. Lastly, patients who did not fill an LABD prescription within the first 90 days posthospitalization were not likely to fill an LABD prescription later. Taken together, the results of this study suggest that many patients with COPD are undertreated. PMID:24833898

Baker, Christine L; Zou, Kelly H; Su, Jun

2014-01-01

327

Long-Acting Injectable vs Oral Antipsychotics for Relapse Prevention in Schizophrenia: A Meta-Analysis of Randomized Trials  

PubMed Central

Background: While long-acting injectable antipsychotics (LAIs) are hoped to reduce high relapse rates in schizophrenia, recent randomized controlled trials (RCTs) challenged the benefits of LAIs over oral antipsychotics (OAPs). Methods: Systematic review/meta-analysis of RCTs that lasted ?6 months comparing LAIs and OAPs. Primary outcome was study-defined relapse at the longest time point; secondary outcomes included relapse at 3, 6, 12, 18, and 24 months, all-cause discontinuation, discontinuation due to adverse events, drug inefficacy (ie, relapse + discontinuation due to inefficacy), hospitalization, and nonadherence. Results: Across 21 RCTs (n = 5176), LAIs were similar to OAPs for relapse prevention at the longest time point (studies = 21, n = 4950, relative risk [RR] = 0.93, 95% confidence interval [CI]: 0.80–1.08, P = .35). The finding was confirmed restricting the analysis to outpatient studies lasting ?1 year (studies = 12, RR = 0.93, 95% CI:0.71–1.07, P = .31). However, studies using first-generation antipsychotic (FGA)-LAIs (studies = 10, RR = 0.82, 95% CI:0.69–0.97, P = .02) and those published ?1991 (consisting exclusively of all 8 fluphenazine-LAI studies; RR = 0.79, 95% CI: 0.65–0.96, P = 0.02) were superior to OAPs regarding the primary outcome. Pooled LAIs also did not separate from OAPs regarding any secondary outcomes. Again, studies using FGA-LAIs and those published ?1991 were associated with LAI superiority over OAPs, eg, hospitalization and drug inefficacy. Conclusions: In RCTs, which are less representative of real-world patients than naturalistic studies, pooled LAIs did not reduce relapse compared with OAPs in schizophrenia patients. The exceptions were FGA-LAIs, mostly consisting of fluphenazine-LAI studies, which were all conducted through 1991. Because this finding is vulnerable to a cohort bias, studies comparing FGA-LAI vs second-generation antipsychotics-LAI and LAI vs OAP RCTs in real-world patients are needed. PMID:23256986

Correll, Christoph U.

2014-01-01

328

Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity.  

PubMed

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

Pawar, Dilip; Mangal, Sharad; Goswami, Roshan; Jaganathan, K S

2013-11-01

329

Association between previous health care use and initiation of inhaled corticosteroid and long-acting ? 2-adrenergic agonist combination therapy among US patients with asthma  

Microsoft Academic Search

Background: Combination inhaled corticosteroid and long-acting ?2-adrenergic agonist (ICS\\/LABA) therapy is recommended for patients whose asthma is not adequately controlled by other maintenance therapies and for those with moderate to severe asthma.Objectives: This study examined the appropriateness of initiation of ICS\\/LABA combination therapy based on health care use criteria and the proportions of US patients filling prescriptions for either of

Christopher M. Blanchette; Steven D. Culler; Daniel Ershoff; Benjamin Gutierrez

2009-01-01

330

Type III collagen is essential for growth acceleration of human osteoblastic cells by ascorbic acid 2-phosphate, a long-acting vitamin C derivative  

Microsoft Academic Search

Collagen has been reported to be essential for the proliferation of various kinds of cells including human osteoblastic cells [Takamizawa, S., Maehata, Y., Imai, K., Senoo, H., Sato, S., Hata, R., 2004. Effects of ascorbic acid and ascorbic acid 2-phosphate, a long-acting vitamin C derivative, on the proliferation and differentiation of human osteoblast-like cells. Cell Biol. Int. 28, 255–265], but

Yojiro Maehata; Shinji Takamizawa; Shigeyuki Ozawa; Kazuhito Izukuri; Yasumasa Kato; Sadao Sato; Masaichi-Chang-il Lee; Akinori Kimura; Ryu-Ichiro Hata

2007-01-01

331

Effects of ascorbic acid and ascorbic acid 2-phosphate, a long-acting vitamin C derivative, on the proliferation and differentiation of human osteoblast-like cells  

Microsoft Academic Search

In order to investigate the effect of ascorbic acid (AsA) and ascorbic acid 2-phosphate (Asc 2-P), a long-acting vitamin C derivative, on the growth and differentiation of human osteoblast-like cells, we supplemented the culture medium of MG-63 cells with various concentrations (0.25 to 1 mM) of these factors. Asc 2-P significantly stimulated nascent cell growth at all concentrations in the

Shinji Takamizawa; Yojiro Maehata; Katsuyuki Imai; Haruki Senoo; Sadao Sato; Ryu-Ichiro Hata

2004-01-01

332

A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain.  

PubMed

Guidelines for opioid treatment of chronic non-malignant pain recommend long-acting over short-acting opioid formulations. The evidence for this recommendation is weak. This study is a randomized, double-blind, double-dummy, 8-week comparison of long-acting dihydrocodeine tablets (DHC-Continus) with short-acting dihydrocodeine tablets in 60 patients with chronic non-malignant pain who were referred to a multidisciplinary pain clinic. All patients used codeine-paracetamol tablets before the trial, and paracetamol was added in both groups during the trial. The primary outcome was stability in pain intensity, measured as the difference between the highest and least pain intensity reported on an 11-point numerical rating scale in a 7-day diary. The secondary outcomes were differences in quality of life, quality of sleep, depression, and episodes of breakthrough pain between the 2 formulations. Spontaneously reported adverse events were recorded. In all, 38 patients completed the trial, and 22 withdrew before the end. The reasons for withdrawal were adverse events, lack of efficacy, or both, and were similar between the groups. There were no significant differences in stability of pain intensity between groups. There were no significant differences between groups in quality of sleep, depression, health-related quality of life, or adverse events. Breakthrough pain was experienced in both groups during the trial. Long-acting dihydrocodeine was not observed to be superior for any of the outcomes in this trial. The results of this study do not support current guidelines recommending long-acting opioids. PMID:24345428

Pedersen, Line; Borchgrevink, Petter Christian; Breivik, Harald Petter; Fredheim, Olav Magnus Søndenå

2014-05-01

333

The reassertion profiles of long acting ? 2-adrenoceptor agonists in the guinea pig isolated trachea and human recombinant ? 2-adrenoceptor  

Microsoft Academic Search

Long acting ?2-adrenoceptor agonists as exemplified by salmeterol and formoterol, exhibit reassertion behaviour in isolated airway preparations. This phenomenon is the inhibition of relaxation by a ?2-antagonist (e.g. sotalol), followed by the re-establishment of the relaxation when all drugs have been washed out and in the absence of any further agonist addition to the bathing solution. In this study we have

S. Patel; S. Summerhill; C. Perros-Huguet; M. A. Trevethick

2011-01-01

334

POROUS WALL, HOLLOW GLASS MICROSPHERES  

SciTech Connect

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.

Sexton, W.

2012-06-30

335

Preparation of magnetite dextran microspheres by ultrasonication  

NASA Astrophysics Data System (ADS)

An improved method of preparing magnetite-dextran microspheres by ultrasonication is proposed. Several parameters were evaluated and the characteristics of the microspheres investigated by scanning electron microscope (SEM), atomic force microscope (AFM), particle size analyzer and magnetometer. The results show that the initial Fe/dextran ratio is the most effective parameter for both the size and the magnetic properties.

Xia, Zefeng; Wang, Guobin; Tao, Kaixiong; Li, Jianxing

2005-05-01

336

Polarization conversion in a silica microsphere  

E-print Network

We experimentally demonstrate controlled polarization-selective phenomena in a whispering gallery mode resonator. We observed efficient (approx. 75%) polarization conversion of light in a silica microsphere coupled to a tapered optical fiber, optimizing the polarization of the light propagating along the fiber. We present a simple model treating the microsphere as a ring resonator to explain the observed behavior.

