Note: This page contains sample records for the topic long-acting plga microspheres from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: November 12, 2013.
1

Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.  

PubMed

The goal of this project was to prepare long-acting lanreotide acetate poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and in vitro release, safety and toxicology of these preparations. Long-acting lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period were prepared by a multiple-emulsion solvent evaporation method. Physical characterization, as well as the analysis of the in vivo and in vitro release, safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent evaporation had smooth surfaces, uniform particle size and stable lanreotide loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA microspheres could continuously release lanreotide for 5 weeks. The safety of these long acting lanreotide microspheres was good in the following animal models: active systemic anaphylaxis test in guinea pigs, passive cutaneous anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test after subcutaneous administration in rabbits and muscle stimulation test in rabbits. Furthermore, no significant acute toxicity or chronic toxicity was observed after administration of lanreotide acetate PLGA microspheres in beagle dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that were prepared in this study exhibited beneficial characteristics in apparent property and structural stability, as well as in release trends in vivo and in vitro. PMID:22972523

Wang, Shuang; Wu, Mingsheng; Li, Dan; Jiao, Mingli; Wang, Lan; Zhang, Haifeng; Liu, Huaiyu; Wang, Daifeng; Han, Bing

2012-08-27

2

Preparation of bleomycin A2-PLGA microspheres and related in vitro and in vivo studies.  

PubMed

The goals of these studies were to prepare bleomycin (BLM) A(2)-poly(lactic-co-glycolic acid) (PLGA) microspheres and to investigate their in vitro release, pharmacokinetics, pharmacodynamics, and toxicology of this product. Long-acting BLM A(2)-PLGA microspheres were prepared using multiple emulsion solvent evaporation, and the related characteristics of the microspheres were investigated. The prepared microspheres were administered to dogs via intramuscular injection. The plasma concentration of BLM A(2) in dogs was detected using liquid chromatography-mass spectrometry. The pharmacodynamics of BLM A(2)-PLGA microspheres were investigated in a golden hamster model. The acute and chronic toxicities were investigated in a rat model. The inductive effects of BLM microspheres versus a conventional formulation on pulmonary injuries were compared in a mouse model. BLM A(2)-PLGA microspheres were released stably over 20 days and exhibited a significant inhibition of oral squamous carcinoma. The acute toxicity study suggested that doses up to 128 mg/kg were acceptable, and the chronic toxicity study showed no significant chronic toxicity. The study in mice showed less pulmonary toxicity with BLM microsphere formulation compared with the conventional formulation. As a novel microsphere drug formulation, BLM A(2)-PLGA microspheres showed a significant slow-release effect. These data may provide a new clinical medication option for patients with oral cancer. PMID:21344412

Zhang, Haifeng; Gao, Yang; Lv, Wei; Jiao, Chengfeng; Duan, Minghua; Liu, Huaiyu; Han, Bing

2011-02-22

3

Preparation of pingyangmycin PLGA microspheres and related in vitro/in vivo studies.  

PubMed

Using a multiple emulsion solvent evaporation method, pingyangmycin was entrapped in poly(lactic-co-glycolic acid) (PLGA) to prepare a long-acting pingyangmycin PLGA microsphere formulation that can be sustainably released with high entrapment efficiency. Meanwhile, the effects of stirring speed during the multiple emulsion solvent evaporation process were also taken into consideration. Investigation of the in vitro release properties showed that the microsphere formulations could sustainably release the drug over nearly 28 d, and, moreover, it could stably control pingyangmycin release over nearly 24 d when intramuscularly injected into dogs. No serious toxic effect was observed in an acute toxicity test in mice. A subcutaneous xenotransplant model of hepatoma H(22) in mice was established for pharmacodynamic studies and the results showed that the process of preparing pingyangmycin PLGA microsphere formulations was feasible and that intramuscular injection of this microsphere formulation resulted in anti-tumor activity in vivo. PMID:20688141

Han, Bing; Wang, Hao-Tian; Liu, Huai-Yu; Hong, Hua; Lv, Wei; Shang, Zu-Hui

2010-08-03

4

Protein-loaded PLGA-PEG-PLGA microspheres: a tool for cell therapy  

Microsoft Academic Search

A promising strategy to repair injured organs is possible by delivering a growth factor via poly-(D,L lactide-co-glycolide) (PLGA) microspheres; the latter are coated with adhesion molecules that serve as a support for cell delivery. At present, PLGA is not the optimal choice of polymer because of poor or incomplete protein release. The use of a more hydrophilic PLGA-PEG-PLGA (A-B-A) copolymer

Van-Thanh Tran; Jean-Pierre Karam; Xavier Garric; Jean Coudane; Jean-Pierre Benoît; Claudia N. Montero-Menei; Marie-Claire Venier-Julienne

5

Heparin Immobilized Porous PLGA Microspheres for Angiogenic Growth Factor Delivery  

Microsoft Academic Search

Purpose  Heparin immobilized porous poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres were prepared for sustained release of basic fibroblast growth factor (bFGF) to induce angiogenesis.Materials and Methods  Porous PLGA microspheres having primary amine groups on the surface were prepared using an oil-in-water (O\\/W) single emulsion method using Pluronic F-127 as an extractable porogen. Heparin was surface immobilized via covalent conjugation. bFGF was loaded into the

Hyun Jung Chung; Hong Kee Kim; Jun Jin Yoon; Tae Gwan Park

2006-01-01

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. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3123-3130, 2013. 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

2013-03-25

7

Elevated temperature accelerated release testing of PLGA microspheres  

Microsoft Academic Search

Drug release from four different poly(lactic-co-glycolic) acid (PLGA) microsphere formulations was evaluated under “real-time” (37 °C) and accelerated release testing conditions of elevated temperature (45, 53, 60 and 70 °C) and increase in flow rate (4–35 ml\\/min) using United States Pharmacopeia (USP) apparatus 4. Formulation 5 K (composed of low Mw PLGA) exhibited diffusion-controlled kinetics in “real-time”. Whereas, formulations 25 K, 28 K and 70 K (composed

Banu S. Zolnik; Pauline E. Leary; Diane J. Burgess

2006-01-01

8

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

PubMed

The objective of this study was to evaluate the effect of polymer and microsphere blending in achieving both a sufficient initial release and a desired continuous release of a peptide from poly(D, L-lactide-co-glycolide) microspheres. Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a solvent-extraction/evaporation process and were characterized for their drug load, bulk density, size distribution, surface area, surface morphology, in vitro drug release, and in vivo efficacy. Combining PLGA polymers that varied in their molecular weights in various ratios yielded microspheres with varied drug release profiles commensurate with the hydration tendencies of the polymers. Increasing the component of lower molecular weight 50:50 hydrophilic PLGA polymer, 8.6 kDa increased the initial drug release. A similar microsphere formulation prepared instead with blending microspheres from individual polymers showed a similar increase. In an animal model, microspheres obtained from polymer or microsphere blends attained a faster onset of testosterone suppression as compared to microspheres from higher molecular weight 50:50 hydrophilic PLGA polymer, 28.3 kDa, alone. These studies illustrated the feasibility of blending polymers or microspheres of varied characteristics in achieving modified drug release. In particular the increased initial release of the peptide could help avoid the therapeutic lag phase usually observed with microencapsulated macromolecules. PMID:10962237

Ravivarapu, H B; Burton, K; DeLuca, P P

2000-09-01

9

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

Microsoft Academic Search

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

Harish B Ravivarapu; Kevin Burton; Patrick P DeLuca

2000-01-01

10

Elevated temperature accelerated release testing of PLGA microspheres.  

PubMed

Drug release from four different poly(lactic-co-glycolic) acid (PLGA) microsphere formulations was evaluated under "real-time" (37 degrees C) and accelerated release testing conditions of elevated temperature (45, 53, 60 and 70 degrees C) and increase in flow rate (4-35 ml/min) using United States Pharmacopeia (USP) apparatus 4. Formulation 5 K (composed of low Mw PLGA) exhibited diffusion-controlled kinetics in "real-time". Whereas, formulations 25 K, 28 K and 70 K (composed of medium and high Mw PLGA) followed erosion-controlled kinetics at 37 degrees C. Temperature-induced degradation of the microspheres was studied by monitoring drug release rates, change in molecular weight and morphological changes. Drug release rates at elevated temperature were used to predict "real-time" release applying the Arrhenius equation. The energy of activation for dexamethasone release from PLGA microspheres was calculated as 19.14 kcal/mol. Molecular weight change measured by gel permeation chromatography followed first order kinetics for both "real-time" and accelerated release. All four formulations exhibited morphological changes (such as surface pore closing and geometry change) at elevated temperature with consequent reduction in burst release. PMID:16644055

Zolnik, Banu S; Leary, Pauline E; Burgess, Diane J

2006-04-27

11

PLGA microspheres containing bee venom proteins for preventive immunotherapy.  

PubMed

Bee venom (BV) allergy is potentially dangerous for allergic individuals because a single bee sting may induce an anaphylactic reaction, eventually leading to death. Currently, venom immunotherapy (VIT) is the only treatment with long-lasting effect for this kind of allergy and its efficiency has been recognized worldwide. This therapy consists of subcutaneous injections of gradually increasing doses of the allergen. This causes patient lack of compliance due to a long time of treatment with a total of 30-80 injections administered over years. In this article we deal with the characterization of different MS-PLGA formulations containing BV proteins for VIT. The PLGA microspheres containing BV represent a strategy to replace the multiple injections, because they can control the solute release. Physical and biochemical methods were used to analyze and characterize their preparation. Microspheres with encapsulation efficiencies of 49-75% were obtained with a BV triphasic release profile. Among them, the MS-PLGA 34kDa-COOH showed to be best for VIT because they presented a low initial burst (20%) and a slow BV release during lag phase. Furthermore, few conformational changes were observed in the released BV. Above all, the BV remained immunologically recognizable, which means that they could continuously stimulate the immune system. Those microspheres containing BV could replace sequential injections of traditional VIT with the remarkable advantage of reduced number of injections. PMID:21356289

Trindade, Reginaldo A; Kiyohara, Pedro K; de Araujo, Pedro S; Bueno da Costa, Maria H

2011-02-26

12

PLGA microsphere bioburden evaluation for radiosterilization dose selection.  

PubMed

The aim of this study was to determine the bioburden of PLGA microspheres produced by the solvent emulsion/extraction process as a means of determining an appropriate gamma-irradiation dose for sterilization. Bioburden was evaluated on the basis of ISO specifications. The analysis of initial microbial contamination was performed on blank microspheres, prepared by a non-aseptic laboratory scale process. A mean bioburden of 36.04 CFU (colony forming units)/110 mg microspheres was determined. Most of the detected germs originated from human commensal flora. According to the ISO dose-selection method, a gamma-irradiation dose of 19.6 kGy was found sufficient to ensure a sterility level of 10(-6). The effect of the selected irradiation dose on both the molecular weight of the polymer and the kinetics of 5-fluorouracil drug release from the microspheres was compared to the European Pharmacopeia recommended irradiation dose (25 kGy). This 20% reduced dose showed a lower extent of molecular weight reduction of PLGA and a better control of 5-FU release from microparticles. This can be related to reduce polymer radiation damage. PMID:11508768

Gèze, A; Venier-Julienne, M C; Cottin, J; Faisant, N; Benoit, J P

13

Distribution and deposition of respirable PLGA microspheres in lung alveoli.  

PubMed

Although treatment of pulmonary tuberculosis with respirable microspheres (MS) with an incorporated antituberculosis drug is expected to be highly effective, this treatment seems to achieve a much lesser effect than expected in the case of killing Mycobacterium tuberculosis residing in the lungs. To elucidate the reason for this weaker effect, we examined the distribution and accumulation of respirable MS consisting of poly(lactic-co-glycolic) acid (PLGA) in rat lungs. For this, we delivered the PLGA MS containing fluorescent coumarin 6 or an antituberculosis agent, rifampicin (RFP), by insufflation via the trachea and then determined the pulmonary distribution by counting the number of the MS in lung cryosections observed under a microscope. In addition, the uptake of MS by alveolar macrophage (AM?) was determined by immunostaining for M? cell marker CD68 and RFP content in the cells. Approximately half of the fluorescent PLGA MS reached the alveoli without entrapment by trachea and primary bronchi and were then ingested by the AM? cells up to 24h after insufflation. RFP in a form of PLGA MS was markedly transported into AM? at an amount 10 times greater than that for the free RFP powder. However, a large proportion of RFP was eliminated from the lungs by 6h after insufflation. PMID:23384687

Hirota, Keiji; Kawamoto, Tadafumi; Nakajima, Takehisa; Makino, Kimiko; Terada, Hiroshi

2013-01-03

14

Sulforaphane-PLGA microspheres for the intra-articular treatment of osteoarthritis.  

PubMed

Sulforaphane (SFN) is a member of the isothiocyanate family that has anti-inflammatory action as well as anti-carcinogenic properties. The authors have devised an intra-articular injectable SFN-PLGA microsphere system that can be used for treating osteoarthritis (OA). The purpose of this study was to evaluate the in vitro and in vivo efficacy of the SFN-PLGA microsphere system. Articular chondrocytes were obtained from knee OA patients and were cultured in monolayers. The optimal concentration of SFN was obtained and the dose of SFN-PLGA microspheres was determined based on the concentration. The in vitro anti-inflammatory effect on markers such as cyclooxygenase (COX)-2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, and matrix metalloproteinase (MMP)-2 was assessed by real-time PCR and Western blotting. The in vivo therapeutic effect of SFN-PLGA microspheres was investigated using surgically-induced rat OA model. Treatment with SFN-PLGA microspheres inhibited the mRNA and protein expression of COX-2, ADAMTS-5 and MMP-2 induced by LPS in articular chondrocytes. Intraarticular SFN-PLGA microspheres delayed the progression of surgically-induced osteoarthritis in rats. In conclusion, SFN-PLGA microspheres can be a useful injectable delivery system for treating osteoarthritis. PMID:23601658

Ko, Ji-Yun; Choi, You-Jeong; Jeong, Geun-Jae; Im, Gun-Il

2013-04-16

15

Local antitumor effects of intratumoral delivery of rlL-2 loaded sustained-release dextran/PLGA-PLA core/shell microspheres.  

PubMed

In this study, we formulated a rIL-2 loaded sustained-release dextran/PLGA-PLA core/shell microsphere, mimicking the paracrine mechanisms of cytokine action, to investigate its local antitumor efficacy. The presented microspheres were formed in two steps: rIL-2 was firstly loaded into dextran particles to keep its bioactivity by a unique method of stabilizing aqueous-aqueous "emulsion"; subsequently, the particles were encapsulated into poly(dl-lactide-co-glycolide)/polylactic acid (PLGA/PLA). A stable sustained release behavior in vitro was achieved for a period of about 25 days. In the subcutaneous colon carcinoma BALB/c mice models, a single dose of microspheres was introtumorally administrated and compared with multiple doses of rIL-2 solution to investigate the long acting effect of microspheres on tumor. The animal experiments showed the local efficacy at tumor site mediated by rIL-2 from a single dose of microspheres was better than that of multiple rIL-2 solution injections. Based on the experimental results, we conclude that rlL-2 loaded sustained-release dextran/PLGA-PLA core/shell microspheres represent a promising approach for local cancer treatment in animals. PMID:23624084

Zhao, Haiping; Wu, Fei; Cai, Yunpeng; Chen, Yinghui; Wei, Liangming; Liu, Zhenguo; Yuan, Weien

2013-04-25

16

Alginate-Chitosan-PLGA Composite Microspheres Enabling Single-Shot Hepatitis B Vaccination  

PubMed Central

Hepatitis B vaccination typically requires a multi-dose administration protocol over a course of 3–6 months. Aiming at developing a single-shot formulation for hepatitis B vaccine (hepatitis B surface antigen (HBsAg)), a novel vaccine delivery system, the composite microspheres of alginate–chitosan–poly(lactic-co-glycolic acid) (PLGA), was synthesized by a two-step preparation. The composite microspheres showed distinct advantages over the conventional PLGA microspheres in aspects of the high loading capacity and the elimination of lyophilizing process. The loading capacity of the composite microspheres was about seven times higher than those in the conventional PLGA microspheres, due to the protein-friendly microenvironment created by the hydrophilic alginate–chitosan cores of the composite microspheres. This vaccine delivery system was shown to be able to induce robust immune responses by single injection and display no significant difference in HBsAg-specific antibody levels compared to the double-injection method.

Zheng, Xiaoling; Huang, Yongzhuo; Dong, Siyu; Liang, Wenquan

2010-01-01

17

Preparation and characterization of PLGA microspheres by the electrospraying method for delivering simvastatin for bone regeneration.  

PubMed

Microparticles formulated from poly (D,L-lactic-co-glycolide) (PLGA), a biodegradable polymer, have been investigated extensively as a drug delivery system. In this study, solid tiny PLGA microspheres were fabricated using the electrospraying method. PLGA polymer was dissolved in dichloromethane (DCM), and the solution was electrosprayed. The electrospraying conditions were adjusted so that the stream ejected from the needle was divided into spheres instead of continuous fibers or irregular-shaped particles. Several experiments were carried out using the PLGA-DCM source solution with different amounts of simvastatin (SIM), a drug that enhances bone regeneration, to understand this drug delivery system. The surface morphology and microstructure of the microspheres formed were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The in vitro experiments on drug loading and drug release behavior of the microspheres suggested a drug encapsulation efficacy >90%. The drug was continuously released from the microspheres for >3 weeks. Other experiments, such as MTT, cell attachment and proliferation and reverse transcription-polymerase chain reaction showed good biocompatibility of the electrosprayed PLGA microspheres, which increased in the presence of SIM. Thus, electrosprayed PLGA microspheres have potential as a drug delivery system and application in bone tissue engineering. PMID:23291448

Nath, Subrata Deb; Son, Sora; Sadiasa, Alexandar; Min, Young Ki; Lee, Byong Taek

2013-01-03

18

Downregulation of endotoxin-induced uveitis by intravitreal injection of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone  

Microsoft Academic Search

We tested the short- and long-term ability of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone to reduce ocular inflammation in rabbits elicited by intravitreal lipopolysaccharide (LPS) injection. PLGA microspheres loaded with dexamethasone were prepared by the solvent evaporation technique from an oil\\/water emulsion and sterilized by gamma irradiation (25 kGy). The microsphere fraction selected was 2:10 (dexamethasone:PLGA) and contained 141 ± 0.38 ?g dexamethasone\\/mg

Emilia Barcia; Rocío Herrero-Vanrell; Ana Díez; Consuelo Alvarez-Santiago; Isabel López; Margarita Calonge

2009-01-01

19

Intra-discal vancomycin-loaded PLGA microsphere injection for MRSA discitis: an experimental study  

Microsoft Academic Search

Objective  To prepare the vancomycin hydrochloride (VA)-loaded poly lactic acid-glycolic acid (PLGA) copolymer microsphere by the multiple\\u000a emulsion method and evaluate its therapeutic effects on infective discitis.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Firstly, the particle diameter distribution, shape, encapsulation efficiency, drug-loaded dosage and release curve of VA-PLGA\\u000a microspheres were evaluated in vitro. Rabbits with methicillin-resistant Staphylococcus aureus infective discitis were treated with VA-PLGA intra-discal injection. Meanwhile,

Fei WangBin; Bin Ni; Zhuangchen Zhu; Fucun Liu; Yu-Zhao Zhu; Jun Liu

2011-01-01

20

Sustained release of PTH(1-34) from PLGA microspheres suppresses osteoarthritis progression in rats.  

PubMed

We previously reported that PTH(1-34) inhibits the terminal differentiation of articular chondrocytes and, in turn, suppresses the progression of osteoarthritis (OA). However, this treatment requires an injection of PTH(1-34) once every 3 days over the treatment period. In this study, we studied the effect of sustained administration of PTH(1-34) in a papain-induced OA rat model. We developed an effective controlled-release system for prolonging the treatment duration of an intra-articular injection for OA treatment in rats. The effects of released PTH(1-34) from PLGA(65:35)-encapsulated PTH(1-34) microspheres (PTH/PLGA) on papain-induced OA in rat knees were studied. Microsphere morphology was observed in vitro by scanning electron microscopy, and microsphere size was determined with a particle size analyzer. The PTH(1-34) encapsulation efficiency and release profile, as well as the toxicity of PTH/PLGA, were examined. The bioactivity of released PTH(1-34) was tested by examining cAMP levels in MC3T3E1 cells. In vivo, we evaluated the changes of localized GAG, Col II, and Col X in the articular cartilage of rat knees. Our results demonstrated that the surface of the PLGA microspheres was smooth, and the size of the microspheres was in the range of 51-127 ?m. PTH/PLGA microspheres sustainably released PTH(1-34) for 19 days with a concentration range of 0.01-100 nM that covered the expected concentration of 10nM at 37°C. The cAMP levels of MC3T3E1 cells were elevated in the response to released PTH(1-34) from PTH/PLGA microspheres, indicating that the released PTH(1-34) is bioactive. Most importantly, intra-articular treatment with either PTH(1-34) (0.1-100 nM) 3 days/injection or PTH/PLGA microspheres (15 days/injection) for 5 weeks revealed the similar effect on suppressing papain-induced OA changes (decreasing GAG and Col II and increasing Col X) in rat knee cartilage. The effect of PTH/PLGA microspheres on suppressing OA progression was similar to that of a once-every-three-day injection of PTH(1-34), indicating that both the sustained and intermittent action of PTH(1-34) effectively suppress OA progression. The developed PLGA microspheres with sustained release and long-term effect may be potent carriers for PTH(1-34) used to treat early OA. PMID:22414620

Eswaramoorthy, Rajalakshmanan; Chang, Chia-Chi; Wu, Shun-Cheng; Wang, Gwo-Jaw; Chang, Je-Ken; Ho, Mei-Ling

2012-03-10

21

Extended release peptide delivery systems through the use of PLGA microsphere combinations.  

PubMed

The purpose of this study was to evaluate the utility of combining polymer matrices to overcome extended lag periods or unacceptably short durations of action intrinsic in the individual polymer systems. Leuprolide, an LHRH superagonist, was incorporated into a variety of poly(lactide-co-glycolide) (PLGA) matrices using a solvent extraction/evaporation method. The in vitro release of Leuprolide from these matrices was evaluated at pH 7.0 and 37 degrees C in phosphate buffer. The formulations were administered to an animal model at 3 or 9 mg kg(-1) doses and serum testosterone levels were followed using a RIA method. A two-part system was made by combining microspheres made from a 75:25 acid terminated PLGA and microspheres made from a 75:25 ester terminated PLGA. This combination elicited chemical castration from 10-100 days. A three-part combination composed of an ester terminated 75:25 PLGA formulation, an ester terminated 50:50 PLGA formulation and an acid terminated 50:50 PLGA formulation also provided a composite profile with an onset of 10 days and a duration of approximately 100 days. Additionally, a single polymer system composed of a high molecular weight ester terminated 75:25 PLGA was employed to produce release over the desired 90-day release period. This study demonstrates that microsphere combinations can potentially provide effective therapies over extended intervals when combined at the proper ratio. PMID:11011769

Burton, K W; Shameem, M; Thanoo, B C; DeLuca, P P

2000-01-01

22

PLGA-microsphere mediated clearance of bilirubin in temporarily hyperbilirubinemic rats: An alternate strategy for the treatment of experimental jaundice  

Microsoft Academic Search

In the present study, we have demonstrated the suitability of microspheres in removal of plasma bilirubin from systemic circulation of hyperbilirubinemic rats. Poly (lactide co-glycolide) microspheres (PLGA microspheres) have been shown to bind with bilirubin in both a concentration and time dependent manner. The binding affinity of bilirubin to microspheres was enhanced when rat serum albumin (RSA) was loaded into

N. Ahmad; K. Arif; S. M. Faisal; M. K. Neyaz; S. Tayyab; M. Owais

2006-01-01

23

In Situ Characterization of the Degradation of PLGA Microspheres in Hyaluronic Acid Hydrogels by Optical Coherence Tomography  

Microsoft Academic Search

The polymeric implant material poly(lactide-co-glycolide) (PLGA) degrades by a process of bulk degradation, which allows it to be used for the controlled release of therapeutic molecules from implants and microspheres. The temporal characterization of PLGA microsphere degradation has been limited by the need to destructively monitor the samples at each time point. In this study, a noninvasive imaging technology, optical

Jennifer Patterson; Patrick S. Stayton; Xingde Li

2009-01-01

24

Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters.  

PubMed

The purpose of this study was to develop a suitable formulation for gentamicin sulfate (GS) that gives a sustained release of the drug. Therefore this drug was loaded into poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres. The effects of various formulation parameters (ethanol, surfactant, osmotic value of the external phase, polymer type and concentration) on particle characteristics (size, loading and release) were investigated. The GS loaded microspheres were prepared using a double emulsion evaporation technique. The results demonstrate that neither ethanol nor surfactants had beneficial effects on the drug loading efficiency (around 4-10%). However, an increase in buffer concentration (and thus osmotic pressure) of the external phase resulted in a substantial increase of GS-loading (from 10 to 28%). Further, an increase of concentration of PLGA in DCM from 10% to 15/20% caused a 4-time increase of the drug loading. The best formulation identified in this study had a loading efficiency of around 70% resulting in PLGA microspheres with a 6% (w/w) loading. The particles showed a burst release of the drug depending on their porosity, followed by a phase of 35 days where hardly any release occurred. The drug was then slowly released for around 25 days likely due to degradation of the microspheres. The drug loading efficiency of GS in PLHMGA was not significantly different from PLGA microspheres (64%). The release of GS from PLHMGA microspheres was faster than that of PLGA because the degradation rate of PLHMGA is more rapid than PLGA. This study shows that prolonged release of gentamicin can be obtained by loading this drug into microspheres made of biodegradable aliphatic polyesters. PMID:21353499

Chaisri, Wasana; Ghassemi, Amir H; Hennink, Wim E; Okonogi, Siriporn

2011-02-25

25

Recent advances in the preparation progress of protein/peptide drug loaded PLA/PLGA microspheres.  

PubMed

Sustained release drug delivery from microparticles is an excellent alternative for daily protein/peptide drug administration protocol. Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are the most commonly used polymer carriers in the development of protein/peptide microspheres. Basically there are three preparation methods for PLA/PLGA microspheres: the solvent extraction/evaporation based multiple emulsion (W/O/W emulsion) method, the phase separation method and the spray drying method. The stability of the protein/pipetide loaded, encapsulation efficiency, and the burst effect of the microspheres are key problems usually met in the preparation of microspheres. In this review the preparation techniques and progress in the development of protein/pipetide microspheres which aimed to stabilize protein/peptide structural integrity, keep the bioactivity of drugs, increase the encapsulation efficiency and improve the release profile were summarized and evaluated. PMID:17520799

Xu, Feng-Hua; Zhang, Qiang

2007-01-01

26

Sequential release of bioactive IGF-I and TGF-? 1 from PLGA microsphere-based scaffolds  

Microsoft Academic Search

Growth factors have become an important component for tissue engineering and regenerative medicine. Insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-?1) in particular have great significance in cartilage tissue engineering. Here, we describe sequential release of IGF-I and TGF-?1 from modular designed poly(l,d-lactic-co-glycolic acid) (PLGA) scaffolds. Growth factors were encapsulated in PLGA microspheres using spontaneous emulsion, and in vitro

Ana Jaklenec; Alexandra Hinckfuss; Bahar Bilgen; Deborah M. Ciombor; Roy Aaron; Edith Mathiowitz

2008-01-01

27

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

28

Acidic Microclimate pH Distribution in PLGA Microspheres Monitored by Confocal Laser Scanning Microscopy  

Microsoft Academic Search

Purpose  The acidic microclimate pH (µpH) distribution inside poly(lactic-co-glycolic acid) (PLGA) microspheres was monitored quantitatively as a function of several formulation variables.\\u000a \\u000a \\u000a \\u000a Methods  A ratiometric method by confocal laser scanning microscopy with Lysosensor yellow\\/blue® dextran was adapted from those previously\\u000a reported, and µpH distribution kinetics inside microspheres was examined during incubation under physiologic conditions for\\u000a 4 weeks. Effects of PLGA molecular weight (MW)

Amy G. Ding; Steven P. Schwendeman

2008-01-01

29

Improvement of survival in C6 rat glioma model by a sustained drug release from localized PLGA microspheres in a thermoreversible hydrogel.  

PubMed

A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature. Therefore, when this formulation is injected into the brain tumor, the PLGA microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or vincristine (VCR)) were incorporated into PLGA microspheres to prepare drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In addition, VCR/PLGA microspheres showed a higher sustained release profile than CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic effect (mean survival) was evaluated in the C6 rat glioma model (control group, 18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the glioma therapy. PMID:22366485

Ozeki, Tetsuya; Kaneko, Daiki; Hashizawa, Kosuke; Imai, Yoshihiro; Tagami, Tatsuaki; Okada, Hiroaki

2012-02-16

30

Effect of Stabilizers on Bioactivity of Peptide-24 in PLGA Microspheres.  

PubMed

In the present study, Poly (D,L-lactide-co-glycolide) microspheres (PLGA MSs) were prepared for delivering a novel oligopeptide derived from rhBMP-2 (Peptide-24). Hydroxypropyl-?-cyclodextrin (HP-?-CD) and Bovine serum albumin (BSA) were used as stabilizers for retaining bioactivity of the oligopeptide. The morphology, diameter, drugloading rates and encapsulation rates of the PLGA MSs were detected and compared. The PLGA MSs were incubated for 3 and 30 days respectively to obtain the release supernatant containing Peptide-24. The structure and bioactivity of released Peptide-24 from PLGA MSs were evaluated through physicochemical detections and cell culture. The structure integrity of the Peptide-24 was confirmed by Far-UV circular dichroism and matrix-assisted laser desorption/ionization time-of-flight Mass Spectrometer (MALDI-TOF-MS) analysis. The interaction between PLGA matrix and loaded Peptide- 24 was verified through Raman. The results showed that the diameter of PLGA MSs was from 8.62 to 15.34 ?m, the loading rate was 0.7-0.8%, and the encapsulation rate was 69.3-85.3%. The released Peptide-24 from PLGA MSs was proved to retain original bioactivity by the cellular activity and alkaline phosphatase (ALP) test. HP-?-CD is a kind of excellent stabilizer for retaining the bioactivity of Peptide-24 in PLGA MSs. PMID:23227911

Wang, Mingbo; Guo, Xiaodong; Tan, Rongwei; She, Zhending; Feng, Qingling

2013-12-01

31

Influence of PEG in PEG-PLGA microspheres on particle properties and protein release.  

PubMed

The aim of the present study was to compare different commercial available types of Poly(d,l-lactide-co-glycolide) (PLGA), multiblock copolymers of PLGA and polyethylene gylcol (PEG) as well as blends of PLGA and PEG regarding the preparation of microparticles and the release behavior of encapsulated protein. Microspheres were prepared by the solvent evaporation technique using the same conditions for each formulation. The encapsulation rate of bovine serum albumin (BSA) was unaffected by the different polymer types, and the mean was 79±4%. Microspheres composed of blends of PLGA and PEG showed a porous structure, a higher specific surface area, an inhomogenous distribution of protein and a higher release rate of BSA than microspheres consisting of PLGA, whereas the release profiles were the same. The specific surface area of microparticle formulations composed of diblock copolymers was the highest with 8.57±0.07m(2)/g emphasized by a highly porous, sponge-like structure. The triblock copolymer formulation revealed nearly spherical particles with a slightly uneven surface. Although the triblock copolymer consists of 10% PEG, the specific surface area was the lowest of all formulations. The rapid hydration due to PEG leads to a swollen matrix, which released the protein in a slow and continuous way. PMID:22306701

Buske, J; König, C; Bassarab, S; Lamprecht, A; Mühlau, S; Wagner, K G

2012-01-28

32

Monitoring of peptide acylation inside degrading PLGA microspheres by capillary electrophoresis and MALDI-TOF mass spectrometry  

Microsoft Academic Search

The purpose of this research was to assess the acylation reactions of peptides, salmon calcitonin (sCT), human parathyroid hormone 1–34 (hPTH1–34) and leuprolide, in poly(lactic-co-glycolic acid) (PLGA) microspheres. Capillary electrophoresis (CE) and matrix-assisted laser desorption\\/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used for determining and monitoring peptide acylation and quantitating acylation products in the degrading PLGA microspheres. In the degrading

Dong Hee Na; Yu Seok Youn; Sang Deuk Lee; Mi-Won Son; Won-Bae Kim; Patrick P. DeLuca; Kang Choon Lee

2003-01-01

33

Formulation and in vitro characterization of inhalable rifampicin-loaded PLGA microspheres for sustained lung delivery.  

PubMed

The solvent evaporation method with premix membrane homogenization was applied, with class-3 ethyl acetate as organic solvent, to produce narrowly size-distributed rifampicin (RIF)-loaded poly(lactide-co-glycolide) (PLGA) microspheres for sustained lung delivery as aerosol. Microsphere formulations (simple or multiple emulsions, different PLGA and RIF concentrations) and process parameters (transmembrane pressure, SPG membrane pore diameter) were investigated as their effects on RIF content, microsphere size, aerodynamic properties of the freeze-dried powder and in vitro release profiles. Narrowly size distributed microspheres with diameters from 2 to 8 ?m, satisfactory RIF contents (from 4.9 to 16.5%), 80% RIF release from 12h to 4 days, and adequate aerodynamic properties were prepared from a multiple emulsion and using SPG membrane pore diameter of 19.9 ?m. The premix membrane homogenization appeared to be a rapid and efficient method to prepare monodisperse drug-loaded microspheres suitable for lung delivery as sustained-release microsphere aerosol. PMID:21596123

Doan, T V P; Couet, W; Olivier, J C

2011-05-10

34

Stabilization and encapsulation of recombinant human erythropoietin into PLGA microspheres using human serum albumin as a stabilizer.  

PubMed

The aim of this study was to prepare recombinant human erythropoietin (rhEPO) loaded poly(lactic-co-glycolic acid) (PLGA) microspheres using human serum albumin (HSA) as a stabilizer. Prior to encapsulation, the rhEPO-HSA mixture microparticles were fabricated using a modified freezing-induced phase separation method. The microparticles were subsequently encapsulated into PLGA microspheres. Process optimization revealed that the polymer concentration in the organic phase and the sodium chloride (NaCl) concentration in the outer water phase of the s/o/w emulsion played critical roles in determining the properties of the resultant microspheres. An in vitro release test showed that rhEPO was released from PLGA microspheres in a sustained manner up to 30 days. A single injection of rhEPO-loaded PLGA microspheres in Sprague-Dawley rats resulted in elevated hemoglobin and red blood cell concentrations for about 33 days. The stability of the rhEPO within the PLGA microspheres was systematically investigated by size-exclusion high-performance liquid chromatography (SEC-HPLC), SDS-PAGE, western blot and in vivo biological activity assay. The stability of rhEPO released from rhEPO-loaded microspheres was also examined by western blot. The results suggested that the integrity of rhEPO was successfully protected during the encapsulation process and the release period from polymeric matrices. PMID:21699969

He, Jintian; Feng, Meiyan; Zhou, Xianglian; Ma, Shufen; Jiang, Yang; Wang, Ying; Zhang, Hongxia

2011-06-15

35

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

PubMed Central

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

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

2013-01-01

36

Phase separation behavior of fusidic acid and rifampicin in PLGA microspheres.  

PubMed

The purpose of this study was to characterize the phase separation behavior of fusidic acid (FA) and rifampicin (RIF) in poly(d,l-lactic acid-co-glycolic acid) (PLGA) using a model microsphere formulation. To accomplish this, microspheres containing 20% FA with 0%, 5%, 10%, 20%, and 30% RIF and 20% RIF with 30%, 20% 10%, 5%, and 0% FA were prepared by solvent evaporation. Drug-polymer and drug-drug compatibility and miscibility were characterized using laser confocal microscopy, Raman spectroscopy, XRPD, DSC, and real-time video recordings of single-microsphere formation. The encapsulation of FA and RIF alone, or in combination, results in a liquid-liquid phase separation of solvent-and-drug-rich microdomains that are excluded from the polymer bulk during microsphere hardening, resulting in amorphous spherical drug-rich domains within the polymer bulk and on the microsphere surface. FA and RIF phase separate from PLGA at relative droplet volumes of 0.311 ± 0.014 and 0.194 ± 0.000, respectively, predictive of the incompatibility of each drug and PLGA. When coloaded, FA and RIF phase separate in a single event at the relative droplet volume 0.251 ± 0.002, intermediate between each of the monoloaded formulations and dependent on the relative contribution of FA or RIF. The release of FA and RIF from phase-separated microspheres was characterized exclusively by a burst release and was dependent on the phase exclusion of surface drug-rich domains. Phase separation results in coalescence of drug-rich microdroplets and polymer phase exclusion, and it is dependent on the compatibility between FA and RIF and PLGA. FA and RIF are mutually miscible in all proportions as an amorphous glass, and they phase separate from the polymer as such. These drug-rich domains were excluded to the surface of the microspheres, and subsequent release of both drugs from the microspheres was rapid and reflected this surface location. PMID:22482935

Gilchrist, Samuel E; Rickard, Deborah L; Letchford, Kevin; Needham, David; Burt, Helen M

2012-04-18

37

PLGA microspheres by Supercritical Emulsion Extraction: a study on insulin release in myoblast culture.  

PubMed

Supercritical Emulsion Extraction in a Continuous operation layout is proposed for the production of poly-lactic-co-glycolic acid (PLGA) microspheres loaded with insulin, selected as a model of bioactive signal. Microspheres with different mean sizes of 2??m (±0.9??m) and 3??m (±2.2??m) and insulin loadings of 3 and 6?mg/g were obtained by processing different water-oil-water emulsions; an encapsulation efficiency of about 60% w/w was measured in all cases. Insulin release profiles from PLGA microspheres were also characterized in two different media (Phosphate-Buffered Saline and Dulbecco's Modified Eagle Medium) and kinetic constants were estimated by using a model proposed in literature. The produced microspheres were, then, used for the cultivation of rat embryonic ventricular myoblasts in a serum-free medium to monitor the biological effect of the released insulin. The best cell viability and proliferation, supported by released insulin, was monitored when microspheres with mean size of 3??m loaded with 3?mg/g of insulin were added. PMID:23786568

Della Porta, Giovanna; Falco, Nunzia; Giordano, Emanuele; Reverchon, Ernesto

2013-06-21

38

SOX9 gene plus heparinized TGF-? 3 coated dexamethasone loaded PLGA microspheres for inducement of chondrogenesis of hMSCs.  

PubMed

Microparticulated types of scaffolds have been widely applied in stem cell therapy and the tissue engineering field for the regeneration of wound tissues. During application of simple genes or growth factors and cell delivery vehicles, we designed a method that employs dexamethsone loaded PLGA microspheres consisting of polyplexed SOX9 genes plus heparinized TGF-? 3 on the surface of polymeric microspheres prepared using a layer-by-layer (LbL) method. The fabrication of the polyplexed SOX9 genes plus heparinized TGF-? 3 and their subsequent coating onto dexamethsone loaded PLGA microspheres represents a method for functionalization of the polymeric matrix. The use of SOX9 gene plus heparinized TGF-? 3 coated dexamethsone loaded PLGA microspheres was evaluated to determine their potential as both gene carriers and cell delivery vehicle. By adhesion of hMSCs onto SOX9 gene plus heparinized TGF-? 3 coated dexamethsone loaded PLGA microspheres, the chondrogenesis-related specific genes of collagen type II were increased 30 times comparing to control. Also, the specific extracellular matrix of glycosaminoglycan (GAG) production of hMSCs adhered onto SOX9 gene plus heparinized TGF-? 3 coated dexamethasone loaded PLGA microspheres increased more 2.5 times than control group. Not only in vitro culture but in vivo results, the specific genes of COMP, aggrecan, collagen type II, and SOX9 showed much more gene expressions such as 20, 15, 10, 8 times. PMID:22795539

Park, Ji Sun; Yang, Han Na; Woo, Dae Gyun; Jeon, Su Yeon; Park, Keun-Hong

2012-07-11

39

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

Microsoft Academic Search

A novel chitin-based microsphere was developed for anti-cancer drug-delivery purpose in the present study. These biodegradable microspheres were prepared by directly blending chitin with different contents of poly(d,l-lactide-co-glycolide 50:50) (PLGA 50\\/50) in dimethylacetamide–lithium chloride solution, and following it by coagulating in water via wet phase inversion. Scanning electron microscopy (SEM) micrography of the blend microsphere showed that there are numerous

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

2002-01-01

40

Gamma-irradiation effects on biopharmaceutical properties of PLGA microspheres loaded with SPf66 synthetic vaccine.  

PubMed

Gamma-irradiation is currently the method of choice for terminal sterilization of drug delivery systems made from biodegradable polymers. However, the consequences of gamma-sterilization on the immune response induced by microencapsulated antigens have not yet been reported in the literature. The aim of the present work was to evaluate the effect of gamma-irradiation on the biopharmaceutical properties of PLGA microspheres containing SPf66 malarial antigen. Microspheres were prepared by a (w/o/w) double emulsion/solvent extraction method. Once prepared, part of the formulation was irradiated at a dose of 25 kGy using 60Co gamma as radiation source. The in vitro results obtained showed that the gamma-irradiation exposure had no apparent effect on SPf66 integrity and formulation properties such us morphology, size and peptide loading. Only the release rate of SPf66 was slightly faster after gamma-irradiation. Subcutaneous administration of irradiated and non-irradiated microspheres into mice induced a similar immune response (IgG, IgG1, IgG2a levels) and was comparable to that obtained with SPf66 emulsified with Freund's complete adjuvant. These observations illustrate the applicability of gamma-irradiation as a method of terminal sterilization of microparticulate delivery systems based on chemically synthesized antigens encapsulated into biodegradable PLGA microspheres. PMID:18280123

Igartua, Manoli; Hernández, Rosa M A; Rosas, Jaiver Eduardo; Patarroyo, Manuel Elkin; Pedraz, José Luís

2007-12-25

41

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

PubMed

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

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

2013-02-27

42

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

2006-02-21

43

The Effect of Temozolomide/Poly(lactide-co-glycolide) (PLGA)/Nano-Hydroxyapatite Microspheres on Glioma U87 Cells Behavior  

PubMed Central

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

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

2012-01-01

44

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

Microsoft Academic Search

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

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

1997-01-01

45

Biodegradable insulin-loaded PLGA microspheres fabricated by three different emulsification techniques: investigation for cartilage tissue engineering.  

