These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Effect of antioxidants on the stability of ONO-1301, a novel long-acting prostacyclin agonist, loaded in PLGA microspheres.  

PubMed

The purpose of this study was to investigate the physicochemical stability of ONO-1301 in poly(lactide-co-glycolide) microspheres (PLGA MS) under storage for 28 days in the absence or presence of butylated hydroxytoluene (BHT) or ?-tocopherol as antioxidant. First, we observed the hydrolysed product: (i) in acidic solution and oxidized product and (ii) in PLGA MS under storage in HPLC study, each structure was determined by liquid chromatography-nuclear magnetic resonance/mass spectrometry. Second, ONO-1301-loaded PLGA MS containing 10% BHT was shown to be superior to ONO-1301-loaded PLGA MS without BHT, in the standpoint of the stability under storage or in vitro drug-release test, and AUC(0-28) following subcutaneous injection in rats. Finally, ONO-1301-loaded PLGA MS with 10% BHT were demonstrated to be significantly more effective than ONO-1301-loaded PLGA MS without BHT in a murine sponge model of angiogenesis. In conclusion, BHT is an effective antioxidant on the stability of ONO-1301 in PLGA MS under storage. PMID:23094609

Uchida, Takahiro; Hazekawa, Mai; Morisaki, Tomomi; Yoshida, Miyako; Sakai, Yoshiki

2013-01-01

2

IVIVC from Long Acting Olanzapine Microspheres  

PubMed Central

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

Faraj, Jabar A.; DeLuca, Patrick P.

2014-01-01

3

The angiogenic effect of ONO-1301, a novel long-acting prostacyclin agonist loaded in PLGA microspheres prepared using different molecular weights of PLGA, in a murine sponge model.  

PubMed

The purpose of this study was to evaluate the angiogenic effect of topical application of three types of ONO-1301-loaded poly (lactide-co-glycolide) microspheres (ONO-1301 PLGA MS). ONO-1301 PLGA MS were prepared with PLGA 5010, 5020 and 5050 (with molecular weights of 10?K, 20?K and 50?K, respectively), using the solvent evaporation method. The lactide:glycolide ratio was fixed at 50:50; only the molecular weight was varied. The microspheres had an average diameter of almost 25?µm, and a loading efficiency of at least 70%. The sustained-release effect and its dependence on the molecular weight of the polymer used was confirmed in an in vitro drug-release test and by measuring subcutaneous plasma levels after administration of the three types of ONO-1301 PLGA MS to rats for 28 days. In the murine sponge model, the three types of ONO-1301 PLGA MS were administered to mice in a subcutaneously placed sponge and hemoglobin and hepatocyte growth factor (HGF) levels in the sponge were measured at predefined intervals up to 28 days. The hemoglobin and HGF levels obtained were significantly higher than those obtained after daily administration of ONO-1301 powder. Additional in vivo fluorescence imaging showed that PLGA MS remained in the sponge for 28 days. In conclusion, the three types of ONO-1301 PLGA MS prepared with PLGA three different molecular weight suppress the burst release, stimulate angiogenesis on topical application in a murine sponge model. This formulation may therefore be capable of improving the clinical picture in some types of vascular disease. PMID:23937583

Hazekawa, Mai; Morihata, Kana; Yoshida, Miyako; Sakai, Yoshiki; Uchida, Takahiro

2014-11-01

4

Development of Risperidone PLGA Microspheres  

PubMed Central

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

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

2014-01-01

5

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

2011-07-01

6

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

E-print Network

Review Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres delivery PLGA Autocatalysis Bulk degradation Degradable polymer PLGA microspheres are widely studied in otherwise uniformly bulk-eroding polymer microspheres. The aim of this review is to highlight mechanistic

Braatz, Richard D.

7

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

PubMed

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

Yang, Yang; Gao, Yongliang; Mei, Xingguo

2013-01-01

8

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

9

Biodegradation and biocompatibility of PLA and PLGA microspheres  

Microsoft Academic Search

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

James M Anderson; Matthew S Shive

1997-01-01

10

PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy  

PubMed Central

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

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

2015-01-01

11

MBG/PLGA composite microspheres with prolonged drug release.  

PubMed

Mesoporous bioactive glass (MBG) and composite microspheres with MBG particles embedded in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) matrix have been prepared and used to load gentamicin (GS). The in vitro drug release experiments from both MBG and composite microspheres were conducted in distilled water and phosphate buffered saline (PBS) solution at 37 degrees C for more than 30 days. In both water and PBS, GS release from the MBG was very fast with about 60 wt % of the loaded drug released in the first 24 h, and more than 80 wt % released in two days. MBG/PLGA composite microspheres showed an initial release of about 33 wt % in the first day, and 48 wt % in 2 days, and a subsequent sustained release lasting for more than 4 weeks in PBS. MBG/PLGA composite microspheres may be used as an alternative drug release system, especially as a bone void filler for bone repair due to their combined advantages of sustained release of antibiotics and apatite-forming ability. PMID:18777577

Li, Xia; Wang, Xiupeng; Zhang, Lingxia; Chen, Hangrong; Shi, Jianlin

2009-04-01

12

Preparation and in vitro evaluation of etoposide-loaded PLGA microspheres for pulmonary drug delivery.  