Bianucci, P; Robertson, J W; Shvets, G; Shih, C K

2007-01-01

337

Microsphere estimates of blood flow: Methodological considerations  

SciTech Connect

The microsphere technique is a standard method for measuring blood flow in experimental animals. Sporadic reports have appeared outlining the limitations of this method. In this study the authors have systematically assessed the effect of blood withdrawals for reference sampling, microsphere numbers, and anesthesia on blood flow estimates using radioactive microspheres in dogs. Experiments were performed on 18 conscious and 12 anesthetized dogs. Four blood flow estimates were performed over 120 min using 1 {times} 10{sup 6} microspheres each time. The effects of excessive numbers of microspheres pentobarbital sodium anesthesia, and replacement of volume loss for reference samples with dextran 70 were assessed. In both conscious and anesthetized dogs a progressive decrease in gastric mucosal blood flow and cardiac output was observed over 120 min. This was also observed in the pancreas in conscious dogs. The major factor responsible for these changes was the volume loss due to the reference sample withdrawals. Replacement of the withdrawn blood with dextran 70 led to stable blood flows to all organs. The injection of excessive numbers of microspheres did not modify hemodynamics to a greater extent than did the injection of 4 million microspheres. Anesthesia exerted no influence on blood flow other than raising coronary flow. The authors conclude that although blood flow to the gastric mucosa and the pancreas is sensitive to the minor hemodynamic changes associated with the microsphere technique, replacement of volume loss for reference samples ensures stable blood flow to all organs over a 120-min period.

von Ritter, C.; Hinder, R.A.; Womack, W.; Bauerfeind, P.; Fimmel, C.J.; Kvietys, P.R.; Granger, D.N.; Blum, A.L. (Univ. of the Witwatersrand, Johannesburg (South Africa) Louisianna State Univ. Medical Center, Shreveport (USA) Universitaire Vaudois (Switzerland))

1988-02-01

338

Effect of n-HA content on the isothermal crystallization, morphology and mechanical property of n-HA/PLGA composites  

SciTech Connect

Graphical abstract: Effect of n-HA content on the isothermal crystallization, morphology and mechanical property of n-HA/PLGA composites was studied in details. The results showed that the addition of higher content of g-n-HA was favorable to promote the crystallization better in g-n-HA/PLGA composites, but it could also cause more agglomeration in PLGA matrix, as a result of worse mechanical properties, and the addition content of 3 wt% g-n-HA to PLGA matrix was an appropriate proportion, which had the highest bending strength among these g-n-HA/PLGA composites, and it might be potential to be used in biomedical fields in future. Highlights: ? The effect of n-HA content on the n-HA/PLGA composites was studied in detail. ? Isothermal crystallization, microstructure and mechanical property were studied. ? The relation between n-HA content and properties of n-HA/PLGA composite was found. ? An appropriate proportion of n-HA in n-HA/PLGA composite was obtained. - Abstract: A serials of g-n-HA/PLGA composites with surface-modified g-n-HA of 1%, 3%, 6%, 10% and 15% in weight were prepared by solution mixing. The isothermal crystallization, morphology and mechanical property of g-n-HA/PLGA composites were investigated by differential scanning calorimeter (DSC), scanning electron microscope (SEM) and electromechanical universal tester. The results showed that Avrami equation was suitable for describing the isothermal crystallization process in this system, and the crystallization rate of g-n-HA/PLGA composites containing more than 3 wt% g-n-HA was basically accord with the relational expression of T{sub 110} {sub °C} > T{sub 105°C} > T{sub 115°C} > T{sub 120°C}. Moreover, at the same Tc, crystallization rate was greatly enhanced with the increasing of g-n-HA acting as nucleate. However, the addition of higher content of g-n-HA would cause more agglomeration in PLGA matrix, so that the mechanical properties of g-n-HA/PLGA composites would gradually decrease. In conclusion, the addition of higher content of g-n-HA was favorable to promote the crystallization better in g-n-HA/PLGA composites, but it could also cause more agglomeration in PLGA matrix, result in worse mechanical properties, and the addition content of 3 wt% g-n-HA to PLGA matrix was an appropriate proportion, which had the highest bending strength among these g-n-HA/PLGA composites, and it might be potential to be used in biomedical fields in future.

Liuyun, Jiang, E-mail: jlytxg@163.com [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Chengdong, Xiong [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Lixin, Jiang [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Graduated School of Chinese Academy of Sciences, Beijing 100039 (China); Dongliang, Chen; Qing, Li [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China)

2013-03-15

339

Once-daily glycopyrronium bromide, a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease: a systematic review of clinical benefit  

PubMed Central

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

Ulrik, Charlotte Suppli

2012-01-01

340

Impact of Pay for Performance on Prescribing of Long-Acting Reversible Contraception in Primary Care: An Interrupted Time Series Study  

PubMed Central

Background The aim of this study was to evaluate the impact of Quality and Outcomes Framework (QOF), a major pay-for-performance programme in the United Kingdom, on prescribing of long-acting reversible contraceptives (LARC) in primary care. Methods Negative binomial interrupted time series analysis using practice level prescribing data from April 2007 to March 2012. The main outcome measure was the prescribing rate of long-acting reversible contraceptives (LARC), including hormonal and non hormonal intrauterine devices and systems (IUDs and IUSs), injectable contraceptives and hormonal implants. Results Prescribing rates of Long-Acting Reversible Contraception (LARC) were stable before the introduction of contraceptive targets to the QOF and increased afterwards by 4% annually (rate ratios ?=?1.04, 95% CI?=?1.03, 1.06). The increase in LARC prescribing was mainly driven by increases in injectables (increased by 6% annually), which was the most commonly prescribed LARC method. Of other types of LARC, the QOF indicator was associated with a step increase of 20% in implant prescribing (RR?=? 1.20, 95% CI?=? 1.09, 1.32). This change is equivalent to an additional 110 thousand women being prescribed with LARC had QOF points not been introduced. Conclusions Pay for performance incentives for contraceptive counselling in primary care with women seeking contraceptive advice has increased uptake of LARC methods. PMID:24694949

Arrowsmith, Myat E.; Majeed, Azeem; Lee, John Tayu; Saxena, Sonia

2014-01-01

341

Surface hydrophilization of electrospun PLGA micro-\\/nano-fibers by blending with Pluronic ® F-108  

Microsoft Academic Search

Poly(lactide-co-glycolide) (PLGA) has been widely explored as scaffolds in tissue engineering. However, its hydrophobicity can adversely affect events such as protein adsorption and downstream cell adhesion in tissue engineering applications. Although surface modification techniques (high energy radiation\\/chemical treatment) to modify the hydrophobicity of PLGA can be useful at the macroscopic scale, their usefulness for micro-\\/nano-meter scale objects can be limited

Rajesh Vasita; Gopinath Mani; C. Mauli Agrawal; Dhirendra S. Katti

2010-01-01

342

Tissue-engineered cartilage by in vivo culturing of chondrocytes in PLGA–collagen hybrid sponge  

Microsoft Academic Search

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

Takashi Sato; Guoping Chen; Takashi Ushida; Tomoo Ishii; Naoyuki Ochiai; Tetsuya Tateishi

2001-01-01

343

Preparation and characterization of PLGA particles for subcutaneous controlled drug release by membrane emulsification.  

PubMed

Uniformly sized microparticles of poly(D,L-lactic-co-glycolic) (PLGA) acid, with controllable median diameters within the size range 40-140 microm, were successfully prepared by membrane emulsification of an oil phase injected into an aqueous phase, followed by solvent removal. Initially, simple particles were produced as an oil in water emulsion, where dichloromethane (DCM) and PLGA were the oil phase and water with stabiliser was the continuous phase. The oil was injected into the aqueous phase through an array type microporous membrane, which has very regular pores equally spaced apart, and two different pore sizes were used: 20 and 40 microm in diameter. Shear was provided at the membrane surface, causing the drops to detach, by a simple paddle stirrer rotating above the membrane. Further tests involved the production of a primary water in oil emulsion, using a mechanical homogeniser, which was then subsequently injected into a water phase through the microporous membrane to form a water in oil in water emulsion. These tests used a water-soluble model drug (blue dextran) and encapsulation efficiencies of up to 100% were obtained for concentrations of 15% PLGA dissolved in the DCM and injected through a 40 microm membrane. Solidification of the PLGA particles was followed by removal of the DCM through the surrounding aqueous continuous phase. Different PLGA concentrations, particle size and osmotic pressures were considered in order to find their effect on encapsulation efficiency. Osmotic pressure was varied by changing the salt concentration in the external aqueous phase whilst maintaining a constant internal aqueous phase salt concentration. Osmotic pressure was found to be a significant factor on the resulting particle structure, for the tests conducted at lower PLGA concentrations (10% and 5% PLGA). The PLGA concentration and particle size distribution influence the time to complete the solidification stage and a slow solidification, formed by stirring gently overnight, provided the most monosized particles and highest encapsulation efficiency. PMID:17919891

Gasparini, G; Kosvintsev, S R; Stillwell, M T; Holdich, R G

2008-02-15

344

Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis.  