PubMed

Growth, differentiation and migration factors facilitate the engineering of tissues but need to be administered with defined gradients over a prolonged period of time. In this study insulin as a growth factor for cartilage tissue engineering and a biodegradable PLGA delivery device were used. The aim was to investigate comparatively three different microencapsulation techniques, solid-in-oil-in-water (s/o/w), water-in-oil-in-water (w/o/w) and oil-in-oil-in-water (o/o/w), for the fabrication of insulin-loaded PLGA microspheres with regard to protein loading efficiency, release and degradation kinetics, biological activity of the released protein and phagocytosis of the microspheres. Insulin-loaded PLGA microspheres prepared by all three emulsification techniques had smooth and spherical surfaces with a negative zeta potential. The preparation technique did not affect particle degradation nor induce phagocytosis by human leukocytes. The delivery of structurally intact and biologically active insulin from the microspheres was shown using circular dichroism spectroscopy and a MCF7 cell-based proliferation assay. However, the insulin loading efficiency (w/o/w about 80%, s/o/w 60%, and o/o/w 25%) and the insulin release kinetics were influenced by the microencapsulation technique. The results demonstrate that the w/o/w microspheres are most appropriate, providing a high encapsulation efficiency and low initial burst release, and thus these were finally used for cartilage tissue engineering. Insulin released from w/o/w PLGA microspheres stimulated the formation of cartilage considerably in chondrocyte high density pellet cultures, as determined by increased secretion of proteoglycans and collagen type II. Our results should encourage further studies applying protein-loaded PLGA microspheres in combination with cell transplants or cell-free in situ tissue engineering implants to regenerate cartilage. PMID:21168535

Andreas, Kristin; Zehbe, Rolf; Kazubek, Maja; Grzeschik, Karolina; Sternberg, Nadine; Bäumler, Hans; Schubert, Helmut; Sittinger, Michael; Ringe, Jochen

2010-12-17

46

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

47

Preparation of porous PLGA microspheres with thermoreversible gel to modulate drug release profile of water-soluble drug: bleomycin sulphate.  

PubMed

Bleomycin sulphate-loaded porous microspheres were prepared using modified solvent evaporation method (w/o/w) using PLGA50:50 as a polymeric system. The prepared microspheres were incorporated in pluronic (F127) based thermoreversible gel to develop a depot formulation. Various process parameters as solvent evaporation temperature and formulation parameters such as surfactant concentration, volume of internal and external phase and drug-to-polymer ratio were optimized for enhancing percentage drug entrapment, percentage drug loading and desired release profile by controlling size and porosity of the microspheres. Microspheres were characterized for particle size, zeta potential, surface morphology, percentage drug loading and in vitro drug release study after incorporated in gel. The formulated microspheres were porous in nature and showed biphasic in vitro drug release profile. The microspheres incorporated in pluronic (F127) gel showed sustained release up to 1 week and may be useful for treatment of squamous cell carcinoma with better therapeutic effect. PMID:20128747

Chaudhari, Kiran R; Shah, Neha; Patel, Hetal; Murthy, Rayasa

2010-01-01

48

Monitoring of peptide acylation inside degrading PLGA microspheres by capillary electrophoresis and MALDI-TOF mass spectrometry.  

PubMed

The purpose of this research was to assess the acylation reactions of peptides, salmon calcitonin (sCT), human parathyroid hormone 1-34 (hPTH1-34) and leuprolide, in poly(lactic-co-glycolic acid) (PLGA) microspheres. Capillary electrophoresis (CE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used for determining and monitoring peptide acylation and quantitating acylation products in the degrading PLGA microspheres. In the degrading PLGA microspheres of sCT and hPTH1-34, the acylation products were observed and determined to be adducts with glycolic acid units from degradable PLGA polymer by MALDI-TOF MS. In the microsphere of leuprolide, however, the acylation product was not observed even after 28 days of incubation at the release medium, which represents the different stabilities among peptides according to the primary structure. As the leuprolide contains tyrosine and serine having hydroxyl group of nucleophilic amino acids, the acylation reaction of peptide is shown to be mainly due to the primary amino groups of N-terminus or lysine residue. The complementary use of CE and MALDI-TOF MS will be useful for searching the counter measures as well as determining the peptide acylation in the manufactured formulations on the market. PMID:14568410

Na, Dong Hee; Youn, Yu Seok; Lee, Sang Deuk; Son, Mi-Won; Kim, Won-Bae; DeLuca, Patrick P; Lee, Kang Choon

2003-10-30

49

PLGA microspheres encapsulating siRNA anti-TNFalpha: efficient RNAi-mediated treatment of arthritic joints.  

PubMed

The aim of this study was to investigate potentialities of poly(dl-lactide-co-glycolide) (PLGA) microspheres for the delivery of small interfering RNAs (siRNAs) against tumor necrosis factor ? (TNF-?) to achieve prolonged and efficient inhibition of TNF-? for the treatment of rheumatoid arthritis (RA). PLGA microspheres were prepared by a modified multiple emulsion-solvent evaporation method. The formulations were characterized in terms of morphology, mean diameter and siRNAs distribution, encapsulation efficiency, and in vitro release kinetics. The efficiency of this system was then evaluated both in vitro and in vivo using the murine monocytic cell line J774 and a pre-clinical model of RA, respectively. siRNA-encapsulating PLGA microspheres were characterized by a high encapsulation efficiency and a slow and prolonged anti-TNF-? siRNAs. Our results provide evidence that, upon intra-articular administration, PLGA microspheres slowly releasing siRNAs effectively inhibited the expression of TNF-? in arthritic joints. Our system might represent an alternative strategy for the design of novel anti-rheumatic therapies based on the use of RNA interference in RA. PMID:22922428

Présumey, J; Salzano, G; Courties, G; Shires, M; Ponchel, F; Jorgensen, C; Apparailly, F; De Rosa, G

2012-08-16

50

Effect of a freeze-dried CMC\\/PLGA microsphere matrix of rhBMP-2 on bone healing  

Microsoft Academic Search

The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic\\u000a protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than\\u000a would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary\\u000a to fashion microsphere-loaded CMC implants that were simple to

Jay A. Schrier; Betsy F. Fink; Janet B. Rodgers; Henry C. Vasconez; Patrick P. DeLuca

2001-01-01

51

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

Microsoft Academic Search

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

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

2000-01-01

52

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

PubMed

Hyaluronic acid (HA) was used as an internal phase additive to improve the loading efficiency of ofloxacin, a hydrophilic drug encapsulated by hydrophobic polylactic-co-glycolic acid (PLGA) materials, through a double emulsion (water-in-oil-in-water) solvent extraction/evaporation method. Results from laser distribution analysis show that polyelectrolyte additives have low impact on the average particle size and distribution of the microspheres. The negatively charged HA increases the drug loading efficiency as well as the amount of HA in microspheres. Burst release can be observed in the groups with the polyelectrolyte additives. The release rate decreases with the amount of HA inside the microspheres in all negatively charged polyelectrolyte-added microsphere groups. PMID:24092200

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

2013-01-01

53

Preparation and characterization of rifampicin-PLGA microspheres/sodium alginate in situ gel combination delivery system.  

PubMed

We prepared a complex drug delivery system consisted of rifampicin-poly(lactic-co-glycolic acid) (PLGA) microspheres in combination with sodium alginate in situ gel. The microspheres were obtained by using a solvent evaporation method, the mean diameter was 1.748 ?m and the span of particle distribution was 0.78. The combination delivery system was obtained by adding microspheres to sodium alginate solution followed by physically mixing. In an in vitro study of drug release monitored for 11 days, the release of rifampicin from combination delivery system was slower than microspheres. The cumulative release percent of rifampicin from combination delivery system was 91.83 ± 1.26%, which was lower than 97.36 ± 3.41% of rifampicin released from microspheres. An in vivo fluorescence imaging study suggests that the gel adhered to lungs within 24h, and microspheres stayed in lungs at least for 504 h (21 days). In vivo drug release study indicates that the maximum local rifampicin concentration in lungs was 48.60 ± 15.67 ?g mL(-1) 5h after administration. After 21 days, the local rifampicin concentration was 0.81±0.14?gmL(-1), which was above the minimum inhibitory concentration of rifampicin. The combination delivery system significantly prolonged RFP release compared to microspheres, from which RFP released could only be detected for 10 days. This approach to control the release of rifampicin using PLGA microspheres/in situ gel combination delivery system in conjunction with interventional technology is useful for improving anti-tuberculosis treatment effectiveness for patients. PMID:22424828

Hu, Chunhui; Feng, Hanzhou; Zhu, Chunyan

2012-03-03

54

Effect of ?-Sterilization Process on Plga Microspheres Loaded with Insulin-Like Growth Factor – I (Igf-I)  

Microsoft Academic Search

The influence of ?-sterilization on the physicochemical properties of a controlled release formulation for the insulin-like growth factor-I (IGF-I) was investigated in this study. Recombinant human insulin-like growth factor-I (rhIGF-I) was efficiently entrapped in poly (D,L-lactide-co-glycolide) (PLGA) microspheres by water-in-oil-in-water (W\\/O\\/W) solvent evaporation technique. Microspheres were irradiated at a dose of 25 kGy and evaluated by means of scanning electron

C. Carrascosa; L. Espejo; S. Torrado; J. J. Torrado

2003-01-01

55

Control of drug loading efficiency and drug release behavior in preparation of hydrophilic-drug-containing monodisperse PLGA microspheres  

Microsoft Academic Search

We prepared monodisperse poly(lactide-co-glycolide) (PLGA) microspheres containing blue dextran (BLD)—a hydrophilic drug—by membrane emulsification technique. The\\u000a effects of electrolyte addition to the w2 phase and significance of the droplet size ratio between primary (w1\\/o) and secondary (w1\\/o\\/w2) emulsions during the preparation of these microspheres was examined. The droplet size ratio was evaluated from the effect\\u000a of stirring rate of the

Fuminori Ito; Hiroyuki Fujimori; Hiroyuki Honnami; Hiroyoshi Kawakami; Kiyoshi Kanamura; Kimiko Makino

2010-01-01

56

PLGA microspheres containing plasmid DNA: preservation of supercoiled DNA via cryopreparation and carbohydrate stabilization.  

PubMed

Biodegradable microspheres containing plasmid DNA have potential uses as mediators of transfection in cells, particularly phagocytic cells such as macrophages. However, the hydrophilic nature and the structural instability of supercoiled DNA preclude its facile encapsulation in polymer matrixes such as poly(d, l-lactic-co-glycolic acid) (PLGA) by traditional methods. We initially studied the microencapsulation of plasmid DNA using the established water-in-oil-in-water double-emulsion solvent-evaporation method and found that (1) the encapsulation efficiency was low (about 20%), (2) the microencapsulation procedure nicked (degraded) the supercoiled DNA, and (3) lyophilization of the microsphere also nicked the DNA. We have therefore designed a new microsphere preparation method (called cryopreparation) to specifically address these concerns. Using the cryopreparation method, the aqueous phase of the primary emulsion containing the plasmid DNA is frozen and then subjected to homogenization. Because there is no shear stress inside a solid, we hypothesized that freezing the aqueous phase of the primary emulsion would help to preserve the supercoiled plasmid DNA during formation of the secondary emulsion. We also hypothesized that the formation of crystals from buffers within the primary emulsion was a causative factor for nicking during freezing or lyophilization, and that disruption of the crystal formation by the addition of saccharides into the primary emulsion would improve the supercoiled-DNA content of the spheres. Our results support the two hypotheses. Not only was the supercoiled-DNA content increased from 39% to over 85%, but the encapsulation efficiency was also elevated from 23% to over 85%. PMID:9874713

Ando, S; Putnam, D; Pack, D W; Langer, R

1999-01-01

57

Surface morphology and in vitro release performance of double-walled PLLA\\/PLGA microspheres entrapping a highly water-soluble drug  

Microsoft Academic Search

Double-walled microspheres trapping gentamicin sulphate were prepared from poly(l-lactic acid) (PLLA) and poly(l-lactic-co-glycolic acid) (PLGA) as a delivery system for highly hydrophilic antibiotics. The surface and cross-section morphology of the microspheres were characterized by SEM and FTIR. The diameters of the microspheres were ranging from about 50?m to 700?m. A low initial burst was achieved. The encapsulation efficiency was more

Hongxiang Tan; Jiandong Ye

2008-01-01

58

Immune responses after local administration of IgY loaded-PLGA microspheres in gut-associated lymphoid tissue in pigs  

Microsoft Academic Search

Oral vaccination of large animals using PLGA MS (poly(d,l-lactide-co-glycolide)microspheres) appeared to be more challenging than immunization of mice. The purpose of this study was to deliver to GALT an immunogenic model protein (IgY), free or encapsulated by spray-drying in PLGA MS, and to evaluate systemic immune response in SPF Large White pigs. Pigs were surgically processed for local administration of

Anne-Marie Torché; Mireille Le Dimna; Pascal Le Corre; Alain Mesplède; Sébastien Le Gal; Roland Cariolet; Marie-Frédérique Le Potier

2006-01-01

59

Surface morphology and in vitro release performance of double-walled PLLA/PLGA microspheres entrapping a highly water-soluble drug  

NASA Astrophysics Data System (ADS)

Double-walled microspheres trapping gentamicin sulphate were prepared from poly( L-lactic acid) (PLLA) and poly( L-lactic-co-glycolic acid) (PLGA) as a delivery system for highly hydrophilic antibiotics. The surface and cross-section morphology of the microspheres were characterized by SEM and FTIR. The diameters of the microspheres were ranging from about 50 ?m to 700 ?m. A low initial burst was achieved. The encapsulation efficiency was more than 70% and the cumulative drug release was about 40% for 30 days. The results indicated that the double-walled microspheres were able to achieve higher encapsulation efficiency and lower initial burst for highly water-soluble drugs.

Tan, Hongxiang; Ye, Jiandong

2008-11-01

60

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

61

[FTIR characterization of the secondary structure of a staphylokinase variant (K35R) encapsulated within PLGA microspheres].  

PubMed

The secondary structure of a staphylokinase variant (K35R, DGR) encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres was quantitatively examined by Fourier transform infrared (FTIR) spectroscopy. Resolution enhancement technique and Fourier deconvolution were combined with band with curve-fitting procedures to quantitate the spectral information from the amide I bands. Nine component bands were found under the broad, nearly featureless amide I bands and assigned to alpha-helix, beta-sheet, turn and irregular (random) structures. The changes of bands at 1 651 and 1 623 cm(-1) after encapsulation were discussed. PMID:17020023

He, Jin-Tian; Wang, Gai-Zhen; Song, Hou-Yan

2006-07-01

62

Preparation and in vitro and in vivo evaluation of HupA PLGA microsphere.  

PubMed

Acetylcholinesterase inhibitors (AChEIs), including Huperzine A (HupA), have been the mainstay of treatment for Alzheimer's disease (AD). However, AChEIs can cause gastrointestinal side effects, which has been related to the high Cmax and short tmax after oral administration. Clinical trials have verified that extended-release formulation with lower Cmax and prolonged tmax, such as rivastigmine patch, could perform a similar efficacy with significantly improved tolerability compared with the oral formulations. In this study, we developed an extended-release microspheres formulation of HupA (called as HAM) with poly(lactide-co-glycolide) (PLGA) as drug carrier. HAM has showed the loading rate as 1.35% (w/w) and yielded 42% with mean particle size at 72.6 ?m. In vitro and in vivo pharmacokinetics studies have showed that HAM produced a relatively smooth and continuous drug concentration in 14 days. Furthermore, in vivo pharmacokinetics data have demonstrated that the Cmax was lower and the tmax was considerably later in single intramuscular administration of HAM (1,000 ?g/kg) than the counterparts in single intragastric administration of HAT (75 ?g/kg/d). Meanwhile, HAM has performed a continuous inhibition to brain AChE activity in normal rats and improvement of memory deficit in A?1-40 i.c.v. infused AD rat model for 14 days. The results have suggested that HAM has performed good extended-release properties and good prolonged pharmacological efficacy in vivo in the 2-week period, and could exert a similar efficacy with significantly lowered gastrointestinal side effects as compared with oral formulation. PMID:23455202

Ye, Liang; Fu, Fenghua; Liu, Wanhui; Sun, Kaoxiang; Li, Youxin; He, Jie; Yu, Xin; Yu, Pengfei; Tian, Jingwei

2013-03-01

63

Morphological changes in degrading PLGA and P(DL)LA microspheres: implications for the design of controlled release systems.  

PubMed

The in vitro degradation of microspheres of polymers of lactic and glycolic acids were investigated by monitoring the mass loss from the device, the molecular weight of the polymer and the morphological changes of the particles with time. Two different sequences of morphological changes were found to be operative, depending upon the polymer from which they were made--one, (I) for the high molecular weight P(DL)LA, and the other, (II) for all PLGAs and the low molecular weight P(DL)LA. Microspheres of category I showed clear evidence of heterogeneous degradation, where the initially dense microsphere developed a hollow interior. Microspheres of category II plasticized on hydration due to reduction in the Tg of the polymer below the incubation temperature of 37 degrees C. There was suppression of release of entrapped globular proteins from microspheres that underwent plasticization (category II), while slow and sustained release was seen from those that did not (category I). It is proposed that plasticization renders the matrix of category II microspheres non-porous, which prevents release by pore-diffusion. The mass loss profiles of PLGA were found to be different from those reported in the literature, in that the rates of mass loss after an initial lag time were not as rapid as has been reported. The experimental conditions used, namely the use, or otherwise, of agitation, is suggested as the reason for these differences and the need to draw a correlation between in vitro experimental conditions and in visa behaviour is emphasized. PMID:11695641

Viswanathan, N B; Patil, S S; Pandit, J K; Lele, A K; Kulkarni, M G; Mashelkar, R A

64

PLGA and PHBV Microsphere Formulations and Solid-State Characterization: Possible Implications for Local Delivery of Fusidic Acid for the Treatment and Prevention of Orthopaedic Infections  

Microsoft Academic Search

Purpose  To develop and characterize the solid-state properties of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(3-hydroxybutyric\\u000a acid-co-3-hydroxyvaleric acid) (PHBV) microspheres for the localized and controlled release of fusidic acid (FA).\\u000a \\u000a \\u000a \\u000a Methods  The effects of FA loading and polymer composition on the mean diameter, encapsulation efficiency and FA released from the\\u000a microspheres were determined. The solid-state and phase separation properties of the microspheres were characterized

Chiming Yang; David Plackett; David Needham; Helen M. Burt

2009-01-01

65

Effect of cyclodextrins on alpha-chymotrypsin stability and loading in PLGA microspheres upon S/O/W encapsulation.  

PubMed

The potential of cyclodextrins to stabilize alpha-chymotrypsin upon encapsulation in Poly(lactic-co-glycolic) acid (PLGA) microspheres using a solid-in-oil-in-water (s/o/w) technique was investigated. Two cyclodextrins, hydroxyl-propyl-beta-cyclodextrin (HPbetaCD) and methyl-beta-cyclodextrin (MbetaCD), one insoluble and the other soluble in methylene chloride, were used. The results demonstrate that HPbetaCD failed to stabilize alpha-chymotrypsin upon encapsulation. Specifically, 19% of the protein was aggregated and the specific activity of the enzyme was reduced to ca. 50% of that prior to encapsulation. In contrast, MbetaCD significantly decreased the formation of aggregates to 3% and the retained specific activity of the enzyme was approximately 90%. The co-lyophilization of alpha-chymotrypsin with MbetaCD prior to encapsulation was a requisite to preserve the protein stability in microspheres. Furthermore, MbetaCD prevented the loss of protein during the preparation of microspheres and the encapsulation efficiency was improved to 90%. Release experiments showed the use of MbetaCD modified the release profile: the burst release decreased from 54% (in the absence of the excipient) to 36%. The results suggest that MbetaCD might be a suitable excipient to improve protein stability in s/o/w encapsulation procedures. PMID:16493595

Castellanos, Ingrid J; Flores, Giselle; Griebenow, Kai

2006-04-01

66

Exenatide-loaded PLGA microspheres with improved glycemic control: in vitro bioactivity and in vivo pharmacokinetic profiles after subcutaneous administration to SD rats.  

PubMed

A subcutaneous exenatide delivery system was developed and characterized in vitro and in vivo. The results clearly showed that the exenatide loaded PLGA microspheres prepared by using a non-aqueous processing medium had low burst release and high drug encapsulation efficiency. Exenatide loaded in the microspheres preserved its bioactivity. The pharmacokinetics parameters were determined after subcutaneous administration of microspheres to SD rats. The plasma concentration of the single dose of the sustained-release microspheres attained C(max) of 108.19±14.92 ng/ml at t(max) of 1.33±0.58 h and the t(½) was 120.65±44.18 h. There was a linear correlation between the in vitro and in vivo release behavior (R²=0.888). Exenatide loaded microspheres may prove to have great potential for clinical use. PMID:23770254

Xuan, Jiming; Lin, Yaling; Huang, Jingbin; Yuan, Fei; Li, Xiaoqing; Lu, Ying; Zhang, He; Liu, Junjie; Sun, Zhiguo; Zou, Hao; Chen, Yan; Gao, Jing; Zhong, Yanqiang

2013-06-14

67

PLGA Microsphere-Mediated Growth Hormone Release Hormone Expression Induces Intergenerational Growth  

Microsoft Academic Search

To improve animal growth, growth hormone-releasing hormone (GHRH) expression vectors that maintain constant GHRH expression can be directly injected into muscles. To deliver the GHRH expression vectors, biodegradable microspheres have been used as a sustained release system. Although administering GHRH through microspheres is a common practice, the intergenerational effects of this delivery system are unknown. To investigate the intergenerational effects

Xiao-Hui Ren; Yong-Liang Zhang; Hu-Ying Luo; Hong-Yi Li; Song-Cai Liu; Ming-Jun Zhang; Song-Ying Ouyang; Qian-Yun Xi; Qing-Yan Jiang

2009-01-01

68

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

PubMed

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

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

2008-03-08

69

Ammonolysis-induced solvent removal: a facile approach for solidifying emulsion droplets into PLGA microspheres.  

PubMed

An ammonolysis-based microencapsulation technique useful for the preparation of biodegradable microspheres was described in this study. A dispersed phase consisting of poly- d, l-lactide- co-glycolide, progesterone, and methyl chloroacetate was emulsified in an aqueous phase. Upon addition of ammonia solution, the emulsion droplets were quickly transformed into poly- d, l-lactide- co-glycolide microspheres laden with progesterone. Rapid solvent removal was accompanied by ammonolysis. The chemical reaction converted water-immiscible methyl chloroacetate to water-miscible chloroacetamide and methanol. Chloroacetamide formation was proved by (1)H NMR and ESI-MS studies. Thermogravimetric analysis showed that the microspheres contained only small amounts of residual methyl chloroacetate. Incorporation efficiencies of progesterone ranged from 64.3 +/- 1.1 to 72.8 +/- 0.3%, depending upon microsphere formulations. X-ray powder diffractometry analysis substantiated that no polymorphic transition of progesterone occurred during microencapsulation. To evaluate the feasibility of this new method against the commonly used microencapsulation method, microspheres were also prepared by a typical dichloromethane-based solvent evaporation process. The important attributes of microspheres prepared from both methods were characterized for comparison. The new ammonolysis-based microencapsulation process showed interesting features distinct from those of the solvent evaporation process. The microencapsulation process reported in this study might be applicable in loading pharmaceuticals into various polymeric microspheres. PMID:18031011

Kim, Jayoung; Hong, Dasom; Chung, Younglim; Sah, Hongkee

2007-11-22

70

The preparation and characterization of anti-VEGFR2 conjugated, paclitaxel-loaded PLLA or PLGA microspheres for the systemic targeting of human prostate tumors  

Microsoft Academic Search

Purpose  The objective of this study was to manufacture paclitaxel (PTX) loaded polymeric microspheres, that were surface conjugated\\u000a with antibodies to vascular endothelial growth factor receptor 2 (anti-VEGFR2), for systemic targeting to angiogenic sites\\u000a in prostate tumors.\\u000a \\u000a \\u000a \\u000a Methods  Microspheres were manufactured in the 1–3 ?m size range from poly (l-lactic acid) (PLLA) or poly (lactide-co-glycolide) (PLGA)\\u000a by a modified solvent evaporation method using

Jianjun Lu; John K. Jackson; Martin E. Gleave; Helen M. Burt

2008-01-01

71

Anti-cancer drug diffusion within living rat brain tissue: an experimental study using [ 3H](6)-5-fluorouracil-loaded PLGA microspheres  

Microsoft Academic Search

This study was performed (i) to monitor the diffusion of the anti-cancer drug 5-fluorouracil (5-FU) and (ii) to elucidate the fate of poly(lactide-co-glycolide) (PLGA) based microspheres within living rat brain tissue upon intracranial implantation. Drug-loaded microparticles were prepared using a solvent emulsion\\/extraction process and administered into healthy and C6 glioma-bearing Sprague–Dawley rats. The same surgical procedure was carried out with

Valérie-Gaëlle Roullin; Jean-Robert Deverre; Laurent Lemaire; François Hindré; Marie-Claire Venier-Julienne; Raymond Vienet; Jean-Pierre Benoit

2002-01-01

72

Retinal ganglion cells survival in a glaucoma model by GDNF\\/Vit E PLGA microspheres prepared according to a novel microencapsulation procedure  

Microsoft Academic Search

The present experimental work describes the use of a novel protein encapsulation method to achieve protection of the biological factor during the microencapsulation procedure. With this aim, the protein is included in poly(lactic-co-glycolic acid) (PLGA) microspheres without any preliminary manipulation, in contrast to the traditional S\\/O\\/W (solid-in-oil-in-water) method where the bioactive substance is first dissolved and then freeze-dried in the

Patricia Checa-Casalengua; Caihui Jiang; Irene Bravo-Osuna; Budd A. Tucker; Irene T. Molina-Martínez; Michael J. Young; Rocío Herrero-Vanrell

2011-01-01

73

Immune Augmentation of Single Contact Hepatitis B Vaccine by Using PLGA Microspheres as an Adjuvant  

PubMed Central

The present study was aimed to replace the alum type adjuvant for hepatitis B vaccine. The hepatitis B vaccine was encapsulated in poly (DL-lactide-co-glycolide) microspheres by solvent evaporation technique. The formulated microspheres were characterized in terms of morphology, particle size analysis, in vitro release study and in vivo immune response in male Wistar rats. The FT IR spectrum illustrates the characteristics bands of poly (DL-lactide-co-glycolide) microspheres and hepatitis B vaccine at 1750 cm-1 and 1650 cm-1, respectively. The hepatitis B vaccine loaded poly (DL-lactide-co-glycolide) microspheres were able to release antigens till day 42. Significant enhancement of specific antibodies to HBsAg was produced till day 90 after a single administration of HBsAg encapsulated poly (DL-lactide-co-glycolide) microspheres. However, the conventional alum adsorbed hepatitis B vaccine was not found to produce any significant specific antibody levels till day 90 after a single dose. The results showed that poly (DL-lactide-co-glycolide) microspheres show potential as an adjuvant for hepatitis B vaccine.

Sivakumar, S. M.; Sukumaran, N.; Murugesan, R.; Shanmugarajan, T. S.; Anbu, J.; Sivakumar, L.; Anilbabu, B.; Srinivasarao, G.; Ravichandran, V.

2008-01-01

74

Extended release peptide delivery systems through the use of PLGA microsphere combinations  

Microsoft Academic Search

The purpose of this study was to evaluate the utility of combining polymer matrices to overcome extended lag periods or unacceptably short durations of action intrinsic in the individual polymer systems. Leuprolide, an LHRH superagonist, was incorporated into a variety of poly(lactide co-glycolide) (PLGA) matrices using a solvent extraction\\/evaporation method. The in vitro release of Leuprolide from these matrices was

K. W. Burton; M. Shameem; B. C. Thanoo; P. P. Deluca

2000-01-01

75

Leptospira immunoglobulin-like protein A variable region (LigAvar) incorporated in liposomes and PLGA microspheres produces a robust immune response correlating to protective immunity.  

PubMed

Subunit vaccines are attractive as an intervention strategy against leptospirosis, an important zoonotic disease afflicting both humans and livestock. However, the success of subunit vaccines has been hampered by weak or short-term immunity and unavailability of nontoxic, potent adjuvants. In the present study, the variable region of recombinant Leptospira immunoglobulin like protein A (LigAvar) incorporated into conventional liposomes and PLGA microspheres produced robust immune responses that induced significant protection against virulent Leptospira interrogans serovar Pomona challenge in hamsters. Four-week-old hamsters were immunized subcutaneously with LigAvar incorporated into conventional liposomes or adsorbed on aluminum hydroxide (alum) and subsequently boosted after 3 weeks. Additionally, LigAvar incorporated into PLGA microspheres was evaluated as a single dose vaccine. All animals were challenged intraperitoneally 3 weeks after booster with a lethal dose (10 x MLD50) of virulent L. interrogans serovar Pomona. Animals were bled at various time points to evaluate antibody response, then sacrificed. Splenocytes were isolated and assayed for lymphocyte proliferation and cytokine profiles in response to recall antigen. Our results indicate that both liposomes and microspheres prove to be better adjuvants compared to conventional alum as revealed by enhanced antibody titers, lymphocyte proliferation and significant enhancement in both Th1(IL-12, IFN-gamma) and Th2 (IL-4, IL-10) cytokines. Moreover, LigAvar associated with liposomes and microspheres is able to provide better protection than LigAvar with alum as revealed by enhanced survival and reduced histopathological lesions in vital organs. Taken together, the data of the present study suggests that both liposomes and PLGA microspheres are promising adjuvants for use with future subunit vaccines for prevention of leptospirosis. PMID:19022317

Faisal, Syed M; Yan, WeiWei; McDonough, Sean P; Chang, Yung-Fu

2008-11-18

76

Controlled release of imatinib mesylate from PLGA microspheres inhibit craniopharyngioma mediated angiogenesis.  

PubMed

Poly(lactic-co-glycolic acid) microspheres loaded with imatinib mesylate has been developed as a new therapeutic strategy to prevent craniopharyngioma recurrence. Microspheres composed of different lactic/glycolic acid ratios, molecular weights and drug compositions were synthesized and loaded with imatinib mesylate by modified double-emulsion/solvent evaporation technique and subsequently characterized by particle-size distribution, scanning electron microscopy, encapsulation efficiency and in vitro drug release. Inhibitory potential of imatinib containing microspheres on tumor neovascularization was investigated on craniopharyngioma tumor samples by rat cornea angiogenesis assay. Results showed that microspheres in different LA:GA ratios [LA:GA 50:50 (G50), 75:25 (G25), 85:15 (G15)] considerably reduced neovascularization induced by recurrent tumor samples in an in vivo angiogenesis assay (P < 0.01). Our data indicate that local delivery of imatinib mesylate to the post-surgical tumoral cavity using biodegradable microspheres may be a promising biologically selective approach to prevent the recurrence of craniopharyngiomas, via inhibition of neovascularization. PMID:23053813

Karal-Yilmaz, Oksan; Ozkan, Abdulkadir; Akgun, Emel; Kukut, Manolya; Baysal, Kemal; Avsar, Timucin; Kilic, Turker

2012-10-10

77

Effect of the molecular weight of poly(ethylene glycol) used as emulsifier on alpha-chymotrypsin stability upon encapsulation in PLGA microspheres.  

PubMed

Poly(ethylene glycol) (PEG) was used as emulsifier to prepare alpha-chymotrypsin-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres by a solid-in-oil-in-water (s/o/w) technique. The effect of the molecular weight of PEG on protein stability was assessed by the determination of the amount of insoluble aggregates, the activity loss and the magnitude of structural perturbations. In addition, the effect of the molecular weight of PEG on the encapsulation efficiency, microsphere characteristics and release kinetics was investigated. X-ray photoelectron spectroscopy (XPS) was employed to characterize the surface chemistry of the microspheres. Microspheres were prepared using PEG with molecular weight of 6,000, 8,000, 10,000, 12,000 and 20,000. The results indicate that PEG 20,000 was the most effective emulsifier when producing alpha-chymotrypsin-loaded microspheres with respect to protein stability. The aggregate formation was decreased from 18% to 3%; the protein inactivation and the encapsulation-induced structural perturbations were largely prevented. XPS confirmed that PEG was largely located on the surface of microspheres. The molecular weight of PEG affected the microspheres' characteristics and release kinetics. Microspheres prepared with PEG 20,000 showed improved encapsulation efficiency (80%) and a continuous release (for 50 days) with the lowest amount of initial release. It is demonstrated that the selection of the optimum molecular weight of PEG when used as emulsifier in the preparation of microspheres is a critical factor in the development of sustained-release formulations for the delivery of proteins. PMID:16259754

Castellanos, Ingrid J; Flores, Giselle; Griebenow, Kai

2005-10-01

78

Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.  

PubMed

We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600?nm to 19?µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug. PMID:22263669

Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

2012-01-23

79

Chemotherapy with PLGA microspheres containing docetaxel decreases angiogenesis in human hepatoma xenograft  

Microsoft Academic Search

To investigate the antiangiogenic effect of sustained-release poly (lactic-co-glycolic acid) microspheres containing docetaxel\\u000a (PMCD) in human hepatoma xenograft. PMCD were prepared by solvent evaporation method with an encapsulation efficiency of 98.7%\\u000a and a release period of about 3 weeks in vitro. PMCD were intratumorally injected once for mice bearing a human hepatocellular\\u000a carcinoma. On day 21 post-treatment, the inhibition rate of

Zhi-kui Chen; Min-xian Cai; Jing Yang; Li-wu Lin; En-sheng Xue; Jing Huang; Hong-fen Wei; Xiu-juan Zhang; Li-ming Ke

80

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

Microsoft Academic Search

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

Tae Hyoung Kim; Haeshin Lee; Tae Gwan Park

2002-01-01

81

Methylprednisolone-loaded PLGA microspheres: a new formulation for sustained release via intra-articular administration. A comparison study with methylprednisolone acetate in rats.  

PubMed

Methylprednisolone (MP) released by poly(d,l-lactide-co-glycolide) microspheres (PLGA MS) was monitored in plasma after intra-articular (i.a.) administration into rat joint. A validated LC-ESI-MS/MS method was used to quantify the plasmatic concentrations of MP. The calculated pharmacokinetic parameters were compared to those obtained after the i.a. administration of a commercially available suspension of MP acetate (MPA). Different pharmacokinetic profiles were observed in the two formulations, and a lower peak level (C(max) = 13.7 ± 4.3 ng · mL(-1)) and AUC(0-72 h) (198 ± 45 ng · mL(-1) · h) were observed for MP-PLGA MS than MPA (C(max) = 18.4 ± 2.7 ng · mL(-1)) and AUC(0-72 h) (943 ± 249 ng · mL(-1) · h). The administration of MP-PLGA MS resulted in a rapid increase in the MP concentration at 30 min, with a t(max) at 0.8 ± 0.3 h. Instead, for the MPA suspension the t(max) was 32.0 ± 13.9 h. These differences were indirectly confirmed by the evaluation of the extra-articular effects, namely, carrageenan-induced paw edema, since MP-PLGA MS showed a lower anti-inflammatory activity than MPA. PMID:21850665

Panusa, Alessia; Selmin, Francesca; Rossoni, Giuseppe; Carini, Marina; Cilurzo, Francesco; Aldini, Giancarlo

2011-08-17

82

Enhancing initial release of peptide from poly(d,l-lactide-co-glycolide) (PLGA) microspheres by addition of a porosigen and increasing drug load.  

PubMed

The objective of this study was to evaluate formulation variables such as drug load and addition of a porosigen in achieving an increased initial release of peptide from poly(d,l-lactide-co-glycolide) (PLGA) microspheres by altering carrier characteristics. Leuprolide acetate-loaded PLGA microspheres were prepared by a solvent-extraction-evaporation process and were characterized for their drug load (HPLC assay), bulk density (tapping method), size distribution (dynamic light scattering), specific surface area (Brunauer-Emmett-Teller [BET] analysis), surface morphology (scanning electron microscopy), in vitro drug release (at 37 degrees C), and in vivo efficacy (suppression of rat serum testosterone). Increasing the drug load, and adding various amounts of calcium chloride to organic and aqueous phases of the emulsion during processing yielded particles with increased porosity, lower bulk density, higher specific surface area, and accordingly higher initial release. In an animal model, these formulations showed a faster onset of testosterone suppression compared to microspheres without higher drug load or calcium chloride. The approaches employed in this study were found to be effective in avoiding the therapeutic lag phase usually observed with microencapsulated macromolecular drugs. PMID:10810758

Ravivarapu, H B; Lee, H; DeLuca, P P

2000-01-01

83

Release of PLGA–encapsulated dexamethasone from microsphere loaded porous surfaces  

Microsoft Academic Search

The aim of the present study was to investigate the morphology and function of a drug eluting metallic porous surface produced\\u000a by the immobilization of poly lactide-co-glycolide microspheres bearing dexamethasone onto plasma electrolytically oxidized\\u000a Ti–6Al–7Nb medical alloy. Spheres of 20 ?m diameter were produced by an oil-in-water emulsion\\/solvent evaporation method and\\u000a thermally immobilized onto titanium discs. The scanning electron microscopy investigations

G. J. S. Dawes; L. E. Fratila-Apachitei; B. S. Necula; I. Apachitei; G. J. Witkamp; J. Duszczyk

2010-01-01

84

Release of PLGA-encapsulated dexamethasone from microsphere loaded porous surfaces  

PubMed Central

The aim of the present study was to investigate the morphology and function of a drug eluting metallic porous surface produced by the immobilization of poly lactide-co-glycolide microspheres bearing dexamethasone onto plasma electrolytically oxidized Ti–6Al–7Nb medical alloy. Spheres of 20 ?m diameter were produced by an oil-in-water emulsion/solvent evaporation method and thermally immobilized onto titanium discs. The scanning electron microscopy investigations revealed that the size distribution and morphology of the attached spheres had not changed significantly. The drug release profiles following degradation in phosphate buffered saline for 1000 h showed that, upon immobilisation, the spheres maintained a sustained release, with a triphasic profile similar to the non-attached system. The only significant change was an increased release rate during the first 100 h. This difference was attributed to the effect of thermal attachment of the spheres to the surface.

Fratila-Apachitei, L. E.; Necula, B. S.; Apachitei, I.; Witkamp, G. J.; Duszczyk, J.

2009-01-01

85

Bone regeneration using a microstereolithography-produced customized poly(propylene fumarate)/diethyl fumarate photopolymer 3D scaffold incorporating BMP-2 loaded PLGA microspheres.  

PubMed

Bony defects have been three-dimensionally (3D) created in many clinical circumstances; however, many defects cannot be reconstructed because most of the current bony substitutes cannot provide the necessary exact 3D structure. Therefore, to overcome this limitation, a 3D scaffold with embedded growth factor-delivering microspheres was developed by solid free-form fabrication (SFF) technology using computer-aided design/manufacturing (CAD/CAM). In this study, BMP-2-loaded poly(DL-lactic-co-glycolic acid) (PLGA) microspheres were incorporated into a 3D scaffold that was fabricated using a microstereolithography (MSTL) system with a suspension of microspheres and a poly(propylene fumarate) (PPF)/diethyl fumarate (DEF) photopolymer. By measuring release profiles in vitro, we verified that the fabricated microsphere-containing 3D scaffold could gradually release growth factor. The effects of BMP-2 were also assessed in vitro by observing cell differentiation using MC3T3-E1 pre-osteoblasts. Finally, we confirmed that SFF scaffolds created by MSTL were superior to traditional scaffolds produced using a particulate leaching/gas foaming method. In addition, based on in vivo tests, the scaffolds that released BMP-2 promoted bone formation. Based on these results, we concluded that our 3D scaffold might be a useful tool for enhancing reconstruction quality in many complex bony defects that should be reconstructed using a customized 3D scaffold. PMID:20933279

Lee, Jin Woo; Kang, Kyung Shin; Lee, Seung Ho; Kim, Jun-Young; Lee, Bu-Kyu; Cho, Dong-Woo

2010-10-08

86

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

2013-07-17

87

Chitin\\/PLGA blend microspheres as a biodegradable drug delivery system: a new delivery system for protein  

Microsoft Academic Search

Novel chitin\\/PLGAs and chitin\\/PLA based microspheres were developed for the delivery of protein. These biodegradable microspheres were prepared by polymers blending and wet phase-inversion methods. The parameters such as selected non-solvents, temperature of water and ratio of polylactide to polyglycolide were adjusted to improve thermodynamic compatibility of individual polymer (chitin and PLGAs or chitin\\/PLA), which affects the hydration and degradation

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

2003-01-01

88

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.

Chue, Pierre

2007-01-01

89

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.

90

Critical effect of freezing/freeze-drying on sustained release of FITC-dextran encapsulated within PLGA microspheres.  

PubMed

The cause of initial burst release of hydrophilic macromolecular drugs from biodegradable polymeric microspheres was identified. Poly(D,L-lactic-co-glycolic acid) microspheres encapsulating fluorescein isothiocyanate (FITC)-labled dextran was prepared by a double emulsion solvent evaporation method. The extent of initial burst release was examined by varying the formulation process conditions such as solvent evaporation, washing, freezing, and freeze-drying. Confocal microscopy was employed to analyze the underlying mechanism of burst release. The extent of burst release was gradually reduced after the repeated washing of embryonic microspheres before freeze-drying, indicating that FITC-dextran molecules entrapped within unhardened microspheres were slowly diffused out. However, freezing and subsequent drying processes of the embryonic microspheres resulted in much increased extent of burst release, suggesting that the initial burst release was primarily caused by the rapid diffusion of FITC-dextran through the microporous channels. Confocal microscopic analysis revealed that the freeze-drying process generated water-escaping micro-channels, through which the encapsulated molecules were presumably dumped out. Vacuum-drying was a good alternative choice in reducing the initial burst, compared to freeze-drying. PMID:15129987

Kim, Tae Hyoung; Park, Tae Gwan

2004-03-01

91

Biocompatibility of PDGF-simvastatin double-walled PLGA (PDLLA) microspheres for dentoalveolar regeneration: a preliminary study.  

PubMed

Proper coordination of local signal to harmonize mitogenesis and osteogenic differentiation is one of the prerequisites to optimize dentoalveolar regeneration. In the study, we purpose to fabricate controlled-release microspheres encapsulating platelet-derived growth factor (PDGF) and simvastatin by coaxial electrohydrodynamic atomization. The microspheres demonstrated a distinct core and shell structure encapsulating PDGF and simvastatin respectively, and the encapsulation efficiency was 82.45-92.16% in-core and 51.37-71.34% in-shell. Sequential release of PDGF and simvastatin was seen in simvastatin-in-core and PDGF-in-shell (SP) design, and simultaneous release was achieved in PDGF-in-core and simvastatin-in-shell (PS) design. All microspheres demonstrated acceptable biocompatibility in vivo, with increased proliferation, reduced apoptosis, and reduced inflammation while PDGF or simvastatin was encapsulated. The PS design significantly reduced apoptosis than control, whereby significant and persistent enhanced proliferation was noted in SP group. The thickness of fibrotic capsules surrounding microspheres significantly reduced in both SP and PS group at day 14. The finding demonstrates that synergism of PDGF and simvastatin favored biocompatibility. Further investigations will aim on confirming the regenerative effect of SP and PS microspheres in a more clinically relevant model. PMID:22696306

Chang, Po-Chun; Chung, Min-Chun; Lei, Chenlu; Chong, Li Yen; Wang, Chi-Hwa

2012-06-14

92

Mycobacterium hsp65 DNA entrapped into TDM-loaded PLGA microspheres induces protection in mice against Leishmania ( Leishmania ) major infection  

Microsoft Academic Search

Heat shock proteins (HSPs) are highly conserved among different organisms. A mycobacterial HSP65 DNA vaccine was previously shown to have prophylactic and immunotherapeutic effects against Mycobacterium tuberculosis infection in mice. Here, BALB\\/c mice were immunized with mycobacterial DNA-hsp65 or with DNA-hsp65 and trehalose dymicolate (TDM), both carried by biodegradable microspheres (MHSP\\/TDM), and challenged with Leishmania (Leishmania) major. MHSP\\/TDM conferred protection

Eduardo Antonio Ferraz Coelho; Carlos Alberto Pereira Tavares; Karla de Melo Lima; Célio Lopes Silva; José Maciel Rodrigues; Ana Paula Fernandes

2006-01-01

93

Stabilization of alpha-chymotrypsin at the CH2Cl2/water interface and upon water-in-oil-in-water encapsulation in PLGA microspheres.  