PubMed

Pulmonary drug delivery has become a promising route in the treatment of lung diseases because of better local retention and lower systemic penetration. In this study, etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres were designed with potential pulmonary delivery properties. The microspheres were prepared via improved emulsion-solvent evaporation method. Physicochemical characteristics, micromeritics properties and in vitro drug release behavior of the microspheres were then evaluated. Results showed that etoposide-loaded PLGA microspheres were spherical in shape with smooth surface with size (11.8 ± 1.25) ?m. Particles remained stable without any changing in size and morphology after dried by the freeze-drying method. Etoposide was loaded into PLGA microspheres in an amorphous state with high drug loading ((7.7 ± 0.3)%) and encapsulation efficiency ((84.2 ± 2.9)%). Results of micromeritics properties also demonstrated that etoposide-loaded PLGA microspheres were very suitable for pulmonary delivery. In addition, in vitro drug release study indicated a sustained release profile fitted with the Ritger-Peppas equation for up to 20 days. In conclusion, the etoposide-loaded PLGA microspheres were promising for pulmonary delivery, and etoposide could be sustained released from the PLGA microspheres. PMID:24107001

Feng, Ruihua; Zhang, Zhiyue; Li, Zhongwen; Huang, Guihua

2014-05-01

13

Heuristic modeling of macromolecule release from PLGA microspheres.  

PubMed

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

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

2013-01-01

14

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

PubMed

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

Desai, Kashappa-Goud H; Schwendeman, Steven P

2013-01-10

15

Active self-healing encapsulation of vaccine antigens in PLGA microspheres  

PubMed Central

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

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

2013-01-01

16

Development of new reverse micellar microencapsulation technique to load water-soluble drug into PLGA microspheres.  

PubMed

The objective of this study was to develop a new reverse micelle-based microencapsulation technique to load tetracycline hydrochloride into PLGA microspheres. To do so, a reverse micellar system was formulated to dissolve tetracycline hydrochloride and water in ethyl formate with the aid of cetyltrimethylammonium bromide. The resultant micellar solution was used to dissolve 0.3 to 0.75 g of PLGA, and microspheres were prepared following a modified solvent quenching technique. As a control experiment, the drug was encapsulated into PLGA microspheres via a conventional methylene chloride-based emulsion procedure. The microspheres were then characterized with regard to drug loading efficiency, their size distribution and morphology. The reverse micellar procedure led to the formation of free-flowing, spherical microspheres with the size mode of 88 microm. When PLGA microspheres were prepared following the conventional methylene chloride-based procedure, most of tetracycline hydrochloride leached to the aqueous external phase: A maximal loading efficiency observed our experimental conditions was below 5%. Their surfaces had numerous pores, while their internal architecture was honey-combed. In sharp contrast, the new reverse micellar encapsulation technique permitted the attainment of a maximal loading efficiency of 63.19 +/- 0.64%. Also, the microspheres had smooth and pore-free surfaces, and hollow cavities were absent from their internal matrices. The results of this study demonstrated that PLGA microspheres could be successfully prepared following the new reverse micellar encapsulation technique. PMID:15832828

Kim, Hyunjoo; Cho, Mihyun; Sah, Hongkee

2005-03-01

17

Gamma Irradiation of Active Self-healing PLGA Microspheres for Efficient Aqueous Encapsulation of Vaccine Antigens  

PubMed Central

Purpose To investigate the effect of ?-irradiation of poly(lactic-co-glycolic acid) (PLGA)/Al(OH)3/0 or 5 wt% diethyl phthalate (DEP) microspheres for active self-healing encapsulation of vaccine antigens. Methods Microspheres were irradiated with 60Co at 2.5 and 1.8 MRad and 0.37 and 0.20 MRad/h. Encapsulation of tetanus toxoid (TT) was achieved by mixing Al(OH)3-PLGA microspheres with TT solution at 10-38°C. Electron paramagnetic resonance (EPR) spectroscopy was used to examine free radical formation. Glass transition temperature (Tg) and molecular weight of PLGA was measured by differential scanning calorimetry and gel permeation chromatography, respectively. Loading and release of TT were examined by modified Bradford, amino acid analysis, and ELISA assays. Results EPR spectroscopy results indicated absence of free radicals in PLGA microspheres after ?-irradiation. Antigen-sorbing capacity, encapsulation efficiency, and Tg of the polymer were also not adversely affected. When DEP-loaded microspheres were irradiated at 0.2 MRad/h, some PLGA pores healed during irradiation and PLGA healing during encapsulation was suppressed. The molecular weight of PLGA was slightly reduced when DEP-loaded microspheres were irradiated at the same dose rate. These trends were not observed at 0.37 MRad/h. Gamma irradiation slightly increased TT initial burst release. Apart from the slightly higher polymer molecular weight decline caused by higher irradiation dose in case of DEP-loaded microspheres, the small increase in total irradiation dose from 1.8 to 2.5 MRad had insignificant effect on the polymer and microspheres properties analyzed. Conclusion Gamma irradiation is a plausible approach to provide a terminally sterilized, self-healing encapsulation PLGA excipient for vaccine delivery. PMID:23515830