PubMed

Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogen Trypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug for T. b. gambiense acute infection. An in vitro effectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore, in vivo therapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases. PMID:25445702

Arias, José L; Unciti-Broceta, Juan D; Maceira, José; Del Castillo, Teresa; Hernández-Quero, José; Magez, Stefan; Soriano, Miguel; García-Salcedo, José A

2015-01-10

345

Morphological Effects of HA on the Cell Compatibility of Electrospun HA/PLGA Composite Nanofiber Scaffolds  

PubMed Central

Tissue engineering is faced with an uphill challenge to design a platform with appropriate topography and suitable surface chemistry, which could encourage desired cellular activities and guide bone tissue regeneration. To develop such scaffolds, composite nanofiber scaffolds of nHA and sHA with PLGA were fabricated using electrospinning technique. nHA was synthesized using precipitation method, whereas sHA was purchased. The nHA and sHA were suspended in PLGA solution separately and electrospun at optimized electrospinning parameters. The composite nanofiber scaffolds were characterized by FE-SEM, EDX analysis, TEM, XRD analysis, FTIR, and X-ray photoelectron. The potential of the HA/PLGA composite nanofiber as bone scaffolds in terms of their bioactivity and biocompatibility was assessed by culturing the osteoblastic cells onto the composite nanofiber scaffolds. The results from in vitro studies revealed that the nHA/PLGA composite nanofiber scaffolds showed higher cellular adhesion, proliferation, and enhanced osteogenesis performance, along with increased Ca+2 ions release compared to the sHA/PLGA composite nanofiber scaffolds and pristine PLGA nanofiber scaffold. The results show that the structural dependent property of HA might affect its potential as bone scaffold and implantable materials in regenerative medicine and clinical tissue engineering. PMID:24719853

Haider, Adnan; Gupta, Kailash Chandra; Kang, Inn-Kyu

2014-01-01

346

Multifunctional Bi2S3/PLGA nanocapsule for combined HIFU/radiation therapy.  

PubMed

A multifunctional organic-inorganic hybrid nanocapsule based on Bi2S3-embedded poly (lactic-co-glycolic acid) (PLGA) nanocapsule has been elaborately designed to combine the merits of both polymeric shell structure and Bi2S3 nanoparticles. Hydrophobic Bi2S3 nanoparticles were successfully introduced into the PLGA nanocapsules via a facile and efficient water/oil/water (W/O/W) emulsion strategy. The elastic polymeric PLGA shell provides the excellent capability of ultrasound contrast imaging to the Bi2S3/PLGA. Meanwhile, the potential of these microcapsules to enhance the high intensity focused ultrasound (HIFU) therapy was demonstrated. Importantly, this research provided the first example of both in vitro and in vivo to demonstrate the radiosensitization effect of Bi2S3-embedded PLGA hybrid nanocapsules against prostate cancer under external X-ray irradiation. Thus, the successful integration of the Bi2S3 and PLGA nanocapsules provided an alternative strategy for the highly efficient ultrasound guided HIFU/RT synergistic therapy. PMID:24973300

Yao, Ming-hua; Ma, Ming; Chen, Yu; Jia, Xiao-qing; Xu, Guang; Xu, Hui-xiong; Chen, Hang-rong; Wu, Rong

2014-09-01

347

Efficient Production of Retroviruses Using PLGA/bPEI-DNA Nanoparticles and Application for Reprogramming Somatic Cells  

PubMed Central

Reprogramming of somatic cells to pluripotent cells requires the introduction of factors driving fate switches. Viral delivery has been the most efficient method for generation of induced pluripotent stem cells. Transfection, which precedes virus production, is a commonly-used process for delivery of nucleic acids into cells. The aim of this study is to evaluate the efficiency of PLGA/ bPEI nanoparticles in transfection and virus production. Using a modified method of producing PLGA nanoparticles, PLGA/bPEI-DNA nanoparticles were examined for transfection efficiency and virus production yield in comparison with PLGA-DNA, bPEI-DNA nanoparticles or liposome-DNA complexes. After testing various ratios of PLGA, bPEI, and DNA, the ratio of 6:3:1 (PLGA:bPEI:DNA, w/w/w) was determined to be optimal, with acceptable cellular toxicity. PLGA/bPEI-DNA (6:3:1) nanoparticles showed superior transfection efficiency, especially in multiple gene transfection, and viral yield when compared with liposome-DNA complexes. The culture supernatants of HEK293FT cells transfected with PLGA/bPEI-DNA of viral constructs containing reprogramming factors (Oct4, Sox2, Klf4, or c-Myc) successfully and more efficiently generated induced pluripotent stem cell colonies from mouse embryonic fibroblasts. These results strongly suggest that PLGA/bPEI-DNA nanoparticles can provide significant advantages in studying the effect of multiple factor delivery such as in reprogramming or direct conversion of cell fate. PMID:24098810

Do, Eun Kyoung; Cheon, Hyo Cheon; Heo, Soon Chul; Kwon, Yang Woo; Jeong, Geun Ok; Kim, Ba Reun; Kim, Jae Ho

2013-01-01

348

PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses  

PubMed Central

The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-? ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96® Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund’s adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of ?15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund’s adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL responses in vivo. PMID:22619507

Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

2012-01-01

349

A novel in vitro release technique for peptide containing biodegradable microspheres.  

PubMed

The purpose of this study was to develop and evaluate a dialysis in vitro release technique for peptide-containing poly(d, l-lactide-co-glycolide) (PLGA) microspheres (ms) that would correlate with in vivo data. Using a luteinizing hormone- releasing hormone analogue (LHRH), Orntide acetate, solubility and stability were determined in 0.1 M phosphate buffer (PB), pH 7.4, and in 0.1 M acetate buffer (AB), pH 4.0, with high-performance liquid chromotography (HPLC), and peptide permeability through a dialysis membrane (molecular weight cut-off 300,000) was determined. Orntide ms were prepared by a dispersion/solvent extraction/evaporation method and characterized for drug content (HPLC), particle size distribution (laser diffraction method), and surface morphology (scanning electron microscopy). In vitro release was studied in PB using a conventional extraction method and with a new dialysis method in AB. Gravimetric analyses of polymer mass loss and matrix hydration, and peptide adsorption to blank PLGA ms (50:50, M(w) 28 022) were carried out in PB and AB upon incubation at 37 degrees C. Serum Orntide and testosterone levels in rats after administration of Orntide ms were determined by radioimmunoassay. Orntide acetate solubility was influenced by pH; approximately 2.3 mg/mL dissolved in PB and > 18 mg/mL in AB. Stability was pH- and temperature-dependent. The peptide was very stable at pH 4.0, 4 degrees C, but degraded rapidly at pH 7.4, 37 degrees C. Peptide permeability through the dialysis membrane was accelerated by agitation and >95% equilibrium was reached within 48 hours. The overall release rate was higher with the dialysis method. Mass loss of the Orntide ms was faster in AB (50% loss in 3 weeks; 95% in 35 days) than in PB (65% in 35 days). In contrast, hydration after 35 days was 4-fold higher in PB. The nonspecific adsorption to blank ms was greater in PB (128 microg Orntide/10 mg PLGA) compared with AB (< 5 microg Orntide/ 10 mg PLGA). Administration of 30-day Orntide PLGA ms to rats resulted in an initial serum Orntide level of 21 ng/mL after 6 hours and a Cmax of 87 ng/mL after 6 days. Testosterone levels were suppressed immediately after ms administration (3 mg Orntide /Kg) from 5.2 ng/mL to 0.3 ng/mL (after 24 hours) and remained suppressed for 38 days. Orntide acetate solubility and degradation kinetics were markedly influenced by pH of the buffer systems and mass loss; matrix hydration, as well as the nonspecific adsorption to blank ms, was pH-dependent. The in vitro release profile obtained with the dialysis method in AB correlated well with the in vivo data, thereby providing a more reliable prediction of in vivo performance. PMID:14727853

Kostanski, J W; DeLuca, P P

2000-01-01

350

Microsphere radioembolization of liver malignancies: current developments.  