PubMed

Protein inactivation and aggregation are serious drawbacks in the encapsulation of proteins in bioerodible polymers by water-in-oil-in-water (w/o/w) encapsulation. The model protein alpha-chymotrypsin was employed to investigate whether its stabilization towards the major stress factors in the w/o/w encapsulation procedure would allow for the encapsulation and release of non-aggregated and active protein. Due to the formation of amorphous aggregates alpha-chymotrypsin is an excellent sensor to probe unfolding events. Furthermore, its enzymatic activity is highly sensitive towards the presence of organic solvents. alpha-Chymotrypsin in aqueous solution showed substantial aggregation and activity loss when it was homogenized with CH(2)Cl(2) due to adsorption to the interface. Its w/o/w encapsulation in poly(lactic-co-glycolic)acid (PLGA) microspheres caused formation of 35% non-covalent aggregates and reduced the specific activity by 14%. Screening for efficient excipients revealed that co-dissolving the protein with maltose and polyethylene glycol (PEG, M(w) 5000) in the first aqueous phase reduced interface-induced protein aggregation and inactivation. Employing these excipients during encapsulation led to a reduction in alpha-chymotrypsin inactivation (10%) and aggregation (12%). Optimizing the effect of PEG by also dissolving the excipient in the organic phase prior to encapsulation further decreased the amount of non-covalent aggregates to 7% and loss in activity to 5%. The data obtained demonstrate that the w/o emulsification step is the main stress-factor in the w/o/w encapsulation procedure but subsequent encapsulation steps also cause some protein aggregation. PMID:12695064

Pérez-Rodriguez, Caroline; Montano, Nashbly; Gonzalez, Karilys; Griebenow, Kai

2003-04-14

94

Influence of PEI as a Core Modifying Agent on PLGA Microspheres of PGE1, A Pulmonary Selective Vasodilator  

PubMed Central

This study tests the hypothesis that large porous poly (lactic-co-glycolic acid) (PLGA) microparticles modified with polyethyleneimine (PEI) are viable carriers for pulmonary delivery of prostaglandin E1 (PGE1) used in the treatment of pulmonary arterial hypertension (PAH), a pulmonary vascular disorder. The particles were prepared by a double-emulsion solvent evaporation method with PEI-25 kDa in the internal aqueous phase to produce an osmotic pressure gradient. Polyvinyl alcohol (PVA) was used for external coating of the particles. The particles were examined for morphology, size, aerodynamic diameter, surface area, pore volume and in-vitro release profiles. Particles with optimal properties for inhalation were tested for in-vivo pulmonary absorption, metabolic stability in rat lung homogenates, and acute toxicity in rat bronchoalveolar lavage fluid and respiratory epithelial cells, Calu-3. The micromeritic data indicated that the PEI-modified particles of PGE1 are optimal for inhalation. Incorporation of PEI in the formulations resulted in an increased entrapment efficiency–83.26±3.04% for particles with 1% PVA and 95.48±0.46% for particles with 2% PVA. The amount of cumulative drug released into the simulated interstitial lung fluid was between 50.8±0.76% and 55.36±0.06%. A remarkable extension of the circulation half-life up to 6.0–6.5 hours was observed when the formulations were administered via the lungs. The metabolic stability and toxicity studies showed that the optimized formulations were stable at physiological conditions and relatively safe to the lungs and respiratory epithelium. Overall, this study demonstrates that large porous inhalable polymeric microparticles can be a feasible option for non-invasive and controlled release of PGE1 for treatment of PAH.

Gupta, Vivek; Ahsan, Fakhrul

2011-01-01

95

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

96

Long-acting hormonal contraception.  

PubMed

For 30 years, the combined oral contraceptive pill has been an almost automatic choice for effective contraception in sexually active adolescent women. Nevertheless, consideration of the criteria of a hypothetical "ideal" contraceptive suggests that long-acting progestogen-only methods may have considerable advantages for some adolescents. These would include greater efficacy, easier compliance, avoidance of estrogenic side effects, and potentially greater privacy. The disadvantages of menstrual irregularity, progestogenic side effects including weight gain, and the initial greater medicalization of the method, particularly implants, must be weighed against the wishes and preferences of the adolescent. A number of studies of the uptake and utilization of these methods in adolescence have arisen, particularly from the United States. These are reviewed together with experience from programs in the United Kingdom. PMID:9238299

Bromham, D R

1997-06-17

97

Leptospira immunoglobulin-like protein A variable region (LigAvar) incorporated in liposomes and PLGA microspheres produces a robust immune response correlating to protective immunity  

Microsoft Academic Search

Subunit vaccines are attractive as an intervention strategy against leptospirosis, an important zoonotic disease afflicting both humans and livestock. However, the success of subunit vaccines has been hampered by weak or short-term immunity and unavailability of nontoxic, potent adjuvants. In the present study, the variable region of recombinant Leptospira immunoglobulin like protein A (LigAvar) incorporated into conventional liposomes and PLGA

Syed M. Faisal; WeiWei Yan; Sean P. McDonough; Yung-Fu Chang

2009-01-01

98

Inhalable large porous microspheres of low molecular weight heparin: in vitro and in vivo evaluation.  

PubMed

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

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

2008-03-21

99

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

PubMed Central

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

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

2008-01-01

100

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

2013-08-09

101

Controlled release of amoxicillin from hydroxyapatite-coated poly(lactic-co-glycolic acid) microspheres  

Microsoft Academic Search

Negatively charged poly(lactic-co-glycolic acid) (PLGA) microspheres with an encapsulated hydrophilic antibiotic (amoxicillin) have been prepared by the solid-in-oil-in-water (s\\/o\\/w) method using the anionic surfactant, sodium dodecyl sulfate (SDS). Drug encapsulation efficiency is over 40%. Successful coating of hydroxyapatite (HA) on these negatively charged PLGA microspheres has been achieved by a dual constant composition method in 3–6 h. The HA-coated PLGA microspheres

Qingguo Xu; Jan T. Czernuszka

2008-01-01

102

Bone regeneration using a microstereolithography-produced customized poly(propylene fumarate)\\/diethyl fumarate photopolymer 3D scaffold incorporating BMP2 loaded PLGA microspheres  

Microsoft Academic Search

Bony defects have been three-dimensionally (3D) created in many clinical circumstances; however, many defects cannot be reconstructed because most of the current bony substitutes cannot provide the necessary exact 3D structure. Therefore, to overcome this limitation, a 3D scaffold with embedded growth factor-delivering microspheres was developed by solid free-form fabrication (SFF) technology using computer-aided design\\/manufacturing (CAD\\/CAM). In this study, BMP-2-loaded

Jin Woo Lee; Kyung Shin Kang; Seung Ho Lee; Jun-Young Kim; Bu-Kyu Lee; Dong-Woo Cho

103

Biological potency of microsphere encapsulated plasmid DNA  

Microsoft Academic Search

We evaluated the utility of three in vitro methods to monitor the biological potency of PLGA encapsulated DNA. For each assay we also determined whether the biological activity was influenced by the structural profile of DNA isomers. Collectively, the results indicate that all three methods can be used to evaluate the biological activity of DNA extracted from PLGA microspheres, but

Tang Hao; Una McKeever; Mary Lynne Hedley

2000-01-01

104

Biodegradable microspheres in drug delivery.  

PubMed

General aspects of biodegradable microspheres prepared from natural and synthesized polymers used in drug delivery systems are reviewed first from various viewpoints: characteristics of biodegradable polymers (physicochemical properties, bioerosion mechanism, biocompatibility), preparation method for the microspheres, drug release from parenteral products and briefly nonparenteral products. The relationship between release pattern and pharmacological activity of therapeutic peptides and proteins and rational controlled release design are also discussed. In the latter half, successful sustained release depot formulations of peptides, leuprorelin acetate, and thyrotropin-releasing hormone (TRH), utilizing poly(lactic acid) (PLA) and poly(lactic/glycolic acid) (PLGA) microspheres are reviewed with respect to preparation, drug release, biocompatibility, pharmacological effects, and results of clinical studies. Thereafter, studies on antitumor therapy by chemoembolization using PLGA microspheres containing an angiogenesis inhibitor (TNP-470) are described as an example of targeted drug delivery with biodegradable microspheres. PMID:8521523

Okada, H; Toguchi, H

1995-01-01

105

Determinants of Release Rate of Tetanus Vaccine from Polyester Microspheres  

Microsoft Academic Search

Controlled-release formulations based on poly(lactic) (PLA) and poly(lactic\\/glycolic) acid (PLGA) microspheres containing tetanus vaccine were designed. The polymers forming the microspheres were L-PLA of different molecular weights and DL-PLGA, 50:50. These microspheres were prepared by two solvent elimination procedures, both using a double emulsion, and were characterized for size, morphology, and toxoid release kinetics. The influence of formulation variables such

Maria J. Alonso; Smadar Cohen; Tae G. Park; Rajesh K. Gupta; George R. Siber; Robert Langer

1993-01-01

106

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.

Moskowitz, E; Jennings, B

1996-01-01

107

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

Microsoft Academic Search

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

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

108

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.

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

2013-01-01

109

Application of USP Apparatus 4 and In Situ Fiber Optic Analysis to Microsphere Release Testing  

Microsoft Academic Search

The objective of this study was to determine the applicability of USP Apparatus 4 and in situ fiber optic UV analysis to in vitro release testing of poly (lactic-co-glycolic acid) (PLGA) microspheres. The release of dexamethasone from microspheres prepared with both high and low Mw PLGA was evaluated. Dexamethasone release profiles obtained using USP apparatus 4 were compared with those

B. S. Zolnik; J. L. Raton; D. J. Burgess

110

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

Microsoft Academic Search

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

Xudong Cao; Molly S. Shoichet

1999-01-01

111

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

PubMed

Implantable and poly (d,l-lactide-co-glycolide) (PLGA) microparticles were developed to deliver temozolomide (TM) continuously in interstitial chemotherapy for glioma. The therapeutic effect of temozolomide/PLGA was evaluated in a rat C6 glioma model. C6 cells were implanted orthotopically into 100 rat brains in 5 groups (n=20 each): sham operation group, control group, local delivery of blank PLGA microspheres group, oral TM group, and local delivery of TM/PLGA group. Rats in oral TM group were orally administered temozolomide, and rats in TM/PLGA group were locally implanted with TM/PLGA microspheres. Ten rats were selected randomly from each group for observing the survival time, and the other 10 rats were killed on POD 14 to measure proliferation activity and apoptosis of the gliomas. Head MRI examination was performed before the rats were killed. The median survival time of sham operation group, control group, blank PLGA microspheres group, oral TM group, and TM/PLGA group was 19.5, 20, 19, 27, and 46.5 days, respectively. MRI demonstrated that the tumor volume was reduced in oral TM group and interstitial TM/PLGA group. PCNA-positive cell staining showed that proliferation activity of tumor cells treated with interstitial TM/PLGA therapy significantly decreased when compared with that of tumor cells treated with oral TM therapy. The apoptosis of C6 cells in interstitial TM/PLGA group significantly increased when compared with that in oral TM group. Interstitial TM/PLGA was effective in treating intracranial C6 rat gliomas and could prove to be a potential chemotherapy agent for human malignant gliomas. PMID:20396980

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

2010-04-16

112

Encapsulation of plasmid DNA in biodegradable poly( d, l-lactic-co-glycolic acid) microspheres as a novel approach for immunogene delivery  

Microsoft Academic Search

A plasmid DNA encoding bacterial ?-galactosidase gene was encapsulated in poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. Plasmid DNA extracted from PLGA microspheres retained both structural and functional integrity as evidenced by its restriction endonuclease digestion pattern and its ability to transfect COS-1 cells in vitro. PLGA microspheres protected plasmid DNA from digestion by deoxyribonuclease I (DNase I) in vitro. The encapsulation efficiency

Daqing Wang; Deborah R. Robinson; Glen S. Kwon; John Samuel

1999-01-01

113

Size effect of PLGA spheres on drug loading efficiency and release profiles  

Microsoft Academic Search

Drug delivery systems (DDS) based on poly (lactide-co-glycolide) (PLGA) microspheres and nanospheres have been separately\\u000a studied in previous works as a means of delivering bioactive compounds over an extended period of time. In the present study,\\u000a two DDS having different sizes of the PLGA spheres were compared in morphology, drug (dexamethasone) loading efficiency and\\u000a drug release kinetics in order to

G. J. S. Dawes; L. E. Fratila-Apachitei; K. Mulia; I. Apachitei; G.-J. Witkamp; J. Duszczyk

2009-01-01

114

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

115

Repair effect of diabetic ulcers with recombinant human epidermal growth factor loaded by sustained-release microspheres.  

PubMed

In this study the w/o/w extraction-evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The microspheres were characterized for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical microspheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-loaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear antigen (PCNA) in the epidermis layer with the microsphere treatment was significantly larger than those of the control groups. Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair. PMID:18989647

Dong, Xiaoqing; Xu, Jun; Wang, Weicai; Luo, Hao; Liang, Xiaofei; Zhang, Lei; Wang, Hanjie; Wang, Penghua; Chang, Jin

2008-11-07

116

Influence of formulation parameters on the characteristics of poly(D, L-lactide-co-glycolide) microspheres containing poly(L-lysine) complexed plasmid DNA.  

PubMed

This study describes the influence of polymer type, surfactant type/concentration, and target drug loading on the particle size, plasmid DNA (pDNA) structure, drug loading efficiency, in vitro release, and protection from DNase I degradation of poly(D, L-lactide-co-glycolide) (PLGA) microspheres containing poly(L-lysine) (PLL) complexed pDNA. PLGA microspheres containing pDNA-PLL were prepared using the water-in-oil-in-water (w-o-w) technique with poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) as surfactants in the external aqueous phase. A complex ratio of 1:0.33 (pDNA-PLL, w/w) enhanced the stability of pDNA during microsphere preparation. Higher pDNA-PLL loading efficiency (46.2%) and supercoiled structure (64.9%) of pDNA were obtained from hydrophobic PLGA (M(w) 31000) microspheres compared with hydrophilic PLGA or low-molecular-weight PLGA microspheres. The particle size decreased from 6.6 to 2.2 microm when the concentration of PVA was increased from 1 to 7%. At the same concentration of surfactant, PVA stabilized microspheres showed higher pDNA-PLL loading efficiency (46.2%) than PVP stabilized microspheres (24.1%). Encapsulated pDNA in PLGA microspheres was protected from enzymatic degradation and maintained in the supercoiled form. The pDNA-PLL microspheres showed in vitro release of 95.9 and 84.9% within 38 days from the low-molecular-weight PLGA and hydrophilic PLGA microspheres, respectively, compared to 54.2% release from the hydrophobic, higher-molecular-weight PLGA microspheres. The results suggest loading and release of pDNA-PLL complex can be influenced by surfactant concentration and polymer type. PMID:10425333

Capan, Y; Woo, B H; Gebrekidan, S; Ahmed, S; DeLuca, P P

1999-08-01

117

Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes  

Microsoft Academic Search

Objectives: The intracellular antibiotic efficiency of gentamicin-loaded microspheres in the context of Brucella-infected murine monocytes was examined in vitro with a view to developing improved therapies for the treatment of brucellosis. Methods: Biodegradable microspheres made of end-group capped and uncapped poly(lactide-co- glycolide) 50:50 (PLGA 50:50 and PLGA 50:50H) and containing gentamicin sulphate were used to target Brucella abortus-infected J774 monocyte-macrophages.

Sandra Prior; Bruno Gander; Concepción Lecároz; Juan M. Irache; Carlos Gamazo

118

Osteogenic differentiation of human mesenchymal stem cells using RGD-modified BMP2 coated microspheres  

Microsoft Academic Search

Micro-structured scaffolds formed with poly(lactic- co -glycolic acid) (PLGA) microspheres were composed of adhesion molecules and growth factors. PLGA microspheres, constructed with Arg-Gly-Asp (RGD) peptide and bone morphogenic protein 2 (BMP-2) were created as a stem cell delivery vehicle. In this study, a high potential for cell adhesion and differentiation of human mesenchymal stem cells (hMSCs) was achieved by constructing

Ji S. Park; Han N. Yang; Su Y. Jeon; Dae G. Woo; Kun Na; Keun-Hong Park

2010-01-01

119

Poly(D,L-Lactic-co-Glycolic Acid) microsphere delivery of adenovirus for vaccination  

Microsoft Academic Search

Purpose: To study the effect of encapsulation of recombinant adenovirus type 5 encoding ?-galactosidase (Ad5-?gal) in poly (D,L- lactic-co-glycolic acid) (PLGA) microspheres on viral delivery to professional antigen presenting cells (APCs) in vitro, viral dissemination in vivo, and induction of protective immune responses in vivo. Methods: PLGA microspheres containing Ad5-?gal were prepared by a double emulsion solvent evaporation method. Encapsulation

Daqing Wang; Ommoleila Molavi; M. E. Christine; Praveen Elamanchili; Glen S. Kwon; John Samuel

2007-01-01

120

Biodegradable Triblock Copolymer Microspheres Based on Thermosensitive Sol-Gel Transition  

Microsoft Academic Search

Purpose. The purpose of this study is to design microspheres for sustained protein delivery using thermosensitive, biodegradable triblock copolymer, poly (d,l-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (d,l-lactide-co-glycolide) (PLGA-PEG-PLGA) without using organic solvent.

YoungMin Kwon; SungWan Kim

2004-01-01

121

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. I. Preparation and characterization.  

PubMed

We developed poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres and investigated the effects of various processing parameters on the characteristics of these microspheres. The advantage of these blend microspheres is that the carbon-carbon double bonds along the PPF backbone could be used for their immobilization in a PPF scaffold. Microspheres containing the model drug Texas red dextran were fabricated using a double emulsion-solvent extraction technique. The effects of the following six processing parameters on the microsphere characteristics were investigated: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) (PVA) in the internal aqueous phase, and PVA concentration in the external aqueous phase. Our results showed that the microsphere surface morphology was affected most by the viscosity of the polymer solution. Microspheres fabricated with a kinematic viscosity of 39 centistokes had a smooth, nonporous surface. In most microsphere formulations, the model drug was dispersed uniformly in the polymer matrix. For all fabricated formulations, the average microsphere diameter ranged between 19.0 and 76.9 microm. The external PVA concentration and vortex speed had most effect on the size distribution. Entrapment efficiencies varied from 60 to 98% and were most affected by the amount of internal aqueous phase, vortex speed, and polymer viscosity. Overall, we demonstrated the ability to fabricate PPF/PLGA blend microspheres with similar surface morphology, entrapment efficiency, and size distribution as conventional PLGA microspheres. PMID:15227673

Kempen, Diederik H R; Lu, Lichun; Zhu, Xun; Kim, Choll; Jabbari, Esmaiel; Dhert, Wouter J A; Currier, Bradford L; Yaszemski, Michael J

2004-08-01

122

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 6weeks. 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

2013-08-15

123

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

124

Management of diabetic cats with long-acting insulin.  

PubMed

This article provides an overview of the most important information regarding the long-acting insulins glargine, detemir, and protamine zinc insulin in diabetic cats. Dosing protocols are described in detail, which achieve high remission rates and optimal glycemic control. Complications and factors that typically cause insulin resistance are also examined. PMID:23522171

Roomp, Kirsten; Rand, Jacquie S

2013-03-01

125

Repair effect of diabetic ulcers with recombinant human epidermal growth factor loaded by sustained-release microspheres  

Microsoft Academic Search

In this study the w\\/o\\/w extraction-evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The microspheres were characterized\\u000a for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation\\u000a effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical\\u000a microspheres

XiaoQing Dong; Jun Xu; WeiCai Wang; Hao Luo; XiaoFei Liang; Lei Zhang; HanJie Wang; PengHua Wang; Jin Chang

2008-01-01

126

Comparison of Long-Acting Bevacizumab Formulations in the Treatment of Choroidal Neovascularization in a Rat Model  

PubMed Central

Abstract Objective The objective of this study was to compare the reduction in size of experimentally induced choroidal neovascularization (CNV) in rat eyes treated with bevacizumab, poly(ethylene-glycol) (PEG)-bevacizumab conjugate (b-PEG), and poly(lactic-co-glycolic acid) (PLGA)-encapsulated bevacizumab (b-PLGA). Methods Forty-eight eyes from 24 rats were divided into 4 groups of 12 eyes. In each group, 3 eyes were assigned to a treatment subgroup, each receiving a different injection—control, bevacizumab, b-PEG, and b-PLGA. In all eyes, laser photocoagulation was used to rupture Bruch's membrane. In group 1, laser was followed by injection, which was then followed by harvesting the rats to assess the CNV area. All 3 steps were separated by a 2-week interval. In groups 2, 3, and 4, injection preceded laser photocoagulation by a variable interval and all rats were harvested 2 weeks postlaser treatment. In group 2, laser and injection were separated by 2 weeks. In group 3, laser followed injection by 4 weeks. In group 4, laser followed injection by 6 weeks. The CNV area was measured for each subgroup and compared against its control. Pairwise comparisons were conducted to assess for statistically significant differences between subgroups. Results All subgroups in groups 1, 2, and 4 showed statistically significant reduction of CNV area (P<0.05). In group 3, the b-PEG and b-PLGA subgroups showed a 9.0% (P=0.384) and 20.3% (P=0.077) reduction in CNV area versus control, whereas there was no reduction in CNV area in the bevacizumab subgroup. However, this was not found to be statistically significant. In group 4, b-PEG was more effective than bevacizumab and b-PLGA. Conclusion The reduction in CNV area in all treatment subgroups, with the exception of those in group 3, suggests successful creation of the 2 bevacizumab formulations while retaining its active antiangiogenic properties. Further studies varying in dosages and timing of injection and laser are needed to evaluate the formulations' long-acting efficacy.

Pan, Carolyn K.; Durairaj, Chandrasekar; Kompella, Uday B.; Agwu, Ogechi; Oliver, Scott C.N.; Quiroz-Mercado, Hugo; Mandava, Naresh

2011-01-01

127

Nanoscaled buffering zone of charged (PLGA)n-b-bPEI micelles in acidic microclimate for potential protein delivery application  

PubMed Central

Poly(lactide-co-glycolide) (PLGA) has most often been employed for the controlled release of protein formulations because of its safety profile with non-toxic degradation products. Nevertheless, such formulations have been plagued by a local acidic microenvironment and protein-polymer interactions, which result in chemical and physical denaturation of loaded proteins and often unfavorable release profiles. This study investigated the pH change of inner PLGA microsphere (MS) using charged (PLGA)n-b-branched polyethyleneimine (bPEI) micelles. The designed micelles can be transformed into either micelle or reverse micelle (RM) depending on the solvent and RM can form microspheres. In addition, (PLGA)n-b-bPEI can be modified into (PLGA)n-b-(carboxylated bPEI) via carboxylation of the primary amines. Cationic micelle (CM) or anionic micelle (AM) were complexed with counter-charged proteins leading to nanosized particles (approximately 100 nm). In the micelle/protein complexes, the micelles mostly maintained their proton buffering capacity, and consequently, prevented or delayed the typical decrease in pH caused by degradation of PLGA in aqueous solution. Reconstitutable micelle/protein complexes allowed for increased and fine-tuned protein loading (~20 wt% when using CM1 (CM prepared from PLGA36kDa-b-bPEI25kDa)/insulin complexes) in PLGA MS. In CM2 (CM prepared from (PLGA36kDa)2-b-bPEI25kDa)/insulin (4 of weight ratio (WR) of micelle to protein; WR4)-loaded PLGA MS, CM2 strongly prevented the micellar nanoenvironmental pH (pH 6.6 within 5 days and then approximately pH 8.5) to be acidified in PLGA MS for 9 weeks, unlike CM2-free PLGA MS. In conclusion, our findings propose that the proton buffering capacity and protein loading in PLGA MS can be tuned by controlling the complexation ratios of micelles and proteins, polymeric architectures of (PLGA)n-b-bPEI copolymers and WR of micelle/protein complexes and PLGA (or RM).

Kang, Han Chang; Lee, Ji Eun; Bae, You Han

2012-01-01

128

Bupivacaine, a long-acting local anesthetic, in anorectal surgery  

Microsoft Academic Search

Summary  The long-acting local anesthetic, bupivacaine, was used in a series of 467 anorectal patients, both inpatients and outpatients.\\u000a Bupivacaine was found to be safe and effective. Like other local anesthetics, it has none of the operative and postoperative\\u000a complications frequently associated with general or spinal anesthetics. Its longer duration of action makes it extremely useful\\u000a in anorectal operations on hospitalized

Lawrence D. Ramalho; Eugene P. Salvati; Robert J. Rubin

1976-01-01

129

The Pharmacokinetics of Long-Acting Antipsychotic Medications.  

PubMed

The depot antipsychotics are synthesized by esterification of the active drug to a long chain fatty acid and the resultant compound is then dissolved in a vegetable oil, with the exception of some molecules of new generation characterized by microcrystalline technologies. The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate The pharmacokinetics of depot antipsychotic medications are such that an intramuscular injection given at intervals of from 1 to 4 weeks will produce adequate plasma concentrations that are sufficient to prevent relapse over the dosage interval. Such medication is useful in patients who do not reliably take their oral medication. The pharmacokinetics and clinical actions of various depot formulations of antipsychotic drugs have been extensively studied. The clinical pharmacokinetics of the depot antipsychotics for which plasma level studies are available (i.e. fluphenazine enanthate and decanoate, haloperidol decanoate, bromperidol decanoate, clopenthixol decanoate, flupenthixol decanoate, perphenazine onanthat, pipotiazine undecylenate, pipotiazine palmitate, fluspirilene, Long-acting injectable risperidone, olanzapine pamoate, paliperidone palmitate, Long-acting iloperidone, Long-acting injectable aripiprazole) are reviewed. The proper study of these agents has been handicapped until recently by the necessity of accurately measuring subnanomolar concentrations in plasma. Their kinetic properties, the relationship of plasma concentrations to clinical effects, and conversion from oral to injectable therapy are discussed. PMID:23343447

Spanarello, Stefano; La Ferla, Teresa

2013-01-04

130

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.

Cazzola, M; Matera, M G

2008-01-01

131

Facile control of porous structures of polymer microspheres using an osmotic agent for pulmonary delivery.  

PubMed

It has been challenging to prepare polymeric microspheres with controlled porous structures for many biomedical applications, particularly for pulmonary drug delivery. Here, we report the use of bovine serum albumin (BSA) as an osmotic agent in order to control the porous structure of poly(D,L-lactide-co-glycolide) (PLGA) microspheres prepared by a double emulsion method. BSA was useful to induce osmosis between internal and external water phases during the double emulsion process, resulting in the fabrication of microspheres with controllable, uniform porous structures. The pore size of PLGA microspheres was controlled independently from the particle size by this approach. The use of BSA as an osmotic agent reduced the initial burst of model proteins (e.g., insulin and VEGF) entrapped in the porous microspheres, and the sustained release of VEGF was achieved for two weeks in vitro. This approach to controlling porous structures of polymer microspheres could be useful to develop novel pulmonary drug delivery systems. PMID:20553775

Lee, Jangwook; Oh, Yu Jin; Lee, Sang Kyung; Lee, Kuen Yong

2010-05-26

132

Porous bone morphogenetic protein-2 microspheres: polymer binding and in vitro release.  

PubMed

This research compared the binding and release of recombinant human bone morphogenetic protein 2 (rhBMP-2) with a series of hydrophobic and hydrophilic poly-lactide-co-glycolide (PLGA) copolymers. Porous microspheres were produced via a double emulsion process. Binding and incorporation of protein were achieved by soaking microspheres in buffered protein solutions, filtering, and comparing protein concentration remaining to nonmicrosphere-containing samples. Protein release was determined by soaking bound microspheres in a physiological buffer and measuring protein concentration (by reversed-phase high-performance liquid chromatography) in solution over time. Normalized for specific surface area and paired by polymer molecular weight, microspheres made from hydrophilic 50:50 or 75:25 PLGA bound significantly more protein than microspheres made from the corresponding hydrophobic PLGA. Increased binding capacity correlated with higher polymer acid values. With certain polymers, rhBMP-2 adsorption was decreased or inhibited at high protein concentration, but protein loading could be enhanced by increasing the protein solution:PLGA (volume:mass) ratio or by repetitive soaking. Microspheres of various PLGAs released unbound protein in 3 days, whereas the subsequent bound protein release corresponded to mass loss. RhBMP-2 binding to PLGA was controlled by the acid value, protein concentration, and adsorption technique. The protein released in 2 phases; the first occurred over 3 days regardless of PLGA used and emanated from unbound, incorporated protein, while the second was controlled by mass loss and therefore was dependent on the polymer molecular weight. Overall, control of rhBMP-2 delivery is achievable by selection of PLGA microsphere carriers. PMID:14727876

Schrier, J A; DeLuca, P P

2001-10-07

133

Combination therapy of surgical tumor resection with implantation of a hydrogel containing camptothecin-loaded poly(lactic-co-glycolic acid) microspheres in a C6 rat glioma model.  

PubMed

We have developed a drug-loaded poly(lactic-co-glycolic acid) (PLGA) microsphere-containing thermoreversible gelation polymer (TGP) (drug/PLGA/TGP) formulation as a novel device for implantation after surgical glioma resection. TGP is a thermosensitive polymer that is a gel at body temperature and a sol at room temperature. When a drug/PLGA/TGP formulation is injected into a target site, PLGA microspheres in TGP gel localize at the injection site and do not diffuse across the entire brain tissue, and thus, sustained drug release from the PLGA microspheres at the target site is expected. Using in vivo imaging, we confirmed that the implantation of indocyanine green (ICG)/PLGA/TGP formulation exhibited a stronger localization of ICG at the injection site 28 d after injection compared with that of ICG/PLGA formulation. The therapeutic effect (mean survival) was evaluated in a C6 rat glioma model. Surgical tumor resection alone showed almost no effect on survival (controls, 18 d; surgical resection; 18.5 d). Survival was prolonged after the treatment with a camptothecin (CPT; 10 µg)/PLGA/TGP formulation (24 d). The combination treatment of surgical tumor resection and CPT/PLGA/TGP showed almost the same therapeutic effect (24 d) compared with CPT/PLGA/TGP alone, while the combination treatment produced long term survivors (>60 d). Therefore, the CPT/PLGA/TGP formulation can be an effective candidate for localized and sustained long-term glioma therapy. PMID:22466559

Ozeki, Tetsuya; Kaneko, Daiki; Hashizawa, Kosuke; Imai, Yoshihiro; Tagami, Tatsuaki; Okada, Hiroaki

2012-01-01

134

Long-acting Injectable Antipsychotics in First-episode Schizophrenia  

PubMed Central

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

Jeong, Hyun-Ghang

2013-01-01

135

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. II. Controlled drug release and microsphere degradation.  

PubMed

This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38-day period. The initial burst release varied from 5.1 (+/-1.1) to 67.7 (+/-3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for microsphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (+/-0.8) to 27.2 (+/-3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles. PMID:15227674

Kempen, Diederik H R; Lu, Lichun; Zhu, Xun; Kim, Choll; Jabbari, Esmaiel; Dhert, Wouter J A; Currier, Bradford L; Yaszemski, Michael J

2004-08-01

136

The use of submicron\\/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice  

Microsoft Academic Search

Pharmacokinetics and therapeutic efficacy of submicron\\/nanoscale, intracranial implants were evaluated for treating malignant glioblastoma in mice. 9.1% (w\\/w) paclitaxel-loaded polylactide-co-glycolide (PLGA) nanofiber discs (F3) were fabricated and characterized for morphology and size distribution. Along with F3, three other formulations, 9.1% (w\\/w) paclitaxel-loaded PLGA submicron-fiber discs (F2), 16.7% (w\\/w) paclitaxel-loaded PLGA microspheres entrapped in hydrogel matrices (H80 and M80) were intracranially

Sudhir H. Ranganath; Yilong Fu; Davis Y. Arifin; Irene Kee; Lin Zheng; How-Sung Lee; Pierce K.-H. Chow; Chi-Hwa Wang

2010-01-01

137

Evaluation of dosing regimen of respirable rifampicin biodegradable microspheres in the treatment of tuberculosis in the guinea pig  

Microsoft Academic Search

Objectives: The efficacy of rifampicin-loaded polymeric microspheres (RPLGA) delivered to guinea pigs infected with Mycobacterium tuberculosis (H37Rv) was compared with a daily dose of nebulized rifampicin suspension. Methods: Aerosol-infected animals were subjected to multiple dose or single dose treatment with RPLGA, PLGA microspheres or micronized rifampicin suspension aerosols. For comparison with treatment with suspensions of microspheres, additional groups received daily

L. Garcia-Contreras; V. Sethuraman; M. Kazantseva; V. Godfrey; A. J. Hickey

2006-01-01

138

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

139

Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).  

PubMed

The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery for bone tissue engineering. PMID:16392139

Kempen, Diederik H R; Lu, Lichun; Kim, Choll; Zhu, Xun; Dhert, Wouter J A; Currier, Bradford L; Yaszemski, Michael J

2006-04-01

140

A long-acting formulation of a polypeptide drug exenatide in treatment of diabetes using an injectable block copolymer hydrogel.  

PubMed

This study is aimed to develop a long-acting injectable formulation in treatment of type II diabetes. A glucoregulatory polypeptide, exenatide (EXT), was chosen as the model drug, and an aqueous block copolymer system with a sol-gel transition upon the increase of temperature was selected as the delivery matrix of EXT. The thermoreversible hydrogel composed of poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was found to slower the degradation of the polypeptide to a large extent. However, the initial formulation in this study exhibited a significant drug burst effect, which is a common problem to load a hydrophilic small or medium-size polypeptide into a hydrogel. Zinc acetate was then introduced to slow down the EXT release by formation of insoluble Zn-EXT complexes in the thermogel matrix. Yet an incomplete release became another crucial problem, which is also common for peptide and protein delivery. The synergistic effect of three excipients (zinc acetate, PEG, and sucrose) under an appropriate condition overcame these two problems simultaneously, and the sustained release of drug lasted for 1 week. In vivo experiments via mice oral glucose tolerance tests demonstrated an improved glucose tolerance for 1 week after a single subcutaneous injection of the optimal EXT formulation. As a result, a formulation of antidiabetic drugs was set up, and meanwhile a strategy using synergistic excipients to adjust release profiles of peptides from hydrogels was put forward. PMID:23352120

Li, Kun; Yu, Lin; Liu, Xiaojun; Chen, Chang; Chen, Qinghua; Ding, Jiandong

2013-01-23

141

Massive levemir (long-acting) insulin overdose: case report.  

PubMed

A 52-year-old insulin-dependant diabetic man presented to the Emergency Department 2 hours after a deliberate massive overdose of 2100 units of long-acting Levemir insulin and a large quantity of whisky. On initial assessment, his GCS was 3/15 and his capillary blood sugar was 2.6?mmol/L. The patient was given a 50?ml bolus of 50% dextrose, followed by intravenous infusions of both 5% and 10% dextrose. Despite the continuous infusions, he experienced 4 symptomatic hypoglycaemic episodes in the first 12 hours after admission. These were managed with oral glucose, IM glucagon, and further dextrose boluses. Blood electrolytes and pH were monitored throughout. Insulin overdoses are relatively common and often occur with an excess of other drugs or alcohol which can enhance its action. Overdoses can result in persistent hypoglycaemia, liver enzyme derangement, electrolyte abnormalities, and neurological damage. Overall mortality is 2.7% with prognosis poorest in patients who are admitted with decreased Glasgow Coma scale (GCS) 12 hours after overdose. PMID:22924049

Oduru, Mamatha; Ahmad, Mahmood

2012-08-09

142

Development and evaluation of novel biodegradable microspheres based on poly( d, l-lactide- co-glycolide) and poly(?-caprolactone) for controlled delivery of doxycycline in the treatment of human periodontal pocket: In vitro and in vivo studies  

Microsoft Academic Search

This study reports on the development of novel biodegradable microspheres prepared by water-in-oil–water (W\\/O\\/W) double emulsion technique using the blends of poly(d,l-lactide-co-glycolide) (PLGA) and poly(?-caprolactone) (PCL) in different ratios for the controlled delivery of doxycycline (DXY). Doxycycline encapsulation of up to 24% was achieved within the polymeric microspheres. Blend placebo microspheres, drug-loaded microspheres and pristine DXY were analyzed by Fourier

Raghavendra C. Mundargi; S. Srirangarajan; Sunil A. Agnihotri; Sangamesh A. Patil; S. Ravindra; Swati B. Setty; Tejraj M. Aminabhavi

2007-01-01

143

The microclimate pH in poly(D,L-lactide-co-hydroxymethyl glycolide) microspheres during biodegradation.  

PubMed

The microclimate pH (?pH) in biodegradable polymers, such as poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50, commonly falls to deleterious acidic levels during biodegradation, resulting in instability of encapsulated acid-labile molecules. The ?pH distribution in microspheres of a more hydrophilic polyester, poly(D,L-lactide-co-hydroxymethyl glycolide) (PLHMGA), was measured and compared to that in PLGA 50/50 of similar molecular weight and degradation time scales. pH mapping in the polymers was performed after incubation under physiological conditions by using a previously validated ratiometric method employing confocal laser scanning microscopy (CLSM). Confocal ?pH maps revealed that PLHMGA microspheres, regardless of copolymer composition, developed a far less acidic ?pH during 4 weeks of incubation compared with microspheres from PLGA. A pH-independent fluorescent probe marker of polymer matrix diffusion of ?pH-controlling water-soluble acid degradation products, bodipy, was observed by CLSM to diffuse ~3-7 fold more rapidly in PLHMGA compared to PLGA microspheres, consistent with much more rapid release of acids observed from the hydrophilic polymer during bioerosion. Hence, PLHMGA microspheres are less susceptible to acidification during degradation as compared to similar PLGA formulations, and therefore, PLHMGA may be more suitable to deliver acid labile molecules such as proteins. PMID:22819499

Liu, Yajun; Ghassemi, Amir H; Hennink, Wim E; Schwendeman, Steven P

2012-07-21

144

Tricyclic antidepressants as long-acting local anesthetics.  

PubMed

Amitriptyline, nortriptyline, imipramine, doxepin, desipramine, protriptyline, trimipramine, and maprotiline are tricyclic antidepressants (TCAs) used orally in treating major depressive disorders. Recent studies showed that amitriptyline is more potent in blocking the sciatic nerve functions in vivo by local injection than bupivacaine, a long-acting local anesthetic. We therefore tested whether various TCAs could likewise act as local anesthetics in vivo after single injection via the rat sciatic notch. The duration of complete sciatic nerve blockade by TCAs and the time to reach full recovery were measured with neurobehavioral assays and compared with results from bupivacaine. Amitriptyline, doxepin, and imipramine at 5mM elicited a longer complete sciatic nerve blockade than did bupivacaine at 15.4mM (0.5%), whereas trimipramine and desipramine at 5mM produced a shorter blockade. In contrast, nortriptyline, protriptyline, and maprotiline failed to elicit complete sciatic nerve blockade. Thus, TCAs have very different efficacy as local anesthetics in vivo. The duration of rat sciatic nerve blockade in vivo by TCAs is not well correlated with the 50% inhibitory concentration (IC(50)) of TCAs in blocking human cardiac Nav1.5 Na(+) channels expressed in human embryonic kidney cells. With this in vitro expression system, TCAs appear more potent than bupivacaine as Na(+) channel blockers in Nav1.5 Na(+) channels. We suggest that the ability of TCAs to pass through various membrane barriers within peripheral nerve trunks is crucial to their local anesthetic efficacy in vivo. TCAs with a tertiary amine appear more effective in penetrating these membrane barriers than TCAs with a secondary amine. PMID:12749958

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

2003-05-01

145

Short-acting versus Long-acting Medications for the Treatment of ADHD  

PubMed Central

Primary care physicians, pediatricians, and psychiatrists account for approximately 80 percent of attention deficit hyperactivity disorder (ADHD) treatments prescribed in the United States. Selection of short-acting versus long-acting ADHD treatment varies by specialty with long-acting agents representing 56 percent of primary care prescriptions, 64 percent of psychiatrist prescriptions, and 79 percent of pediatric prescriptions. There appears to be a correlation between short-acting versus long-acting treatment selection and age, with long-acting agents accounting for 78 percent of prescriptions for pediatric patients (age 0–17) but only 49 percent of prescriptions for adults (patients aged 18+). A discussion of data is included.

Cascade, Elisa; Kalali, Amir H.; Weisler, Richard H.

2008-01-01

146

Controlled release of bioactive TGF- ? 1 from microspheres embedded within biodegradable hydrogels  

Microsoft Academic Search

Transforming growth factor-?1 (TGF-?1) is of great relevance to cartilage development and regeneration. A delivery system for controlled release of growth factors such as TGF-?1 may be therapeutic for cartilage repair. We have encapsulated TGF-?1 into poly(dl-lactide-co-glycolide) (PLGA) microspheres, and subsequently incorporated the microspheres into biodegradable hydrogels. The hydrogels are poly(ethylene glycol) based, and the degradation rate of the hydrogels

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

2006-01-01

147

Sequential growth factor delivery from complexed microspheres for bone tissue engineering  

Microsoft Academic Search

Aim of the study was to design a 3D tissue-engineering scaffold capable of sequentially delivering two bone morphogenetic proteins (BMP). The novel delivery system consisted of microspheres of polyelectrolyte complexes of poly(4-vinyl pyridine) (P4VN) and alginic acid loaded with the growth factors BMP-2 and BMP-7 which themselves were loaded into the scaffolds constructed of PLGA. Microspheres carrying the growth factors

F. Buket Basmanav; Gamze T. Kose; Vasif Hasirci

2008-01-01

148

Controlled delivery of paracetamol and protein at different stages from core–shell biodegradable microspheres  

Microsoft Academic Search

The core–shell biodegradable microspheres loading human serum albumin (HSA) and paracetamol were fabricated with a hydrophilic alginic acid (ALG) shell and a hydrophobic poly(lactic-co-glycolic acid) (PLGA) core. The two model drugs, HSA and paracetamol, were entrapped in the shell and core, respectively. Theses microspheres were characterized in terms of morphology, mean size and size distribution, drug loading efficiency, in vitro

Weijia Wang; Shaobing Zhou; Lin Sun; Chi Huang

2010-01-01

149

Development of a dialysis in vitro release method for biodegradable microspheres  

Microsoft Academic Search

The purpose of this research was to develop a simple and convenient in vitro release method for biodegradable microspheres\\u000a using a commercially available dialyzer. A 25 KD MWCO Float-a-Lyzer was used to evaluate peptide diffusion at 37°C and 55°C\\u000a in different buffers and assess the effect of peptide concentration. In vitro release of Leuprolide from PLGA microspheres,\\u000a having a 1-month

Susan S. D’Souza; Patrick P. DeLuca

2005-01-01

150

In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and poly(lactide-co-glycolide) microspheres  

Microsoft Academic Search

Treatment of many intracellular infections in the mononuclear phagocytic system (MPS), requires targeting of antibiotics by a drug delivery system. The objective of this study was to examine whether the particular nature of microspheres, made of end-group capped and uncapped poly(lactide) [PLA] and poly(lactide-co-glycolide) [PLGA 50:50 and PLGA 75:25], affect the uptake into and also the activation of monocyte-macrophages. Placebo

Sandra Prior; Bruno Gander; Natalia Blarer; Hans Peter Merkle; Mar??a Luisa Subirá; Juan Manuel Irache; Carlos Gamazo

2002-01-01

151

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

PubMed Central

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

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

2007-01-01

152

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

PubMed

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

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

2002-09-01

153

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

2011-04-12

154

The Acidic Microclimate in Poly(lactide-co-glycolide) Microspheres Stabilizes Camptothecins  

Microsoft Academic Search

Purpose. The camptothecin (CPT) analogue, 10-hydroxycamptothecin (10-HCPT) has been shown previously to remain in its acid-stable (and active) lactone form when encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres (1). The purpose of this study was to determine the principal mechanism(s) of 10-HCPT stabilization.