PubMed

The worldwide incidence of hepatic malignancies, both primary and secondary, exceeds 1 000 000 new cases each year. The poor prognosis of patients suffering from hepatic malignancies has lead to the development of a liver directed therapy which consists of intra-arterial administration of radioactive particles through a catheter. Yttrium-90 ((90)Y) microspheres are increasingly applied for this purpose, and up to now nearly all clinical experience with radioembolization has been obtained with these microspheres. The response rate is very promising in both patients with primary and metastatic liver malignancies. Currently, two commercially available (90)Y microsphere devices are in use clinically, both as a first-line treatment and in a salvage setting. Unfortunately, the use of a pure beta-emitter like (90)Y hampers acquisition of high quality nuclear images for pre-treatment work-up and follow-up. This issue was addressed by the development of holmium-166 ((166)Ho) and rhenium-188 ((188)Re) microspheres, which emit both beta-particles for therapeutic purposes and gamma-photons for nuclear imaging. Moreover, since holmium is paramagnetic it allows for magnetic resonance imaging. (166)Ho loaded poly(L-lactic acid) microspheres have been thoroughly investigated in a preclinical setting, and recently the first clinical results for (188)Re microspheres were reported. This review provides an overview of the current status and (pre-)clinical developments of radioactive microspheres for treatment of liver malignancies. PMID:19521312

Bult, W; Vente, M A D; Zonnenberg, B A; Van Het Schip, A D; Nijsen, J F M

2009-06-01

351

Aceclofenac microspheres: quality by design approach.  

PubMed

The purpose of this study was to prepare polymeric microspheres containing aceclofenac by single emulsion [oil-in-water (o/w)] solvent evaporation method. Two biocompatible polymers, ethylcellulose, and Eudragit® RS100 were used in combination. Seven processing factors were investigated by Plackett-Burman design (PBD) in order to enhance the encapsulation efficiency of the microspheres. A Plackett-Burman design was employed by using the Design-Expert® software (Version-8.0.7.1). The resultant microspheres were characterized for their size, morphology, encapsulation efficiency, and drug release. Imaging of particles was performed by field emission scanning electron microscopy. Interaction between the drug and polymers were investigated by Fourier transform infrared (FTIR) spectroscopy, and X-ray powder diffractometry (XRPD). Graphical and mathematical analyses of the design showed that Eudragit® RS100, and polyvinyl alcohol (PVA) were significant negative effect on the encapsulation efficiency and identified as the significant factor determining the encapsulation efficiency of the microspheres. The low magnitudes of error and the significant values of R(2) in the present investigation prove the high prognostic ability of the design. The microspheres showed high encapsulation efficiency (70.15% to 83.82%). The microspheres were found to be discrete, oval with smooth surface. The FTIR analysis confirmed the compatibility of aceclofenac with the polymers. The XRPD revealed the dispersion of drug within microspheres formulation. Perfect prolonged drug release profile over 12h was achieved by a combination of ethylcellulose, and Eudragit® RS100 polymers. In conclusion, polymeric microspheres containing aceclofenac can be successfully prepared using the technique of experimental design, and these results helped in finding the optimum formulation variables for encapsulation efficiency of microspheres. PMID:24433918

Deshmukh, Rameshwar K; Naik, Jitendra B

2014-03-01

352

Development of PLGA-based itraconazole injectable nanospheres for sustained release  

PubMed Central

Purpose Itraconazole (ITZ) is a synthetic triazole antifungal agent, which is widely used for treatment and prevention of fungal infections. The purpose of this study is to develop ITZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanospheres (PLGA-ITZ-NS) as a new sustained-release formulation for intravenous ITZ administration. Materials and methods PLGA-ITZ-NS were prepared by a nanoprecipitation method and optimized by modifying the surfactant poloxamer 188 concentration and PLGA:ITZ ratio. Their physicochemical properties, including size, zeta potential, external morphology and encapsulation efficiency, were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM) and high performance liquid chromatography (HPLC). The effect of the different selected lyoprotectants with various concentrations on NS particles size and surface charge were also assessed. Rapid and sensitive HPLC and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed to determine ITZ concentrations in formulation and in rat plasma, respectively. Pharmacokinetics of the optimum PLGA-ITZ-NS formulation was compared with the former commercial Sporanox® injection formulation using rats as the animal model. Noncompartmental pharmacokinetic parameters were obtained by WinNonlin® software. Results Optimal PLGA-ITZ-NS had a mean particle size of about 200 nm with a high homogeneity (polydispersity index ?0.2), favorable zeta potential (approximately ?20 to ?30 mV) and encapsulation efficiency (72%). In addition, 2% w/v sucrose was selected as a lyoprotectant for NS freeze-drying. The newly developed LC-MS/MS assay was validated and found to be accurate and precise. The in vivo study showed that the NS formulation has a similar systemic bioavailability to Sporanox® while providing a sustained plasma level (> 100 ng/mL) for up to 24 hours after intravenous administration. Conclusion Our newly developed PLGA-ITZ-NS has shown great sustained release and comparable bioavailability with Sporanox®, therefore having the potential to be an alternative injectable formulation of ITZ. PMID:24311942

Bian, Xiaomei; Liang, Su; John, Jyothy; Hsiao, Cheng-Hui; Wei, Xin; Liang, Dong; Xie, Huan

2013-01-01

353

A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery.  

PubMed

A amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mPEG-PLGA-b-PLL) was synthesized. The chemical structure of this copolymer and its precursors was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), (1)H Nuclear Magnetic Resonance ((1)H NMR) and Gel Permeation Chromatography (GPC). The copolymer was used to prepare nanoparticles (NPs) that were then loaded with either the anti-cancer drug adriamycin or small interfering RNA-negative (siRNA) using a double emulsion method. MTT assays used to study the in vitro cytotoxicity of mPEG-PLGA-b-PLL NPs showed that these particles were not toxic in huh-7 hepatic carcinoma cells. Confocal laser scanning microscopy (CLSM) and flow cytometer analysis results demonstrated efficient mPEG-PLGA-b-PLL NPs-mediated delivery of both adriamycin and siRNA into the cells. In vivo the targeting delivery of adriamycin or siRNA mediated by mPEG-PLGA-b-PLL NPs in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. The targeting delivery results and froze section analysis confirmed that drug or siRNA is deliver to tumor more efficiently by mPEG-PLGA-b-PLL NPs than free drug or Lipofectamine™2000. The high efficiency delivery of mPEG-PLGA-b-PLL NPs mainly due to the enhancement of cellular uptake. These results imply that mPEG-PLGA-b-PLL NPs have a great potential to be used as an effective carriers for adriamycin or siRNA. PMID:22436800

Liu, Peifeng; Yu, Hui; Sun, Ying; Zhu, Mingjie; Duan, Yourong

2012-06-01

354

Surface modified PLGA nanoparticles for brain targeting of Bacoside-A.  

PubMed

The present paper focuses on the development and in vitro/in vivo characterization of nanoparticles composed of poly-(D,L)-Lactide-co-Glycolide (PLGA) loading Bacoside-A, as a new approach for the brain delivery of the neuroprotective drug for the treatment of neurodegenerative disorders (e.g. Alzheimer Disease). Bacoside-A-loaded PLGA nanoparticles were prepared via o/w emulsion solvent evaporation technique. Surface of the nanoparticles were modified by coating with polysorbate 80 to facilitate the crossing of the blood brain barrier (BBB), and the processing parameters (i.e. sonication time, the concentration of polymer (PLGA) and surfactant (polysorbate 80), and drug-polymer ratio) were optimized with the aim to achieve a high production yield. Brain targeting potential of the nanoparticles was evaluated by in vivo studies using Wistar albino rats. The nanoparticles produced by optimal formulation were within the nanosized range (70-200 nm) with relatively low polydispersity index (0.391 ± 1.2). The encapsulation efficiency of Bacoside-A in PLGA nanoparticles was 57.11 ± 7.11%, with a drug loading capacity of 20.5 ± 1.98%. SEM images showed the spherical shape of the PLGA nanoparticles, whereas their low crystallinity was demonstrated by X-ray studies, which also confirmed no chemical interactions between the drug and polymer molecules. The in vitro release of Bacoside-A from the PLGA nanoparticles followed a sustained release pattern with a maximum release of up to 83.04 ± 2.55% in 48 h. When compared to pure drug solution (2.56 ± 1.23 ?g/g tissue), in vivo study demonstrated higher brain concentration of Bacoside-A (23.94 ± 1.74 ?g/g tissue) suggesting a significant role of surface coated nanoparticles on brain targeting. The results indicate the potential of surface modified PLGA nanoparticles for the delivery of Bacoside-A to the brain. PMID:25010261

Jose, S; Sowmya, S; Cinu, T A; Aleykutty, N A; Thomas, S; Souto, E B

2014-10-15

355

SRNL POROUS WALL GLASS MICROSPHERES  

SciTech Connect

The Savannah River National Laboratory (SRNL) has developed a new medium for storage of hydrogen and other gases. This involves fabrication of thin, Porous Walled, Hollow Glass Microspheres (PW-HGMs), with diameters generally in the range of 1 to several hundred microns. What is unique about the glass microballons is that porosity has been induced and controlled within the thin, one micron thick walls, on the scale of 10 to several thousand Angstroms. This porosity results in interesting properties including the ability to use these channels to fill the microballons with special absorbents and other materials, thus providing a contained environment even for reactive species. Gases can now enter the microspheres and be retained on the absorbents, resulting in solid-state and contained storage of even reactive species. Also, the porosity can be altered and controlled in various ways, and even used to filter mixed gas streams within a system. SRNL is involved in about a half dozen different programs involving these PW-HGMs and an overview of some of these activities and results emerging are presented.