Anna Shenderova; Thomas G. Burke; Steven P. Schwendeman

1999-01-01

155

An In Situ Gel-Forming Heparin-Conjugated PLGA-PEG-PLGA Copolymer  

Microsoft Academic Search

Novel heparin-conjugated PLGA-PEG-PLGA hydrogels were prepared via Michael-type addition between thiolated heparin and PLGA-PEG-PLGA diacrylate. The thiolated heparin (HP-SH) was conjugated with thiolacid dihydrazide followed by reduction. The structure and the thiol determination of obtained HP-SH were characterized by 1H NMR and the Ellman method. Anticoagulant activity and pK a of the HP-SH were determined by aPTT test and UV

Eugene Lih; Yoon Ki Joung; Jin Woo Bae; Ki Dong Park

2008-01-01

156

Formulation strategies for the stabilization of tetanus toxoid in poly(lactide-co-glycolide) microspheres.  

PubMed

The development of a single-dose tetanus vaccine based on Poly(Lactic acid) (PLA) or Poly(Lactide-co-Glycolide) (PLGA) microspheres has been complicated due to the instability of tetanus toxoid (TT) inside these systems. Herein we report an attempt to re-design PLGA microspheres by co-encapsulating TT in the dry solid state together with potential protein stabilizers, such as trehalose, bovine serum albumin, alginate, heparin, dextran or poloxamer 188 and by using an appropriate microencapsulation technique. These newly developed PLGA microspheres were able to release in vitro antigenically active TT for at least 5 weeks, the amount released being highly dependent on the stabilizing excipient used. More specifically, results showed that dextran and heparin provided a particularly stabilizing environment for TT inside the microspheres during the polymer degradation process. The efficacy of this strategy was demonstrated by the high, long lasting titers of neutralizing antibodies achieved after in vivo administration of dextran-containing microspheres with a small amount of alum-adsorbed TT, as compared to the commercial adsorbable tetanus vaccine. These findings suggest that future developments in the area of vaccinology depend on ability to combine a detailed knowledge of the microencapsulation technology with a rational choice of stabilizing excipient or combination of excipients. PMID:10460920

Sánchez, A; Villamayor, B; Guo, Y; McIver, J; Alonso, M J

1999-08-20

157

Biodegradable polymeric microspheres with "open/closed" pores for sustained release of human growth hormone.  

PubMed

A new approach for attaining sustained release of protein is introduced, involving a pore-closing process of preformed porous PLGA microspheres. Highly porous biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were fabricated by a single water-in-oil emulsion solvent evaporation technique using Pluronic F127 as an extractable porogen. Recombinant human growth hormone (rhGH) was incorporated into porous microspheres by a simple solution dipping method. For their controlled release, porous microspheres containing hGH were treated with water-miscible solvents in aqueous phase for production of pore-closed microspheres. These microspheres showed sustained release patterns over an extended period; however, the drug loading efficiency was extremely low. To overcome the drug loading problem, the pore-closing process was performed in an ethanol vapor phase using a fluidized bed reactor. The resultant pore-closed microspheres exhibited high protein loading amount as well as sustained rhGH release profiles. Also, the released rhGH exhibited structural integrity after the treatment. PMID:16542746

Kim, Hong Kee; Chung, Hyun Jung; Park, Tae Gwan

2006-02-28

158

In Vitro Release of Vascular Endothelial Growth Factor From Gadolinium-Doped Biodegradable Microspheres  

PubMed Central

A drug delivery vehicle was constructed that could be visualized noninvasively with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was used to fabricate microspheres containing vascular endothelial growth factor (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The microspheres were characterized in terms of size, drug and contrast agent encapsulation, and degradation rate. The PLGA microspheres had a mean diameter of 48 ± 18 ?m. The gadolinium loading was 17 ± 3 ?g/mg polymer and the VEGF loading was 163 ± 22 ng/mg polymer. Electron microscopy revealed that the Gd was dispersed throughout the microspheres and it was confirmed that the Gd loading was sufficient to visualize the microspheres under MRI. VEGF and Gd-DTPA were released from the microspheres in vitro over a period of ?6 weeks in three phases: a burst, followed by a slow steady-state, then a rapid steady-state. Biodegradable Gd-doped microspheres can be effectively used to deliver drugs in a sustained manner, while being monitored noninvasively with MRI.

Faranesh, Anthony Z.; Nastley, Monet T.; de la Cruz, Cristina Perez; Haller, Michael F.; Laquerriere, Patrice; Leong, Kam W.; McVeigh, Elliot R.

2007-01-01

159

Pars Plana Vitrectomy without Long-Acting Gas Tamponade for Primary Rhegmatogenous Retinal Detachment  

Microsoft Academic Search

Purpose: To report the anatomical and visual results of primary pars plana vitrectomy (PPV) without long-acting gas tamponade to repair primary rhegmatogenous retinal detachments (RRDs). Methods: Twenty-seven consecutive patients (27 eyes) with peripheral retinal tears and new RRDs were treated according to the surgical protocol. Patients underwent PPV with fluid-air exchange and endolaser treatment to repair the RRD. Neither long-acting

Kazuki Hotta; Atsuhiko Sugitani; Yuichi Uchino

2004-01-01

160

Novel Depots of Ketorolac Esters Have Long-Acting Antinociceptive and Antiinflammatory Effects  

Microsoft Academic Search

No long-acting nonsteroidal antiinflammatory drug is clini- cally available for the treatment of pain. In this study, we evaluated the antinociceptive and antiinflammatory ef- fects and duration of action of several novel depots of ketorolac esters, such as ketorolac propyl ester, pentyl ester, heptyl ester, and decyl ester, and observed whether they had a long-acting effect. Four studies in Sprague-Dawley

Shyun-Yeu Liu; Ja-Ping Shieh; Jann-Inn Tzeng; Hou Chia-Hui; Yen-Ling Cheng; Kuo-Lun Huang; Jhi-Joung Wang

2005-01-01

161

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

PubMed

An accelerated method to evaluate peptide release from poly(dl-lactide-co-glycolide) (PLGA) depot formulations in short time is described. Peptide-loaded microspheres were made from hydrophilic 50:50 PLGA by a dispersion-solvent extraction technique, and peptide release was studied at 37 degrees C and at higher temperatures in various media. For all accelerated conditions, release was faster at temperatures above the glass transition, Tg, of the host polymer. Complete release of peptide from 8600 MW PLGA was achieved in 35 hours at 50 degrees C in buffered and nonbuffered media containing 0.5% polyvinyl alcohol (PVA). Type of release media and concentration of PVA influenced the release profiles. A PVA concentration of 0.1 to 0.5% was found to prevent aggregation of microspheres at higher temperatures, with an increase in release at the higher PVA concentration. Peptide release was associated with a reduction of pH of the releasing media and increased mass loss. Complete peptide release at pH 4 from 8.6 kd and 28 kd PLGA at 50 and 60 degrees C occurred within 30-40 hours and correlated well with the real-time release at 37 degrees C and pH 7.0. At the higher molecular weight, a slightly longer accelerated release time and higher temperature were required to correlate with the real-time release. The data suggest that by optimization of release conditions such as temperature, surfactant concentration, buffer component, and pH, an accelerated study could be employed to evaluate depot formulations for a given polymer type. PMID:11741203

Shameem, M; Lee, H; DeLuca, P P

1999-01-01

162

Adsorption determines in-vitro protein release rate from biodegradable microspheres: quantitative analysis of surface area during degradation  

Microsoft Academic Search

A model protein, carboxymethylated bovine serum albumin (CM-BSA), was encapsulated within relatively fast degrading and slow degrading poly(d,l-lactide-co-glycolide, PLGA) microspheres using a multiple emulsion solvent evaporation technique. The specific surface area (?), porosity, molecular weight change, and mass erosion of the microspheres during the degradation period were examined in relation to non-specific protein adsorption and the in-vitro protein release kinetics.

George Crotts; Hongkee Sah; Tae Gwan Park

1997-01-01

163

Preparation, characterization, and in vitro testing of poly(lactide-co-glycolide) and dextran magnetic microspheres for in vivo applications  

NASA Astrophysics Data System (ADS)

Many research groups are investigating degradable magnetic particles for magnetic resonance imaging (MRI) contrast agents and as carriers for magnetic drug guidance. These particles are composite materials with a degradable polymer matrix and iron oxide nanoparticles for magnetic properties. The degradable polymer matrix acts to provide colloidal stability and, for drug delivery applications, provides a reservoir for the storage and release of drugs. Natural polymers, like albumin and dextran, which degrade by the action of enzymes; have been used for the polymer matrix. Iron oxide nanoparticles are used for magnetic properties since they can be digested in vivo and have low toxicities. Polylactic acid (PLA) and its copolymers with polyglycolic acid (PLGA) are versatile polymers that degrade by simple hydrolysis without the aid of enzymes. Microspheres are easily formed using the solvent extraction/evaporation method and a wide range of drugs can be encapsulated in them. Magnetic PLGA microspheres suitable for applications were synthesized for the first time in this dissertation. This was accomplished by coating iron oxide nanoparticles with oleic acid to make them dispersible in the organic solvents used in the extraction/evaporation microsphere preparation method. In addition to the magnetic PLGA microspheres, a novel all-aqueous method for preparing crosslinked dextran magnetic microspheres was developed in this dissertation. This method uses free radical polymerization for crosslinking and does not require the use of flammable and harmful solvents. For efficient MRI contrast and magnetic drug guidance, maximized iron oxide content of microspheres is desirable. The two different microsphere preparation methods were optimized for iron oxide content. The effect of iron oxide content on microsphere size and morphology was studied. In addition, an in vitro circulation model was used to evaluate the ability of magnetic microspheres to be guided at physiologic blood flow velocities. The MRI contrast effect was studied as a function of microsphere concentration.

Leamy, Patrick J.

164

Comparative study on sustained release of human growth hormone from semi-crystalline poly( l-lactic acid) and amorphous poly( d, l-lactic-co-glycolic acid) microspheres: morphological effect on protein release  

Microsoft Academic Search

Recombinant human growth hormone (rhGH) was encapsulated by a double emulsion solvent evaporation method within two biodegradable microspheres having different polymer compositions. Semi-crystalline poly(l-lactic acid) (PLA) and amorphous poly(d,l-lactic-co-glycolic acid) (PLGA) were used for the encapsulation of hGH. Protein release profiles from the two microspheres were comparatively evaluated with respect to their morphological difference. Both of the microspheres similarly exhibited

Hong Kee Kim; Tae Gwan Park

2004-01-01

165

Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres.  

PubMed

The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing a staphylokinase variant K35R (DGR) with purpose of preserving the protein stability during both encapsulation and drug release. DGR-loaded microspheres are fabricated using a double-emulsion solvent extraction technique. Prior to encapsulation, the effect of ultrasonication emulsification of DGR solutions with methylene chloride on protein recovery was investigated. Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately 84% DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR solutions significantly improved DGR recovery to >90%. The effects of co-encapsulated PVA and NaCl in the external aqueous phase on the characteristics of the microspheres were investigated. When 2% PVA was co-encapsulated and 2.5% NaCl was added to the external water phase, DGR encapsulation efficiency was significantly increased from 7.1% to 78.1% and DGR was distributed uniformly throughout the microspheres. In vitro release test showed that DGR was released from PLGA microspheres in a sustained manner over 15 days. A large amount of released DGR was inactive in the absence of co-encapsulated PVA. On the contrary, when 2% PVA was co-encapsulated, the released DGR was almost completely intact within 9 days. In conclusion, PLGA microspheres can be an effective carrier for DGR and form a promising depot system. PMID:16413979

He, Jin-Tian; Su, Hua-Bo; Li, Guo-Ping; Tao, Xian-Mei; Mo, Wei; Song, Hou-Yan

2006-01-04

166

?-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

2012-02-01

167

Treatment adherence with early prescription of long-acting injectable antipsychotics in recent-onset schizophrenia.  

PubMed

Although response to treatment for the first episode of schizophrenia is generally favourable, nonadherence with the treatment is the first cause of relapse and rehospitalisation within the next few years. Long-acting injectable antipsychotics (LAIAs) combine the advantages of the newer antipsychotics and the long-acting formulation. The evaluation concerns 25 schizophrenic patients hospitalised for the first time, treated with risperidone long-acting injectable (RLAI) associated with reintegration methods, and followed up for at least 18 months. Clinical observation was completed using Clinical Global Impression (CGI) scale and Global Assessment of Functioning (GAF). Clinical improvement was coupled with a good reintegration rate, very few relapse, or rehospitalisation. Bimonthly injection combined with psychosocial methods improved interactive followup, and therefore patients' compliance with the treatment. Treating with LAIA as early as possible, from the first episode if possible, can reduce relapse, number and duration of rehospitalisation, and cognitive symptoms and improve the quality of life and prognosis. PMID:22966435

Viala, Annie; Cornic, Françoise; Vacheron, Marie-Noëlle

2012-04-03

168

Amyloid as a depot for the formulation of long-acting drugs.  

PubMed

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

2008-02-01

169

Biodegradable microspherical implants containing teicoplanin for the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis  

Microsoft Academic Search

Background  The aim of this study was to prepare poly(d,l-lactide-co-glycolide) (PLGA) microspherical implants containing teicoplanin (TCP) using a double emulsion solvent evaporation method\\u000a and to evaluate its efficacy for the local treatment of chronic osteomyelitis.\\u000a \\u000a \\u000a \\u000a Methods  The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency\\u000a and in vitro release assessments of the formulations were carried out. Sterile TCP–PLGA

Zafer Orhan; Erdal Cevher; Ayca Y?ld?z; Rengin Ah?skal?; Demet Sensoy; Lütfiye Mülaz?mo?lu

2010-01-01

170

Design of Methylprednisolone Biodegradable Microspheres Intended for Intra-articular Administration  

Microsoft Academic Search

This study aimed to design methyprednisolone (MP)-loaded poly(d,l lactide-co-glycolide) (PLGA) microspheres (MS) intended for intra-articular administration. MP was encapsulated in four different\\u000a types of PLGA by using an S\\/O\\/W technique. The effects of ?-irradiation at the dose of 25 kGy were evaluated on the chemical\\u000a and physicochemical properties of MS and the drug release profiles. The S\\/O\\/W technique with hydroxypropylmethylcellulose\\u000a (HPMC)

Francesco Cilurzo; Francesca Selmin; Paola Minghetti; Luisa Montanari

2008-01-01

171

The impact of long-acting medications on attention-deficit/hyperactivity disorder treatment disparities.  

PubMed

Abstract Objective: Long-acting stimulants have increased medication adherence for many children diagnosed with attention deficit/hyperactivity disorder (ADHD), but it is unknown whether the increase has been similar across racial/ethnic groups. Our objective was to determine whether differences in medication utilization and adherence among white, black, and Hispanic ADHD-diagnosed children and adolescents narrowed following the introduction of long-acting stimulants in the 1990s. Methods: We conducted a retrospective analysis of Florida Medicaid claims data from fiscal years 1996-2005. At each of three cross sections, we identified children and adolescents 3-17 years of age with at least two claims with an ADHD diagnosis. We used linear regression to model disparities over the study period in utilization of any ADHD medications (utilization of long-acting medication specifically) and medication adherence, and identified patient level, treatment setting, and geographic contributors to disparities. Results: Although ADHD medication utilization was lower for ADHD-diagnosed minorities than whites in all years, minorities were as likely as whites to switch to long-acting medications. The increase in prescribed days following long-acting medication diffusion was comparable for white and black medication users (40 and 43 days, respectively), but lower for Hispanics (27 days). Geography and provider setting helped to explain disparities in medication utilization overall, but disparities in adherence were not explained by any of the covariates. Conclusions: Despite equivalent switching to long-acting medications in the study period, minorities continued to utilize all ADHD medications less than did whites, and for shorter periods. Provider setting helps explain the ADHD medication utilization gap. High-volume, minority-serving providers are potential targets for future interventions related to improved communication about medication and follow-up after medication initiation. PMID:23952187

Saloner, Brendan; Fullerton, Catherine; McGuire, Thomas

2013-08-01

172

Application of Raman microscopy to biodegradable double-walled microspheres.  

PubMed

Raman mapping measurements were performed on the cross section of the ternary-phase biodegradable double-walled microsphere (DWMS) of poly(D,L-lactide-co-glycolide) (50:50) (PLGA), poly(L-lactide) (PLLA), and poly(epsilon-caprolactone) (PCL), which was fabricated by a one-step solvent evaporation method. The collected Raman spectra were subjected to a band-target entropy minimization (BTEM) algorithm in order to reconstruct the pure component spectra of the species observed in this sample. Seven pure component spectral estimates were recovered, and their spatial distributions within DWMS were determined. The first three spectral estimates were identified as PLLA, PLGA 50:50, and PCL, which were the main components in DWMS. The last four spectral estimates were identified as semicrystalline polyglycolic acid (PGA), dichloromethane (DCM), copper-phthalocyanine blue, and calcite, which were the minor components in DWMS. PGA was the decomposition product of PLGA. DCM was the solvent used in DWMS fabrication. Copper-phthalocyanine blue and calcite were the unexpected contaminants. The current result showed that combined Raman microscopy and BTEM analysis can provide a sensitive characterization tool to DWMS, as it can give more specific information on the chemical species present as well as the spatial distributions. This novel analytical method for microsphere characterization can serve as a complementary tool to other more established analytical techniques, such as scanning electron microscopy and optical microscopy. PMID:20017529

Widjaja, Effendi; Lee, Wei Li; Loo, Say Chye Joachim

2010-02-15

173

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

PubMed

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

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

2009-05-18

174

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

PubMed

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

Wang, Fang Jing; Wang, Chi Hwa

2002-06-17

175

Rat sciatic nerve repair with a poly-lactic-co-glycolic acid scaffold and nerve growth factor releasing microspheres.  

PubMed

The effect of microsphere delivered Nerve Growth Factor (NGF) in a poly-lactic-co-glycolic-acid (PLGA) 85/15 nerve conduit bridging a 10mm rat sciatic nerve gap was assessed, comparing nine groups (n = 6): PLGA conduits filled with saline, saline and NGF, saline with blank microspheres; four different NGF microspheres (5, 20, 50, and 100 mg/ml); an autologous graft and sciatic nerve gap. Histomorphometry, retrograde tracing, electrophysiology, and functional outcomes were evaluated up to 16 weeks. The autologous graft showed the largest fascicular area (0.65 mm(2) ) and had a significantly greater number of myelinated fibers (P < 0.0001). Electrophysiology showed Compound Muscle Action Potential (CMAP) recordings for the autologous graft returning at 6 weeks after nerve transection, reaching their highest amplitude of 3.6 mV at endpoint. No significant differences were found in functional evaluation between groups or between conduits with microspheres and the saline filled conduit. A PLGA 85/15 nerve conduit is capable of sustaining nerve regeneration. The microsphere delivery system does not interfere with regeneration. PMID:21400584

de Boer, Ralph; Knight, Andrew M; Borntraeger, Andreas; Hébert-Blouin, Marie-Noëlle; Spinner, Robert J; Malessy, Martijn J A; Yaszemski, Michael J; Windebank, Anthony J

2011-03-11

176

Development of sustained-release microspheres for the delivery of SAR 1118, an LFA-1 antagonist intended for the treatment of vascular complications of the eye.  

PubMed

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

Yandrapu, Sarath; Kompella, Uday B

2012-12-20

177

PLGA bone plates reinforced with crosslinked PPF  

Microsoft Academic Search

In this study a matrix of poly(propylene fumarate) (PPF) was crosslinked with N-vinylpyrrolidone (NVP), 2-hydroxyethylmethacrylate (HEMA), or a mixture of NVP and ethyleneglycol dimethacrylate (EGDMA) in the presence of poly(lactide-co-glycolide) (PLGA) to reinforce and preserve the form of PLGA bone plates. The degree of crosslinkage varied depending on the crosslinker as shown by the rapid and almost complete leaching of

V. Hasirci; A. E. Litman; D. J. Trantolo; J. D. Gresser; D. L. Wise; H. C. Margolis

2002-01-01

178

Glucose Homeostasis and Safety in Patients with Acromegaly Converted from Long-Acting Octreotide to Pegvisomant  

Microsoft Academic Search

Context: In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported. Objectives: The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size. Design: This was a multicenter,

Ariel L. Barkan; Pia Burman; David R. Clemmons; William M. Drake; Robert F. Gagel; Philip E. Harris

179

Long acting hyaluronate – exendin 4 conjugate for the treatment of type 2 diabetes  

Microsoft Academic Search

Despite clinical exploitation of exendin 4 for the treatment of type 2 diabetes, the significantly short half-life requiring twice a day injection has limited the wide applications. In this work, a protocol for the synthesis of long acting hyaluronate (HA) – exendin 4 conjugate was successfully developed using Michael addition chemistry between vinyl sulfone modified HA (HA-VS) and thiolated exendin

Ji-Hyun Kong; Eun Ju Oh; Su Young Chae; Kang Choon Lee; Sei Kwang Hahn

2010-01-01

180

Kaposi’s Sarcoma after Long-Acting Steroids: Time until Remission and Drug Washout  

Microsoft Academic Search

Long-acting steroids (LAS) are widely used to treat various inflammatory diseases and allergies. They have many adverse effects including the inhibition of the hypothalamopituitary axis that can last several months. LAS are also strong immunosuppressors and can result in severe opportunistic infections and immunodeficiency-related malignancies. However, the time needed for immune recovery after withdrawal of LAS is unknown. Here we

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

2010-01-01

181

Long-acting beta 2-agonists. Role in primary care asthma treatment.  

PubMed Central

OBJECTIVE: To examine the efficacy of long-acting beta 2-agonists and their role in primary care asthma management and to review briefly the pharmacology of these agents. QUALITY OF EVIDENCE: Most data presented were derived from randomized, double-blind, placebo-controlled trials. Studies were selected for relevance to asthma management in primary care. MAIN FINDINGS: Long-acting beta 2-agonist use is associated with improvements in both objective and subjective measures of asthma control. At present no evidence suggests that long-acting beta 2-agonists have anti-inflammatory potential. While salmeterol has a longer duration of action than short-acting beta 2-agonists, its onset of action is slower. Salmeterol and formoterol, therefore, should not be used for relief of acute bronchospasm. CONCLUSION: Long-acting beta 2-agonists could be useful for treating asthma in primary care, particularly for controlling symptoms of nocturnal asthma and exercise-induced asthma and for providing convenient maintenance therapy for patients who require regular use of short-acting beta 2-agonists despite concomitant use of optimal doses of inhaled anti-inflammatory medication.

D'Urzo, A. D.

1997-01-01

182

Reversible inhibition of central precocious puberty with a long acting GnRH analogue.  

PubMed Central

A 7 year old girl with precocious puberty was treated with buserelin, a long acting analogue of gonadotrophin releasing hormone. Spontaneous and stimulated gonadotrophin secretion became prepubertal but returned to pubertal values when buserelin was withdrawn, suggesting that normal sexual maturation should follow cessation of treatment.

Ward, P S; Ward, I; McNinch, A W; Savage, D C

1985-01-01

183

Remission in schizophrenia: Results from a 1-year study of long-acting risperidone injection  

Microsoft Academic Search

PurposeAlthough treatment advances have improved outcomes in schizophrenia, definitions of remission and recovery are still evolving. Recently proposed criteria for remission (mild or less on multiple core-symptom ratings for at least 6 months) have been applied to a 1-year study of long-acting risperidone injection.

Robert A. Lasser; Cynthia A. Bossie; Georges M. Gharabawi; John M. Kane

2005-01-01

184

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

PubMed Central

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

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

2011-01-01

185

Evaluation of protective efficacy using a nonstructural protein NS1 in DNA vaccine-loaded microspheres against dengue 2 virus.  

PubMed

Dengue virus results in dengue fever or severe dengue hemorrhagic fever/dengue shock syndrome in humans. The purpose of this work was to develop an effective antidengue virus delivery system, by designing poly (dl-lactic-co-glycolic) acid/polyethylene glycol (PLGA/PEG) microspheres using a double-emulsion solvent extraction method, for vaccination therapy based on locally and continuously sustained biological activity. Nonstructural protein 1 (NS1) in deoxyribonucleic acid (DNA) vaccine-loaded PLGA/PEG microspheres exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (39%), the mean particle size 4.8 ?m, and a controlled in vitro release profile with a low initial burst (18.5%), lag time (4 days), and continued released protein over 70 days. The distribution of protein on the microspheres surface, outer layer, and core were 3.0%, 28.5%, and 60.7%, respectively. A release rate was noticed to be 1.07 ?g protein/mg microspheres/day of protein release, maintained for 42 days. The cumulative release amount at Days 1, 28, and 42 was 18.5, 53.7, and 62.66 ?g protein/mg microspheres, respectively. The dengue virus challenge in mice test, in which mice received one dose of 20 ?g NS1 protein content of microspheres, in comparison with NS1 protein in Al(OH)3 or PBS solution, was evaluated after intramuscular immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with NS1 protein-loaded PLGA/PEG microspheres (100%). In vivo vaccination studies also demonstrated that NS1 protein-loaded PLGA/PEG microspheres had a protective ability; its steady-state immune protection in rat plasma changed from 4,443 ± 1,384 pg/mL to 10,697 ± 3,197 pg/mL, which was 2.5-fold higher than that observed for dengue virus in Al(OH)3 at 21 days. These findings strongly suggest that NS1 protein-loaded PLGA/PEG microspheres offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers. PMID:23990724

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

2013-08-19

186

Atenolol, sustained-release oxprenolol, and long-acting propranolol in hypertension  

Microsoft Academic Search

The effect of once-daily atenolol, sustained-release oxprenolol (a new formulation of oxprenolol presented as a compressed tablet in a waxed matrix), and long-acting propranolol (a new formulation presented as spheriods in a capsule) was studied in a double-blind crossover trial in 23 carefully selected hypertensive outpatients. After a run-in period with matching placebo each patient received atenolol (100 mg\\/day), sustained-release

J C Petrie; T A Jeffers; O J Robb; A K Scott; J Webster

1980-01-01

187

Randomized Clinical Trial of Long-Acting Somatostatin for Autosomal Dominant Polycystic Kidney and Liver Disease  

Microsoft Academic Search

There are no proven, effective therapies for polycystic kidney disease (PKD) or polycystic liver disease (PLD). We enrolled 42 patients with severe PLD resulting from autosomal dominant PKD (ADPKD) or autosomal dominant PLD (ADPLD) in a randomized, double-blind, placebo-controlled trial of octreotide, a long-acting somatostatin analogue. We randomly assigned 42 patients in a 2:1 ratio to octreotide LAR depot (up

Marie C. Hogan; Tetyana V. Masyuk; Linda J. Page; Vickie J. Kubly; Eric J. Bergstralh; Xujian Li; Bohyun Kim; Bernard F. King; James Glockner; David R. Holmes; Sandro Rossetti; Peter C. Harris; Nicholas F. LaRusso; Vicente E. Torres

2010-01-01

188

Development of nifedipine-loaded coated gelatin microcapsule as a long acting oral delivery  

Microsoft Academic Search

To develop the long acting nifedipine oral delivery with enhanced bioavailability, nifedipine-loaded gelatin microcapsule\\u000a containing nifedipine and ethanol in gelatin shell was prepared using a spray-dryer, and then coated microcapsule was prepared\\u000a by coating the gelatin microcapsule with Eudragit acrylic resin. The dissolution test and the bioavailability of the coated\\u000a microcapsule in rats were evaluated compared to nifedipine powder. The

Dong Xun Li; Jong Oh Kim; Dong Hoon Oh; Won Seok Lee; Myung Ja Hong; Jin Yang Kang; Jong Seo Choi; Jong Soo Woo; Chul Soon Yong; Han-Gon Choi

2009-01-01

189

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.

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

2006-01-01

190

Persistent efficacy of long-acting moxidectin for control of trichostrongylid infections of sheep  

Microsoft Academic Search

The objective was to evaluate long-acting moxidectin (Cydectin® 2% LA for sheep) against trichostrongylids in sheep. We performed a blocked, parallel, controlled clinical trial. We included 45 ewe-lambs, allocated into treated (n=30, 1.0mg moxidectin per kg bw, subcutaneously at base of ear on D 0) or controls (n=15). Animals had been naturally infected (pre-treatment geometric mean epg counts: 233 and

E. Papadopoulos; I. A. Fragkou; V. S. Mavrogianni; D. A. Gougoulis; D. C. Orfanou; E. Gallidis; S. Ptochos; I. A. Taitzoglou; L. Parker; G. C. Fthenakis

2009-01-01

191

Airway Epithelial Integrity Is Protected by a Long-Acting 2Adrenergic Receptor Agonist  

Microsoft Academic Search

Airway epithelial integrity may be impaired by bacterial exopro- ducts, which are able to degrade tight junction-associated proteins such as zonula occludens 1 (ZO-1). We have investigated the protec- tive effect of salmeterol, a long-acting 2-adrenergic agonist, on Pseudomonas aeruginosa-induced alteration of the epithelial junc- tional barrier. We demonstrate in human airway epithelial cells (HAEC) that salmeterol induces a time-dependent

Christelle Coraux; Claire Kileztky; Myriam Polette; Jocelyne Hinnrasky; Jean-Marie Zahm; Philippe Devillier; Sophie de Bentzmann; Edith Puchelle

192

The long-acting glucagon-like peptide-1 analogue, liraglutide, inhibits ?-cell apoptosis in vitro  

Microsoft Academic Search

We here show that GLP-1 and the long-acting GLP-1 analogue, liraglutide, interfere with diabetes-associated apoptotic processes in the ?-cell. Studies using primary neonatal rat islets showed that native GLP-1 and liraglutide inhibited both cytokine- and free fatty acid-induced apoptosis in a dose-dependent manner. The anti-apoptotic effect of liraglutide was mediated by the GLP-1 receptor as the specific GLP-1 receptor antagonist,

Søren Bregenholt; Annette Møldrup; Niels Blume; Allan E. Karlsen; Birgitte Nissen Friedrichsen; Ditte Tornhave; Lotte Bjerre Knudsen; Jacob S. Petersen

2005-01-01

193

Use of long-acting injectable risperidone before and throughout pregnancy in schizophrenia  

Microsoft Academic Search

Data on the use of long-acting injectable (LAI) risperidone, the first atypical depot antipsychotic, during pregnancy are limited. A 35-year-old woman with schizophrenia was given LAI risperidone before and throughout her pregnancy. She gave birth to a female infant weighing 2230 g at 36 weeks and 6 days of pregnancy, following premature rupture of the membranes. The baby had no congenital malformation and

Sung-Wan Kim; Ki-Min Kim; Jae-Min Kim; Il-Seon Shin; Hee-Young Shin; Su-Jin Yang; Jin-Sang Yoon

2007-01-01

194

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

195

A novelin vitro release technique for peptide-containing biodegradable microspheres  

Microsoft Academic Search

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

Janusz W. Kostanski; Patrick P. DeLuca

2000-01-01

196

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

197

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

Microsoft Academic Search

The purpose of this study was to develop and evaluate a dialysisin vitro release technique for peptide-containing poly(d, 1-lactide-coglycolide) (PLGA) microspheres (ms) that would correlate within vitro data. Using a luteinizing hormone- releasing hormone analogue (LHRH), Orntide acetate, solubility and stability were determined\\u000a in 0.1 M phosphate buffer (PB), pH 7.4, and in 0.1 M acetate buffer (AB), pH 4.0,

Janusz W. Kostanski; Patrick P. DeLuca

2000-01-01

198

Synthesis of biodegradable polymer–mesoporous silica composite microspheres for DNA prime-protein boost vaccination  

Microsoft Academic Search

DNA vaccines or proteins are capable of inducing specific immunity; however, the translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein we demonstrate a composite microsphere formulation, composed of mesoporous silica spheres (MPS) and poly(d,l-lactide-co-glycolide) (PLGA), enables the controlled delivery of a prime-boost vaccine via the encapsulation of

Jenny Ho; Yi Huang; Michael K. Danquah; Huanting Wang; Gareth M. Forde

2010-01-01

199

Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non-aqueous solvent evaporation methods  

Microsoft Academic Search

Somatostatin, a therapeutic peptide drug, was entrapped within polymeric microspheres made from high molecular weight poly (d,l-lactide\\/glycolide) (PLGA) or low molecular weight poly (d,l-lactide) (PLA) by various modifications of the O\\/W-solvent evaporation method. The drug was either dispersed as solid (dispersion method), dissolved with the aid of a co-solvent (co-solvent method) or emulsified as an aqueous solution (W\\/O\\/W-multiple emulsion method)

Joachim Herrmann; Roland Bodmeier

1998-01-01

200

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

Microsoft Academic Search

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 poly-lactic-co-glycolic acid (PLGA) microspheres encapsulating VEGF and the in vivo application of nerve conduits supplemented

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

201

Plasma disposition of conventional and long-acting moxifloxacin in sheep after intravenous administration.  

PubMed

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

2012-08-29

202

Patient perspectives on use of long-acting antipsychotics in bipolar disorder: focus on risperidone injection  

PubMed Central

In the last few years, oral second-generation antipsychotics have demonstrated mood-stabilizing properties and are now widely used in the treatment of bipolar disorder. Unfortunately, treatment of this chronic and complex illness is hampered with poor adherence on the part of patients. Long-acting injectable formulations of second-generation antipsychotics could combine the effect of oral second-generation antipsychotics in patients with bipolar disorder and the benefits of depot formulation with the assurance of steady medication delivery and thereby improve adherence. In this context, the efficacy and tolerance of risperidone long-acting injection (RLAI) for maintenance treatment in patients with bipolar disorder is assessed. The relevant studies found RLAI to be effective in preventive treatment of manic but not depressive recurrences in bipolar patients, with good tolerance. RLAI appeared to be particularly suitable for patients with known poor adherence to treatment or severe bipolar disorder (such as patients who relapse frequently). Lastly, if RLAI, unlike the first-generation antipsychotics, does not induce depressive symptoms, the different studies do not enable us to consider its use in monotherapy in the preventive treatment of patients with depressive polarity. Long-acting second-generation antipsychotics in bipolar patients are therefore associated with long-term benefits, but their use in clinical practice needs to be improved.

Samalin, L; Charpeaud, T; Lorabi, O; Llorca, PM

2010-01-01

203

Patient perspectives on use of long-acting antipsychotics in bipolar disorder: focus on risperidone injection.  

PubMed

In the last few years, oral second-generation antipsychotics have demonstrated mood-stabilizing properties and are now widely used in the treatment of bipolar disorder. Unfortunately, treatment of this chronic and complex illness is hampered with poor adherence on the part of patients. Long-acting injectable formulations of second-generation antipsychotics could combine the effect of oral second-generation antipsychotics in patients with bipolar disorder and the benefits of depot formulation with the assurance of steady medication delivery and thereby improve adherence. In this context, the efficacy and tolerance of risperidone long-acting injection (RLAI) for maintenance treatment in patients with bipolar disorder is assessed. The relevant studies found RLAI to be effective in preventive treatment of manic but not depressive recurrences in bipolar patients, with good tolerance. RLAI appeared to be particularly suitable for patients with known poor adherence to treatment or severe bipolar disorder (such as patients who relapse frequently). Lastly, if RLAI, unlike the first-generation antipsychotics, does not induce depressive symptoms, the different studies do not enable us to consider its use in monotherapy in the preventive treatment of patients with depressive polarity. Long-acting second-generation antipsychotics in bipolar patients are therefore associated with long-term benefits, but their use in clinical practice needs to be improved. PMID:20859459

Samalin, L; Charpeaud, T; Lorabi, O; Llorca, Pm

2010-09-07

204

Effect of triple growth factor controlled delivery by a brushite-PLGA system on a bone defect.  

PubMed

Bone regeneration is a complex process that involves multiple cell types, growth factors (GFs) and cytokines. A synergistic contribution of various GFs and a crosstalk between their signalling pathways was suggested as determinative for the overall osteogenic outcome. The purpose of this work was to develop a brushite-PLGA system, which controls the release rate of the integrated growth factors (GFs) to enhance bone formation. The brushite cement implants were prepared by mixing a phosphate solid phase with an acid liquid phase. PDGF (250 ng) and TGF-?1 (100 ng) were incorporated into the liquid phase. PLGA microsphere-encapsulated VEGF (350 ng) was pre-blended with the solid phase. VEGF, PDGF and TGF-?1 release kinetics and tissue distributions were determined using iodinated ((125)I) GFs. In vivo results showed that PDGF and TGF-?1 were delivered more rapidly from these systems implanted in an intramedullary defect in rabbit femurs than VEGF. The three GFs released from the brushite-PLGA system remained located around the implantation site (5 cm) with negligible systemic exposure. Bone peak concentrations of approximately 4 ng/g and 1.5 ng/g of PDGF and TGF-?1, respectively were achieved on day 3. Thereafter, PDGF and TGF-?1 concentrations stayed above 1 ng/g during the first week. The scaffolds also provided a VEGF peak concentration of nearly 6 ng/g on day 7 and a local concentration of approximately 1.5 ng/g during at least 4 weeks. Four weeks post implantation bone formation was considerably enhanced with the brushite-PLGA system loaded with each of the three GFs separately as well as with the combination of PDGF and VEGF. The addition of TGF-?1 did not further improve the outcome. In conclusion, the herein presented brushite-PLGA system effectively controlled the release kinetics and localisation of the three GFs within the defect site resulting in markedly enhanced bone regeneration. PMID:22035848

Reyes, Ricardo; De la Riva, Beatriz; Delgado, Araceli; Hernández, Antonio; Sánchez, Esther; Évora, Carmen

2011-10-28

205

The osteogenic response of mesenchymal stem cells to an injectable PLGA bone regeneration system.  

PubMed

The enrichment of substrates/surfaces with selected functional groups, methyl (-CH3), allyl amine (-NH2), allyl alcohol (-OH) and acrylic acid (-COOH), can be used to trigger mesenchymal stem (MSC) cell differentiation into specified lineages, minimising the need for exogenous biological supplementation. We present the successful translation of this research phenomenon to an injectable two phase injectable PLGA system, utilising plasma techniques, for the repair of bone defects. Modified microspheres were characterised using water contact angel (WCA), X-ray Photon Spectroscopy (XPS) and scanning electron microscopy (SEM). When cultured in contact with MSCs in vitro, the ability of the modified particles, within the 2 phase system, to induce differentiation was characterised using quantitative assays for cell viability and histological analysis for key markers of differentiation throughout the entirety of the three dimensional scaffold. Biological analysis proved that selected modified microspheres have the ability to induce MSC osteogenic (-NH2 modified scaffolds) and chondrogenic (-OH modified scaffolds) differentiation throughout the entirety of the formed scaffold. Therefore optimised plasma modification of microspheres is an effective tool for the production of injectable systems for the repair of bone and cartilage defects. PMID:24044995

Curran, Judith M; Fawcett, Sandra; Hamilton, Lloyd; Rhodes, Nicholas P; Rahman, Cheryl V; Alexander, Morgan; Shakesheff, Kevin; Hunt, John A

2013-09-14

206

Tunable Hydrogel-Microsphere Composites that Modulate Local Inflammation and Collagen Bulking  

PubMed Central

Injectable biomaterials alone may alter local tissue responses, including inflammatory cascades and matrix production (e.g., stimulatory dermal fillers are used as volumizing agents that induce collagen production). To expand upon the available material compositions and timing of presentation, a tunable hyaluronic acid (HA) and poly(lactide-co-glycolide) (PLGA) microsphere composite system was formulated and assessed in subcutaneous and cardiac tissues. HA functionalized with hydroxyethyl methacrylate (HeMA) was used as a precursor to injectable and degradable hydrogels that carry PLGA microspheres (~50 m diameter) to tissues, where the HA hydrogel degradation (~20 or 70 days) and quantity of PLGA microspheres (0–300 mg/ml) are readily varied. When implanted subcutaneously, faster hydrogel degradation and more microspheres (e.g., 75mg/mL) generally induced more rapid tissue and cellular interactions and a greater macrophage response. In cardiac applications, tissue bulking may be useful to alter stress profiles and to stabilize the tissue after infarction, limiting left ventricular (LV) remodeling. When fast degrading HeMA-HA hydrogels containing 75 mg/mL microspheres were injected into infarcted tissue in sheep, LV dilation was limited and the thickness of the myocardial wall and the presence of vessels in the apical infarct region were increased ~35% and ~60%, respectively, compared to empty hydrogels. Both groups decreased volume changes and infarct areas at 8 weeks, compared to untreated controls. This work illustrates the importance of material design in expanding the application of tissue bulking composites to a range of biomedical applications.

Tous, Elena; Weber, Heather M.; Lee, Myung Han; Koomalsingh, Kevin J.; Shuto, Takashi; Kondo, Norihiro; Gorman, Joseph H.; Lee, Daeyeon; Gorman, Robert C.; Burdick, Jason A.

2012-01-01

207

Application of open porous poly(D,L-lactide-co-glycolide) microspheres and the strategy of hydrophobic seeding in hepatic tissue cultivation.  