Wicks, G; Leung Heung, L; Ray Schumacher, R

2008-04-15

356

Characterization of a Polyamine Microsphere and Its Adsorption for Protein  

PubMed Central

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

Wang, Feng; Liu, Pei; Nie, Tingting; Wei, Huixian; Cui, Zhenggang

2013-01-01

357

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

. 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

Park, Jong-Sang

358

The effect of cross-linking on the microstructure, mechanical properties and biocompatibility of electrospun polycaprolactone-gelatin/PLGA-gelatin/PLGA-chitosan hybrid composite  

NASA Astrophysics Data System (ADS)

In this study, multilayered scaffolds composed of polycaprolactone (PCL)-gelatin/poly(lactic-co-glycolic acid) (PLGA)-gelatin/PLGA-chitosan artificial blood vessels were fabricated using a double-ejection electrospinning system. The mixed fibers from individual materials were observed by scanning electron microscopy. The effects of the cross-linking process on the microstructure, mechanical properties and biocompatibility of the fibers were examined. The tensile stress and liquid strength of the cross-linked artificial blood vessels were 2.3 MPa and 340 mmHg, respectively, and were significantly higher than for the non-cross-linked vessel (2.0 MPa and 120 mmHg). The biocompatibility of the cross-linked artificial blood vessel scaffold was examined using the MTT assay and by evaluating cell attachment and cell proliferation. The cross-linked PCL-gelatin/PLGA-gelatin/PLGA-chitosan artificial blood vessel scaffold displayed excellent flexibility, was able to withstand high pressures and promoted cell growth; thus, this novel material holds great promise for eventual use in artificial blood vessels.

Nguyen, Thi-Hiep; Lee, Byong-Taek

2012-06-01

359

Preparation and characterization of gadolinium-loaded PLGA particles surface modified with RGDS for the detection of thrombus  

PubMed Central

Thrombotic disease is a leading cause of death and disability worldwide. The development of magnetic resonance molecular imaging provides potential promise for early disease diagnosis. In this study, we explore the preparation and characterization of gadolinium (Gd)-loaded poly (lactic-co-glycolic acid) (PLGA) particles surface modified with the Arg-Gly-Asp-Ser (RGDS) peptide for the detection of thrombus. PLGA was employed as the carrier-delivery system, and a double emulsion solvent-evaporation method (water in oil in water) was used to prepare PLGA particles encapsulating the magnetic resonance contrast agent Gd diethylenetriaminepentaacetic acid (DTPA). To synthesize the Gd-PLGA/chitosan (CS)-RGDS particles, carbodiimide-mediated amide bond formation was used to graft the RGDS peptide to CS to form a CS-RGDS film that coated the surface of the PLGA particles. Blank PLGA, Gd-PLGA, and Gd-PLGA/CS particles were fabricated using the same water in oil in water method. Our results indicated that the RGDS peptide successfully coated the surface of the Gd-PLGA/CS-RGDS particles. The particles had a regular shape, smooth surface, relatively uniform size, and did not aggregate. The high electron density of the Gd-loaded particles and a translucent film around the particles coated with the CS and CS-RGDS films could be observed by transmission electron microscopy. In vitro experiments demonstrated that the Gd-PLGA/CS-RGDS particles could target thrombi and could be imaged using a clinical magnetic resonance scanner. Compared with the Gd-DTPA solution, the longitudinal relaxation time of the Gd-loaded particles was slightly longer, and as the Gd-load concentration increased, the longitudinal relaxation time values decreased. These results suggest the potential of the Gd-PLGA/CS-RGDS particles for the sensitive and specific detection of thrombus at the molecular level. PMID:24124363

Zhang, Yu; Zhou, Jun; Guo, Dajing; Ao, Meng; Zheng, Yuanyi; Wang, Zhigang

2013-01-01

360

Reducing Prescriptions of Long-Acting Benzodiazepine Drugs in Denmark: A Descriptive Analysis of Nationwide Prescriptions during a 10-Year Period.  

PubMed

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

Eriksen, Sophie Isabel; Bjerrum, Lars

2014-11-10

361

Hormone supplementation protocol using estradiol benzoate and long-acting progesterone is efficient in maintaining pregnancy of anovulatory recipient mares during autumn transitional phase.  

PubMed

The present research sought to determine whether the administration of estradiol benzoate and long-acting progesterone to anovulatory recipient mares could maintain the pregnancy after embryo transfer during the autumn transitional phase. Recipient mares (n=40) received the hormonal supplementation (treated group) whereas the other 36 served as a control. The control group consisted of mares having typical estrous cycles with ovulations, development of a viable corpus luteum and received one transferred embryo 5 days after ovulation. Hormonal administrations in the treated group started 8 days before the embryo transfer. During the first 3 days, the mares received estradiol benzoate (5mg the first day, 3mg the second day and 2mg the third day). At Day 5 subsequent to ovulation, the mares received one administration of 1500mg long-acting progesterone, and the same treatments occurred at the day of embryo transfer. Afterwards, treated mares also received 1500mg long-acting progesterone every 7 days until 120 days of gestation. For both control and treated groups, the recipient mares were classified as acceptable, marginally acceptable or unacceptable for embryo transfer, and the embryo quality was also determined. The pregnancy diagnosis in recipient mares was made at Days 13, 30 and 60 of pregnancy. While the pregnancy rate was greater (P<0.05) in the treated than in the control group, the recipient classification did not influence pregnancy rates. In conclusion, pregnancy in anovulatory recipient mares during the autumn transitional phase can be achieved when estradiol benzoate and progesterone are administered. PMID:25578506

Botelho, Jorge H V; Pessoa, Gabriela O; Rocha, Luiz G P; Yeste, Marc

2015-02-01

362

A Post-hoc Comparison of Paliperidone Palmitate to Oral Risperidone During Initiation of Long-acting Risperidone Injection in Patients with Acute Schizophrenia  

PubMed Central

Objective: First-month data of a 13-week acute schizophrenia study were used to compare paliperidone palmitate to oral risperidone during initiation of long-acting injectable risperidone. Design: Double-blind, randomized study. Setting: Outpatient or inpatient. Participants: Adults with established (?1 year) schizophrenia. Those assigned to risperidone long-acting injectable (n=460) received 25mg on Days 8 and 22 with oral risperidone (l–6mg) supplementation for the first 28 days. The paliperidone palmitate group (n=453) received 150mg eq. on Day 1, l00mg eq. on Day 8, and oral placebo supplementation for the first 28 days. Measurements: Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical Global Impression-Severity score, and responder rate (percentage of patients with ?30% reduction in PANSS total score). An analysis of covariance model estimated least-square mean differences between treatment groups. A post-hoc analysis of efficacy data for the period of interest, i.e., at the time points before and after the first 28 days, was conducted. Results: Positive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical global Impression-Severity scores showed similar efficacy between the treatment groups during the first weeks of treatment, corresponding to the risperidone long-acting injection initiation period. Mean Positive and Negative Syndrome Scale total score at baseline was 84.7 for paliperidone palmitate and 84.4 for oral risperidone, on Day 22 was 73.6 and 74.1, respectively, and on Day 36 was 71.8 and 72.8, respectively. Overall incidence of adverse events in the first 28 days was generally similar (45% for paliperidone palmitate vs. 35% for oral risperidone), except for injection site pain (4.6% vs. 0.7%). Similar active moiety plasma concentrations were obtained during this period. Conclusion: During the first month, paliperidone palmitate without oral supplementation has similar efficacy and safety to oral risperidone (during initiation of risperidone long-acting injectable) in acutely exacerbated schizophrenia. PMID:21922067

Pandina, Gahan; Lane, Rosanne; Nuamah, Isaac; Remmerie, Bart; Coppola, Danielle; Hough, David

2011-01-01

363

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

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

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

364

Utilization, Spending, and Price Trends for Short- and Long-Acting Beta-Agonists and Inhaled Corticosteroids in the Medicaid Program, 1991–2010  

PubMed Central

Background Asthma is a chronic respiratory disease that afflicts millions of people and accounts for substantial utilization of healthcare resources in most industrialized countries, including in the United States. However, the exact cost and utilization of anti-asthma medications in Medicaid in the past 2 decades have not been well studied. Considering the safety issues surrounding the long-acting beta-agonists, guideline updates, and the increase in asthma prevalence, understanding anti-asthma medication prescribing trends is important to payers and patients. Goal The purpose of this study was to analyze the utilization and spending trends for anti-asthmatic agents in the US Medicaid program over the past 2 decades. Methods This study was based on a retrospective, descriptive analysis of trends in utilization of and spending on anti-asthma medications, including short-acting beta-agonists, inhaled corticosteroids, long-acting beta-agonists, and inhaled corticosteroid/long-acting beta-agonist combinations. Quarterly utilization and expenditure data were obtained from the national Medicaid pharmacy files provided by the Centers for Medicare & Medicaid Services from quarter 1 of 1991 through quarter 2 of 2010. Average reimbursement per prescription was calculated each quarter as a proxy for drug price. Results The total number of prescriptions for the studied anti-asthma medications rose from 8.9 million in 1991 to 15.6 million in 2009, peaking at 20.8 million in 2005, the year before Medicare and Medicaid dual-eligible beneficiaries were moved to Medicare Part D. From 1991 to 2009, Medicaid spending on anti-asthma medications overall rose from $180.7 million to $1.3 billion, and spending on inhaled corticosteroid/long-acting beta-agonist combinations rose from $52.8 million in 2001—their first year on the market—to $411.7 million in 2009. The average price per prescription has risen in all the anti-asthma drug classes: overall, spending per prescription has increased 4-fold between 1991 and 2009, significantly faster than the consumer price index (57.5%) over the same period. In quarter 2 of 2010, Medicaid spent more on the combination medication fluticasone-salmeterol—$60 million—than on any other anti-asthma medication. Conclusion Anti-asthma medications are a major and growing expense for state Medicaid programs and can be expected to be the same for Medicare Part D in the future. Increased disease prevalence has in part contributed to the rise in pharmacotherapy cost. Nevertheless, drug therapy is crucial for managing asthma and asthma exacerbations. PMID:25126346

Chiu, Shih-Feng; Kelton, Christina M.L.; Guo, Jeff Jianfei; Wigle, Patricia R.; Lin, Alex C.; Szeinbach, Sheryl L.

2011-01-01

365

Chitosan microspheres prepared by spray drying.  

PubMed

Non-crosslinked and crosslinked chitosan microspheres were prepared by a spray drying method. The microspheres so prepared had a good sphericity and a smooth but distorted surface morphology. They were positively charged. The particle size ranged from 2 to 10 micron. The size and seta potential of the particles were influenced by the crosslinking level. With decreasing amount of crosslinking agent (either glutaraldehyde or formaldehyde), both particle size and zeta potential were increased. Preparation conditions also had some influence on the particle size. DSC studies revealed that the H2 antagonist drug cimetidine, as well as famotidine was molecularly dispersed inside the microspheres, in the form of a solid solution. The release of model drugs (cimetidine, famotidine and nizatidine) from these microspheres was fast, and accompanied by a burst effect. PMID:10502613

He, P; Davis, S S; Illum, L

1999-09-30

366

Organic aerogel microspheres and fabrication method therefor  

DOEpatents

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.

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

367

Organic aerogel microspheres and fabrication method therefor  

DOEpatents

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.

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

1996-04-16

368

21 CFR 870.1360 - Trace microsphere.  

Code of Federal Regulations, 2014 CFR

...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)...

2014-04-01

369

Targeted Delivery of Antibiotics to Intracellular Chlamydial Infections using PLGA Nanoparticles  

PubMed Central

Chlamydia trachomatis and C pneumoniae are intracellular bacterial pathogens that have been shown to cause, or are strongly associated with, diverse chronic diseases. Persistent infections by both organisms are refractory to antibiotic therapy. The lack of therapeutic efficacy results from the attenuated metabolic rate of persistently infecting chlamydiae in combination with the modest intracellular drug concentrations achievable by normal delivery of antibiotics to the inclusions within which chlamydiae reside in the host cell cytoplasm. In this research, we evaluated whether nanoparticles formulated using the biodegradable poly(d-L-lactide-co-glycolide) (PLGA) polymer can enhance the delivery of antibiotics to the chlamydial inclusion complexes. We initially studied the trafficking of PLGA nanoparticles in Chlamydia-infected cells. We then evaluated nanoparticles for the delivery of antibiotics to the inclusions. Intracellular trafficking studies show that PLGA nanoparticles efficiently concentrate in inclusions in both acutely and persistently infected cells. Further, encapsulation of rifampin and azithromycin antibiotics in PLGA nanoparticles enhanced the effectiveness of the antibiotics in reducing microbial burden. Combination of rifampin and azithromycin was more effective than the individual drugs. Overall, our studies show that PLGA nanoparticles can be effective carriers for targeted delivery of antibiotics to intracellular chlamydial infections. PMID:21652065

Toti, Udaya S.; Guru, Bharath R.; Hali, Mirabela; McPharlin, Christopher; Wykes, Susan M.; Panyam, Jayanth; Whittum-Hudson, Judith A.

2011-01-01

370

Toxicity of surface-modified PLGA nanoparticles toward lung alveolar epithelial cells.  

PubMed

In vitro cytotoxicity and inflammatory response following exposure to nanoparticles (NPs) made of poly(lactide-co-glycolide) (PLGA) have been investigated on A549 human lung epithelial cells. Three different PLGA NPs (230 nm) were obtained using different stabilizers (polyvinyl alcohol, chitosan, or Pluronic(®) F68) to form respectively neutral, positively or negatively charged NPs. Polystyrene NPs were used as polymeric but non-biodegradable NPs, and titanium dioxide (anatase and rutile) as inorganic NPs, for comparison. Cytotoxicity was evaluated through mitochondrial activity as well as membrane integrity (lactate dehydrogenase release, trypan blue exclusion, propidium iodide staining). The cytotoxicity of PLGA-based and polystyrene NPs was lower or equivalent to the one observed after exposure to titanium dioxide NPs. The inflammatory response, evaluated through the release of the IL-6, IL-8, MCP-1, TNF-? cytokines, was low for all NPs. However, some differences were observed, especially for negative PLGA NPs that led to a higher inflammatory response, which can be correlated to a higher uptake of these NPs. Taken together, these results show that both coating of PLGA NPs and the nature of the core play a key role in cell response. PMID:23747506

Grabowski, Nadège; Hillaireau, Hervé; Vergnaud, Juliette; Santiago, Letícia Aragão; Kerdine-Romer, Saadia; Pallardy, Marc; Tsapis, Nicolas; Fattal, Elias

2013-10-01

371

Biodegradable polymer (PLGA) coatings featuring cinnamaldehyde and carvacrol mitigate biofilm formation.  

PubMed

Biofilm-associated infections are one of the leading causes of death in the United States. Although infections may be treated with antibiotics, the overuse of antibiotics has led to the spread of antibiotic resistance. Many natural antimicrobial compounds derived from edible plants are safe for human use and target bacteria nonspecifically. Therefore, they may impair biofilm formation with less evolutionary pressure on pathogens. Here, we explore the use of two natural antimicrobial compounds, cinnamaldehyde (CA, from cinnamon) and carvacrol (CARV, from oregano), for biofilm prevention. We have fabricated and characterized films that incorporate CA and CARV into the biodegradable, FDA-approved polymer poly(lactic-co-glycolic acid), PLGA. The addition of CA and CARV to PLGA films not only adds antimicrobial activity but also changes the surface properties of the films, making them more hydrophilic and therefore more resistant to bacterial attachment. An addition of 0.1% CA to a PLGA film significantly impairs biofilm development by Staphylococcus aureus, and 0.1% CARV in PLGA significantly decreases biofilm formation by both Escherichia coli and S. aureus. Pseudomonas aeruginosa, which is less susceptible to CA and CARV, was not affected by the addition of 0.1% CA or CARV to the PLGA coatings; however, P. aeruginosa biofilm was significantly reduced by 1.0% CA. These results indicate that both CA and CARV could potentially be used in low concentrations as natural additives in polymer coatings for indwelling devices to delay colonization by bacteria. PMID:22937881

Zodrow, Katherine R; Schiffman, Jessica D; Elimelech, Menachem

2012-10-01

372

Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers  

NASA Astrophysics Data System (ADS)

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l - 1. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the ?v?3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

Ding, Hong; Yong, Ken-Tye; Roy, Indrajit; Hu, Rui; Wu, Fang; Zhao, Lingling; Law, Wing-Cheung; Zhao, Weiwei; Ji, Wei; Liu, Liwei; Bergey, Earl J.; Prasad, Paras N.