PubMed

In this article, porous poly(D,L-lactide-co-glycolide) (PLGA) microsphere scaffolds with a size of ? 400 ?m and pores of ? 20 ?m were prepared for constructing injectable three-dimensional hepatocyte spheroids. The porous sites of PLGA microspheres provided a spatial space for hepatocyte distribution. Hepatocytes spheroids were cocultured with human umbilical vein endothelial cell, bone marrow mesenchymal stem cell, or NIH/3T3 cells by combining the porous PLGA microspheres with the relatively hydrophobic culture strategy. The combination of open porous microspheres, hepatocytes, and nonparenchymal cells was demonstrated for application in functional hepatic tissue reconstruction. Hepatocellular-specific functions can sustained up to 2 weeks in the support of coculturing with nonparenchymal cells. The spheroidal hepatocyte coculture system had the advantages of an injectable delivery, higher cell seeding density, protection from exerted shear stress, better exchange of nutrients, oxygen and metabolites, and heterotypic cell-cell contact within and between microspheres. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2862-2869, 2013. PMID:23505008

Chou, Ming-Ju; Hsieh, Chin-Hsiung; Yeh, Peng-Lin; Chen, Po-Cheng; Wang, Ching-Hua; Huang, Yi-You

2013-03-18

208

Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo  

PubMed Central

Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3–15 ?m diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification.

Qiao, Chunyan; Zhang, Kai; Jin, Han; Miao, Leiying; Shi, Ce; Liu, Xia; Yuan, Anliang; Liu, Jinzhong; Li, Daowei; Zheng, Changyu; Zhang, Guirong; Li, Xiangwei; Yang, Bai; Sun, Hongchen

2013-01-01

209

[Current alternative in the pharmacotherapy of acromegaly: the long-acting somatostatin analogue octreotide].  

PubMed

Twelve active acromegalic patients (10 women, 2 men) were chronically treated with a long-acting microcapsulated preparation of octreotide (Sandostatin LAR, Novartis). In each case, a growth hormone-producing pituitary adenoma was responsible for the development of acromegaly (microadenomas in 3 and macroadenomas in the rest of the patients). Treatment with long-acting octreotide was indicated for those patients who had not reacted satisfactorily upon previous therapeutic procedures or proved to be unsuitable for irradiation therapy and/or surgery or refused both of these therapies. The preparation was given intramuscularly in every fourth week, generally in a dose of 20-30 mg. After a 6-month treatment, the daily mean of serum growth hormone became suppressed below 2.5 ng/ml in 58.3% of the patients, whereas the growth hormone nadir during oral glucose tolerance test was found at or below 2.5 ng/ml in an even higher proportion of patients (70%). During a 2-year period, the growth hormone-suppressive effect of long-acting octreotide remained stable in all but one patient. The size of the pituitary adenomas remarkably decreased in 50% of this patient cohort. The medication with this preparation was well tolerated. As adverse events, asymptomatic cholelithiasis was detected in 2 patients and biliary sludge-formation in 1 patient. The total number of patients with glucose metabolism disturbances increased only moderately, however, the occurrence of manifest diabetes mellitus became doubled. On the basis of relevant literature data, it can be stated that the mortality rate of successfully treated acromegalics significantly improves. The present retrospective study yields evidence for the microcapsulated octreotide to be an effective tool in the modern therapy of acromegaly. PMID:12063861

Laczi, Ferenc; Magony, Sándor; Julesz, János

2002-05-12

210

A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis  

PubMed Central

OBJECTIVE—To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA).?METHODS—Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20).?RESULTS—Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1).?CONCLUSION—Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.??

Paran, D; Elkayam, O; Mayo, A; Paran, H; Amit, M; Yaron, M; Caspi, D

2001-01-01

211

Clinical pharmacology of paliperidone palmitate a parenteral long-acting formulation for the treatment of schizophrenia.  

PubMed

Paliperidone Palmitate is a long-acting intramuscular atypical antipsychotic drug indicated for the acute maintenance treatment of schizophrenia in adults. Its mechanism of action, like all other atypical agents, is attributed to the antagonism of brain dopamine D2 and serotonin 5-HT2A receptors. The pharmacodynamics, pharmacokinetics, and metabolism of paliperidone palmitate are reviewed. Current studies for clinical efficacy of paliperidone palmitate for both acute and maintenance treatment and adherence in adults with schizophrenia are discussed. Studies for safety and tolerability are also reviewed. PMID:22023179

Gilday, Elizabeth; Nasrallah, Henry A

2012-02-01

212

Pregnancy Intentions, Long-Acting Contraceptive Use, and Rapid Subsequent Pregnancies among Adolescent and Adult First-Time Mothers  

PubMed Central

Problem Greater understanding is needed related to qualitatively-assessed pregnancy intentions and rapid subsequent pregnancies among adolescent and adult mothers. Methods 4-site prospective study of 227 adolescent and adult mothers. Data analyzed to understand the relationship between pregnancy intentions, adolescent status, and use of long-acting contraceptives and rapid subsequent pregnancy. Findings The findings from this study provide evidence of the importance of goal-oriented pregnancy intentions, long-acting contraceptive use, and older age in delaying a second pregnancy. Conclusion Findings reveal the need for clinician awareness of the qualitative pregnancy intentions of young women and potential desired use of long-acting contraceptives.

Waggoner, Miranda R.; Lanzi, Robin Gaines; Klerman, Lorraine V.

2012-01-01

213

Cryopreservable and Tumorigenic Three Dimensional Tumor Culture in Porous Poly(lactic-co-glycolic acid) Microsphere  

PubMed Central

In vitro tumor models that mimic in vivo conditions may be ideal for screening anticancer drugs and their formulations and developing tumors in animal models. Three-dimensional (3-D) culture of cancer cells on polymeric scaffolds can be an option for such models. In the present study, porous poly(lactic acid-co-glycolic acid) (PLGA) microsphere was used both as a cancer cell culture substrate to expand cells and as a cancer cells transplantation vehicle for tumor construction in mice. MCF-7 cells cultured in porous PLGA microspheres in stirred suspension bioreactors expanded by 2.8-fold over seven days and maintained viability. At three months after inoculation with 2 × 106 cells/site, the tumor formation by MCF-7 cells cultured on microspheres was much more effective (4 tumors/5 mice) than its counterpart cultured on plates (1/5). More importantly, cell viability and metabolic activity were not significantly changed even after one freeze-thaw cycle of the 3-D culture. MCF-7 cells cultured on the microspheres and the cells in 3-D after cryopreservation were more resistant to doxorubicin than MCF-7 cells cultured on plates.

Kang, Sun-Woong; Bae, You Han

2009-01-01

214

A Pilot Study of Long-Acting Octreotide for Symptomatic Malignant Ascites (N04C2)  

PubMed Central

Background Effective, non-invasive, palliative strategies for symptomatic malignant ascites unavailable. This trial explored whether octreotide, an inhibitor of vascular endothelial growth factor (VEGF), a putative mediator of ascites, prolongs the interval to next paracentesis. Methods After a baseline paracentesis and a test of short-acting agent, patients with symptomatic ascites were randomly assigned to long-acting octreotide (Sandostatin LAR®) depot 30 mg intramuscularly every month versus 0.9% sodium chloride administered similarly. Patients were then monitored for recurrent, symptomatic ascites. Results 33 patients were enrolled: 16 to the octreotide- and 17 to the control-arm. The median time to next paracentesis was 28 and 14 days in the octreotide- and placebo-arm, respectively (p=0.17). After adjustment for extracted ascites volume and abdominal girth change, no statistically significant difference between groups was observed (hazard ratio= 0.52 with a 95% confidence interval: 0.21, 1.28; p=0.15, per the Cox model). Octreotide-treated patients described less 1-month abdominal bloating (p=0.01), abdominal discomfort (p=0.02), and shortness of breath (p=0.007), although other quality of life symptoms were comparable between arms. Long-acting octreotide was reasonably well tolerated. Conclusion As prescribed in this trial, octreotide did not seem effective in prolonging the time to next paracentesis, although improvements in symptoms suggest that VEGF inhibition merits further investigation.

Jatoi, Aminah; Nieva, Jorge J.; Qin, Rui; Loprinzi, Charles L.; Wos, Edward J.; Novotny, Paul J.; Moore, Dennis F.; Mowat, Rex B.; Bechar, Naftali; Pajon, Eduardo R.; Hartmann, Lynn C.

2013-01-01

215

Second-generation long-acting injectable antipsychotic agents: an overview.  

PubMed

For over 40 years, antipsychotic drugs have been used as long-term maintenance treatment to control symptoms and reduce relapse rates in patients with schizophrenia. 'First-generation' oral agents such as haloperidol and chlorpromazine are associated with high levels of unwanted neurological effects and poor rates of patient adherence.1,2 Long-acting ('depot') injections of antipsychotics were developed to try to improve adherence. 'Second-generation' antipsychotic agents (also known as atypical antipsychotics) were introduced into clinical practice over 16 years ago. Although these agents have a lower propensity to cause extrapyramidal side effects, they are associated with a range of other unwanted effects (e.g. weight gain and its sequelae).1,3,4 Initially, second-generation agents were only available as orally administered medicines. Three long-acting injectable formulations of second-generation antipsychotics are now available in the UK: olanzapine embonate injection (ZypAdhera), paliperidone injection (Xeplion) and risperidone injection (Risperdal Consta). In this article we review the evidence for these agents and discuss the practical implications of their use. PMID:22966099

2012-09-01

216

Rapid nongenomic actions of inhaled corticosteroids on long-acting ?2-agonist transport in the airway  

PubMed Central

Corticosteroids inhibit organic cation transporters (OCTs) that play an important role in drug absorption, tissue distribution and elimination. Corticosteroid sensitivity of bronchodilator trafficking in the airway tissue, however, is poorly understood. To assess the effects of inhaled corticosteroids on airway absorption and disposal mechanisms of long-acting ?2-agonists, human airway epithelial and smooth muscle cell uptake of tritiated formoterol and salmeterol was measured in vitro. Corticosteroids caused a rapid, concentration-dependent inhibition of uptake of the cationic formoterol by airway smooth muscle cells, but not airway epithelial cells. Uptake of the noncharged lipophilic salmeterol was corticosteroid-insensitive in both cell types. In smooth muscle cells, inhaled corticosteroids inhibited formoterol uptake with a novel potency rank order: des-ciclesonide > budesonide > beclomethasone 17-monopropionate > beclomethasone dipropionate > ciclesonide > fluticasone. The inhibitory action was rapidly reversible, and was not enhanced by prolonged corticosteroid exposure or sensitive to a transcription inhibitor. Suppression of OCT3 expression using lentivirus-mediated production of shRNA reduced corticosteroid sensitivity of formoterol uptake by smooth muscle cells. Our data support a corticosteroid insensitive absorption and a corticosteroid sensitive disposition mechanism for cationic long-acting ?2-agonist bronchodilators in the airway. Potency rank order and other ‘classical’ features of anti-inflammatory effects do not apply to inhaled corticosteroids’ rapid drug transport actions.

Horvath, Gabor; Mendes, Eliana S.; Schmid, Nathalie; Schmid, Andreas; Conner, Gregory E.; Fregien, Nevis L.; Salathe, Matthias; Wanner, Adam

2011-01-01

217

Rapid nongenomic actions of inhaled corticosteroids on long-acting ?(2)-agonist transport in the airway.  

PubMed

Corticosteroids inhibit organic cation transporters (OCTs) that play an important role in drug absorption, tissue distribution and elimination. Corticosteroid sensitivity of bronchodilator trafficking in the airway tissue, however, is poorly understood. To assess the effects of inhaled corticosteroids on airway absorption and disposal mechanisms of long-acting ?(2)-agonists, human airway epithelial and smooth muscle cell uptake of tritiated formoterol and salmeterol was measured in vitro. Corticosteroids caused a rapid, concentration-dependent inhibition of uptake of the cationic formoterol by airway smooth muscle cells, but not airway epithelial cells. Uptake of the non-charged lipophilic salmeterol was corticosteroid-insensitive in both cell types. In smooth muscle cells, inhaled corticosteroids inhibited formoterol uptake with a novel potency rank order: des-ciclesonide > budesonide > beclomethasone 17-monopropionate > beclomethasone dipropionate > ciclesonide > fluticasone. The inhibitory action was rapidly reversible, and was not enhanced by prolonged corticosteroid exposure or sensitive to a transcription inhibitor. Suppression of OCT3 expression using lentivirus-mediated production of shRNA reduced corticosteroid sensitivity of formoterol uptake by smooth muscle cells. Our data support a corticosteroid insensitive absorption and a corticosteroid-sensitive disposition mechanism for cationic long-acting ?(2)-agonist bronchodilators in the airway. Potency rank order and other 'classical' features of anti-inflammatory effects do not apply to inhaled corticosteroids' rapid drug transport actions. PMID:21914487

Horvath, Gabor; Mendes, Eliana S; Schmid, Nathalie; Schmid, Andreas; Conner, Gregory E; Fregien, Nevis L; Salathe, Matthias; Wanner, Adam

2011-09-08

218

Short-acting versus long-acting benzodiazepines: discontinuation effects in panic disorders.  

PubMed

An increasing body of evidence suggests that benzodiazepines--which have long been considered the drugs of choice in the treatment of various anxiety disorders due to their relative lack of side effects, lack of adverse drug reaction, their safety, and increased efficacy over other agents--are effective in the treatment of panic disorders. Originally, the benzodiazepines were believed to be devoid of dependence-inducing properties, even at high doses. Recent evidence, however, suggests that discontinuation of both high and normal doses of both short- and long-acting benzodiazepines generally results in similar withdrawal symptoms, including anxiety and sleep and perceptual disturbances. This article presents a brief review of benzodiazepine withdrawal, with an emphasis on the discontinuation of these drugs following treatment of panic disorders. In particular, short-acting and long-acting drugs may present different features following long-term treatment and withdrawal. Preliminary results from a study comparing alprazolam and diazepam are presented to illustrate this point in contrast to expectations: the problems associated with withdrawal of both agents were comparable. PMID:1980701

Burrows, G D; Norman, T R; Judd, F K; Marriott, P F

1990-01-01

219

Metallic coating of microspheres  

SciTech Connect

Extremely smooth, uniform metal coatings of micrometer thicknesses on microscopic glass spheres (microspheres) are often needed as targets for inertial confinement fusion (ICF) experiments. The first part of this paper reviews those methods used successfully to provide metal coated microspheres for ICF targets, including magnetron sputtering, electro- and electroless plating, and chemical vapor pyrolysis. The second part of this paper discusses some of the critical aspects of magnetron sputter coating of microspheres, including substrate requirements, the sticking of microspheres during coating (preventing a uniform coating), and the difficulties in growing the desired dense, smooth, uniform microstructure on continuously moving spherical substrates.

Meyer, S.F.

1980-08-15

220

Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents  

Microsoft Academic Search

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting ?2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol.

Donald P Tashkin; Leonardo M Fabbri

2010-01-01

221

Osteogenic effect of local, long versus short term BMP-2 delivery from a novel SPU-PLGA-?TCP concentric system in a critical size defect in rats.  

PubMed

A concentric delivery system, composed of the three biomaterials SPU, PLGA, and ?TCP (segmented polyurethane, poly[lactic-co-glycolic acid], and ?-tricalcium phosphate) was fabricated as an external, porous ring of ?TCP with a pasty core of a new SPU, mixed with PLGA microspheres. The regenerative effects of two distinct doses of either immediately available or continuously released rhBMP-2 were evaluated in an 8mm, critical calvaria defect in rats. Protein dose and release kinetics affected material resorption rates and the progression of the regeneration process. Groups treated with the empty system alone or in conjunction with free rhBMP-2 did not respond. By contrast, after 12 weeks, approximately 20% and 60% of the defects implanted with systems loaded with 1.6 ?g and 6.5 ?g rhBMP-2, respectively were healed, with all the growth factor being released in the course of 6 weeks. The NMR, FTIR, GPC, DSC, and histological analyses showed that PLGA microsphere degradation occurred independently of the regenerative process. However, the resorption rate of the SPU and ?TCP did depend on the regeneration process, which was governed by dose and release rate of rhBMP-2. Furthermore, the biocompatibility and high capacity of adaptation to the defect convert the herein proposed, new SPU polymer into a potential material for applications in tissue engineering and regenerative medicine. PMID:23797057

Rodríguez-Évora, M; Delgado, A; Reyes, R; Hernández-Daranas, A; Soriano, I; San Román, J; Evora, C

2013-06-21

222

Active Blood Vessel Formation in the Ischemic Hindlimb Mouse Model Using a Microsphere\\/Hydrogel Combination System  

Microsoft Academic Search

Purpose  We hypothesize that the controlled delivery of rhVEGF using a microsphere\\/hydrogel combination system could be useful to achieve\\u000a active blood vessel formation in the ischemic hindlimb mouse model, which is clinically relevant for therapeutic angiogenesis\\u000a without multiple administrations.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A combination of poly(d,l-lactide-co-glycolide) (PLGA) microspheres and alginate hydrogels containing rhVEGF was prepared and injected intramuscularly into the\\u000a ischemic hindlimb site of

Jangwook Lee; Suk Ho Bhang; Byung-Soo Kim; Kuen Yong Lee

2010-01-01

223

Microsphere Degradation in Outer Hydrogel Membranes Creates Macroscopic Porosity to Counter Biofouling-Induced Sensor Degradation  

PubMed Central

Biofouling and tissue inflammation present major challenges toward the realization of long-term implantable glucose sensors. Following sensor implantation, proteins and cells adsorb on sensor surfaces to not only inhibit glucose flux but also signal a cascade of inflammatory events that eventually lead to permeability-reducing fibrotic encapsulation. The use of drug-eluting hydrogels as outer sensor coatings has shown considerable promise to mitigate these problems via the localized delivery of tissue response modifiers to suppress inflammation and fibrosis, along with reducing protein and cell absorption. Biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres encapsulated within a poly (vinyl alcohol) (PVA) hydrogel matrix, presents a model coating where the localized delivery of the potent anti-inflammatory drug dexamethasone has been shown to suppress inflammation over a period of 1-3 months. Here it is shown that the degradation of the PLGA microspheres provides an auxiliary venue to offset the negative effects of protein adsorption. This was realized by: 1) the creation of fresh porosity within the PVA hydrogel following microsphere degradation (which is sustained until the complete microsphere degradation); and 2) rigidification of the PVA hydrogel to prevent its complete collapse onto the newly created void space. Incubation of the coated sensors in PBS buffer led to a monotonic increase in glucose permeability (50%), with a corresponding enhancement in sensor sensitivity over a one-month period. Incubation in serum resulted in biofouling and consequent clogging of the hydrogel microporosity. This however, was partially offset by the generated macroscopic porosity following microsphere degradation. As a result of this, a two-fold recovery in sensor sensitivity for devices with microsphere/hydrogel composite coatings was observed as opposed to similar devices with blank hydrogel coatings. These findings suggest that the use of macroscopic porosity can reduce sensitivity drifts resulting from biofouling and this can be achieved synergistically with current efforts to mitigate negative tissue responses through localized and sustained drug delivery.

Qiang, L.; Burgess, D. J.; Papadimitrakopoulos, F.

2013-01-01

224

In vitro characteristics of poly(lactic-co-glycolic acid) microspheres incorporating gelatin particles loading basic fibroblast growth factor  

Microsoft Academic Search

Aim:To construct a sustained drug release system for basic fibroblast growth factor (bFGF). With this special system, bFGF can be used to repair an injured peripheral nerve, injured spinal cord, or as a carrier for other drugs that need to be released over a long time.Methods:Microsphere composite was prepared by encapsulating bFGF into gelatin particles with poly(lactic-co-glycolic acid) (PLGA) as

Shao-hong Li; Shao-xi Cai; Bing Liu; Kai-wang Ma; Zhen-ping Wang; Xiao-kun Li

2006-01-01

225

Validation of USP apparatus 4 method for microsphere in vitro release testing using Risperdal Consta.  

PubMed

The current manuscript addresses the need for a validated in vitro release testing method for controlled release parenteral microspheres. A USP apparatus 4 method was validated with the objective of possible compendial adaptation for microsphere in vitro release testing. Commercial microspheres (Risperdal Consta) were used for method validation. Accelerated and real-time release tests were conducted. The accelerated method had significantly reduced test duration and showed a good correlation with the real-time release profile (with limited number of sample analysis). Accelerated conditions were used for method validation (robustness and reproducibility). The robustness testing results revealed that release from the microspheres was not flow rate dependent and was not affected by minor variations in the method (such as cell preparation technique, amount of microspheres, flow-through cell size and size of glass beads). The significant difference in the release profile with small variations (± 0.5°C) in temperature was shown to be due to a change in risperidone catalyzed PLGA degradation in response to temperature. The accelerated method was reproducible as changing the system/equipment or the analyst did not affect the release profile. This work establishes the suitability of the modified USP apparatus 4 for possible compendial adaptation for drug release testing of microspheres. PMID:21889583

Rawat, Archana; Stippler, Erika; Shah, Vinod P; Burgess, Diane J

2011-08-24

226

USP apparatus 4 method for in vitro release testing of protein loaded microspheres.  

PubMed

The objective was to develop an in vitro release method for protein loaded poly(lactide-co-glycolide) (PLGA) microspheres. A modified USP apparatus 4 and sample and separate methods were compared using a microsphere formulation encapsulating a model protein, bovine serum albumin (BSA). Microsphere characteristics such as porosity, drug loading, particle size and burst release were significantly affected by the formulation parameters (i.e., phase ratio, internal aqueous phase composition and theoretical drug loading). Incomplete release of BSA was observed using the sample and separate method and this was attributed to microsphere loss during sampling. This problem was overcome using the modified USP apparatus 4 method. However, an unusual decrease in cumulative percent release was observed which was considered to be due to BSA adsorption onto the hydrophobic surfaces of the modified USP apparatus 4. Addition of SDS to the release media prevented BSA adsorption and a zero order release profile was observed. The presence of SDS did not change the microsphere degradation kinetics. The results indicate the importance of understanding protein adsorption and aggregation behavior during in vitro release testing. The USP apparatus 4 method appears to be useful for investigation of in vitro release of protein loaded microspheres. PMID:21376792

Rawat, Archana; Burgess, Diane J

2011-03-03

227

Long-acting parenteral nanoformulated antiretroviral therapy: interest and attitudes of HIV-infected patients.  

PubMed

Aim: To gauge patient interest in receiving long-acting injectable nanoformulated antiretroviral therapy. Methods: Four hundred adult HIV-infected patients currently prescribed antiretroviral therapy were surveyed. ?(2) tests were used for comparisons of interest across groups. Results: Respondents were 68% male and 53% African-American, with a mean age of 47 years. Overall, 73% of patients indicated that they would definitely or probably try injectable nanoformulated antiretroviral therapy; 61% with weekly dosing; 72% every 2 weekly; and 84% monthly. In total, 48% indicated that they were very concerned about the possible side effects and 35% were very concerned about needle use. Conclusion: The majority of respondents indicated that they definitely or probably would try parenteral nanoformulated antiretroviral therapy. Original submitted 24 May 2012; Revised submitted 2 November 2012; Published online 23 April 2013. PMID:23611617

Williams, Jennifer; Sayles, Harlan R; Meza, Jane L; Sayre, Patrick; Sandkovsky, Uriel; Gendelman, Howard E; Flexner, Charles; Swindells, Susan

2013-04-23

228

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.

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

2011-01-01

229

Reversible contraception update: the importance of long-acting reversible contraception.  

PubMed

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

2009-07-01

230

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

PubMed Central

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

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

2012-01-01

231

Microsphere thermal deformeter  

NASA Astrophysics Data System (ADS)

A highly sensitive thermal deformeter was developed for measuring submicron variations in the dimensions of glass microspheres as a function of temperature. This made it possible to determine the maximum temperature at which these microspheres can be DT (deuterium and tritium) filled through permeation without nonreversible deformation in the preparation of inertial confinement fusion targets.

Koo, J. C.

1980-10-01

232

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

PubMed

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

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

2011-11-12

233

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

PubMed

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

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

2012-08-04

234

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, R.S.; Henning, S.A.

1990-12-31

235

A New Psychosocial Tool for Gaining Patient Understanding and Acceptance of Long-acting Injectable Antipsychotic Therapy  

PubMed Central

Nonadherence to antipsychotic medications in serious, persistent mental illness remains a significant clinical challenge. Long-acting therapy was developed to help improve adherence to schizophrenia therapy and provide an effective means for ameliorating symptoms and preventing relapse. The Agency for Health Care Policy and Research/National Institute of Mental Health Schizophrenia Patient Outcomes Research Team recommends that antipsychotic long-acting therapy be strongly considered for patients who have difficulty adhering to an oral medication regimen or who prefer long-acting therapy. Depot conventional formulations have long been available; for clinicians and patients who would rather use an atypical antipsychotic, studies with risperidone long-acting therapy suggest that it is efficacious and well tolerated. A common concern of clinicians who elect to initiate long-acting therapy is how to introduce the possibility of changing from the current oral antipsychotic to an long-acting therapy injection. As with other aspects of patient care, having an established therapeutic relationship with the patient is advantageous for recommending changes in care, but the way in which the idea is approached may improve the likelihood of its acceptance. To help clinicians broach a recommendation of long-acting therapy with their patients, the GAIN approach was designed as a standard interview process for presenting this option. It encompasses (and is an acronym for) goal setting, action planning, initiating treatment, and nurturing motivation. This novel clinical tool is based on the principles of motivational enhancement therapy, a patient-centered approach that seeks to evoke the patient’s own motivation for change, to consolidate the decision to change, and to plan for change. This tool is also based on the Listen-Empathize-Agree-Partner, or LEAP, communication strategy. Motivational enhancement therapy, which is typically brief, has been found effective in several chronic illnesses in both outpatient and inpatient settings. GAIN may be a practical tool for aligning clinician-patient expectations and enhancing long-term maintenance of therapy.

2009-01-01

236

Comparison of antianginal efficacy of one conventional and three long acting beta-adrenoreceptor blocking agents in stable angina pectoris.  

PubMed Central

We compared the antianginal efficacy of one conventional and three long acting beta-adrenoreceptor blocking agents in a randomised manner in 12 patients with stable angina pectoris. An exercise test was performed initially and in the 24th hour after a single daily dose of 160 mg of each beta-blocker at the end of a two week treatment period. In addition, glyceryl trinitrate consumption, anginal attack rate, and activity scores were recorded. No titration studies to an equivalent degree of beta-blockade were undertaken; a fixed dose was used even though these drugs are not equipotent. Conventional propranolol in a single daily dose of 160 mg was as effective in controlling the frequency of anginal attacks as long acting propranolol and sustained release oxprenolol. Exercise tolerance was less with sustained release oxprenolol than with conventional propranolol, long acting propranolol, and nadolol. Nadolol produced a significantly greater reduction in exercise-induced tachycardia than did long acting propranolol, sustained release oxprenolol, and conventional propranolol, and also the lowest anginal attack rate, the lowest trinitrin consumption, and significantly less ST segment depression than the other three. These findings suggest that nadolol is more potent than long acting propranolol, sustained release oxprenolol, and conventional propranolol, and the antianginal benefit at the 24th hour relates to the degree of beta-adrenoreceptor blockade achieved.

Jones, G R; Mir, M A

1981-01-01

237

Paliperidone palmitate versus risperidone long-acting injection in markedly-to-severely ill schizophrenia subjects.  

PubMed

Objective: To examine onset of efficacy of two long-acting injectable atypical antipsychotics in markedly-to-severely ill schizophrenia subjects.Methods: This subgroup analysis included 292 subjects with baseline Clinical Global Impressions-Severity scores of markedly ill or worse from a 13-week, randomized, double-dummy noninferiority study (NCT00589914). Subjects received (a) paliperidone palmitate (PP; 234mg day 1 and 156mg day 8 [corresponding to 150 and 100 milligram equivalents of paliperidone, respectively], both administered in deltoid muscle, followed by once-monthly flexible dosing in deltoid or gluteal muscle) and risperidone long-acting injection (RLAI)-matched placebo injections or (b) RLAI (25mg, days 8 and 22; followed by biweekly flexible dosing) and PP-matched placebo injections. RLAI subjects received oral risperidone days 1-28; PP subjects received oral placebo. Because of RLAI's release profile, data through day 22 correspond to oral risperidone. Assessments included Positive and Negative Syndrome Scale (PANSS) and adverse event (AE) reports. Paired t-tests assessed within-group changes.Results: LS mean (SE) PANSS total scores improved significantly (both p<.001) with PP and oral risperidone by day 4 (-5.0 [0.6] and -3.4 [0.6], respectively) through day 22; and with PP and RLAI through end point (-21.5 [1.9] and -18.6 [1.9], respectively). The between-group difference was significant only at day 4 (p=.006). Proportion of subjects with a ?30% reduction in PANSS total score was not significantly different between the two groups at day 4 and significantly greater with paliperidone palmitate than oral risperidone at days 15 and 22 (26.1% versus 12.7%, p=.013; 41.6% versus 32.0%, p=.048, respectively).Most common AEs (?5% in either treatment group): headache (PP 6.3% and RLAI 14.0%), insomnia (10.6% and 10.7%), somnolence (7.8% and 1.3%), akathisia (7.0% and 5.3%), schizophrenia (8.4% and 5.3%), agitation (5.6% and 2.0%), and injection site pain (5.6% and 1.3%).Conclusions: Using the recommended dosing regimens for PP and RLAI, both PP and oral risperidone (used during RLAI initiation) improved symptoms of schizophrenia in markedly to severely ill subjects at days 4-22. PMID:23446197

Fu, Dong-Jing; Bossie, Cynthia A; Sliwa, Jennifer Kern; Ma, Yi-Wen; Alphs, Larry

2013-02-27

238

Mono- and combination therapy of long-acting bronchodilators and inhaled corticosteroids in advanced COPD.  

PubMed

Beta-2 adrenergic agonists are sympathomimetic agents that stimulate bronchodilation by activation of adenyl cyclase to produce cyclic 3'5' adenosine monophosphate (AMP). Short-acting beta-agonists (SABAs) have a 3- to 6-hour duration of action, and the duration of action of long-acting beta-agonists (LABAs) exceeds 12 hours. Because of their rapid onset of action, SABAs are effective for rescue from symptoms of chronic obstructive pulmonary disease (COPD). LABAs-salmeterol and formoterol-have been shown to significantly improve lung function, health status, and symptom reduction, compared with ipratropium. Despite safety concerns over the use of LABAs as monotherapy in asthma the use of these medications in COPD has generally been described as safe. Novel bronchodilators for COPD in late-stage development include the beta-agonists indacterol and carmoterol. Parasympathetic activity in the large and medium-size airways is mediated through the muscarinic receptors and results in airway smooth-muscle contraction, mucus secretion, and possibly increased ciliary activity. Although short-acting ipratropium has been used as monotherapy or in combination with albuterol the use of long-acting antimuscarinics is superior in improving health outcomes. The use of tiotropium results in improved health status, dyspnea, and exercise capacity, and reduced hyperinflation and COPD exacerbation rate in patients with moderate to severe COPD. Analysis of prospective clinical trial data shows a mortality reduction in subjects treated with tiotropium, despite retrospective review of insurance claims that show an enhanced mortality. Theophylline is a nonselective phosphodiesterase inhibitor that acts as both a weak bronchodilator and a respiratory stimulant. Novel approaches include using the inhalation route to reduce side effects and combination with inhaled corticosteroids (ICS). However, because of its potential adverse effects and narrow therapeutic index, it should only be used when symptoms persist despite optimal bronchodilator therapy. Current guidelines highlight that for COPD patients uncontrolled by bronchodilator monotherapy, combination therapy is recommended. These include LABA/ICS and LAMA/LABA combinations. Bronchodilators and their combination with ICS are central to the management of COPD. The choice of agents is based primarily on disease stage, individual response, cost, side effect profile, and availability. PMID:20496301

Ohar, Jill A; Donohue, James F

2010-05-21

239

Prolong antibiotics release by encapsulating PLGA for hip prosthesis  

Microsoft Academic Search

In this study, encapsulating antibiotic loaded titanium alloy by polylactide-co-polyglycolide copolymer (PLGA) for preventing burst releasing and extending antibiotic releasing time will be make for potential future hip prosthesis with deep infection prevention ability. Antibiotics, vancomycin and cefuroxime, were used to measure their temporal release from titanium disc. The result by elution test showed non PLGA coated of antibiotic loaded

K. H. Chen; G. A. Lai; S. D. Chen; J. C. Shiu; M. L. Yeh

2009-01-01

240

In vitro uptake evaluation in Caco-2 cells and in vivo results in diabetic rats of insulin-loaded PLGA nanoparticles.  

PubMed

PLGA nanoparticles (NPs) are largely developed for biological applications but little is known about their uptake. Therefore, we focused our study on the modalities of insulin-loaded PLGA NPs transport across Caco-2 monolayers, and their hypoglycaemic effect on diabetic rats. Insulin-loaded PLGA NPs were formulated by a double emulsion solvent evaporation process. NPs mean diameter was between 130 and 180 nm. NPs were smooth and spherical with an entrapment efficiency above 80%. Fluorescently labeled NPs were incubated with Caco-2 cells to study the process of uptake and the intracellular fate by flow cytometry and confocal laser scanning microscopy. The kinetic of absorption was time-dependent and occurred by clathrin-mediated endocytosis. The intracellular traffic led to a basolateral exocytosis of NPs. In vitro studies and in vivo intraduodenal administration to diabetic rats showed that NPs were resistant in intestinal conditions long enough to allow both the intestinal absorption of NPs and the delivery of functional insulin in bloodstream. The resulting in vivo hypoglycaemic effect was similar to a long-acting insulin one. As no effect on glycaemia occurred after oral administration, further studies need to be conducted to protect NPs from the degradation occurring at the enteric level. PMID:22940208

Reix, Nathalie; Parat, Audrey; Seyfritz, Elodie; Van der Werf, Remmelt; Epure, Virginia; Ebel, Nicolas; Danicher, Louis; Marchioni, Eric; Jeandidier, Nathalie; Pinget, Michel; Frère, Yves; Sigrist, Séverine

2012-08-23

241

Long-acting anticholinesterases for myasthenia gravis: synthesis and activities of quaternary phenylcarbamates of neostigmine, pyridostigmine and physostigmine  

PubMed Central

The N-monophenylcarbamate analogues of neostigmine methyl sulfate (6) and pyridostigmine bromide (8) together with their precursors (5), (7), and the N(1)-methylammonium analogues of (?)-phenserine (12), (?)-tolserine (14), (?)-cymserine (16) and (?)-phenethylcymserine (18) were synthesized to produce long-acting peripheral inhibitors of acetylcholinesterase or butyrylcholinesterase. Evaluation of their cholinesterase inhibition against human enzyme ex vivo demonstrated that, whereas compounds 5–8 possessed only marginal activity, 12, 14, 16 and 18 proved to be potent anticholinesterases. An extended duration of cholinesterase inhibition was determined in rodent, making them of potential interest as long-acting agents for myasthenia gravis.

Yu, Qian-sheng; Holloway, Harold W.; Luo, Weiming; Lahiri, Debomoy K.; Brossi, Arnold; Greig, Nigel H.

2010-01-01

242

Increased Use of Antipsychotic Long-Acting Injections with Community Treatment Orders  

PubMed Central

Background: Community treatment orders (CTOs) are increasingly being used, despite a weak evidence base, and problems continue regarding Second Opinion Appointed Doctor (SOAD) certification of medication. Aims: The aim of the current study was to describe current CTO usage regarding patient characteristics, prescribed medication and CTO conditions. Method: A 1-year prospective cohort study with consecutive sampling was conducted for all patients whose CTO was registered in a large mental health trust. Only the first CTO for each patient was included. Measures included sociodemographic variables, psychiatric diagnosis, CTO date of initiation and conditions, psychotropic medication and date of SOAD certification for medication. This study was conducted in the first year of CTO legislation in England and Wales. Results: A total of195 patients were sampled (mean age 40.6 years, 65% male, 52% black ethnic origin). There was significant geographical variability in rates of CTO use (?2 = 11.3, p = 0.012). A total of 53% had their place of residence specified as a condition and 29% were required to allow access into their homes. Of those with schizophrenia, 64% were prescribed an antipsychotic long-acting injection (LAI). Of the total group, 7% received high-dose antipsychotics, 10% were prescribed two antipsychotics and only 15% received SOAD certification in time. Conclusions: There was geographical and ethnic variation in CTO use but higher rates of hospital detention in minority ethnic groups may be contributory. Most patients were prescribed antipsychotic LAIs and CTO conditions may not follow the least restrictive principle.

Patel, Maxine X.; Matonhodze, Jane; Baig, Mirza K.; Gilleen, James; Boydell, Jane; Holloway, Frank; Taylor, David; Szmukler, George; Lambert, Tim; David, Anthony S.

2011-01-01

243

Randomized Clinical Trial of Long-Acting Somatostatin for Autosomal Dominant Polycystic Kidney and Liver Disease  

PubMed Central

There are no proven, effective therapies for polycystic kidney disease (PKD) or polycystic liver disease (PLD). We enrolled 42 patients with severe PLD resulting from autosomal dominant PKD (ADPKD) or autosomal dominant PLD (ADPLD) in a randomized, double-blind, placebo-controlled trial of octreotide, a long-acting somatostatin analogue. We randomly assigned 42 patients in a 2:1 ratio to octreotide LAR depot (up to 40 mg every 28 ± 5 days) or placebo for 1 year. The primary end point was percent change in liver volume from baseline to 1 year, measured by MRI. Secondary end points were changes in total kidney volume, GFR, quality of life, safety, vital signs, and clinical laboratory tests. Thirty-four patients had ADPKD, and eight had ADPLD. Liver volume decreased by 4.95% ± 6.77% in the octreotide group but remained practically unchanged (+0.92% ± 8.33%) in the placebo group (P = 0.048). Among patients with ADPKD, total kidney volume remained practically unchanged (+0.25% ± 7.53%) in the octreotide group but increased by 8.61% ± 10.07% in the placebo group (P = 0.045). Changes in GFR were similar in both groups. Octreotide was well tolerated; treated individuals reported an improved perception of bodily pain and physical activity. In summary, octreotide slowed the progressive increase in liver volume and total kidney volume, improved health perception among patients with PLD, and had an acceptable side effect profile.

Masyuk, Tetyana V.; Page, Linda J.; Kubly, Vickie J.; Bergstralh, Eric J.; Li, Xujian; Kim, Bohyun; King, Bernard F.; Glockner, James; Holmes, David R.; Rossetti, Sandro; Harris, Peter C.; LaRusso, Nicholas F.; Torres, Vicente E.

2010-01-01

244

Long-Acting Injectable Antipsychotics for First-Episode Schizophrenia: The Pros and Cons  

PubMed Central

Clinical and psychosocial deterioration associated with schizophrenia occurs within the first few years following the onset of the illness. Therefore, to improve the long-term prognosis, it is important to provide schizophrenia patients with intensive treatment following their first episode. Relapse is highly associated with partial medication adherence or nonadherence in patients with first-episode schizophrenia. Recent studies suggest that long-acting injectable (LAI) antipsychotics compared with oral antipsychotics are more effective for medication adherence and relapse prevention. Moreover, some clinical guidelines for the treatment of schizophrenia suggested that LAI antipsychotics should be considered when patients are nonadherent “at any stage.” Decreased compliance is a common cause of relapse during the initial stages of the disease. Therefore, LAI antipsychotics should be highly considered when treating patients with first-episode schizophrenia. In the present paper, clinical trial data and current guidelines on the use of LAI antipsychotics for first-episode schizophrenia are discussed as well as the pros and cons of this treatment option.

Kim, Borah; Lee, Sang-Hyuk; Yang, Yen Kuang; Park, Jong-Il; Chung, Young-Chul

2012-01-01

245

Adherence challenges and long-acting injectable antipsychotic treatment in patients with schizophrenia.  

PubMed

Medication nonadherence has been associated with persistence of psychotic symptoms, relapse, and hospitalization in patients with schizophrenia. Patients with untreated psychosis are significantly less likely to achieve remission, whereas antipsychotic drug adherence has been associated with recovery. As such, adherence to antipsychotic drug treatment is a key issue for nurses and treatment team members caring for patients who typically are on chronic, progressive disease course. Long-acting injectable (LAI) anti-psychotic drugs, developed to improve adherence and provide and alternative antipsychotic drug treatment fro schizophrenia, have been associated with improved treatment outcomes including reduction of relapse rates approximately 30% and reduction in hospitalizations. However, LAI antipsychotic drugs remain underutilized in the United States despite a growing body of literature supporting positive outcomes of LAI versus oral antipsychotic drugs. Mental health nurses are in a key position to support improved adherence inpatients with schizophrenia through use of practical educational strategies that help patients, family members, and health care providers better understand and manage treatment. PMID:23547305

Kirk Morton, N; Zubek, Donna

2013-03-01

246

Olanzapine long-acting injection: insights from an early case series in the UK  

PubMed Central

Objective: Olanzapine long-acting injection depot (OLAI) has been licensed in the UK since 2008. As a result of the recognition during clinical trials that in 0.07% of injections there may be inadvertent intravenous administration leading to post-injection delirium/sedation syndrome (PDSS), the licence mandates a 3 h observation after each injection and accompaniment of the patient to their final destination. The administration of OLAI may thus necessitate organization of local service provisions. We report on how a single healthcare facility in Northern Ireland has treated three initial patients and present a brief case series on these patients and their clinical outcomes. Methods: In the first three patients with schizophrenia to receive OLAI, the clinical notes were retrospectively examined to provide clinical data. Results: All three patients had acceptable clinical outcomes showing sustained clinical improvement and have continued on OLAI for over 1 year. Observation has been undertaken within an existing daycare unit staffed by nursing staff and occupational therapists for 3 h after each injection. No issues have emerged from the use of this service that has also provided educational and psycho-educational programmes for the patients. No cases of post-injection delirium/sedation syndrome were reported. There have been no additional cost implications. Conclusions: In patients for whom OLAI may be clinically indicated, the utilization of an existing service to provide the 3 h of observation after each injection may represent a solution with a cost-neutral outcome.

McGlennon, Deirdre

2012-01-01

247

Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application.  

PubMed

The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1-22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe-Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R(3)) at the para-position of the P1' benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R(1)) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16-22) with EC(50)s on wild-type HIV-1 in the range of 0.8-1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS. PMID:23177258

Kesteleyn, Bart; Amssoms, Katie; Schepens, Wim; Hache, Geerwin; Verschueren, Wim; Van De Vreken, Wim; Rombauts, Klara; Meurs, Greet; Sterkens, Patrick; Stoops, Bart; Baert, Lieven; Austin, Nigel; Wegner, Jörg; Masungi, Chantal; Dierynck, Inge; Lundgren, Stina; Jönsson, Daniel; Parkes, Kevin; Kalayanov, Genadiy; Wallberg, Hans; Rosenquist, Asa; Samuelsson, Bertil; Van Emelen, Kristof; Thuring, Jan Willem

2012-11-01

248

Flexibly timed once-daily dosing with degludec: a new ultra-long-acting basal insulin.  