2011-04-01

373

PLGA Nanoparticles Formed by Single- or Double-emulsion with Vitamin E-TPGS  

PubMed Central

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible member of the aliphatic polyester family of biodegradable polymers. PLGA has long been a popular choice for drug delivery applications, particularly since it is already FDA-approved for use in humans in the form of resorbable sutures. Hydrophobic and hydrophilic drugs are encapsulated in PLGA particles via single- or double-emulsion. Briefly, the drug is dissolved with polymer or emulsified with polymer in an organic phase that is then emulsified with the aqueous phase. After the solvent has evaporated, particles are washed and collected via centrifugation for lyophilization and long term storage. PLGA degrades slowly via hydrolysis in aqueous environments, and encapsulated agents are released over a period of weeks to months. Although PLGA is a material that possesses many advantages for drug delivery, reproducible formation of nanoparticles can be challenging; considerable variability is introduced by the use of different equipment, reagents batch, and precise method of emulsification. Here, we describe in great detail the formation and characterization of microparticles and nanoparticles formed by single- or double-emulsion using the emulsifying agent vitamin E-TPGS. Particle morphology and size are determined with scanning electron microscopy (SEM). We provide representative SEM images for nanoparticles produced with varying emulsifier concentration, as well as examples of imaging artifacts and failed emulsifications. This protocol can be readily adapted to use alternative emulsifiers (e.g. poly(vinyl alcohol), PVA) or solvents (e.g. dichloromethane, DCM). PMID:24429733

McCall, Rebecca L.; Sirianni, Rachael W.

2013-01-01

374

Biodegradable effect of PLGA membrane in alveolar bone regeneration on beagle dog.  

PubMed

Guided bone regeneration (GBR) is a principle adopted from guided tissue regeneration (GTR). Wherein, GBR is used for the healing of peri-implant bony dehiscences, for the immediate placement of implants into extraction sockets and for the augmentation of atrophic alveolar ridges. This procedure is done by the placement of a resorbable or non-resorbable membrane that will exclude undesirable types of tissue growth between the extraction socket and the soft tissue to allow only bone cells to regenerate in the surgically treated lesion. Here, we investigated the biodegradable effect of polylactic-co-glycolic acid (PLGA) membrane in the alveolar bone on Beagle dogs. Results show that both collagen and PLGA membrane had been fully resorbed, biodegraded, at four weeks post-operative reentry into the alveolar bone. Histological results under light microscopy revealed formation of new bone trabeculae in the extraction sites on both collagen and PLGA membrane. In conclusion, PLGA membrane could be a potential biomaterials for use on GBR and GTR. Nevertheless, further studies will be necessary to elucidate the efficiency and cost effectiveness of PLGA as GBR membrane in clinical. PMID:24833431

Hua, Nan; Ti, Vivian Lao; Xu, Yuanzhi

2014-11-01

375

Active targeting of dendritic cells with mannan-decorated PLGA nanoparticles.  

PubMed

The purpose of this study was to identify an optimum targeted particulate formulation based on mannan (MN)-decorated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), for efficient delivery of incorporated cargo to dendritic cells (DCs). In brief, NPs were formulated from two different types of PLGA; ester-terminated (capped) or COOH-terminated (uncapped) polymer. Incorporation of MN in NPs was achieved either through addition of MN during the process of NP formation or by attachment of MN onto the surface of the freeze dried NPs by physical adsorption or chemical conjugation (to COOH terminated polymer). The formulated NPs were characterized in terms of particle size, Zeta potential and level of MN incorporation. The effect of polymer type and the incorporation method on the extent of fluorescently labelled NP uptake by murine bone marrow-derived DCs have been investigated using flowcytometry. The results of this study showed MN incorporation to enhance the uptake of PLGA NPs by DCs. Among different MN incorporation strategies, covalent attachment of MN to COOH-terminated PLGA-NPs provided the highest level of MN surface decoration on NPs. Maximum NP uptake by DCs was achieved by COOH terminated PLGA NPs containing covalent or adsorbed MN. Therefore, a better chance of success for these formulations for active targeted drug and/or vaccine delivery to DCs is anticipated. PMID:20590403

Ghotbi, Zahra; Haddadi, Azita; Hamdy, Samar; Hung, Ryan W; Samuel, John; Lavasanifar, Afsaneh

2011-05-01

376

Anticancer Activity of Nanoparticles Based on PLGA and its Co-polymer: In-vitro Evaluation  

PubMed Central

Attempts have been made to prepare nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) and doxorubicin. Biological evaluation and physio-chemical characterizations were performed to elucidate the effects of initial drug loading and polymer composition on nanoparticle properties and its antitumor activity. PLGA nanoparticles were formulated by sonication method. Lactide/glycolide ratio and doxorubicin amounts have been tailored. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were employed to identify the presence of doxorubicin within nanospheres. The in vitro release studies were performed to determine the initial ant net release rates over 24 h and 20 days, respectively. Furthermore, cytotoxicity assay was measured to evaluate therapeutic potency of doxorubicin-loaded nanoparticles. Spectroscopy and thermal results showed that doxorubicin was loaded into the particles successfully. It was observed that lactide/glycolide content of PLGA nanoparticles containing doxorubicin has more prominent role in tuning particle characteristics. Doxorubicin release profiles from PLGA 75 nanospheres demonstrated that the cumulative release rate increased slightly and higher initial burst was detected in comparison to PLGA 50 nanoparticles. MTT data revealed doxorubicin induced antitumor activity was enhanced by encapsulation process, and increasing drug loading and glycolide portion. The results led to the conclusion that by controlling the drug loading and the polymer hydrophilicity, we can adjust the drug targeting and blood clearance, which may play a more prominent role for application in chemotherapy. PMID:24523742

Amjadi, Issa; Rabiee, Mohammad; Hosseini, Motahare-Sadat

2013-01-01

377

Method for introduction of gases into microspheres  

DOEpatents

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.

Hendricks, Charles D. (Livermore, CA); Koo, Jackson C. (San Ramon, CA); Rosencwaig, Allan (Danville, CA)

1981-01-01

378

Spectral and Spatial Characterization of Protein Loaded PLGA Nanoparticles  

PubMed Central

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

Zidan, Ahmed S.; Rahman, Ziyaur; Habib, Muhammad J.; Khan, Mansoor A.

2011-01-01

379

MAPLE deposition of PEG:PLGA thin films  

NASA Astrophysics Data System (ADS)

We report on MAPLE deposition of thin films of PEG:PLGA blends. The films were analyzed in terms of morphology, chemical composition, wettability, and optical constants. These properties were particularly discussed in correlation with film thickness. The film thickness was increased by increasing the deposition rate (i.e., laser fluence). This method was effective for fluences up to 1 J/cm2, above which the efficiency of the deposition leveled off. Moreover, with increasing fluence above 1 J/cm2, important changes in the polymeric films were noticed: the surface roughness increased abruptly (up to ˜200 nm), the polymers lost their chemical integrity and their optical constants underwent significant changes. In addition, surface wettability decreased considerably, water contact angle reaching ˜90°; this was attributed to increased surface roughness and to orientation of the hydrophobic groups toward the surfaces of the films. An alternative method for obtaining thicker films was employed, by prolonging the deposition time while maintaining a constant, relatively low, deposition rate (i.e., fluence). In this case, the properties of the films were significantly less affected.

Paun, Irina Alexandra; Ion, Valentin; Moldovan, Antoniu; Dinescu, Maria

2012-01-01

380

Preparation and application of cellulose triacetate microspheres.  