PubMed

Insulin treatment in type 1 and type 2 diabetes (T1D and T2D) is highly efficacious, but in practice, non-adherence and ineffective dose titration limit its effectiveness. Barriers to more effective insulin treatment are numerous, including hypoglycaemia, fear of hypoglycaemia and concern about weight gain. The regular treatment timing needed with conventional basal insulins [neutral protamine Hagedorn (NPH) insulin and the first-generation analogues glargine and detemir] may also make adherence to these treatments problematic for many patients. Indeed, surveys indicate that the rigidity of this schedule induces some patients with T1D and T2D to omit insulin doses. Degludec is a novel, ultra-long-acting basal insulin analogue that is as effective as insulin glargine, but significantly reduces patients' risk of nocturnal hypoglycaemia. Because of its peakless, extended and highly predictable glucose-lowering effect, once-daily dosing on a flexible schedule may be feasible with degludec. Studies testing this possibility suggest that degludec tolerates day-to-day variation in dose timing while maintaining full efficacy and low risk of nocturnal hypoglycaemia. Degludec would appear to be an appropriate choice for patients being considered for a basal analogue, and it may be particularly well suited to patients with unpredictable social or work schedules, those who travel frequently and those who find rigid scheduling of their insulin injections a burden or barrier to regular treatment. PMID:23577589

Josse, R G; Woo, V

2013-04-11

249

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

PubMed

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

Yamashita, Makoto

2010-01-01

250

Long-Acting Beta-Agonists And The Risk of Intensive Care Unit Admission in Children  

PubMed Central

Objective A possible association between long-acting beta-agonists (LABA) and severe asthma exacerbations including death remains controversial. We examined whether LABA in the setting of combination therapy with inhaled corticosteroids (ICS) increases the risk of near-fatal asthma in children using a case-control study design. Methods Medical records from admissions for asthma exacerbations in children 4 to 18 years of age during the 2005 calendar year at Children’s Hospital of Pittsburgh of UPMC were reviewed. Cases and controls were determined by pediatric intensive care (PICU) and floor admission, respectively. Exposure was defined by LABA use in combination with ICS versus ICS alone. Results Records from 156 PICU and 207 pediatric floor admissions were reviewed. Records were excluded for non-asthma admissions, complicated pneumonias, debilitating comorbid disorders and multiple admissions leaving 85 PICU and 96 floor admissions. LABA use in combination with ICS did not increase the risk of PICU admission (OR 1.07, 95% CI 0.46–2.52), compared to ICS only without LABA. After adjusting for demographics, asthma severity, history of PICU admissions and concurrent infection, LABA/ICS use still did not increase the risk of PICU admission (aOR 0.84, 95% CI 0.26–2.76), compared to ICS alone. There were no deaths and five intubations within the study period. Conclusions The combination of LABA and ICS did not appear to increase the risk of near-fatal asthma in children.

Jacobs, Tammy S.; Jones, Bobby L.; MacGinnitie, Andrew J.

2013-01-01

251

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.

Di Lorenzo, Rosaria; Brogli, Alice

2010-01-01

252

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

PubMed

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

Thompson, M S

1996-11-30

253

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.

Beeh, Kai M; Beier, Jutta

2010-01-01

254

Risperidone long-acting injection: pharmacokinetics following administration in deltoid versus gluteal muscle in schizophrenic patients.  

PubMed

Long-acting injectable (LAI) risperidone for intramuscular injection into the gluteal muscle every 2 weeks is approved for schizophrenia. The deltoid muscle provides a more accessible injection site and could therefore facilitate patient acceptance of an injectable medication. Two studies in chronic schizophrenic subjects evaluated the pharmacokinetics and tolerability of LAI risperidone administered into the deltoid muscle. The pharmacokinetics following deltoid injection and bioequivalence between deltoid and gluteal administration were assessed in an open-label, single-dose, crossover, fully powered bioavailability study. Tolerability and safety of deltoid LAI risperidone were investigated in an open-label multiple-dose study in subjects who were previously being treated with gluteal injections of LAI risperidone. Patients received 4 sequential intramuscular injections of LAI risperidone, administered every 2 weeks into the deltoid muscle. Deltoid and gluteal injections of LAI risperidone were shown to be bioequivalent at equal doses with respect to peak and total plasma exposure and exhibited dose-proportional pharmacokinetics, independent of injection site. In addition, deltoid injection was safe and well tolerated. Injection of LAI risperidone into the deltoid muscle can be considered an alternative route of administration, because deltoid and gluteal injections are interchangeable in terms of drug exposure, with no additional safety or tolerability issues. PMID:20097933

Thyssen, An; Rusch, Sarah; Herben, Virginie; Quiroz, Jorge; Mannaert, Erik

2010-01-23

255

Inhaled combination therapy with long-acting beta 2-agonists and corticosteroids in stable COPD.  

PubMed

Long-acting beta(2)-agonists (LABAs) have been shown to be effective first-line bronchodilators in the treatment of COPD patients, and inhaled corticosteroids (ICSs) have been shown to reduce the frequency and/or severity of exacerbations in COPD patients. The concomitant use of a LABA and an ICS can influence both airway obstruction (ie, smooth muscle contraction, increased cholinergic tone, and loss of elastic recoil), and airway inflammation (ie, increased numbers of neutrophils, macrophages, and CD8+ lymphocytes, elevated interleukin-8 and tumor necrosis factor-alpha levels, and protease/antiprotease imbalance). They are also able to reduce the total number of bacteria adhering to the respiratory mucosa in a concentration-dependent manner without altering the bacterial tropism for mucosa, and to preserve ciliated cells. Several clinical trials support the concept of inhaled combination therapy with LABAs and corticosteroids in stable COPD patients. This type of therapy not only improves airflow obstruction but also provides clinical benefits, as manifested by sustained reduction in overall symptoms, improvements in health-related quality of life, and reductions in exacerbations. All of these effects are very important because, despite recent advances in our understanding of COPD and its treatment, therapy remains suboptimal for a considerable number of patients. PMID:15249466

Cazzola, Mario; Dahl, Ronald

2004-07-01

256

Pharmacological, pharmacokinetic, and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker.  

PubMed

Benidipine is a dihydropyridine-derived calcium channel blocker developed in Japan, with several unique mechanisms of action, that is, triple calcium channels (L, N, and T) blocking action with a membrane approach. Benidipine has relatively high vascular selectivity and is expected to show protective effects on vascular endothelial cells. Renal protective effects of benidipine also have been shown in several basic and clinical studies. Moreover, anti-oxidative action and enhancing nitric oxide production have been noted with this drug, following its cardio-protective effects in patients with ischemic heart diseases. In fact, benidipine exerted a better prognostic effect than other calcium channel blockers in the therapy for patients with vasospastic angina. In addition, benidipine showed reliable antihypertensive, renoprotective effects if used in combination with angiotensin II type 1 receptor blockers (ARBs) when adequate anti-hypertensive effects are not achieved by ARBs alone, indicating that benidipine is an useful calcium channel blocker in combination therapy for hypertension. Benidipine was launched on the Japanese market 14 years ago, but few severe side effects have been reported, suggesting that this is a drug with established safety and long-acting pharmacological effects. PMID:16565579

Yao, Kozo; Nagashima, Ken; Miki, Hiroyuki

2006-03-25

257

The effect of porosity on drug release kinetics from vancomycin microsphere/calcium phosphate cement composites.  

PubMed

The influence of porosity on release profiles of antibiotics from calcium phosphate composites was investigated to optimize the duration of treatment. We hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable microspheres prior admixing to calcium phosphate bone cement, the influence of porosity of the cement matrix on vancomycin release could be reduced. Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid) copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were added to calcium phosphate cement (CPC) at different powder to liquid ratios (P/L), resulting in different porosities of the cement composites. The effect of differences in P/L ratio on drug release kinetics was compared for both the direct addition of vancomycin-HCl to the cement liquid and for cement composites modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy (SEM) was used to visualize surface and cross section morphology of the different composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the specific surface area and pore size distribution of these matrices. It could be clearly shown, that variations in P/L ratio influenced both the porosity of cement and vancomycin release profiles. Antibiotic activity during release study was successfully measured using an agar diffusion assay. However, vancomycin-HCl encapsulation into PLGA polymer microspheres decreased porosity influence of cement on drug release while maintaining antibiotic activity of the embedded substance. PMID:21948487

Schnieders, Julia; Gbureck, Uwe; Vorndran, Elke; Schossig, Michael; Kissel, Thomas

2011-09-21

258

Hydrophobic ion pair formation between leuprolide and sodium oleate for sustained release from biodegradable polymeric microspheres.  

PubMed

Leuprolide acetate, an analogue of luteinizing hormone-releasing hormone (LH-RH), was hydrophobically ion paired with a long chain fatty acid, sodium oleate, in an aqueous solution. Solution behaviors of the complex formed between leuprolide and sodium oleate were investigated in terms of aqueous solubility, turbidity, particle size, and zeta potential as a function of molar ratio between the two species. It was found that with increasing the stoichiometric molar amounts of sodium oleate to leuprolide approached up to 2.5-3, the solution became gradually turbid with increasing particle sizes, indicating leuprolide precipitation as a result of hydrophobic ion pairing. On the other hand, beyond that critical molar ratio range, the solution turned into clear with much reduced particle size, indicative of micelle formation. The hydrophobically modified leuprolide-oleate complex was lyophilized and directly encapsulated within biodegradable poly(D, L-lactic-co-glycolic acid) (PLGA) microspheres via a single oil-in-water (O/W) emulsion method. Microsphere morphology, leuprolide release behavior, and polymer mass erosion profiles were examined in comparison to the PLGA microspheres prepared with free leuprolide. PMID:10967441

Choi, S H; Park, T G

2000-08-10

259

Development of a dialysis in vitro release method for biodegradable microspheres.  

PubMed

The purpose of this research was to develop a simple and convenient in vitro release method for biodegradable microspheres using a commercially available dialyzer. A 25 KD MWCO Float-a-Lyzer was used to evaluate peptide diffusion at 37 degrees C and 55 degrees C in different buffers and assess the effect of peptide concentration. In vitro release of Leuprolide from PLGA microspheres, having a 1-month duration of action, was assessed using the dialyzer and compared with the commonly used sample and separate method with and without agitation. Peptide diffusion through the dialysis membrane was rapid at 37 degrees C and 55 degrees C in all buffers and was independent of peptide concentration. There was no detectable binding to the membrane under the conditions of the study. In vitro release of Leuprolide from PLGA microspheres was tri-phasic and was complete in 28 days with the dialysis technique. With the sample and separate technique, linear release profiles were obtained with complete release occurring under conditions of agitation. Diffusion through the dialysis membrane was sufficiently rapid to qualify the Float-a-Lyzer for an in vitro release system for microparticulate dosage forms. Membrane characteristics render it useful to study drug release under real-time and accelerated conditions. PMID:16353991

D'Souza, Susan S; DeLuca, Patrick P

2005-10-06

260

Tailoring properties of microsphere-based poly(lactic-co-glycolic acid) scaffolds.  

PubMed

Biodegradable polymer scaffolds are being extensively investigated for uses in tissue engineering because of their versatility in fabrication methods and range of achievable chemical and mechanical properties. In this study, poly(lactic-co-glycolic acid) (PLGA) was used to make various types of microspheres that were processed into porous scaffolds that possessed a wide range of properties. A heat sintering step was used to fuse microspheres together around porogen particles that were subsequently leached out, allowing for a 10-fold increase in mechanical properties over other PLGA scaffolds. The sintering temperature was based on the glass transition temperature that ranged from 43 to 49°C, which was low enough to enable drug loading. Degradation times were observed to be between 30 and 120 days, with an initial compressive modulus ranging from 10 to 100?MPa, and after 5 days of degradation up to 10?MPa was retained. These scaffolds were designed to allow for cell ingrowth, enable drug loading, and have an adjustable compressive modulus to be applicable for soft or hard tissue implants. This study combined well-established methods, such as double emulsion microspheres, polymer sintering, and salt leaching, to fabricate polymer scaffolds useful for different tissue engineering applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. PMID:23533090

Clark, Amanda; Milbrandt, Todd A; Hilt, J Zach; Puleo, David A

2013-03-27

261

Effects of surfactants on the properties of PLGA nanoparticles.  

PubMed

The objective of this study was to investigate the physical characteristics of poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) coated with two surfactants, Pluronic or the commonly used polyvinyl alcohol (PVA); and determine their in vitro efficiency as drug carriers for cancer therapy. Free surfactant cytotoxicity results indicated that Pluronic F127 (PF127) was most cytocompatible among the Pluronics tested and hence chosen for coating PLGA NPs for further studies. Release studies using doxorubicin (DOX) as a drug model showed sustained release of DOX from both PVA- and PF127-coated PLGA NPs (PLGA-PVA and PLGA-PF127, respectively) over 28 days. Further, there was no significant difference in human dermal fibroblasts and human aortic smooth muscle cell survival when exposed to both types of NPs. Cellular uptake studies demonstrated that uptake of both nanoparticle types was dose-dependent for both prostate and breast cancer cells. However, these cancer cells internalized more PLGA-PF127 NPs than PLGA-PVA NPs. Moreover, studies showed that drug-loaded PLGA-PF127 NPs not only killed more cancer cells than drug-loaded PLGA-PVA NPs, but also overcame drug resistance in LNCaP, MDA-MB-231, and MDA-MB-468 cancer cells on re-exposure. These results indicate that PLGA-PF127 NPs can form a promising system that not only delivers anti-cancer drugs, but also overcomes drug resistance, which is prevalent in most cancer cells. PMID:22566409

Menon, Jyothi U; Kona, Soujanya; Wadajkar, Aniket S; Desai, Foram; Vadla, Anupama; Nguyen, Kytai T

2012-05-05

262

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

PubMed

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 (t(1/2)). 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

2013-06-10

263

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

Microsoft Academic Search

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

Leanne Groban

2003-01-01

264

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

Microsoft Academic Search

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

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

2010-01-01

265

[Clinical observations on long-acting oral contraceptives--a report of 43,373 (author's transl)].  

PubMed

Long-acting oral contraceptives (OCs) for women were available for clinical experimentation in 1969. Through the country, 29 provinces, cities, and autonomous regions participated in this expirement. Based upon the cases between 1969 and 1976 findings from this expirement can be summarized as follows: 1) the 3 types of long-acting OCs have proved to be very effective, and the rate of breast cancer and cervical cancer is lower than the normal rate. The childbearing ability can be restored rapidly after discontinued use of the contraceptives. The impact on menses and metaboliism is not very serious. The health of the users and the newborn babies has not been found to be endangered. Statistics show that long-acting OCs are comparatively more secure measures for birth control; 2) some users have experienced dizziness, nausea, and excessive leukorrhea, and discontdiscontinued because of discomfort and inconvenience. This situation has some impact on the popular use of long-acting OCs. Research and studies are underway on a reduced dosage and reduction of side effects; 3) women who suffer from hepatitis, nephritis, a history of liver and kidney problems, breast tumors, cervical cancer, diabetes, active low blood sugar, or a history of having over-sized babies, or an overweight problem should not use OCs. Women who suffer from high blood pressure can only use OCs with a doctor's advice and caution. PMID:263034

1979-04-01

266

Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia.  

PubMed

Introduction: Prophylactic treatment with replacement clotting factor is the recommended regimen for patients with severe hemophilia to prevent bleeding episodes. However, currently available replacement clotting factors are limited by their relatively short half-lives and require intravenous injections up to three times weekly to maintain protective levels, which can impact compliance and, thus, patient outcomes. Areas covered: The potential advantages of long-acting coagulation factors, including reduced injection frequency, increased treatment adherence, and improved clinical outcomes, are discussed. Fragment crystallizable (Fc) fusion technology is introduced and the development of long-acting recombinant factor VIII Fc (rFVIIIFc) and recombinant factor IX Fc (rFIXFc) fusion proteins for the treatment of hemophilia A and B, respectively, are described. Preclinical and clinical studies of rFVIIIFc and rFIXFc showing improved pharmacokinetics over currently available products are reviewed. Expert opinion: Long-acting coagulation factors, including rFVIIIFc and rFIXFc, have the potential to change current paradigms of care for hemophilia A and B, respectively. Less frequent infusions may provide prolonged protection from bleeding and bleed resolution with fewer injections. In addition, long-acting coagulation factors provide an opportunity for improved individualized treatment for hemophilia. PMID:23930915

Shapiro, Amy

2013-09-01

267

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.

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

2013-01-01

268

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

Microsoft Academic Search

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

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

2011-01-01

269

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

PubMed

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

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

2012-10-20

270

Preclinical pharmacokinetics and tissue distribution of long-acting nanoformulated antiretroviral therapy.  

PubMed

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; Alnouti, Yazen

2013-04-22

271

Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking.  

PubMed

The treatment of cocaine addiction remains a challenge. The dopamine replacement approach in cocaine addiction involves the use of a competing dopaminergic agonist that might suppress withdrawal and drug craving in abstinent individuals. Although it has long been postulated that such an approach may be therapeutically successful, preclinical or clinical evidence showing its effectiveness to prevent relapse is scant. We used in rats a procedure that involved substitution of the N-substituted benztropine analog 3?-[bis(4'-fluorophenyl)methoxy]-tropane (AHN-1055), a long-acting dopamine uptake inhibitor (DUI), for cocaine. Maintenance treatment was self-administered. After extinction, reinstatement of drug seeking was induced by cocaine priming. We measured the contents of brain-derived neurotrophic factor (BDNF), c-Fos and Fas-associated death domain (FADD) proteins in the medial prefrontal cortex (mPFC) following reinstatement. DUI, but not amphetamine, substitution led to extinction of active lever presses, as did saline substitution. DUI substitution significantly reduced cocaine-induced reinstatement of drug-seeking behavior, which was strongly elicited after saline substitution. Rats passively yoked to DUI also showed reduced cocaine-primed reinstatement. Reductions in drug seeking during reinstatement were matched by downward shifts in the contents of BDNF, c-Fos and FADD proteins in the mPFC, which were elevated in relapsing rats. These data indicate that DUI substitution not only leads to extinction of self-administration behavior but also prevents reinstatement of drug seeking induced by cocaine re-exposure. Thus, DUI substitution therapy using compounds with low abuse potential, even if received passively in the context previously paired with drug taking, may provide an effective treatment for stimulant addiction. PMID:22741574

Velázquez-Sánchez, Clara; Ferragud, Antonio; Ramos-Miguel, Alfredo; García-Sevilla, Jesús A; Canales, Juan J

2012-06-28

272

?? 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

2012-03-13

273

Octreotide: a long-acting inhibitor of endogenous hormone secretion for human metabolic investigations.  

PubMed

Octreotide is a recently available, FDA-approved, long-acting analog of somatostatin. The efficacy and tolerability of octreotide were evaluated in a series of protocols in healthy volunteers to assess its suitability for use in clinical investigations involving short-term inhibition of endogenous hormone secretion. Prolonged (270 minutes) hyperglycemic clamps were used to assess octreotide-mediated suppression of glucose-stimulated endogenous insulin secretion. Compared with a saline-control infusion, octreotide (30 ng/kg/min) suppressed stimulated insulin (P < .0001) and C-peptide (P < .0001) concentrations to basal levels. During insulin-induced hypoglycemia (plasma glucose < 40 mg/dL), octreotide (30 ng/kg/min) effectively suppressed the secretion of glucagon (P < .05) and growth hormone (P < .0005). In islet cell clamp studies, octreotide (30 ng/kg/min) suppressed C-peptide (P < .001), glucagon (P < .01), and growth hormone concentrations to below basal (fasting) levels in all subjects. Subsequent infusion of exogenous insulin, glucagon, and growth hormone resulted in predictable and stable concentrations of each hormone during octreotide-mediated suppression of their endogenous secretion. Consistent with the long half-life of octreotide (approximately 90 minutes), the concentrations of all three hormones remained suppressed below basal levels throughout a 60-minute observation period following the termination of octreotide infusion. In separate high-dose octreotide infusion studies, octreotide (60 ng/kg/min) did not produce any apparent additional metabolic effects, but was associated with an unacceptable degree of gastrointestinal side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8289671

Krentz, A J; Boyle, P J; Macdonald, L M; Schade, D S

1994-01-01

274

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.

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

2012-01-01

275

Bronchodilatory effects of NVA237, a once daily long-acting muscarinic antagonist, in COPD patients.  

PubMed

NVA237 is a novel, once daily inhaled long-acting muscarinic antagonist administered via a dry powder inhaler. This study aimed to assess the 24-h bronchodilatory effect following 14 days of treatment with inhaled NVA237 in patients with mild, moderate or severe COPD. This was a randomized, double-blind, placebo-controlled, two-period, crossover, multicenter study. A total of 33 patients (? 40 years; smoking history of ? 10 pack-years) were randomized to receive NVA237 50 ?g once daily followed by placebo or placebo followed by NVA237 50 ?g for 14 days. Treatment periods were separated by a 7-14 day washout period. The primary variable was the mean forced expiratory volume in 1 s (FEV(1)) derived from the area under the curve (AUC) between 0 and 24 h post-dose on Day 14. The 24-h FEV(1) profiles showed a consistent bronchodilator effect for NVA237 versus placebo on Day 14. Least square (LS) mean difference in FEV(1) AUC(0-24 h) values between NVA237 and placebo was 163 mL (P < 0.001). There were significant increases in mean FEV(1) AUC(0-12 h) (LS mean difference 165 mL, P = 0.001) and FEV(1) AUC(12-24 h) (161 mL, P < 0.001) versus placebo. NVA237 significantly improved peak FEV(1) (by 208 mL, P < 0.001) and trough FEV(1) (by 154 mL, P = 0.003) versus placebo on Day 14. NVA237 was well tolerated; all adverse events were mild or moderate in intensity and not related to study drug. NVA237 50 ?g once daily was well tolerated and showed significant and sustained 24-h bronchodilation in patients with COPD. PMID:21144724

Fogarty, Charles; Hattersley, Helen; Di Scala, Lilla; Drollmann, Anton

2010-12-08

276

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

2009-05-28

277

Long acting injectable versus oral naltrexone maintenance therapy with psychosocial intervention for heroin dependence: A quasi-experiment  

PubMed Central

Objective To conduct a quasi-experimental comparison of early clinical outcomes between injectable, sustained release, depot naltrexone formulation versus oral naltrexone maintenance therapy. Method Early retention and urine results were compared between patients participating in two concurrently run randomized clinical trials of oral (N = 69) and long acting injectable naltrexone maintenance therapy with psychosocial therapy (N = 42). Retention in treatment and opiate use in the first 8-weeks post-detoxification were compared. Results Long acting injectable naltrexone produced significantly better outcome than oral naltrexone on days retained in treatment and one measure of opiate use; other measures were not significantly different, but differences were in the same direction. In subanalyses, there were interaction effects between baseline heroin severity and type of treatment. In subanalyses, heroin users with more severe baseline use showed better retention in oral naltrexone maintenance combined with intensive psychotherapy (Behavior Naltrexone Therapy) as compared to retention of severe users treated with long acting naltrexone injections combined with standard cognitive-behavioral psychotherapy; less severe heroin users evidenced better outcomes when treated with long acting injectable naltrexone. Conclusions This quasi-experimental analysis provides tentative indications of superior outcomes for heroin dependent patients treated with long acting injectable naltrexone compared to oral naltrexone. The finding that heroin users with more severe baseline use achieved better outcomes with oral naltrexone is most probably attributable to the intensive nature of the psychosocial treatments provided, and points to the opportunity for continued research in augmenting injectable naltrexone with psychosocial strategies to further improve outcome especially in more severe users. The results should be considered exploratory given the quasi-experimental nature of the study.

Brooks, Adam C.; Comer, Sandra D.; Sullivan, Maria A.; Bisaga, Adam; Carpenter, Kenneth; Raby, Wilfrid M.; Yu, Elmer; O'Brien, Charles P.; Nunes, Edward V.

2009-01-01

278

The long-acting ?-adrenoceptor agonist, indacaterol, inhibits IgE-dependent responses of human lung mast cells  

PubMed Central

Background and purpose: The long-acting ?2-adrenoceptor agonist, indacaterol, has been developed as a bronchodilator for the therapeutic management of respiratory diseases. The aim of the present study was to determine whether indacaterol has any anti-inflammatory activity. To this end, the effects of indacaterol on human lung mast cell responses were investigated. Experimental approach: The effects of indacaterol, and the alternative long-acting ?-agonists formoterol and salmeterol, were investigated on the IgE-dependent release and generation of histamine, cysteinyl-leukotrienes and prostaglandin D2 from human lung mast cells. Moreover, the extent to which long-term (24–72 h) incubation of mast cells with long-acting ?-agonists impaired the subsequent ability of ?-agonists to inhibit mast cell responses was assessed. Key results: Indacaterol was as potent and as efficacious as the full agonist, isoprenaline (EC50, ?4 nmol·L?1), at inhibiting the IgE-dependent release of histamine from mast cells. Formoterol was a full agonist whereas salmeterol was a partial agonist as inhibitors of histamine release. All three long-acting ?-agonists were effective inhibitors of the IgE-dependent generation of cysteinyl-leukotrienes and prostaglandin D2. Long-term incubation of mast cells with long-acting ?-agonists led to a reduction in the subsequent ability of ?-agonists to stabilize mast cell responses. This tendency to induce functional desensitization was least evident for indacaterol. Conclusions and implications: Indacaterol is an effective inhibitor of the release of mediators from human lung mast cells. This suggests that, as well as bronchodilation, mast cell stabilization may constitute an additional therapeutic benefit of indacaterol.

Scola, Anne-Marie; Loxham, Matthew; Charlton, Steven J; Peachell, Peter T

2009-01-01

279

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

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 poly-lactic-co-glycolic acid (PLGA) microspheres encapsulating VEGF 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 microspheres with a diameter <53 ?m. 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 24h, 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 throughout 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

2011-10-07

280

Tetanus toxoid and synthetic malaria antigen containing poly(lactide)\\/poly(lactide-co-glycolide) microspheres: importance of polymer degradation and antigen release for immune response  

Microsoft Academic Search

The importance of in vitro degradation of poly(lactide)\\/poly(lactide-co-glycolide) (PLA\\/PLGA) microspheres and of the concomitant in vitro release of a natural and a synthetic antigen for eliciting immune response was studied in mice. A variety of PLAs and PLGAs differing in molecular weight (Mw of 14–130 kDa) and in polymer composition (lactic\\/glycolic acid ratio of 100:00, 75:25, and 50:50) were examined

Claudio Thomasin; Giampietro Corradin; Ying Men; Hans P. Merkle; Bruno Gander

1996-01-01

281

Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction\\/evaporation method  

Microsoft Academic Search

The surface and internal morphology, drug distribution and release kinetics at 22°C of polyesters such as PCL (polycaprolactone) and PLGA (poly(dl-lactic-co-glycolic acid)) 65:35 microspheres containing BSA (bovine serum albumin) have been investigated in order to understand the relationship amongst morphology, drug distribution and in vitro release profiles and to develop controlled release devices for marine fishes in tropical area. CLSM

Yi-Yan Yang; Tai-Shung Chung; Ngee Ping Ng

2001-01-01

282

Preparation and characterization of melittin-loaded poly ( dl-lactic acid) or poly ( dl-lactic-co-glycolic acid) microspheres made by the double emulsion method  

Microsoft Academic Search

The water soluble peptide, melittin, isolated from bee venom and composed of twenty-six amino acids, was encapsulated in poly (dl-lactic acid, PLA) and poly (dl-lactic-co-glycolic acid, PLGA) microspheres prepared by a multiple emulsion [(W1\\/O)W2] solvent evaporation method. The aim of this work was to develop a controlled release injection that would deliver the melittin over a period of about one

Fude Cui; Dongmei Cun; Anjin Tao; Mingshi Yang; Kai Shi; Min Zhao; Ying Guan

2005-01-01

283

Depot long-acting somatostatin analog (Sandostatin-LAR) is an effective treatment for acromegaly.  

PubMed

Octreotide (Sandostatin) is a synthetic analog of somatostatin, an endogenous GH inhibitory peptide that has been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly. When given sc in divided daily doses, it lowers serum GH to less than 5 micrograms/L in approximately 50% of cases. Data suggest that continuous infusions of somatostatin analogs may be more effective in lowering GH. We have evaluated Sandostatin-LAR, a new long-acting preparation of Sandostatin, in eight patients with acromegaly. After an initial pharmacokinetic study, patients received a minimum of 10 im injections of Sandostatin-LAR (20, 30, or 40 mg) at 28- or 42-day intervals. Serum GH levels decreased from 10.7 +/- 2.8 micrograms/L (mean +/- SE) at baseline to a nadir of 2.6 +/- 0.4 micrograms/L after the tenth injection, and to less than 5 micrograms/L in every patient. Serum insulin-like growth factor-I decreased from 927 +/- 108 ng/mL at baseline to 472 +/- 59 ng/mL at the end of the sixth injection and returned to normal (< 500 ng/mL) in seven of the eight patients. This was associated with significant improvements in headache, arthralgia, and sweating. There was no evidence of octreotide accumulation, and the drug was well tolerated. To date, no gallstones have occurred, and serial pituitary imaging has revealed no increase in the size of the initial pituitary tumor. In particular, two previously untreated patients have shown complete regression of the initial microadenoma and have serum GH values of less than 2.5 micrograms/L. Sandostatin-LAR is an effective and well-tolerated treatment for patients with acromegaly. Undoubtedly the initial indication for Sandostatin-LAR will be in the patient who is not cured after surgery and radiotherapy, but our experience suggests that it may be used as a primary treatment in some acromegalics. PMID:7593436

Stewart, P M; Kane, K F; Stewart, S E; Lancranjan, I; Sheppard, M C

1995-11-01

284

Long-acting morphine following hip or knee replacement: A randomized, double-blind, placebo-controlled trial  

PubMed Central

BACKGROUND: Patients undergoing total hip or knee replacement surgery experience unmanaged pain during postoperative physiotherapy sessions. It was theorized that a baseline opioid would improve pain management. OBJECTIVES: To examine the effectiveness of adding long-acting oral morphine to a routine postoperative regimen for total hip or knee replacement surgery. METHODS: The present study was a double-blind, randomized, placebo-controlled trial for patients undergoing total hip or knee replacement surgery. All patients received routine postoperative analgesia; in addition, the treatment group received long-acting oral morphine 30 mg orally twice daily for three days, while the control group received placebo capsules. The primary end point was a decrease in pain scores by two points on a 0- to 10-point pain rating scale. Secondary end points included adverse effects, acute confusion, pain-related interferences in function and sleep, length of stay and patient satisfaction. RESULTS: Two hundred patients were enrolled in the present study (March 2004 to March 2006). Although the groups were large enough to yield statistical significance, most pain scores did not reach the predetermined improvement for clinical significance. Additionally, there was an increase in opioid usage (P<0.0001), vomiting (P=0.0148) and oversedation (P=0.08). There were no statistically significant changes in function or sleep. Improved satisfaction with pain management was minimal (P=0.052). DISCUSSION: The present study was undertaken to determine the value of adding a long-acting opioid (morphine) to the usual care of patients undergoing total hip or total knee replacement surgery. The results yielded minimally improved pain scores and additional adverse effects (vomiting and oversedation). Published research in which long-acting opioids (oxycodone) were used for similar postoperative procedures did not robustly report improved pain scores. In addition, patients using a long-acting opioid (oxycodone) during the postoperative period reported somnolence, dizziness and confusion. Statistically, the patients in the present study showed higher confusion scores and no improvement for pain-related interferences with activity or walking. The treatment group did report increased satisfaction; however, the significance was weak. CONCLUSIONS: Thirty milligrams twice per day of long-acting morphine from days 1 to 3 following total hip and total knee replacement surgery provided minimal improvements in pain scores, and more adverse effects in the treatment group. The overall strength of evidence for improved outcomes is minimal and thus not supported.

Musclow, Shirley L; Bowers, Tabatha; Vo, Hanna; Glube, Mark; Nguyen, Thong

2012-01-01

285

Fabrication of PLGA nanoparticles with a fluidic nanoprecipitation system  

PubMed Central

Particle size is a key feature in determining performance of nanoparticles as drug carriers because it influences circulating half-life, cellular uptake and biodistribution. Because the size of particles has such a major impact on their performance, the uniformity of the particle population is also a significant factor. Particles comprised of the polymer poly(lactic-co-glycolic acid) (PLGA) are widely studied as therapeutic delivery vehicles because they are biodegradable and biocompatible. In fact, microparticles comprised of PLGA are already approved for drug delivery. Unfortunately, PLGA nanoparticles prepared by conventional methods usually lack uniformity. We developed a novel Fluidic NanoPrecipitation System (FNPS) to fabricate highly uniform PLGA particles. Several parameters can be fine-tuned to generate particles of various sizes.

2010-01-01

286

Comparison of morphology and mechanical properties of PLGA bioscaffolds.  

PubMed

In this study, bioscaffolds using poly(DL-lactide-co-glycolide) acid (PLGA) were fabricated and studied. The gas foaming/salt leaching technique in a batch foaming setup was employed, and the effects of material composition of PLGA on the morphology and mechanical properties using this process were investigated. Two material compositions of PLGA 50/50 and 85/15 were used, and characterization of scaffolds fabricated with these materials showed that a lower relative density can be achieved with an increasing poly(DL-lactide) acid (PDLLA) content; however, higher open-cell porosity was obtained with lower PDLLA content. Furthermore, the effect of PLGA composition on modulus of the scaffolds was minor. PMID:18458364

Leung, L; Chan, C; Baek, S; Naguib, Hani

2008-04-15

287

In vitro and in vivo release properties of brilliant blue and tumour necrosis factor-alpha (TNF-alpha) from poly(D,L-lactic-co-glycolic acid) multiphase microspheres.  

PubMed

The dissolution properties of two model compounds, brilliant blue and tumour necrosis factor (TNF-alpha), from poly(D,L-lactic-co-glycolic acid) (PLGA) multiphase microspheres were investigated. In addition, the in vivo release of TNF-alpha from the microspheres, in mice, was studied. The microspheres were prepared by an anhydrous multiple emulsion solvent evaporation method. Multiphase microspheres containing brilliant blue exhibited a three phase release profile in vitro, and displayed a significantly lower level of dye released during the initial phase compared to conventional matrix-type microspheres. Slow release of the dye was observed during the second phase, which was followed by a disintegration of the polymer wall during the third phase of the release process. In vitro dissolution profiles of TNF-alpha were calculated by compensation for the simultaneous degradation of the protein in the dissolution medium. The initial burst release of TNF-alpha was significantly reduced with the multiphase microspheres. The three phase release profile, as seen with the dye, was not observed for the microspheres containing the TNF-alpha. The rate of release of the protein from the microspheres was determined in vivo by analysing the residual level of TNF-alpha remaining in the particles following intraperitoneal administration of the microspheres to mice. The release of the protein from the microspheres in vivo was significantly faster than predicted from the results of the in vitro studies. The absence of an initial burst release of TNF-alpha from the multiphase microspheres was reflected in a significant reduction in the plasma level of TNF-alpha when compared to the matrix-type microspheres and a solution of the protein. The controlled release property of the multiphase microspheres is expected to overcome the adverse reactions due to dose dumping that occurs following the local administration of TNF-alpha. PMID:10575629

Iwata, M; Nakamura, Y; McGinity, J W

288

Costs and effects of long-acting risperidone compared with oral atypical and conventional depot formulations in Germany.  

PubMed

Schizophrenia is one of the most expensive psychiatric conditions because of high direct and indirect costs associated with the nature of the illness, its resistance to treatment and the consequences of relapse. Long-acting risperidone is a new formulation of an atypical antipsychotic drug that also offers the improvements in compliance associated with haloperidol depot. The aim of this simulation study was to compare the benefits and costs of three pharmacological treatment strategies comprising first-line treatment with long-acting risperidone injection, a haloperidol depot or an oral atypical antipsychotic agent, over a 5-year period in Germany. A discrete event simulation model was developed to compare three treatment scenarios from the perspective of major third-party payers (sickness funds and social security 'Sozialversicherung'). The scenarios comprised first-line treatment with haloperidol depot (scenario 1), long-acting risperidone (scenario 2) and oral olanzapine (scenario 3). Switches to second or third-line options were allowed when side-effects occurred or a patient suffered more than a fixed number of relapses. The model accounted for fixed patient characteristics, and on the basis of these, simulated patient histories according to several time-dependent variables. The time horizon for this model was limited to 5 years, and in accordance with German guidelines, costs and effects were discounted by between 3 and 10%. Direct costs included medication, type of physician visits and treatment location. Indirect costs were not included. Information on treatment alternatives, transition probabilities, model structure and healthcare utilization were derived from the literature and an expert panel. Outcomes were expressed in terms of the number and duration of psychotic episodes, cumulative symptom scores, costs, and quality-adjusted life-years (QALY). Univariate sensitivity analyses were carried out, as were subgroup analyses based on disease severity and for patients at high risk of being non-compliant. The long-acting risperidone strategy was calculated to avoid 0.23 and 0.33 relapses per patient, decrease the cumulative symptom score by 25 and 33 points, and decrease the costs by 2017 Euro and 6096 Euro per patient (1608 Euro and 5422 Euro discounted), compared with the haloperidol depot and olanzapine strategies, respectively, over a 5-year period (year of costing 2004). Among high-risk non-compliant patients, long-acting risperidone was estimated to avoid 0.23 and 0.47 relapses and save 4822 Euro and 10,646 Euro per patient (4107 Euro and 9490 Euro discounted), compared with the haloperidol depot and olanzapine strategies, respectively. Sensitivity analyses showed that the results were robust and mainly sensitive to changes in the reported relative effectiveness of atypical and conventional formulations for preventing symptom recurrence, and in the relative compliance with oral and long-acting formulations. In this model, long-acting risperidone is a dominant strategy compared with a haloperidol depot or oral atypical antipsychotic agent, being both more effective and less costly over a 5-year period. Results for long-acting risperidone are even more favourable among patients at high risk of being noncompliant or with more severe disease. PMID:16416761

Laux, Gerd; Heeg, Bart; van Hout, Ben A; Mehnert, Angelika

2005-01-01

289

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

290

ORIENTATION-SPECIFIC IMMOBILIZATION OF BMP2 ON PLGA SCAFFOLDS  

Microsoft Academic Search

A variety of synthetic bone graft materials such as the polymer poly(lactic-co-glycolic acid) (PLGA) have been investigated as alternatives to current tissue based bone graft materials. In this study, efforts have been made to improve the tissue-PLGA interface by immobilizing bone morphogenetic protein-2 (BMP-2) in an oriented manner on scaffolds using covalently immobilized heparin. The results demonstrated a four-fold increase

Randall K. Hilliard

2007-01-01

291

Interaction of recombinant human bone morphogenetic protein-2 with poly(d,l lactide-co-glycolide) microspheres.  

PubMed

The combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) with poly(d,l lactide-co-glycolide) (PLGA) porous microspheres provided for "sustained release" of the protein from the microspheres. Soaking 50:50 PLGA microspheres in a buffered rhBMP-2 solution for a sufficient period of time to permit equilibrium binding enabled quantification of "free" and "bound" protein. "Free" protein is defined as protein present within the porous matrix of the microspheres, whereas "bound" refers to protein adsorbed to PLGA surfaces. Kinetics of the rhBMP-2-microsphere association revealed that equilibrium was attained within 8 hr for two buffer systems (arginine/histidine, pH 6.50; and glutamic acid/sodium glutamate, pH 4.50). Increasing the concentration of the rhBMP-2 stock solution used for the interaction studies from 0.025 to 1.0 mg/ml increased the amount of rhBMP-2 adsorbed and the concentration of free rhBMP-2. Beyond a 1.0 mg/mL concentration, only free rhBMP-2 levels increased. Linearized Langmuir treatment of the adsorption data yielded values corresponding to monolayer coverage of the microspheres (Cm) and the equilibrium adsorption constant (K) of 0.17 microgram/cm2 and 7.57 ml/mg, respectively. Studies performed to determine the effect of ionic strength revealed that increasing NaCl and buffer concentration decreased the amount of protein adsorbed. rhBMP-2 release studies, conducted in an isotonic phosphate buffered saline, pH 7.4 vehicle, revealed that free rhBMP-2 was released during an initial period of 72-96 hr. Following this period, there was no discernible release of rhBMP-2 from the microspheres for up to 7 days, suggesting that the bound protein would remain at a defect site and release slowly upon erosion of the polymer. Mass balances performed by using an extraction buffer of high ionic strength confirmed this prediction. PMID:9552326

Duggirala, S S; Mehta, R C; DeLuca, P P

1996-04-01

292

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

293

Inhaled steroid\\/long-acting ?2 agonist combination products provide 24 hours improvement in lung function in adult asthmatic patients  

Microsoft Academic Search

BACKGROUND: The combination of inhaled corticosteroids (ICS) and long-acting ?2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol\\/fluticasone propionate (SFC, Seretide™ GSK, UK) and formoterol\\/budesonide (FBC, Symbicort™, AstraZeneca, UK) are commercially available. OBJECTIVES: The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products

Jan Lötvall; Stephen Langley; Ashley Woodcock

2006-01-01

294

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

Microsoft Academic Search

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

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

2010-01-01

295

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

296

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

Microsoft Academic Search

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

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

2011-01-01

297

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

298

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

Microsoft Academic Search

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

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

2008-01-01

299

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

2013-03-20

300

The Potential Role of Long-acting Injectable Antipsychotics in People with Schizophrenia and Comorbid Substance Use  

PubMed Central

Objective Treatment of schizophrenia in patients with comorbid substance use (alcohol/illicit drug use, abuse or dependence) presents challenges for public health systems. Substance use in people with schizophrenia is up to four times greater than the general population and is associated with medication nonadherence and poor outcomes. Therefore, continuous antipsychotic treatment in this population may pose more of a challenge than for those with schizophrenia alone. Many clinical trials and treatment recommendations in schizophrenia do not take into consideration substance use as people with comorbid substance use have typically been excluded from most antipsychotic trials. Nonetheless, antipsychotic treatment appears to be as efficacious in this population, although treatment discontinuation remains high. The objective of this review was to highlight the importance and utility of considering long-acting injectable antipsychotics for patients with schizophrenia and comorbid substance use. Methods We did a literature search using PubMed with key words schizophrenia and substance use/abuse/dependence, nonadherence, antipsychotics, long acting injectables, relapse, and psychosocial interventions. We limited our search to human studies published in English and 4,971 articles were identified. We focused on clinical trials, case reports, case series, reviews and meta-analyses resulting in 125 articles from 1975-2011. Results Our review suggests the potential role of long-acting injectables for people with comorbid substance use and schizophrenia in leading to improvements in psychopathology, relapse prevention, fewer rehospitalizations, and better outcomes. Conclusions While more research is needed, long-acting antipsychotics should be considered an important option in the management of people with schizophrenia and comorbid substance use.

Koola, Maju Mathew; Wehring, Heidi J.; Kelly, Deanna L.