PubMed

Cellulose triacetate was prepared via reacting of a mixture of acetic anhydride and acetic acid containing sulfuric acid as catalyst with ramie fiber obtained from a biomass of ramie. The cellulose triacetate with a degree of substitution (DS) 2.93 of the ramie fiber was obtained. The honeycomb-like cellulose triacetate microspheres with an average diameter of 14 microm were made from the cellulose triacetate solution. The optimum conditions for preparing the microspheres were determined as cellulose triacetate/dichloromethane ratio 1:7 (w/w), and 0.75% sodium dodecylsulfonate. The cellulose triacetate microspheres were characterized using FT-IR, NMR, XRD, and SEM. Application of the microspheres as an adsorbent for removing disperse dyes in water was investigated under the temperatures from 15 to 50 degrees C, pHs from 4 to 9, and the weight of cellulose triacetate microspheres from 0.03 to 0.09 g. The cellulose triacetate microspheres exhibited a 16.5mg/g capability to remove DR dye from water at 50 degrees C and pH 7. PMID:20060644

Fan, Xiushan; Liu, Zhao-Tie; Liu, Zhong-Wen

2010-05-15

381

Metronidazole loaded pectin microspheres for colon targeting.  

PubMed

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit(R) S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. PMID:19492406

Vaidya, Ankur; Jain, Aviral; Khare, Piush; Agrawal, Ram K; Jain, Sanjay K

2009-11-01

382

Nonlinear elasticity of microsphere heaps  

NASA Astrophysics Data System (ADS)

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.

Ortiz, Carlos P.; Daniels, Karen E.; Riehn, Robert

2014-08-01

383

Suppression of postoperative pain by the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine.  

PubMed

The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine, was evaluated for the suppression of acute postoperative pain. Subjects having two impacted third molars removed at two appointments received either the experimental combination or standard treatment in a randomized, crossover design. The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery, 1.5% etidocaine with 1:200,000 epinephrine five minutes before surgery, and 100 mg flurbiprofen three hours after surgery. Standard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery, 2% lidocaine with 1:100,000 epinephrine five minutes before surgery, and a second dose of the oxycodone-acetaminophen combination three hours after surgery. Pain intensity was rated hourly from one to seven hours after surgery, using a variety of ordinal and analog scales. The flurbiprofen-etidocaine combination resulted in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients. This study shows that pretreatment with a nonsteroidal anti-inflammatory drug, flurbiprofen, in combination with a long-acting local analgesic, etidocaine, suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability. PMID:6586802

Dionne, R A; Wirdzek, P R; Fox, P C; Dubner, R

1984-04-01

384

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

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

Gopal, Srihari; Berwaerts, Joris; Nuamah, Isaac; Akhras, Kasem; Coppola, Danielle; Daly, Ella; Hough, David; Palumbo, Joseph

2011-01-01

385

A Holy Grail of asthma management: toward understanding how long-acting ?2-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids  

PubMed Central

There is unequivocal evidence that the combination of an inhaled corticosteroid (ICS)—i.e. glucocorticoid—and an inhaled long-acting ?2-adrenoceptor agonist (LABA) is superior to each component administered as a monotherapy alone in the clinical management of asthma. Moreover, Calverley and colleagues (Lancet 2003, 361: 449–456; N Engl J Med 2007, 356: 775–789) reporting for the ‘TRial of Inhaled STeroids ANd long-acting ?2-agonists (TRISTAN)' and ‘TOwards a Revolution in COPD Health (TORCH)' international study groups also demonstrated the superior efficacy of LABA/ICS combination therapies over ICS alone in the clinical management of chronic obstructive pulmonary disease. This finding has been independently confirmed indicating that the therapeutic benefit of LABA/ICS combination therapies is not restricted to asthma and may be extended to other chronic inflammatory diseases of the airways. Despite the unquestionable benefit of LABA/ICS combination therapies, there is a vast gap in our understanding of how these two drugs given together deliver superior clinical efficacy. In this article, we review the history of LABA/ICS combination therapies and critically evaluate how these two classes of drugs might interact at the biochemical level to suppress pro-inflammatory responses. Understanding the molecular basis of this fundamental clinical observation is a Holy Grail of current respiratory diseases research as it could permit the rational exploitation of this effect with the development of new ‘optimized' LABA/ICS combination therapies. PMID:18071293

Giembycz, M A; Kaur, M; Leigh, R; Newton, R

2007-01-01

386

Short versus long-acting local anaesthetic in open carpal tunnel release: which provides better preemptive analgesia in the first 24 hours?  

PubMed

Open carpal tunnel release is commonly performed under local anaesthesia. No study has compared intra-operative short- versus long-acting local anaesthetics as preemptive analgesics in carpal tunnel surgery. In this single-blinded prospective study, 100 consecutive carpal tunnel releases were performed by a single surgeon at one institution with either lignocaine (n = 50) or ropivacaine (n = 50). Allocation was performed via the method of alternation. Subjects were given a questionnaire to answer the following: (1) time to first incidence of pain, (2) quality of first night's sleep, and (3) mean numerical pain scores in the first 24 hours. The time to the first postoperative pain was significantly shorter in the lignocaine group (5.58 vs. 9.17 hours, p < 0.035). There were no significant difference in the incidence of poor first night's sleep (16% vs. 26%, p = 0.28) or mean pain scores in the first day (3.6 vs. 2.9, p = 0.16). Existing evidence advocates for long-acting intraoperative local anaesthetic because it results in a longer duration of postoperative analgesia, however, our study suggests that it may also result in a poorer first night's sleep. PMID:23413849

Chan, Z H; Balakrishnan, V; McDonald, A

2013-01-01

387

In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters  

PubMed Central

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

2014-01-01

388

In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters  

NASA Astrophysics Data System (ADS)

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.

Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming

2014-08-01

389

Cost-Effectiveness Analysis of Switching Antipsychotic Medication to Long-Acting Injectable Risperidone in Patients with Schizophrenia: A 12- and 24Month Follow-Up from the e-STAR Database in Spain  

Microsoft Academic Search

Background: The availability of long-acting injectable risperidone may increase adherence to antipsychotic treatment and lead to improved clinical and economic outcomes for patients with schizophrenia. Objectives: To investigate the cost effectiveness of treatment with long-acting injectable risperidone compared with previous antipsychotic regimens in patients with schizophrenia enrolled in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain. Methods: e-STAR is

Jose M. Olivares; Alfonso Rodriguez-Martinez; Jose A. Buron; David Alonso-Escolano; Alexander Rodriguez-Morales

2008-01-01

390

Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells  

PubMed Central

Background Because of the described hazards related to inhalation of manufactured nanoparticles, we investigated the lung toxicity of biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles displaying various surface properties on human bronchial Calu-3 cells. Methods Positively and negatively charged as well as neutral nanoparticles were tailored by coating their surface with chitosan, Poloxamer, or poly (vinyl alcohol), respectively. Nanoparticles were characterized in terms of size, zeta potential, and surface chemical composition, confirming modifications provided by hydrophilic polymers. Results Although nanoparticle internalization by lung cells was clearly demonstrated, the cytotoxicity of the nanoparticles was very limited, with an absence of inflammatory response, regardless of the surface properties of the PLGA nanoparticles. Conclusion These in vitro results highlight the safety of biodegradable PLGA nanoparticles in the bronchial epithelium and provide initial data on their potential effects and the risks associated with their use as nanomedicines. PMID:22114491

Mura, Simona; Hillaireau, Herve; Nicolas, Julien; Le Droumaguet, Benjamin; Gueutin, Claire; Zanna, Sandrine; Tsapis, Nicolas; Fattal, Elias

2011-01-01

391

PLGA-chitosan/PLGA-alginate Nanoparticle Blends as Biodegradable Colloidal Gels for Seeding Human Umbilical Cord Mesenchymal Stem Cells  

PubMed Central

The natural polymers chitosan and alginate represent an attractive material choice for biodegradable inplants. These were used as coating materials to make positively and negatively charged PLGA nanoparticles, respectively. After blending at total solids concentration >10% wt/vol, these oppositely charged nanoparticles yielded a cohesive colloidal gel. Electrostatic forces between oppositely charged nanoparticles produced a stable 3-D porous network that may be extruded or molded to the desired shape. This high concentration colloidal system demonstrated shear-thinning behavior due to the disruption of interparticle interactions. Once the external force was removed, the cohesive property of the colloidal gel was recovered. Scanning electron micrographs of dried colloidal networks revealed an organized, 3-D microporous structure. Rheological studies were employed to probe the differences in plasticity and shear sensitivity of colloidal gels. Viability tests of hUCMSCs seeded on the colloidal gels also demonstrated the negligible cytotoxicity of the materials. All the results indicated the potential application of the biodegradable colloidal gels as an injectable scaffold in tissue engineering and drug release. PMID:21254383

Wang, Qun; Jamal, Syed; Detamore, Michael S.; Berkland, Cory

2010-01-01

392