2012-01-01

301

Optimizing Medical Therapy of Acromegaly: Beneficial Effects of Cabergoline in Patients Uncontrolled with Long-Acting Release Octreotide  

Microsoft Academic Search

Background: Previous data indicate a beneficial effect of cabergoline (CAB) association to somatostatin analogs (SA) in acromegalics resistant to SA monotherapy. Objective: To assess the efficacy of CAB association on acromegalics with high IGF-I on stable long-acting release octreotide (OCT-LAR) (30 mg\\/28 days). Design, Subjects and Methods: 34 patients (17 male, 25–85 years, 33 macroadenomas) were enrolled in this prospective

Raquel S. Jallad; Marcello D. Bronstein

2009-01-01

302

Patients' and clinicians' attitude towards long-acting depot antipsychotics in subjects with a first episode of psychosis  

PubMed Central

Objectives: The acceptance and use of long-acting depot antipsychotics has been shown to be influenced by the attitudes of patients and clinicians. Depot treatment rates are low across countries and especially patients with first-episode psychosis are rarely treated with depot medication. The aim of this article was to review the literature on patients’ and clinicians’ attitudes towards long-acting depot antipsychotics in subjects with first-episode psychosis. Methods: A systematic search of Medline, Embase, PsycINF and Google Scholar was conducted. Studies were included if they reported original data describing patients’ and clinicians’ attitudes towards long-acting depot antipsychotic in subjects with first-episode psychosis. Results: Six studies out of a total of 503 articles met the inclusion criteria. Four studies conveyed a negative and two a positive opinion of clinicians toward depot medication. No systematic study directly addressed the attitude of patients with first-episode psychosis. Psychiatrists frequently presume that patients with first-episode psychosis would not accept depot medication and that depots are mostly eligible for chronic patients. Conclusions: Full information of all patients especially those with first episode psychosis in a therapeutic relationship that includes shared decision-making processes could reduce the negative image and stigmatization attached to depots.

Theodoridou, Anastasia; Fusar-Poli, Paolo; Kaiser, Stefan; Jager, Matthias

2013-01-01

303

Requirements or incentives by government for the use of long-acting contraceptives. Board of Trustees, American Medical Association.  

PubMed

Following the approval of the long-acting contraceptive levonorgestrel (the Norplant Contraceptive System) for use by women, government officials have required or proposed uses of levonorgestrel that are problematic. One court ordered a woman convicted of child abuse to use levonorgestrel as a condition of her probation; legislators have proposed that women on welfare be paid to use levonorgestrel. Court-ordered use of long-acting contraceptives because of child abuse raises serious questions about a person's fundamental rights to refuse medical treatment, to be free of cruel and unusual punishment, and to procreate. The state's compelling interest in protecting children from abuse may be served by less intrusive means than imposing contraception on parents who have committed child abuse. If government benefits were based on the use of long-acting contraceptives, individuals would have to assume a potentially serious health risk before receiving their benefits. Government benefits should not be made contingent on the acceptance of a health risk. PMID:1545467

1992-04-01

304

Hepatic cytoreduction followed by a novel long-acting somatostatin analog: A paradigm for intractable neuroendocrine tumors metastatic to the liver  

Microsoft Academic Search

Background. Optimal management of symptomatic neuroendocrine tumors that metastasize to the liver is controversial. We investigated aggressive hepatic cytoreduction and postoperative administration of octreotide long-acting release (LAR), a long-acting somatostatin analog. Methods. Between December 1992 and August 2000, 31 patients underwent hepatic surgical cytoreduction (20 carcinoid, 10 islet cell, and 1 medullary). All patients had progressive symptoms refractory to conventional

Mathew H. Chung; Joseph Pisegna; Mitchell Spirt; Armando E. Giuliano; Wei Ye; Kenneth P. Ramming; Anton J. Bilchik

2001-01-01

305

Sterilized ibuprofen-loaded poly(D,L-lactide-co-glycolide) microspheres for intra-articular administration: effect of gamma-irradiation and storage.  

PubMed

The aim of this study was to prepare and characterize a controlled-release system (microspheres) loaded with ibuprofen, for intra-articular administration, to extend its anti-inflammatory effect in the knee joint cavity. Among the bioresorbable polymers employed, poly(D,L-lactic-co-glycolic) acid (PLGA) (13137 Da) was chosen because of its high biocompatiblity. Microspheres were produced by the solvent evaporation process from an O/W emulsion. Labrafil M 1944 CS was included in the formulation as an additive in order to modulate the release rate of the non-steroidal anti-inflammatory drug (NSAID). Once prepared, the microspheres were sobre-sterilized by gamma-irradiation. The effect of the irradiation dose (25 kGy) exposure, at low temperature, on the formulation was evaluated. The sterilization procedure employed did not alter the physicochemical characteristics of the formulation. Dissolution profiles of formulations behaved similarly and overlapped (f2=87.23, f1=4.2) before and after sterilization. Size Exclusion Chromatography (SEC) revealed no significant changes in the polymer molecular weight. Additionally, a stability study of the sterilized formulation was carried out using microsphere storage conditions of 4 degrees C in a vacuum desiccator for 1 year. The results obtained after storing the sterilized microspheres show no significant alterations in the ibuprofen release rate (f2 = 85.06, f1 = 4.32) or in the molecular weight of the PLGA (12957 Da). The employment of low molecular weight PLGA polymers resulted as advantageous, due to the practical absence of degradation after gamma irradiation (25 kGy) exposure at low temperature. PMID:15762322

Fernández-Carballido, A; Herrero-Vanrell, R; Molina-Martínez, I T; Pastoriza, P

2004-09-01

306

Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents  

PubMed Central

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting ?2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs. A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans. The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy. Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients.

2010-01-01

307

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

308

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

309

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

PubMed

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

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

2012-12-20

310

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

311

Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination.  

PubMed

DNA vaccines or proteins are capable of inducing specific immunity; however, the translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein we demonstrate a composite microsphere formulation, composed of mesoporous silica spheres (MPS) and poly(D,L-lactide-co-glycolide) (PLGA), enables the controlled delivery of a prime-boost vaccine via the encapsulation of plasmid DNA (pDNA) and protein in different compartments. Method with modified dual-concentric-feeding needles attached to a 40 kHz ultrasonic atomizer was studied. These needles focus the flow of two different solutions, which passed through the ultrasonic atomizer. The process synthesis parameters, which are important to the scale-up of composite microspheres, were also studied. These parameters include polymer concentration, feed flowrate, and volumetric ratio of polymer and pDNA-PEI/MPS-BSA. This fabrication technique produced composite microspheres with mean D[4,3] ranging from 6 to 34 microm, depending upon the microsphere preparation. The resultant physical morphology of composite microspheres was largely influenced by the volumetric ratio of pDNA-PEI/MPS-BSA to polymer, and this was due to the precipitation of MPS at the surface of the microspheres. The encapsulation efficiencies were predominantly in the range of 93-98% for pDNA and 46-68% for MPS. In the in vitro studies, the pDNA and protein showed different release kinetics in a 40 day time frame. The dual-concentric-feeding in ultrasonic atomization was shown to have excellent reproducibility. It was concluded that this fabrication technique is an effective method to prepare formulations containing a heterologous prime-boost vaccine in a single delivery system. PMID:20117207

Ho, Jenny; Huang, Yi; Danquah, Michael K; Wang, Huanting; Forde, Gareth M

2010-02-01

312

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

PubMed

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

Wang, Yan; Burgess, Diane J

2013-06-27

313

Porous microsphere and its applications.  

PubMed

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

2013-03-15

314

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.

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

2013-01-01

315

Effects of surface modification of PLGA-PEG-PLGA nanoparticles on loperamide delivery efficiency across the blood-brain barrier.  

PubMed

In this study, we developed a nanoparticle system for drug delivery across the blood-brain barrier (BBB). The nanoparticle consisting of loperamide and poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer were prepared by the nanoprecipitation method; then the nanoparticles were coated with poloxamer 188 or polysorbate 80. The effects of poloxamer 188 or polysorbate 80 on the physicochemical and pharmaceutical properties of the coated nanoparticles were investigated. Loperamide, which does not cross the blood-brain barrier (BBB) but exerts antinociceptive effects after direct injection into the brain, was encapsulated by different polymeric materials and used as a model drug. The in vitro BBB penetration study shows that the surfactant-coated PLGA-PEG-PLGA nanoparticles could have penetration of 14.4-21.2%, which was better than the PLGA-PEG-PLGA nanoparticles (PEP) (8.2%) and the PLGA nanoparticles (PN) (4.3%). The biopsy studies also confirm that the PEP coated by surfactant could increase the penetration. The results of nanoparticles accumulation in brain tissue show that the PEP coated by surfactant had a much higher concentration than both the PEP and the PN. Moreover, the maximal possible antinociception effect (MPE) for the surfactant-coated PEP was 21-35% at 150?min after administering the drug intravenously, which was significantly better than just the PEP (MPE: 11.6%). The results of the formalin test show that the surfactant-coated PEP administered intravenously 150?min prior to the formalin injection could greatly reduce the pain response in the first phase. The results demonstrate that the surfactant-coated PEP could help to deliver loperamide across the BBB. PMID:22207601

Chen, Yung-Chu; Hsieh, Wen-Yuan; Lee, Wen-Fu; Zeng, Ding-Tai

2011-12-29

316

Persistent activity of moxidectin long-acting injectable formulations against natural and experimentally enhanced populations of lice infesting cattle.  

PubMed

A study was conducted under a common protocol in Wisconsin and Wyoming, USA, to evaluate therapeutic and persistent efficacy of two long-acting injectable formulations of moxidectin against lice populations infesting cattle. At each site, 30 beef calves were blocked into groups of three based on naturally acquired Linognathus vituli populations, then randomly assigned to treatments within blocks. Treatments, injected subcutaneously into the proximal third of the ear on Day 0, included saline, a long-acting oil-based formulation containing 10% moxidectin given at the rate of 1 mg moxidectin/kg body weight (M10/1.0), or a long-acting oil-based formulation containing 15% moxidectin given at the rate of 0.75 mg moxidectin/kg b.w. (M15/0.75). Species of sucking and chewing lice were quantified on nine predilection sites before treatment, then 28, 63, 98, 133 and 168 days after treatment. During intervals between lice counts after Day 28, study animals from the three treatment groups were commingled for 32 days with two lice-free sentinels plus four to six seeder calves with infestations of both sucking and chewing lice. Following each 32-day commingling interval, seeder and sentinel animals were removed, and principal animals were sorted into pens by treatment. Lice were quantified on sentinel animals on the day of removal, and lice were quantified on principal study animals 3 days after removal of sentinel and seeders. Moxidectin was generally not efficacious against Bovicola bovis in the injectable formulations tested, whereas Haematopinus eurysternus infestations were inadequate to judge product effectiveness. Based on geometric means, both M15/0.75 and M10/1.0 provided statistically significant therapeutic efficacy against existing infestations of L. vituli and Solenopotes capillatus (100% efficacy on Day 28), and provided persistent protection against reinfestation with L. vituli and S. capillatus (efficacy >97%) for at least 133 days following treatment. PMID:15041096

Cleale, R M; Lloyd, J E; Smith, L L; Grubbs, M A; Grubbs, S T; Kumar, R; Amodie, D M

2004-03-25

317

Antibacterial activity of clarithromycin loaded PLGA nanoparticles.  

PubMed

Novel drug delivery systems such as nanoparticles (NPs) have been proved to enhance the effectiveness of many drugs. Clarithromycin is a broad spectrum macrolide antibiotic, used in many infectious conditions like upper and lower respiratory tract infections, and skin and other soft tissue infections. This paper describes the preparation and enhanced in vitro antibacterial activities of clarithromycin loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles. A modified quasi-emulsion solvent diffusion (MQESD) method was used to prepare clarithromycin (CLR) NPs. The antibacterial activity of the NPs was evaluated using the agar well diffusion method against Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623), Salmonella typhi (PTCC 1609), Staphylococcus aureus (PTCC 1112) and Streptococcus pneumoniae (PTCC 1240). The inhibition zone diameters related to each nano formulation were compared with those for untreated CLR at the same concentrations. The results indicated that the mean inhibition zone diameters of NPs against all the bacteria tested were significantly higher than those of untreated CLR, particularly in the case of S. aureus. The increased potency of CLR NPs may be related to some physicochemical properties of NPs like modified surface characteristics, lower drug degradation, and increased drug adsorption and uptake. PMID:22393833

Valizadeh, H; Mohammadi, G; Ehyaei, R; Milani, M; Azhdarzadeh, M; Zakeri-Milani, P; Lotfipour, F

2012-01-01

318

Tetracycline-HCl-loaded poly(DL-lactide-co-glycolide) microspheres prepared by a spray drying technique: influence of gamma-irradiation on radical formation and polymer degradation.  

PubMed

Tetracycline-HCl (TCH)-loaded microspheres were prepared from poly(lactide-co-glycolide) (PLGA) by spray drying. The drug was incorporated in the polymer matrix either in solid state or as w/o emulsion. The spin probe 4-hydroxy-2,2,6, 6-tetramethyl-piperidine-1-oxyl (TEMPOL) and the spin trap tert-butyl-phenyl-nitrone (PBN) were co-encapsulated into the TCH-loaded and placebo particles. We investigated the effects of gamma-irradiation on the formation of free radicals in polymer and drug and the mechanism of chain scission after sterilization. Gamma-Irradiation was performed at 26.9 and 54.9 kGy using a 60Co source. The microspheres were characterized especially with respect to the formation of radicals and in vitro polymer degradation. Electron paramagnetic resonance (EPR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), high-performance liquid chromatography (HPLC), gas chromatography-mass spectroscopy (GC-MS), and scanning electron microscopy (SEM) were used for characterization of the microspheres. Using EPR spectroscopy, we successfully detected gamma-irradiation induced free radicals within the TCH-loaded microspheres, while unloaded PLGA did not contain radicals under the same conditions. The relatively low glass transition temperature of the poly(dl-lactide-co-glycolide) (37-39 degrees C) seems to favor subsequent reactions of free radicals due to the high mobility of the polymeric chains. Because of the high melting point of TCH (214 degrees C), the radicals can only be stabilized in drug loaded microspheres. In order to determine the mechanism of polymer degradation after exposure to gamma-rays, the spin trap PBN and the spin probe TEMPOL were encapsulated in the microspheres. gamma-Irradiation of microspheres containing PBN resulted in the formation of a lipophilic spin adduct, indicating that a polymeric radical was generated by random chain scission. Polymer degradation by an unzipping mechanism would have produced hydrophilic spin adducts of PBN and monomeric radicals of lactic or glycolic acid. These degradation products were not detected by EPR. This result is confirmed by the observation that possible diamagnetic reaction products of low molecular weight, consisting of TEMPOL and lactide or glycolide monomers, could not be detected by GC-MS. While an irradiation dose-dependent decrease in molecular weight of PLGA could be verified in agreement with the literature, TCH content of the microspheres was not affected by the exposure to gamma-rays. It can be concluded that EPR spectroscopy in combination with GPC, DSC, and HPLC allows a detailed characterization of the impact of gamma-sterilization on biodegradable parenteral drug delivery systems. PMID:10210719

Bittner, B; Mäder, K; Kroll, C; Borchert, H H; Kissel, T

1999-05-01

319

Anticancer efficacy of perillyl alcohol-bearing PLGA microparticles.  

PubMed

In the present study, a novel poly-lactic glycolic acid (PLGA)-based microparticle formulation of perillyl alcohol (POH) was prepared and characterized. Further, its efficacy was evaluated against di-methyl benzo anthracene-induced skin papilloma in Swiss albino mice. The characterization studies showed that POH-bearing PLGA microparticles were of the size 768 ± 215 nm with a ?-potential value of -7.56 ± 0.88 mV. The entrapment efficiency of the active drug in particles was 42.4% ± 3.5%. POH-bearing PLGA microparticles were stable and released entrapped drug gradually over an extended time period. The in vitro efficacy of POH-bearing PLGA microparticles was evaluated by examining their differential cytotoxicity and assessing their ability to inhibit epidermoid carcinoma cell line (A253). The POH-based microparticles when administered to tumor-bearing animals caused greater tumor regression and increased survival rate (?80%) as compared with the group receiving free form of POH (survival rate 40%). The superiority of POH-PLGA microparticles over free form of POH was further evident from their ability to modulate apoptosis-regulating factors. PMID:22275821

Farazuddin, Mohammad; Sharma, Bhawna; Khan, Aijaz Ahmed; Joshi, Beenu; Owais, Mohammad

2012-01-05

320

Improvement of drug elution in thin mineralized collagen coatings with PLGA-PEG-PLGA micelles.  

PubMed

A mineralized collagen (MC) coating on metallic implants has shown great potential as orthopedic material due to high biological responses. However, their drug delivery capacity remains unsatisfactory since a serious burst release may occur and long-term release is hard to be achieved. Aiming to improve the drug-eluting capability, we incorporated drug-loaded PLGA-PEG-PLGA (PPP) micelles into the thin coating. The in vitro release profiles showed that the burst release in the initial 8 h of the modified coating decreased from 81% to 58% compared to MC coating alone; meanwhile, the release duration was prolonged from 3 days to 1 week. Additionally, the release kinetics of vancomycin hydrochloride (VH, the model drug) could be adjusted by changing the size and concentration of PPP micelles. Interestingly, less initial release of VH caused by micelle immobilization did not affect the antibacterial activity in the early stage of implantation according to the antimicrobial test. The cytocompatibility assay demonstrated that the VH-loaded PPP micelles did not have negative effect on the bioactivity of coating which greatly enhanced cell activity compared to bare Ti substrates. Thus, the MC coatings with PPP micelles could be an effective implant route for bone repair. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3256-3265, 2013. PMID:23606374

Ling, Ting; Yu, Mengfei; Weng, Wenjian; Wang, Huiming; Cheng, Kui; Lin, Jun; Du, Piyi

2013-04-18

321

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

PubMed

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. PMID:23982346

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

2013-09-26

322

Dual agents loaded PLGA nanoparticles: Systematic study of particle size and drug entrapment efficiency  

Microsoft Academic Search

PLGA nanoparticles simultaneously loaded with vincristine sulfate (VCR) and quercetin (QC) were prepared via O\\/W emulsion solvent evaporation. Six independent processing parameters and PLGA characteristics were assessed systematically to enhance the incorporation of the dual agents with different properties (VCR and QC, hydrophilic and hydrophobic molecule, respectively) into PLGA nanoparticles and control particle size. Approaches investigated for the enhancement of

Xiangrong Song; Yu Zhao; Shixiang Hou; Fangyuan Xu; Rongli Zhao; Junyao He; Zheng Cai; Yuanbo Li; Qiuhong Chen

2008-01-01

323

Barium Vanadate Microspheres  

NASA Astrophysics Data System (ADS)

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

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

2009-11-01

324

NVA237, a long-acting muscarinic antagonist, as an emerging therapy for chronic obstructive pulmonary disease.  

PubMed

Bronchodilation with a long-acting muscarinic antagonist (LAMA) or long-acting ?(2)-agonist is central to the management of chronic obstructive pulmonary disease (COPD). Tiotropium, the first LAMA available for use in COPD, has been shown to be an effective bronchodilator and is generally safe and well tolerated. However, tiotropium has limitations that include a high incidence of dry mouth, slow onset of action and, in some studies, a part of the patient population did not achieve clinically significant bronchodilation. It also remains unclear whether tiotropium reduces progressive deterioration of lung function in patients with COPD. An ideal LAMA would provide clinically meaningful bronchodilation, deliver symptom relief, prevent disease progression, improve exercise tolerance and health status, prevent and treat complications and exacerbations and reduce mortality risk. A 24-h duration of action, rapid onset of action and a good safety and tolerability profile are also desirable. The once-daily LAMA, NVA237 (glycopyrronium bromide), may meet some of these characteristics. NVA237 has high selectivity for the muscarinic type-3 (M(3)) receptor which might potentially result in a higher therapeutic index than tiotropium, which is less selective for M(3). Phase II studies showed that NVA237 once daily provides clinically significant 24-h bronchodilation with a rapid onset of action and a favourable safety and tolerability profile. Phase III studies are ongoing that will assess the long-term safety and efficacy of NVA237. PMID:21511677

Vogelmeier, Claus; Banerji, Donald

2011-04-20

325

Dose determination of the persistent activity of moxidectin long-acting injectable formulations against various nematode species in cattle.  

PubMed

The effectiveness, safety and production-enhancing benefit (improved weight gains) of moxidectin long-acting injection given subcutaneously in the ear at the rates of 0.75, 1.0 and 1.5mg/kg bw were evaluated in three studies under common protocol. The only adverse reaction to treatment was a mild (<2 tablespoons in volume), and for the most part transient (<28 days for the treatment rate of 1.0mg/kg bw) injection site swelling as noted in a minority of the animals (12.2% of the animals treated at the rate of 1.0mg/kg bw). Regardless of study site, post-treatment interval or dose rate, average daily gains were improved over control cattle by approximately 33%. Reductions in strongyle EPG counts relative to controls were > or = 90% for all dose rates of moxidectin for a post-treatment period of 42 days (Wisconsin), 84 days (Arkansas) and 140 days (Louisiana). In Arkansas and Louisiana, the majority (>80%) of post-treatment strongyle eggs, as determined by coproculture, were Cooperia spp. As determined by sequential necropsies, periods of continuous, post-treatment protection (> or = 90% efficacy in at least two out of three studies) for moxidectin long-acting injection given at the rate of 1.0 mg/kg bw were 90 days (adult Haemonchus spp.), 120 days (Dictyocaulus viviparus and adult Ostertagia and Oesophagostomum) and 150 days (Ostertagia spp. EL4). PMID:16481112

Yazwinski, T A; Williams, J C; Smith, L L; Tucker, C; Loyacano, A F; Derosa, A; Peterson, P; Bruer, D J; Delay, R L

2006-02-14

326

Neuroprotection of nerve growth factor-loaded microspheres on the D2 dopaminergic receptor positive-striatal neurones in quinolinic acid-lesioned rats: a quantitative autoradiographic assessment with iodobenzamide  

Microsoft Academic Search

Huntington's disease (HD) results from the degeneration of striatal neurones, mainly ?-aminobutyric acid (GABA)ergic projection neurones and lately cholinergic interneurones. The use of trophic factors as agents able to prevent such neural degeneration is a promising strategy. The aim of this study was to validate nerve growth factor-loaded (NGF-loaded) poly-d,l-lactide-co-glycolide (PLGA) microspheres for treatment of HD in a rat model

Christelle Gouhier; Sylvie Chalon; Marie-Claire Venier-Julienne; Sylvie Bodard; Jean-Pierre Benoit; Jean-Claude Besnard; Denis Guilloteau

2000-01-01

327

The effects of long-acting ?2-agonists plus inhaled corticosteroids for early reversibility in patients with airway obstruction  

PubMed Central

Background Salbutamol, as a short-acting ?2-agonist, was popularly used in the past for detection of reversibility in patients with airway obstruction when it was the only drug available in the treatment of airway obstruction. Today, the combination of long-acting ?2-agonists (LABA) and inhaled glucocorticoids are the first choice of therapy, with or without the presence of reversibility, in patients with airway obstruction. We aimed to compare the efficacy of salbutamol and long acting ?2-agonists plus inhaled glucocorticoids for early reversibility test in patients with airway obstruction. Methods Symptomatic patients (cough, dyspnea, and/or wheezing) with airway obstruction according to pulmonary function testing (FEV1/FVC value less than 70% of expected) who had never used bronchodilators before or had not received short- or long-acting inhaled bronchodilator therapy within the most recent 12 hours were evaluated. Reversibility measurements were made by administering the combination of long-acting ?2-agonists (LABA) and inhaled glucocorticoids after 15 minutes. Results A total of 90 patients were evaluated. The mean age of patients was 57.3±17.7 (range, 8-88) years and the male-to-female ratio was 69/21. The baseline pulmonary function test results were mean FVC; 2,747±1,181 mL and 74.7%±21.4%, mean FEV1; 1,716±825 mL and 57.5%±19.0%, mean FEV1/FVC; 61.4%±7.4%. The bronchodilator drugs given before reversibility testing were as salmeterol/fluticasone (FTC/SAL), formoterol/budesonide (BUD/FOR), beclomethasone dipropionate/formoterol (BDP/FOR) and salbutamol (SLB) in 24, 22, 24 and 20 patients, respectively. The reversibility was positive in 33 (36.7%) patients. The absolute change and percentage of change in mean FEV1 were 206±252 mL, 13.2%±16.6% for FTC/SAL group, 273±201 mL, 14%±8% for BUD/FOR group, 240±151 mL, 18.7%±15.9% for BUD/FOR groupand 171±116 mL, 13.3%±11.8% for SLB group. There was no statistically significant for reversibilty results between LABAs/inhaledsteroids and SLB group. And the patients with positivere versibility test were significantly higher in both of BUD/FOR and BDP/FOR groups than SLB group. Conclusions We think that performance of an early reversibility test using the combination of a LABA and an inhaled corticosteroid for treatment would enhance both the education of the patient in using the device and the reliability of the drug. And, we suggest that: “you should make the reversibility test with Long-Acting ?2-Agonists plus Inhaled Corticosteroids which used in treatment of obstructive lung diseases”.

Dirican, Adem; Tuna, Tibel

2013-01-01

328

Interaction of PLGA and trimethyl chitosan modified PLGA nanoparticles with mixed anionic/zwitterionic phospholipid bilayers studied using molecular dynamics simulations  

NASA Astrophysics Data System (ADS)

Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer. Nanoparticles of PLGA are commonly used for drug delivery applications. The interaction of the nanoparticles with the cell membrane may influence the rate of their uptake by cells. Both PLGA and cell membranes are negatively charged, so adding positively charged polymers such as trimethyl chitosan (TMC) which adheres to the PLGA particles improves their cellular uptake. The interaction of 3 nm PLGA and TMC-modified-PLGA nanoparticles with lipid bilayers composed of mixtures of phosphatidylcholine and phosphatidylserine lipids was studied using molecular dynamics simulations. The free energy profiles as function of nanoparticles position along the normal direction to the bilayers were calculated, the distribution of phosphatidylserine lipids as a function of distance of the particle from the bilayer was calculated, and the time scale for particle motion in the directions parallel to the bilayer surface was estimated.

Novak, Brian; Astete, Carlos; Sabliov, Cristina; Moldovan, Dorel

2012-02-01

329

Silicon Microspheres for Terahertz Communication  

NASA Astrophysics Data System (ADS)

Silicon microspheres can be used for free space optical communication applications in the THz communication bands. The morphology dependent resonances of the microsphere have quality factors of 100000, which provide the narrow linewidths for high resolution filtering, Raman lasers, modulators, and CMOS compatible detectors.

Akatlar, Onur; Serpengüzel, Ali

2007-04-01

330

Risperidone long-acting injection in the treatment of schizophrenia spectrum illnesses: A retrospective chart review of 19 patients in the Vancouver Community Mental Health Organization (Vancouver, Canada)  

Microsoft Academic Search

Background: Schizophrenia is a chronic debilitating disease that affects ~110,000 Canadians (0.55% lifetime prevalence). Risperidone long-acting injection (RLAI) is the first injectable, long-acting, atypical antipsychotic drug marketed in Canada.Objective: The aim of this study was to assess the clinical effectiveness and hospitalization rates of patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder treated with RLAI in a community mental health

Soma Ganesan; Mario McKenna; Ric M. Procyshyn; Sheldon Zipursky

2007-01-01

331

Is Slow-Onset Long-Acting Monoamine Transport Blockade to Cocaine as Methadone is to Heroin? Implication for Anti-Addiction Medications  

Microsoft Academic Search

The success of methadone in treating opiate addiction has suggested that long-acting agonist therapies may be similarly useful for treating cocaine addiction. Here, we examined this hypothesis, using the slow-onset long-acting monoamine reuptake inhibitor 31,345, a trans-aminotetralin analog, in a variety of addiction-related animal models, and compared it with methadone's effects on heroin's actions in the same animal models. Systemic

Xiao-Qing Peng; Zheng-Xiong Xi; Xia Li; Krista Spiller; Jie Li; Lauren Chun; Kuo-Ming Wu; Mark Froimowitz; Eliot L Gardner

2010-01-01

332

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

Microsoft Academic Search

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

ND Grace; SO Knowles

2006-01-01

333

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

334

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

335

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

PubMed Central

Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable bioimaging features. We accomplished this through esterification reactions of PLGA to generate polymers modified with nanocrystals. The PLGA nanoparticles formed from modified PLGA polymers that were functionalized with either gold nanocrystals or quantum dots exhibited favorable features for computed tomography and optical imaging, respectively.

Mieszawska, Aneta J.; Gianella, Anita; Cormode, David P.; Zhao, Yiming; Meijerink, Andries; Langer, Robert; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.

2013-01-01

336

A facile synthesis of PLGA encapsulated cerium oxide nanoparticles: release kinetics and biological activity  

NASA Astrophysics Data System (ADS)

In the present article a facile synthesis of cerium oxide nanoparticles (CNPs) encapsulated in PLGA microparticles is reported. The release kinetics of the CNPs from the PLGA matrix was investigated under acidic, basic and near-neutral pH. A diffusion model was applied to determine the diffusivity of the CNPs from the PLGA matrix. The morphology of the degraded PLGA particles was characterized by high resolution SEM. Superoxide dismutase (SOD) mimetic activity was retained in released CNPs for a longer period of time (~90 days) under different pH. PLGA encapsulated CNP showed excellent biocompatibility. This study demonstrates a potential strategy to deliver CNPs using biodegradable PLGA that ensures a slow release of the CNPs over a long period of time. Thus, the synthesized PLGA encapsulated CNPs could find potential applications in tissue engineering like bone remodelling and regeneration, and protection from disorders caused by neurodegeneration.In the present article a facile synthesis of cerium oxide nanoparticles (CNPs) encapsulated in PLGA microparticles is reported. The release kinetics of the CNPs from the PLGA matrix was investigated under acidic, basic and near-neutral pH. A diffusion model was applied to determine the diffusivity of the CNPs from the PLGA matrix. The morphology of the degraded PLGA particles was characterized by high resolution SEM. Superoxide dismutase (SOD) mimetic activity was retained in released CNPs for a longer period of time (~90 days) under different pH. PLGA encapsulated CNP showed excellent biocompatibility. This study demonstrates a potential strategy to deliver CNPs using biodegradable PLGA that ensures a slow release of the CNPs over a long period of time. Thus, the synthesized PLGA encapsulated CNPs could find potential applications in tissue engineering like bone remodelling and regeneration, and protection from disorders caused by neurodegeneration. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr12131j

Singh, Virendra; Singh, Sanjay; Das, Soumen; Kumar, Amit; Self, William T.; Seal, Sudipta

2012-03-01

337

[Studies on the new long-acting anti-cancer preparation, 5-fluorouracil-polyglycolic acid composite].  

PubMed

Polymer polyglycolic acid is biocompatible in the body. A needle-shaped long-acting anti-cancer preparation (F-PGA needle) was prepared by compounding polyglycolic acid and the anti-cancer drug 5-Fluorouracil (5-FU). The release of 5-FU from the needle was maintained for about 10 days, and the needle disappeared after one year. A clinical study with the F-PGA needle was made on patients with terminal carcinomas. Shrinkage of tumors and tumor necrosis were observed in two patients with metastatic liver carcinomas. The F-PGA needle supplies high-dose 5-FU locally for a long time with fewer side effects by embedding it into the tumor tissue. Therefore the F-PGA needle can be said to be promising in the treatment of unresectable cancer as a topical application of chemotherapy. PMID:6089666

Hirano, M; Sakatoku, M; Yamashita, R; Iwa, T

1984-08-01

338

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

PubMed Central

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

Wallin, A; Melander, B; Rosenhall, L; Sandstrom, T; Wahlander, L

1990-01-01

339

Long-acting methylphenidate reduces collision rates of young adult drivers with attention-deficit/hyperactivity disorder.  

PubMed

This study investigated whether methylphenidate delivered through a long-acting transdermal system (MTS) would reduce collision rates of young adult drivers with attention-deficit/hyperactivity disorder (ADHD).Seventeen young adults completing the study (mean [SD] age, 20.82 [2.40] years; 14 men and 13 white) met the following inclusion criteria: ADHD diagnoses but not routinely taking ADHD medication, previously responsive to ADHD medication, active drivers with more than 1 collision or citation in the past 2 years, and no significant comorbidities. In this open-labeled, crossover design drivers were randomly assigned either to the no-medication condition for 3 months and then MTS for 3 months or to the reverse sequence. In-car video monitoring of routine driving occurred during these 6 months. At baseline and after each condition, participants completed the Conners Adult ADHD Rating Scale and the Cox Assessment of Risky Driving Scale, and their blood pressure, heart rate, and body weight were monitored.Compared with the no-medication condition, participants in the MTS condition self-reported fewer total ADHD (P < 0.04) and inattentive symptoms (P = 0.014) and a trend for risky driving behaviors (P = 0.059) and had fewer video-recorded collisions (P < 0.005) and other problematic driving events. There were no significant changes in blood pressure, heart rate, or body weight across conditions or any significant skin reactions to the MTS patch.This is the first study demonstrating that long-acting methylphenidate improves activities of daily living among young adults with ADHD. Specifically, methylphenidate improved safety in routine driving while reducing ADHD symptoms with minimal adverse effects. PMID:22367664

Cox, Daniel J; Davis, Margaret; Mikami, Amori Yee; Singh, Harsimran; Merkel, Richard L; Burket, Roger

2012-04-01

340

Adverse effects associated with second-generation antipsychotic long-acting injection treatment: a comprehensive systematic review.  

PubMed

As second-generation antipsychotic long-acting injections (SGA-LAIs) are rapidly replacing depot first-generation antipsychotics as first-line agents in treating schizophrenia spectrum disorders, a systematic assessment of their adverse effects is timely. English-language, peer-reviewed articles reporting original data on the safety and tolerability of SGA-LAIs were identified electronically by searching the MEDLINE, EMBASE, PsycINFO, and DARE databases and the Cochrane Library (January 2001-April 2013). In addition to second-generation (atypical) antipsychotics and long-acting injection (depot) antipsychotics, a separate search was performed for each available drug: aripiprazole LAI, olanzapine pamoate, paliperidone palmitate, and risperidone LAI. Articles were excluded if they were review articles, post hoc analyses, analyses of subsets of patients enrolled in previous trials, single case reports, case series studies, small naturalistic studies (involving less than 50 patients), studies providing no safety data, and studies lasting less than 8 weeks. Of 181 articles identified from the search, 140 were excluded; thus, 41 articles met the inclusion criteria. Predictably, the reviewed information revealed that SGA-LAIs have safety profiles consistent with their oral parent formulations. However, they seem to also show unforeseen and worrisome safety signals. Indeed, the routine use of olanzapine-LAI in clinical practice could be limited not only by the well-known risk of postinjection syndrome, whose clinical management remains a matter of concern, but also by the risk of worsening of psychosis. The reviewed information seems to suggest that worsening of psychotic symptoms and depression could also be associated with both risperidone-LAI and paliperidone palmitate. The leading cause of death among patients enrolled in risperidone-LAI studies was suicide. Given the exponential growth in the clinical use of SGA-LAIs, further studies must be urgently performed in order to confirm or exclude the potential safety signals associated with such drugs. PMID:23776129

Gentile, Salvatore

2013-06-17

341

Long-acting beta2-adrenergic formoterol and salmeterol induce the apoptosis of B-chronic lymphocytic leukaemia cells.  

PubMed

B-cell chronic lymphocytic leukaemia (B-CLL) is a neoplastic disorder characterized by defective apoptosis, cell accumulation in G0/G1, and high expression of BCL2 oncogene. Intracellular cyclic adenosine monophosphate (cAMP) accumulation increases the chemosensitivity of B-CLL cells in vitro and in vivo. In the present study, we investigated the effects of beta2-adrenergic compounds, well known cAMP-inducing drugs, on the in vitro survival of leukaemia cells. In contrast to the short-acting beta2-mimetic (beta2Mim) salbutamol, a consistent pro-apoptotic effect was observed with the long-acting beta2Mim salmeterol and formoterol. Normal B cells isolated from control donors were totally resistant to the above molecules. These compounds also increased chlorambucil- and fludarabine-induced death of B-CLL cells. Blockade of beta-adrenergic receptor signalling or cAMP did not alter B-CLL apoptosis with beta2 Mimagents. Leukaemia cell apoptosis by beta2Mim correlated with an increase in calcium influx, decreased bcl-2 protein and mRNA levels, increase in BAX gene expression and a marked rise in BCL2/BAX mRNA ratios. Interleukin-4, a cytokine that increases bcl-2 expression in B-CLL cells, rescued leukaemia cell from apoptosis with beta2Mim. These data show that long-acting beta2-adrenergic agents promote apoptotic leukaemia cell death through an adrenoreceptor- and cAMP-independent, Ca2+-dependent mechanism. PMID:14687023

Mamani-Matsuda, Maria; Moynet, Daniel; Molimard, Mathieu; Ferry-Dumazet, Hélène; Marit, Gérald; Reiffers, Josy; Mossalayi, M Djavad; Mossalayi, M Diavad

2004-01-01

342

Short- and long-term peripheral nerve regeneration using a poly-lactic-co-glycolic-acid scaffold containing nerve growth factor and glial cell line-derived neurotrophic factor releasing microspheres.  

PubMed

Addition of neural growth factors to bioengineered scaffolds may improve peripheral nerve regeneration. The aim of this study is to evaluate the short- and long term effect of microsphere delivered nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF) in the 10 mm rat sciatic nerve gap. Eighty-four rats were assigned to seven groups (n = 6) at two endpoints (6 and 16 weeks): saline, saline NGF, saline NGF-microspheres, saline GDNF, saline GDNF-microspheres, saline blank microspheres, and autologous nerve graft. Total fascicular area and total number of myelinated fibers at mid-tube increased in all conduit groups between 6 and 16 weeks. Autologous, saline NGF-microsphere and saline GDNF-microsphere groups reached maximal histomorphometric values by 6 weeks (p < 0.05). Compound muscle action potentials returned after 6 weeks for the autologous graft and continued to increase to a level of 3.6 ± 1.9 mV at endpoint. No significant differences were found between study groups as measured by ankle angle. These experiments show an initial beneficial effect of incorporation of NGF- or GDNF-microspheres in a PLGA 85/15 nerve conduit, since histomorphometric values reached their maximum by 6 weeks compared to control groups. These results do not yet extrapolate into improved electrophysiological or functional improvement. PMID:22615148

de Boer, Ralph; Borntraeger, Andreas; Knight, Andrew M; Hébert-Blouin, Marie-Noëlle; Spinner, Robert J; Malessy, Martijn J A; Yaszemski, Michael J; Windebank, Anthony J

2012-05-21

343

Convective microsphere monolayer deposition  

NASA Astrophysics Data System (ADS)

There is perhaps no simpler way of modifying surface chemistry and morphology than surface deposition of particles. Micron-sized microspheres were deposited into thin films via rapid convective deposition, similar to the `coffee ring effect' using a similar method to that studied by Prevo and Velev, Langmuir, 2003. By varying deposition rate and blade angle, the optimal operating ranges in which 2D close-packed arrays of microspheres existed were obtained. Self-assembly of colloidal particles through a balance of electrostatic and capillary forces during solvent evaporation was revealed. These interactions were explored through a model comparing the residence time of a particle in the thin film and the characteristic time of capillary-driven crystallization to describe the morphology and microstructure of deposited particles. Co-deposition of binary suspensions of micron and nanoscale particles was tailored to generate higher-quality surface coatings and a simple theory describes the immergence of instabilities that result in formation of stripes. Optical and biomedical applications that utilize the described nanoscale control over surface morphology will also be discussed.

Gilchrist, James

2011-03-01

344

Osteogenic Differentiation of Human Bone Marrow Stromal Cells in Hydroxyapatite-Loaded Microsphere-Based Scaffolds  

PubMed Central

Calcium-based minerals have consistently been shown to stimulate osteoblastic behavior in vitro and in vivo. Thus, use of such minerals in biomaterial applications has become an effective method to enhance bone tissue engineered constructs. In the present study, for the first time, human bone marrow stromal cells (hBMSC) were osteogenically differentiated on scaffolds consisting only of hydroxyapatite (HAp)-loaded poly(d,l-lactic acid-co-glycolic acid) (PLGA) microspheres of high monodispersity. Scaffold formulations included 0, 5, 10, and 20 wt% Hap, and the hBMSC were cultured for 6 weeks. Results demonstrated suppression of some osteogenic genes during differentiation in the HAp group, but higher end-point glycosaminoglycan and collagen content in 10% and 20% HAp samples, as evidenced by biochemical tests, histology, and immunohistochemistry. After 6 weeks of culture, constructs with 0% and 5% HAp had average compressive moduli of 0.7±0.2 and 1.5±0.9?kPa, respectively, whereas constructs with 10% and 20% HAp had higher average moduli of 17.6±4.6 and 18.9±8.1?kPa, respectively. The results of this study indicate that HAp inclusion in microsphere-based scaffolds could be implemented as a physical gradient in combination with bioactive signal gradients seen in previous iterations of these microsphere-based scaffolds to enhance osteoconduction and mechanical integrity of a healing site.

Dormer, Nathan H.; Qiu, Yue; Lydick, Anna M.; Allen, Nicholas D.; Mohan, Neethu; Berkland, Cory J.

2012-01-01

345

The bone formation in vitro and mandibular defect repair using PLGA porous scaffolds.  

PubMed

Highly porous scaffolds of poly(lactide-co-glycolide) (PLGA) were prepared by solution-casting/salt-leaching method. The in vitro degradation behavior of PLGA scaffold was investigated by measuring the change of normalized weight, water absorption, pH, and molecular weight during degradation period. Mesenchymal stem cells (MSCs) were seeded and cultured in three-dimensional PLGA scaffolds to fabricate in vitro tissue engineering bone, which was investigated by cell morphology, cell number and deposition of mineralized matrix. The proliferation of seeded MSCs and their differentiated function were demonstrated by experimental results. To compare the reconstructive functions of different groups, mandibular defect repair of rabbit was made with PLGA/MSCs tissue engineering bone, control PLGA scaffold, and blank group without scaffold. Histopathologic methods were used to estimate the reconstructive functions. The result suggests that it is feasible to regenerate bone tissue in vitro using PLGA foams with pore size ranging from 100-250 microm as scaffolding for the transplantation of MSCs, and the PLGA/MSCs tissue engineering bone can greatly promote cell growth and have better healing functions for mandibular defect repair. The defect can be completely recuperated after 3 months with PLGA/MSCs tissue engineering bone, and the contrastive experiments show that the defects could not be repaired with blank PLGA scaffold. PLGA/MSCs tissue engineering bone has great potential as appropriate replacement for successful repair of bone defect. PMID:16025492

Ren, Tianbin; Ren, Jie; Jia, Xiaozhen; Pan, Kefeng

2005-09-15

346

Microfluidic chip-based fabrication of PLGA microfiber scaffolds for tissue engineering.  

PubMed

In this paper, we have developed a method to produce poly(lactic- co-glycolic acid) (PLGA) microfibers within a microfluidic chip for the generation of 3D tissue engineering scaffolds. The synthesis of PLGA fibers was achieved by using a polydimethylsiloxane (PDMS)-based microfluidic spinning device in which linear streams of PLGA dissolved in dimethyl sulfoxide (DMSO) were precipitated in a glycerol-containing water solution. By changing the flow rate of PLGA solution from 1 to 50 microL/min with a sheath flow rate of 250 or 1000 microL/min, fibers were formed with diameters that ranged from 20 to 230 microm. The PLGA fibers were comprised of a dense outer surface and a highly porous interior. To evaluate the applicability of PLGA microfibers generated in this process as a cell culture scaffold, L929 fibroblasts were seeded on the PLGA fibers either as-fabricated or coated with fibronectin. L929 fibroblasts showed no significant difference in proliferation on both PLGA microfibers after 5 days of culture. As a test for application as nerve guide, neural progenitor cells were cultured and the neural axons elongated along the PLGA microfibers. Thus our experiments suggest that microfluidic chip-based PLGA microfiber fabrication may be useful for 3D cell culture tissue engineering applications. PMID:18512874

Hwang, Chang Mo; Khademhosseini, Ali; Park, Yongdoo; Sun, Kyung; Lee, Sang-Hoon

2008-05-30

347

Poly(ethylene glycol) as stabilizer and emulsifying agent: a novel stabilization approach preventing aggregation and inactivation of proteins upon encapsulation in bioerodible polyester microspheres.  

PubMed

Protein aggregation and inactivation are major problems associated with the encapsulation of pharmaceutical proteins in biodegradable microspheres. The objectives of this study were to identify the causes of aggregation and inactivation of two model enzymes upon solid-in-oil-in-water (s/o/w) encapsulation in poly(lactic-co-glycolic) acid (PLGA) microspheres in order to rationally develop approaches assuring their stability. S/o/w encapsulation of gamma-chymotrypsin in PLGA microspheres caused aggregation of ca. 30% and halved its specific activity. Co-lyophilization with poly(ethylene glycol) (PEG) substantially reduced the loss in enzyme activity but 8% of the protein still aggregated during encapsulation. Model studies performed under conditions relevant to the encapsulation procedure allowed pinpointing the cause of gamma-chymotrypsin instability, which was mainly the formation of the oil-in-water emulsion. To prevent aggregation in this encapsulation step, the most commonly used emulsifying agent polyvinyl alcohol (PVA) was replaced by PEG because it is known to reduce protein aggregation at interfaces. The use of PEG as the emulsifying agent in the aqueous and organic phase prevented gamma-chymotrypsin inactivation and aggregation during encapsulation. The stabilization approach also worked for the model protein horseradish peroxidase and thus is of a general nature. PMID:12586511

Castellanos, Ingrid J; Crespo, Rubén; Griebenow, Kai

2003-02-14

348

Biomimetic silica microspheres in biosensing.  

PubMed

Lipid vesicles spontaneously fuse and assemble into a lipid bilayer on planar or spherical silica surfaces and other substrates. The supported lipid bilayers (SLBs) maintain characteristics of biological membranes, and are thus considered to be biomembrane mimetic systems that are stable because of the underlying substrate. Examples of their shared characteristics with biomembranes include lateral fluidity, barrier formation to ions and molecules, and their ability to incorporate membrane proteins into them. Biomimetic silica microspheres consisting of SLBs on solid or porous silica microspheres have been utilized for different biosensing applications. The advantages of such biomimetic microspheres for biosensing include their increased surface area to volume ratio which improves the detection limits of analytes, and their amenability for miniaturization, multiplexing and high throughput screening. This review presents examples and formats of using such biomimetic solid or porous silica microspheres in biosensing. PMID:20336023

Chemburu, Sireesha; Fenton, Kyle; Lopez, Gabriel P; Zeineldin, Reema

2010-03-17

349

Monodisperse double-walled microspheres loaded with chitosan-p53 nanoparticles and doxorubicin for combined gene therapy and chemotherapy  

PubMed Central

We have designed and evaluated a dual anticancer delivery system to provide combined gene therapy and chemotherapy. Double-walled microspheres consisting of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(lactic acid) (PLA) shell were fabricated via the precision particle fabrication (PPF) technique. We make use of the advantages of double-walled microspheres to deliver chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53) and/or doxorubicin (Dox), loaded in the shell and core phases, respectively. Different molecular weights of PLA were used to form the shell layer for each formulation. The microspheres were monodisperse with a mean diameter of 65 to 75 ?m and uniform shell thickness of 8 to 17 ?m. Blank and Dox-loaded microspheres typically exhibited a smooth surface with relatively few small pores, while chi-microspheres containing p53 nanoparticles, with and without Dox, presented rough and porous surfaces. The encapsulation efficiency of Dox was significantly higher when it was encapsulated alone compared to co-encapsulation with chi-p53 nanoparticles. The encapsulation efficiency of chi-p53 nanoparticles, on the other hand, was not affected by the presence of Dox. As desired, chi-p53 nanoparticles were released first, followed by simultaneous release of chi-p53 nanoparticles and Dox at a near zero-order rate. Thus, we have demonstrated that the PPF method is capable of producing double-walled microspheres and encapsulating dual agents for combined modality treatment, such as gene therapy and chemotherapy.

Xu, Qingxing; Xia, Yujie; Wang, Chi-Hwa; Pack, Daniel W.

2012-01-01

350

Monodisperse double-walled microspheres loaded with chitosan-p53 nanoparticles and doxorubicin for combined gene therapy and chemotherapy.  

PubMed

We have designed and evaluated a dual anticancer delivery system to provide combined gene therapy and chemotherapy. Double-walled microspheres consisting of a poly(d,l-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(lactic acid) (PLA) shell were fabricated via the precision particle fabrication (PPF) technique. We make use of the advantages of double-walled microspheres to deliver chitosan-DNA nanoparticles containing the gene encoding the p53 tumor suppressor protein (chi-p53) and/or doxorubicin (Dox), loaded in the shell and core phases, respectively. Different molecular weights of PLA were used to form the shell layer for each formulation. The microspheres were monodisperse with a mean diameter of 65 to 75 ?m and uniform shell thickness of 8 to 17 ?m. Blank and Dox-loaded microspheres typically exhibited a smooth surface with relatively few small pores, while chi-microspheres containing p53 nanoparticles, with and without Dox, presented rough and porous surfaces. The encapsulation efficiency of Dox was significantly higher when it was encapsulated alone compared to co-encapsulation with chi-p53 nanoparticles. The encapsulation efficiency of chi-p53 nanoparticles, on the other hand, was not affected by the presence of Dox. As desired, chi-p53 nanoparticles were released first, followed by simultaneous release of chi-p53 nanoparticles and Dox at a near zero-order rate. Thus, we have demonstrated that the PPF method is capable of producing double-walled microspheres and encapsulating dual agents for combined modality treatment, such as gene therapy and chemotherapy. PMID:22981564

Xu, Qingxing; Xia, Yujie; Wang, Chi-Hwa; Pack, Daniel W

2012-09-07

351

Comparison of resource use by COPD patients on inhaled therapies with long-acting bronchodilators: a database study  

PubMed Central

Background The purpose of this analysis was to compare health care costs and utilization among COPD patients who had long-acting beta-2 agonist (LABA) OR long-acting muscarinic antagonist (LAMA); LABA AND LAMA; or LABA, LAMA, AND inhaled corticosteroid (ICS) prescription claims. Methods This was a 12 month pre-post, retrospective analysis using COPD patients in a national administrative insurance database. Propensity score and exact matching were used to match patients 1:1:1 between the LABA or LAMA (formoterol, salmeterol, or tiotropium), LABA and LAMA (tiotropium/formoterol or tiotropium/salmeterol), and LABA, LAMA and ICS (bronchodilators plus steroid) groups. Post-period comparisons were evaluated with analysis of covariance. Costs were evaluated from a commercial payer perspective. Results A total of 523 patients were matched using 29 pre-period variables (e.g., demographics, medication exposure). Post-match assessments indicated balance among the cohorts. COPD-related costs differed among groups (LABA or LAMA $2,051 SE = 91; LABA and LAMA $2,823 SE = 62; LABA, LAMA and ICS $3,546 SE = 89; all p < .0001) with the differences driven by study medication costs. However, non-study COPD medication costs were higher for the LABA or LAMA therapy group ($911 SE = 91) compared to the LABA and LAMA therapy group ($668 SE = 58; p = 0.0238) and non-study respiratory medications were approximately $100 greater for the LABA or LAMA therapy group relative to both LABA and LAMA (p = .0018) and LABA, LAMA, and ICS (p = .0071) therapy groups. While there was no observed difference in outpatient costs, there was a slightly higher number of outpatient visits per patient in the LABA and LAMA (25.5 SE = 0.9, p = 0.0070) relative to the LABA or LAMA therapy group (22.3 SE = 0.8) and higher utilization (89.7% of patients) with COPD visits in the LABA and LAMA therapy group relative to both the LABA or LAMA (73.8%; p < .0001) and LABA, LAMA and ICS therapy groups (85.3; p = 0.0305). Conclusions Significant cost differences driven mainly by pharmaceuticals were observed among LABA or LAMA, LABA and LAMA and LABA, LAMA and ICS therapies. A COPD-related cost offset was observed from single bronchodilator to two bronchodilators. Addition of an ICS with two bronchodilators resulted in higher treatment costs without reduction in other COPD-related costs compared with two bronchodilators.

2011-01-01

352

The fabrication of nano-hydroxyapatite on PLGA and PLGA/collagen nanofibrous composite scaffolds and their effects in osteoblastic behavior for bone tissue engineering.  

PubMed

Bone is a nanocomposite consisting of two main components, nano-hydroxyapatite (n-HA) and Type I collagen (Col). The aim is to exploit the nano-scale functional and material characteristics of natural bone in order to modulate cellular functions for optimal bone repair in bone graft systems. Here, we present an effective and novel technique in obtaining n-HA in cognate with native apatite on electrospun nanofibers within minutes without any pre-treatment. Using an alternate calcium and phosphate (Ca-P) solution dipping method, n-HA was formed on poly(lactide-co-glycolide) acid (PLGA) and blended PLGA/Col nanofibers. The presence of the functional groups of collagen significantly hastened n-HA deposition closed to nine-fold. The quantity of n-HA impinged upon the specific surface area, whereby mineralized PLGA/Col had a greater surface area than non-mineralized PLGA/Col, whereas n-HA did not significantly improve the specific surface area of mineralized PLGA compared to pure PLGA. The novelty of the process was that n-HA on PLGA had a positive modulation on early osteoblast capture (within minutes) compared to pure PLGA. Contrary, cell capture on mineralized PLGA/Col was comparable to pure PLGA/Col. Interestingly, although n-HA impeded proliferation during the culture period (days 1, 4 and 7), the cell functionality such as alkaline phosphatase (ALP) and protein expressions were ameliorated on mineralized nanofibers. The amount of n-HA appeared to have a greater effect on the early stages of osteoblast behavior (cell attachment and proliferation) rather than the immediate/late stages (proliferation and differentiation). PMID:19358900

Ngiam, Michelle; Liao, Susan; Patil, Avinash J; Cheng, Ziyuan; Chan, Casey K; Ramakrishna, S

2009-04-07

353

In vivo conjunctival reconstruction using modified PLGA grafts for decreased scar formation and contraction.  

PubMed

The in vivo reconstruction of conjunctiva was investigated by using modified poly(lactide-co-glycolide) (PLGA) 50/50 scaffolds. The porous PLGA matrices were prepared by a solvent-casting particulate-leaching method with NaCl, then modified with collagen, hyaluronic acid (HA) or/and human amniotic membrane (AM) component. The growth of corneal epithelial cells and human stromal fibroblasts on the scaffolds was investigated in vitro. All the modified PLGA scaffolds demonstrated enhanced cell adhesion and proliferation as compared to PLGA untreated, and the number of cells proliferated after 1 week was increased in the order of PLGA<PLGA/collagen=PLGA/collagen/AM/collagen/AM/HA, which was the same order as the adhesion of the cells onto the surfaces. Conjunctival wounds were created on the eyes of white rabbits bilaterally and PLGA/collagen/HA scaffolds were grafted for 4 weeks to evaluate the regeneration of ocular surface tissue at the wounds. At postoperative 4 weeks, all the wounds were completely covered with epithelial membranes. However, the contraction was minimal (6%) in the wound grafted with the modified PLGA, while that of the ungrafted wound was substantially large (25%). In addition, the collagen fibers regenerated within the scaffolds were characterized by a random array of a loose network that resembled natural conjunctiva. On the contrary, an aligned array of dense collagen fibers formed in the ungrafted wounds. Our results indicated that the modified PLGA graft as an acellular bed might allow the reconstruction of the damaged conjunctival tissue with less scar formation and contraction. PMID:14559019

Lee, Sang Young; Oh, Jung Hwan; Kim, Jae Chan; Kim, Young Ha; Kim, Soo Hyun; Choi, Jung Woo

2003-12-01

354

PLGA Micro and Nanoparticles Loaded Into Gelatin Scaffold for Controlled Drug Release  

Microsoft Academic Search

Curcumin and bovine serum albumin (BSA) were used as model drugs and loaded into micro- and nanoparticles of biodegradable poly(lactic-co-glycolic acid) (PLGA). The PLGA was incorporated into hydrophilic and biocompatible gelatin scaffolds to design a controlled drug release system. The gelatin scaffolds were cross-linked using glutaraldehyde. The controlled delivery of drugs from biologically active PLGA micro- and nanoparticles was measured

Waseem Asghar; Muhymin Islam; Aniket S. Wadajkar; Yuan Wan; Azhar Ilyas; Kytai T. Nguyen; Samir M. Iqbal

2012-01-01

355

Changes in use of long-acting contraceptive methods in the U.S., 2007-2009  

PubMed Central

Objectives To examine trends in use of long-acting reversible contraceptive (LARC) methods — the IUD and implant — and the extent to which these methods have replaced permanent sterilization and less-effective short-acting methods. Design We tabulated data from female survey respondents overall and by demographic subgroups. We performed t-tests of the differences in the proportions of female contraceptors using LARC in 2007 and 2009. We also looked at use of LARC, sterilization, other methods and no method among women at risk of unintended pregnancy. Setting Secondary analysis of the 2002 and 2006–2010 National Survey of Family Growth, an in-home, nationally representative survey of women 15–44. Patients All female respondents to the surveys. Interventions None. Main outcome measures Current use of LARC methods in 2009, and change in use from 2007. Results The proportion of contraceptors using LARC increased significantly from 2.4% in 2002 to 3.7% in 2007 and 8.5% in 2009. The increase occurred among women in almost every age, race, education and income group. Among women at risk of unintended pregnancy, increases in LARC use more than offset decreases in sterilization. Conclusions LARC methods (primarily IUDs) are contributing to an increase in contraceptive effectiveness in the United States.

Finer, Lawrence B.; Jerman, Jenna; Kavanaugh, Megan L.

2012-01-01

356

Chemoimmunoprophylaxis against bovine tropical theileriosis in young calves: a comparison between buparvaquone and long-acting oxytetracycline.  

PubMed

Eighteen seven to 21-day-old crossbred (Bos taurus cross Bos indicus) calves were allocated to four groups (A to D). Groups A and B each consisted of six calves and groups C and D three calves each. Each calf in groups A, B and C was inoculated with ground-up tick supernate (GUTS) equivalent to two infected acini prepared from Theileria annulata-infected Hyalomma anatolicum anatolicum. Each calf in group A was also given a single intramuscular injection of buparvaquone, 2.5 mg kg-1 bodyweight simultaneously with GUTS, whereas each calf in group B was given a single intramuscular injection of long-acting oxytetracycline, 20 mg kg-1 bodyweight following inoculation of GUTS. In calves of group A clinicopathological reactions were negligible, whereas in calves of group B mild to severe reactions were observed resulting in the death of three of the six calves. All the calves of group C (infected, untreated controls) died of acute theileriosis. All the surviving calves of groups A and B withstood a lethal homologous challenge given on day 30 after immunisation, indicating no difference in the immune status of the surviving calves of the two groups. Group D, challenge control, all calves died of theileriosis within 18 days of challenge. PMID:2382047

Dhar, S; Malhotra, D V; Bhushan, C; Gautam, O P

1990-07-01

357

Effects of long-acting somatostatin analogues on adrenal growth and phosphoribosyl pyrophosphate formation in experimental diabetes.  

PubMed

Adrenal growth and increased adrenal function occur in experimental diabetes. Previously, we have shown that phosphoribosyl pyrophosphate (PRPP) and PRPP synthetase increased rapidly between 3 and 7 days after induction of diabetes with streptozotocin (STZ), with less marked changes in enzymes of the pentose phosphate pathway. The present study examines the earlier phase of 1-3 days following induction of diabetes, seeking to elucidate whether control of PRPP production is a result of diabetic hyperglycaemia, or to a more general re-ordering of hormonal factors. To investigate this question, the role of insulin and two different long-acting somatostatin analogues, Angiopeptin and Sandostatin, were used in a well-established animal model. PRPP was chosen specifically as a target for these studies in view of its central role in nucleotide formation and nicotinamide mononucleotide synthesis via Nampt which is the rate-limiting step in the synthesis of NAD and which has been shown to have multiple roles in cell signalling in addition to its known function in glycolysis and energy production. Treatment with the somatostatin analogues ab initio effectively abolished the adrenal growth, the increase in PRPP formation and the rise of PRPP synthetase activity in the first 7 days of diabetes, without having any significant effect on blood glucose values. This suggests that elevated glucose per se is not responsible for the diabetic adrenal hypertrophy and implies that growth factors/hormones, regulated by somatostatin analogues, play a significant role in adrenal growth processes. PMID:22264286

Kunjara, Sirilaksana; Greenbaum, A Leslie; Sochor, Milena; Ali, Murad; Flyvbjerg, Allan; Grønbaek, Henning; McLean, Patricia

2012-02-01

358

Effects of long-acting somatostatin analogues on adrenal growth and phosphoribosyl pyrophosphate formation in experimental diabetes  

PubMed Central

Adrenal growth and increased adrenal function occur in experimental diabetes. Previously, we have shown that phosphoribosyl pyrophosphate (PRPP) and PRPP synthetase increased rapidly between 3 and 7 days after induction of diabetes with streptozotocin (STZ), with less marked changes in enzymes of the pentose phosphate pathway. The present study examines the earlier phase of 1–3 days following induction of diabetes, seeking to elucidate whether control of PRPP production is a result of diabetic hyperglycaemia, or to a more general re-ordering of hormonal factors. To investigate this question, the role of insulin and two different long-acting somatostatin analogues, Angiopeptin and Sandostatin, were used in a well-established animal model. PRPP was chosen specifically as a target for these studies in view of its central role in nucleotide formation and nicotinamide mononucleotide synthesis via Nampt which is the rate-limiting step in the synthesis of NAD and which has been shown to have multiple roles in cell signalling in addition to its known function in glycolysis and energy production. Treatment with the somatostatin analogues ab initio effectively abolished the adrenal growth, the increase in PRPP formation and the rise of PRPP synthetase activity in the first 7 days of diabetes, without having any significant effect on blood glucose values. This suggests that elevated glucose per se is not responsible for the diabetic adrenal hypertrophy and implies that growth factors/hormones, regulated by somatostatin analogues, play a significant role in adrenal growth processes.

Kunjara, Sirilaksana; Greenbaum, A Leslie; Sochor, Milena; Ali, Murad; Flyvbjerg, Allan; Gr?nbaek, Henning; McLean, Patricia

2012-01-01

359

Development of a novel long-acting antidiabetic FGF21 mimetic by targeted conjugation to a scaffold antibody.  

PubMed

Fibroblast growth factor (FGF)21 improves insulin sensitivity, reduces body weight, and reverses hepatic steatosis in preclinical species. We generated long-acting FGF21 mimetics by site-specific conjugation of the protein to a scaffold antibody. Linking FGF21 through the C terminus decreased bioactivity, whereas bioactivity was maintained by linkage to selected internal positions. In mice, these CovX-Bodies retain efficacy while increasing half-life up to 70-fold compared with wild-type FGF21. A preferred midlinked CovX-Body, CVX-343, demonstrated enhanced in vivo stability in preclinical species, and a single injection improved glucose tolerance for 6 days in ob/ob mice. In diet-induced obese mice, weekly doses of CVX-343 reduced body weight, blood glucose, and lipids levels. In db/db mice, CVX-343 increased glucose tolerance, pancreatic ?-cell mass, and proliferation. CVX-343, created by linkage of the CovX scaffold antibody to the engineered residue A129C of FGF21 protein, demonstrated superior preclinical pharmacodynamics by extending serum half-life of FGF21 while preserving full therapeutic functionality. PMID:23720456

Huang, Jie; Ishino, Tetsuya; Chen, Gang; Rolzin, Paul; Osothprarop, Trina F; Retting, Kelsey; Li, Lingna; Jin, Ping; Matin, Marla J; Huyghe, Bernard; Talukdar, Saswata; Bradshaw, Curt W; Palanki, Moorthy; Violand, Bernard N; Woodnutt, Gary; Lappe, Rodney W; Ogilvie, Kathleen; Levin, Nancy

2013-05-29

360

Long-acting human serum albumin-thioredoxin fusion protein suppresses bleomycin-induced pulmonary fibrosis progression.  

PubMed

Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory cells and reactive oxygen species (ROS), such as superoxide anion radical (O2(·-)). There is currently no effective treatment of IPF. We previously developed a human serum albumin (HSA)-thioredoxin 1 (Trx) fusion protein (HSA-Trx) designed to overcome the unfavorable pharmacokinetic and short pharmacological properties of Trx, an antioxidative and anti-inflammatory protein. In this study, we examined the therapeutic effect of HSA-Trx on an IPF animal model of bleomycin (BLM)-induced pulmonary fibrosis. A pharmacokinetic study of HSA-Trx or Trx in BLM mice showed that the plasma retention and lung distribution of Trxc was markedly improved by fusion with HSA. A weekly intravenous administration of HSA-Trx, but not Trx, ameliorated BLM-induced fibrosis, as evidenced by a histopathological analysis and pulmonary hydroxyproline levels. HSA-Trx suppressed active-transforming growth factor (TGF)-? levels in the lung and inhibited the increase of inflammatory cells in bronchoalveolar lavage fluid, pulmonary inflammatory cytokines, and oxidative stress markers. An in vitro EPR experiment using phosphate-buffered saline-stimulated neutrophils confirmed the O2(·-) scavenging ability of HSA-Trx. Furthermore, post-treatment of HSA-Trx had a suppressive effect against BLM-induced fibrosis. These results suggest that HSA-Trx has potential as a novel therapeutic agent for IPF, because of its long-acting antioxidative and anti-inflammatory modulation effects. PMID:23442250

Tanaka, Ryota; Watanabe, Hiroshi; Kodama, Azusa; Chuang, Victor Tuan Giam; Ishima, Yu; Hamasaki, Keisuke; Tanaka, Ken-ichiro; Mizushima, Tohru; Otagiri, Masaki; Maruyama, Toru

2013-02-26

361

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

NASA Astrophysics Data System (ADS)

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

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

2011-12-01

362

Effect of the covalent modification with poly(ethylene glycol) on alpha-chymotrypsin stability upon encapsulation in poly(lactic-co-glycolic) microspheres.  

PubMed

The effectiveness of the covalent modification of alpha-chymotrypsin with methoxy poly(ethylene glycol) (PEG) to afford its stabilization during encapsulation in poly(lactic-co-glycolic) acid (PLGA) microspheres by a solid-in-oil-in-water method was investigated. alpha-Chymotrypsin was chemically modified with PEG (M(w) = 5000) using molar ratios of PEG-to-chymotrypsin ranging from 0.4 to 96. Various conjugates were obtained and the amount of PEG modification was determined by capillary electrophoresis. In this investigation, only those conjugates with PEG/chymotrypsin molar ratios between approximately 1 and 8 were considered because higher levels of modification caused protein instability even before encapsulation. The stability and functionality of the chymotrypsin formulations were investigated before encapsulation by measuring enzyme kinetics, thermal stability, and tertiary structure intactness, and after the initial lyophilization process by determining the secondary structure content. These stability parameters were related to select ones after encapsulation in PLGA microspheres (specifically, the amount of insoluble aggregates, residual enzyme activity, and magnitude of protein structural perturbations). The results show that the more stable the protein conformation before encapsulation was, the higher was the retention of the specific activity after encapsulation. In contrast, no relationship was found between the protein stability before encapsulation and the magnitude of encapsulation-induced protein aggregation. Even the lowest level of modification (PEG-to-chymotrypsin molar ratio of 0.7) drastically reduced the amount of insoluble aggregates from 18% for the nonmodified protein to 4%. The results demonstrate that PEG modification was able to largely prevent chymotrypsin aggregation and activity loss upon solid-in-oil-in-water encapsulation in PLGA microspheres. It is demonstrated that it is essential to optimize the degree of protein modification to ascertain protein stability upon encapsulation. PMID:15570602

Castellanos, Ingrid J; Al-Azzam, Wasfi; Griebenow, Kai

2005-02-01

363

Effect of salts on lysozyme stability at the water-oil interface and upon encapsulation in poly(lactic-co-glycolic) acid microspheres.  

PubMed

Encapsulation of proteins in poly(lactic-co-glycolic) acid (PLGA) microspheres by the water-in-oil-in-water (w/o/w) technique is very challenging because of the inherent physical instability of proteins. In particular, exposure of proteins to the first water-in-oil emulsion causes unwanted interface-induced protein inactivation and aggregation. We tested whether salts could afford stabilization of a model protein, hen egg-white lysozyme, against the detrimental events occurring at the w/o interface and subsequently upon w/o/w encapsulation. First, we investigated the effect of salts on the specific enzyme activity and generation of soluble precipitates and insoluble aggregates upon emulsification of an aqueous lysozyme solution with methylene chloride. It was found that lysozyme precipitation occurred upon emulsification. The amount of precipitate formed at salt concentrations between 10-100 mM was related to the position of the anion in the electroselectivity series (SO(4) (2-) > SCN(-) > Cl(-) > H(2)PO(4) (-)) while high salt concentrations (1M) led to > 80% of lysozyme precipitation regardless of the salt. The precipitates consisted of buffer-soluble protein precipitates and water-insoluble noncovalent aggregates. Lysozyme precipitation, aggregation, and inactivation upon emulsification were largely prevented in the presence of 50 mM KH(2)PO(4) while KSCN caused an increase in these detrimental events. Second, it was tested whether the improved structural integrity of lysozyme at the w/o interface would improve its stability upon w/o/w encapsulation in PLGA microspheres. Some conditions indeed led to improved stability, particularly codissolving lysozyme with 50 mM KH(2)PO(4) reduced loss in the specific activity and aggregation. In conclusion, the type and concentration of salts is a critical parameter when encapsulating protein in PLGA microspheres. PMID:12701149

Pérez, Caroline; Griebenow, Kai

2003-06-30

364

Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles.  

PubMed

We have previously demonstrated that the cellular association, cytotoxicity, and in vivo anti-tumor efficacy of paclitaxel are significantly greater when delivered in PLGA microparticles compared to nanoparticles. The purpose of this research is to test the hypothesis that mucoadhesive chitosan promotes adhesion of PLGA particles to mucus on the tumor epithelium, resulting in enhanced cellular association and cytotoxicity of paclitaxel. PLGA particles containing paclitaxel or Bodipy(®) were prepared and chitosan was either adsorbed or chemically conjugated to the particle surface. The cellular association and cytotoxicity of paclitaxel in 4T1 cells was determined. A 4-10 fold increase in cellular association of paclitaxel was observed when chitosan was adsorbed or conjugated to the PLGA particles. Chitosan-conjugated PLGA microparticles were most cytotoxic with an IC(50) value of 0.77 ?M. Confocal microscopy demonstrated that chitosan-PLGA microparticles adhered to the surface of 4T1 cells. Pretreatment of either 4T1 cells or chitosan-PLGA particles with mucin resulted in significant increase in cellular association of paclitaxel. A linear correlation was established between theoretical amount of chitosan used and experimentally determined amount of chitosan adsorbed or conjugated to PLGA nanoparticles. In conclusion, cellular association and cytotoxicity of paclitaxel was significantly enhanced when delivered in chitosan-PLGA particles. PMID:21356285

Chakravarthi, Sudhir S; Robinson, Dennis H

2011-02-26

365

Electrospun PLGA–silk fibroin–collagen nanofibrous scaffolds for nerve tissue engineering  

Microsoft Academic Search

Electrospun nanofibrous scaffolds varying different materials are fabricated for tissue engineering. PLGA, silk fibroin, and\\u000a collagen-derived scaffolds have been proved on good biocompatibility with neurons. However, no systematic studies have been\\u000a performed to examine the PLGA–silk fibroin–collagen (PLGA-SF-COL) biocomposite fiber matrices for nerve tissue engineering.\\u000a In this study, different weight ratio PLGA-SF-COL (50:25:25, 30:35:35) scaffolds were produced via electrospinning. The

Guanglin Wang; Xudong Hu; Wei Lin; Changchao Dong; Hui Wu

2011-01-01

366

Preparation, Characterization and Evaluation of Targeting Potential of Amphotericin B-Loaded Engineered PLGA Nanoparticles  

Microsoft Academic Search

Purpose  The objective of present work was to develop a mannose-anchored, engineered nanoparticulate system for efficient delivery\\u000a of amphotericin B to macrophages. Furthermore, the effect of spacer on macrophage targeting was also evaluated.\\u000a \\u000a \\u000a \\u000a Methods  PLGA was conjugated to mannose via direct coupling (M-PLGA) and via PEG spacer (M-PEG-PLGA), and engineered PLGA nanoparticles\\u000a (M-PNPs and M-PEG-PNPs) were prepared from respective conjugates. These prepared

Manoj Nahar; Narendra K. Jain

2009-01-01

367

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

368

Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis  

Microsoft Academic Search

The goal of this investigation is to develop poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of antibiotics such as nafcillin to osteoblasts. This is important in order to treat Staphylococcus aureus-mediated osteomyelitis. The latter is often chronic and highly resistant to antibiotics. Nafcillin (a penicillinase-resistant penicillin)-loaded nanoparticles were prepared by a single emulsion\\/solvent evaporation method. In vitro drug release studies were

Rajeev Raghavan Pillai; Shankari N Somayaji; Monica Rabinovich; Michael C Hudson; Kenneth E Gonsalves

2008-01-01

369

NanoCipro Encapsulation in Monodisperse Large Porous PLGA Microparticles  

PubMed Central

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

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

2007-01-01

370

Initial Development and Characterization of PLGA Nanospheres Containing Ropivacaine  

PubMed Central

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

Moraes, Carolina Morales; de Matos, Angelica Prado; de Lima, Renata; Rosa, Andre Henrique; de Paula, Eneida

2008-01-01

371

Preparation of biodegradable magnetic microspheres with poly(lactic acid)-coated magnetite  

NASA Astrophysics Data System (ADS)

Poly(lactic acid) (PLA)-coated magnetic nanoparticles were made using uncapped PLA with free carboxylate groups. The physical properties of these particles were compared to those of oleate-coated or oleate/sulphonate bilayer (W40) coated magnetic particles. Magnetic microspheres (MMS) with the matrix material poly(lactide-co-glycolide) (PLGA) or PLA were then formed by the emulsion solvent extraction method with encapsulation efficiencies of 40%, 83% and 96% for oleate, PLA and oleate/sulfonate-coated magnetic particles, respectively. MMS made from PLA-coated magnetite were hemocompatible and produced no hemolysis, whereas the other MMS were hemolytic above 0.3 mg/mL of blood.

Zhao, Hong; Saatchi, Katayoun; Häfeli, Urs O.

2009-05-01

372

Multi-arm histidine copolymer for controlled release of insulin from poly(lactide-co-glycolide) microsphere.  

PubMed

For long-term, sustained protein delivery, a new, star-shaped block copolymer composed of methoxy poly(ethylene glycol) (mPEG), branched oligoethylenimine (bOEI), and poly(l-histidine) (pHis) was synthesized via the multi-initiation and ring-opening polymerization (ROP) of His N-carboxy anhydride (NCA) on bOEI with a PEG conjugation. The resulting mPEG-bOEI-pHis (POH) had strong buffering capacity within the neutral-to-acidic pH range and was complexed with insulin (Ins) via an electrostatic attraction plus hydrophobic interactions, resulting in the formation of a dual-interaction complex (DIC, weight ratio 2) of approximately 30-60 nm in size. This DIC tolerated high salt concentrations without destabilization, supporting the existence of hydrophobic interactions, and protected Ins from the organic solvent/water interface. The DIC in poly(lactide-co-glycolide) microspheres (PLGA MS) as a long-term Ins delivery formulation was evenly distributed via a double-emulsion method. The DIC-loaded PLGA MS offered a higher Ins loading and a lower initial burst than Ins-loaded PLGA MS. This formulation possessed near zero-order release kinetics (for at least one month). In streptozotocin (STZ)-induced diabetic rats, a DIC-loaded PLGA MS formulation was able to maintain blood-glucose levels at 200-350 mg/dL for the first two weeks and even lower levels (100-200 mg/dL) for the next two weeks. Thus, a new POH polymer and its complex with a drug protein could have potential biological application as a long-term, sustained protein delivery system. PMID:22959184

Park, Wooram; Kim, Dongin; Kang, Han Chang; Bae, You Han; Na, Kun

2012-09-06

373

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

Microsoft Academic Search

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

John Imuetinyan-Jesu Azeke Jr.

2007-01-01

374

Tetracycline-HCl-loaded poly( dl-lactide-co-glycolide) microspheres prepared by a spray drying technique: influence of ?-irradiation on radical formation and polymer degradation  

Microsoft Academic Search

Tetracycline-HCl (TCH)-loaded microspheres were prepared from poly(lactide-co-glycolide) (PLGA) by spray drying. The drug was incorporated in the polymer matrix either in solid state or as w\\/o emulsion. The spin probe 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPOL) and the spin trap tert-butyl-phenyl-nitrone (PBN) were co-encapsulated into the TCH-loaded and placebo particles. We investigated the effects of ?-irradiation on the formation of free radicals in polymer

B Bittner; K Mäder; C Kroll; H.-H Borchert; T Kissel

1999-01-01

375

The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.  

PubMed

Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

1999-08-01

376

The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.  

PubMed Central

Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site.

Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

1999-01-01

377

Persistent efficacy and blood sera analysis of a long-acting (LA) formulation of moxidectin against Rhipicephalus (Boophilus) microplus on treated cattle  

Technology Transfer Automated Retrieval System (TEKTRAN)

The therapeutic and persistent efficacy of a single subcutaneous injection of a long-acting (LA) formulation of moxidectin at a concentration of 1 mg per kg of body weight were determined against Rhipicephalus (Boophilus) microplus (Canestrini), along with the concentration-time blood sera profile i...

378

Effects of long-acting melatonin implants on the reproductive performance of Corriedale, Borderdale, Romney, Coopworth, and Perendale ewes in New Zealand  

Microsoft Academic Search

Two experiments compared the effect of long-acting melatonin implants (Regulin®) on the reproductive performance of commercial sheep flocks joined in late spring or early summer. A third experiment used melatonin implants in an attempt to induce an early January mating in Romney ewes. In Experiment 1, Corriedale and Borderdale ewes in five flocks in the South Island had joining dates

T. W. Knight; P. D. Muir; J. F. Smith; G. H. Scales; T. C. Reid; S. R. McPhee; L. D. Staple

1992-01-01

379

Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome  

Microsoft Academic Search

Objective: Ghrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader-Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive

Kathleen De Waele; Stacey L Ishkanian; Roberto Bogarin; Charmaine A Miranda; Mohammad A Ghatei; Stephen R Bloom; Daniele Pacaud; Jean-Pierre Chanoine

2008-01-01

380

Different Brain Responses to Hypoglycemia Induced by Equipotent Doses of the Long-Acting Insulin Analog Detemir and Human Regular Insulin in Humans  

Microsoft Academic Search

OBJECTIVE—The acylated long-acting insulin analog detemir is more lipophilic than human insulin and likely crosses the blood-to-brain barrier more easily than does human insulin. The aim of these studies was to assess the brain\\/hypothalamus responses to euglycemia and hypoglycemia in humans during intravenous infusion of equipotent doses of detemir and human

Paolo Rossetti; Francesca Porcellati; Natalia Busciantella Ricci; Paola Candeloro; Patrizia Cioli; Geremia B. Bolli; Carmine G. Fanelli

2008-01-01

381

Efficacy and blood sera analysis of a long-acting formulation of moxidectin against Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)on treated cattle  

Technology Transfer Automated Retrieval System (TEKTRAN)

The therapeutic and persistent efficacy of a single subcutaneous injection of a long-acting (LA) formulation of moxidectin at a concentration of 1 mg per kg of body weight were determined against Rhipicephalus (Boophilus) microplus (Canestrini), along with the concentration-time blood sera profile i...

382

Advances in Microsphere Insulation Systems  

NASA Astrophysics Data System (ADS)

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

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

2004-06-01

383

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

PubMed

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 due to polymer bioerosion. The msp are fine microcapsules with polycores containing the peptide at a high concentration and are easily injectable through a conventional fine needle. Leuprorelin msp made with PLGA(75/25)-14,000 or PLA-15,000 released the drug in a zero-order fashion, maintained constant serum drug levels and attained persistent objective suppression of the pituitary-gonadal system ('chemical castration') over 1 or 3 months after i.m. or s.c. injection into animals. These results indicate that depot formulations may be potentially useful in the therapy of endocrine diseases in humans. In this paper, studies on the formulation, drug release and pharmacological effects in animals for these leuprorelin depot formulations are reviewed. PMID:10837564

Okada

1997-10-13

384

Development and Testing of Solid Dose Formulations Containing Polysialic Acid Insulin Conjugate: Next Generation of Long-Acting Insulin  

PubMed Central

Background The need for lifelong, daily insulin injections can have a dramatic effect on patient compliance, can be painful, and runs the risk of local infections. Furthermore, needle-stick injuries are common, and the issue of needle disposal is troublesome. Injecting a long-acting insulin analog with needle-free administration would be a significant improvement for diabetic subjects, but is not currently feasible. To achieve a constant, reliable delivery of a novel, long-acting insulin analog, Lipoxen's SuliXen® (polysialylated insulin) in a solid dosage form capable of being delivered without a needle has been developed. The aim of this study was to evaluate the feasibility of Lipoxen's SuliXen delivery with the Glide solid dose injector, Glide SDI®. Materials and Methods A formulation containing 14 kDa polysialic acid (PSA)-recombinant human insulin conjugate was manufactured at Lipoxen PLC and transferred to Glide Pharma. The PSA–insulin conjugate solution was incorporated into different excipients at Glide Pharma (excipients 1 and 2), and formulations were manufactured containing implants with doses of 0.3 and 1.0 IU of insulin, respectively. Two different polymeric excipients were investigated for their suitable release profiles. The physicomechanical properties of the formulations were characterized in terms of solid dosage form strength (via three-point bend and compression) and disintegration time at 37°C. A preclinical efficacy study was performed in a nondiabetic rat model (Sprague-Dawley). Results The study demonstrated successful incorporation of PSA–insulin conjugate into formulations compatible for use with the solid dose injector. Physicochemical characterization indicated that each formulation produced was physically robust. For excipient 1, the compressive stress and three-point-bend-test values recorded for the 0.3 IU formulation were 106.99 ± 14.3 MPa and 30.6 ± 1.4 N (force in newtons), respectively. Corresponding values for the 1.0 IU dose were 53.10 ± 10.2 MPa and 16.66 ± 1.0 N. For excipient 2, the compressive stress and three-point-bend-test values recorded for the 0.3 IU dose were 53.10 ± 10.2 MPa and 7.64 ± 0.9 N, respectively, whereas the corresponding values recorded for the 1.0 IU dose were 41.61 ± 7.4 MPa and 13.18 ± 1.3 N. Each formulation successfully penetrated a laboratory substrate, achieving 100% penetration in each case. In vivo analysis demonstrated that PSA–insulin conjugate shows prolongation of activity (at least two-fold more compared to insulin) for more than 5 hours in the rat model. Conclusion Even though additional work may be required, for example, to develop several fixed dose formulations, the preliminary results show that solid dosage forms incorporating PSA–insulin conjugate maintained the prolongation of PSA–insulin conjugate activity in the rat model. Convenient and easy to use, the solid dose injector will not only ensure diabetic patient compliance and trust but also provide cost-effective solutions for safe, reliable, and controlled needle-free injection of PSA–insulin conjugate.

Zhang, Rongsheng; Jain, Sanjay; Rowland, Martin; Hussain, Nasir; Agarwal, Mohak; Gregoriadis, Gregory

2010-01-01

385

Impact on Intracortical Myelination Trajectory of Long Acting Injection Versus Oral Risperidone in First-Episode Schizophrenia  

PubMed Central

Context Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. Objectives Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. Design Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and six months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. Main outcome measure ICM volume change scores adjusted for the change in the HCs. Results ICM volume increased significantly (p=.005) in the RLAI and non-significantly (p=.39) in the RisO groups compared to the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05). Conclusions The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.

Bartzokis, George; Lu, Po H.; Raven, Erika P.; Amar, Chetan P.; Detore, Nicole R.; Couvrette, Alexander J.; Mintz, Jim; Ventura, Joseph; Casaus, Laurie R.; Luo, John S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.

2013-01-01

386

Long Acting Injection Versus Oral Risperidone in First-Episode Schizophrenia: Differential Impact on White Matter Myelination Trajectory  

PubMed Central

Context Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. Objectives Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. Design Two groups of SZ subjects (RLAI, N=11; and RisO, N=13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. Main outcome measure WM volume change scores. Results WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. Conclusions The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions.

Bartzokis, George; Lu, Po H.; Amar, Chetan P.; Raven, Erika P.; Detore, Nicole R.; Altshuler, Lori L.; Mintz, Jim; Ventura, Joseph; Casaus, Laurie R.; Luo, John S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.

2011-01-01

387

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

PubMed

This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N=1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150 mg eq.), day 8 (100 mg eq.), and once-monthly flexible dosing as deltoid or gluteal injections on day 36 (50 mg eq. or 100 mg eq.) and day 64 (50 mg eq. or 100 mg eq. or 150 mg eq.) or b) RIS-LAI: gluteal injections days 8 and 22 (25mg), days 36, 50 (25 or 37.5mg) and days 64, 78 (25, 37.5 or 50mg). RIS-LAI-treated patients received oral supplementation with RIS 1-6 mg/day (days 1 to 28), and PP-treated patients received oral placebo. The safety analysis set (n=1214) included 58% men, 78% white, with mean (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28). Mean (SD) change from baseline to endpoint in PANSS total score decreased similarly in both groups; PP (-18.6 [15.45]) and RIS-LAI (-17.9 [14.24]). PP treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [-1.62;2.38], per-protocol analysis set [primary analysis]). The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings. PMID:21092748

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

2010-11-16

388

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

PubMed Central

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 (1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, (2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10?min after cocaine, and (3) assessing the immunological responses of monkeys to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the 2-h observation period following a dose of 3.2?mg/kg cocaine. Cocaine failed to produce reliable changes in electrocardiograph (ECG) parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5–10?min, and saline-like HR measures restored within 20–40?min of DM CocE administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans.

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

2011-01-01

389

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.

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

2012-01-01

390

Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection.  

PubMed

We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness. PMID:20368393

Sugaya, Norio; Ohashi, Yasuo

2010-04-05

391

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.

Koo, Otilia May Yue; Rubinstein, Israel

2013-01-01

392