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

2013-01-01

18

Fabrication and characterization of porous poly(lactic- co -glycolic acid) (PLGA) microspheres for use as a drug delivery system  

Microsoft Academic Search

In this work, Simvastatin (SIM) loaded porous poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using the W\\/O\\/W1\\/W2 double emulsion and solvent evaporation method. The\\u000a optimal conditions for fabricating porous PLGA microspheres were determined to be 20% distilled water (v\\/v), 10% PLGA (m\\/v),\\u000a and a 4:1 ratio of internal polyvinyl alcohol (PVA) to dichloromethane (DCM). The pores size distribution of porous PLGA

Trinh-Quang Bao; Nguyen-Thi Hiep; Yang-Hee Kim; Hun-Mo Yang; Byong-Taek Lee

2011-01-01

19

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

Microsoft Academic Search

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

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

2007-01-01

20

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

Microsoft Academic Search

Hepatitis B vaccination typically requires a multi-dose administration protocol over a course of 3–6 months. Aiming at developing\\u000a a single-shot formulation for hepatitis B vaccine (hepatitis B surface antigen (HBsAg)), a novel vaccine delivery system,\\u000a 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\\u000a the conventional PLGA microspheres in aspects

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

2010-01-01

21

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

PubMed Central

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

Cross, Daisy P.

2014-01-01

22

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

23

Stability study of full-length antibody (anti-TNF alpha) loaded PLGA microspheres.  

PubMed

Antibodies (Abs) require the development of stable formulations and specific delivery strategies given their susceptibility to a variety of physical and chemical degradation pathways. In this study, the encapsulation of an antibody into polylactide-co-glycolide (PLGA) based microspheres was explored to obtain a controlled-release of the incorporated drug. In order to avoid stability issues, a solid-in-oil-in-water (s/o/w) method was preferred. The solid phase was made of anti-TNF alpha monoclonal antibody (MAb) spray-dried microparticles, and the PLGA microspheres were produced using two different polymers (i.e., Resomer(®) RG505 and Resomer(®) RG755S). The stability of the MAb incorporated into the microspheres was investigated under three conditions (5 ± 3°C, 25 ± 2°C/60% RH and 40 ± 2°C/75% RH) for 12 weeks. During this stability study, it was demonstrated that the MAb loaded PLGA microspheres were stable when stored at 5 ± 3°C and that the Resomer(®) RG755S, composed of 75%(w/w) lactic acid as PLGA, was preferred to preserve the stability of the system. Storage at temperatures higher than 5°C led to antibody stability issues such as aggregation, fragmentation and loss of activity. The release profiles were also altered. Physical ageing of the system associated with changes in the glass transition temperature and enthalpy of relaxation was noticed during the storage of the MAb loaded PLGA microspheres. PMID:24792974

Marquette, S; Peerboom, C; Yates, A; Denis, L; Langer, I; Amighi, K; Goole, J

2014-08-15

24

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

PubMed

Calcium phosphate (CaP) cements show an excellent biocompatibility and often have a high mechanical strength, but in general degrade relatively slow. To increase degradation rates, macropores can be introduced into the cement, e.g., by the inclusion of biodegradable microspheres into the cement. The aim of this research is to develop an injectable PLGA microsphere/CaP cement with sufficient setting/cohesive properties and good mechanical and physical properties. PLGA microspheres were prepared using a water-in-oil-in-water double-emulsion technique. The CaP-cement used was Calcibon, a commercially available hydroxyapatite-based cement. 10:90 and 20:80 dry wt% PLGA microsphere/CaP cylindrical scaffolds were prepared as well as microporous cement (reference material). Injectability, setting time, cohesive properties and porosity were determined. Also, a 12-week degradation study in PBS (37 degree C) was performed. Results showed that injectability decreased with an increase in PLGA microsphere content. Initial and final setting time of the PLGA/CaP samples was higher than the microporous sample. Porosity of the different formulations was 40.8% (microporous), 60.2% (10:90) and 69.3% (20:80). The degradation study showed distinct mass loss and a pH decrease of the surrounding medium starting from week 6 with the 10:90 and 20:80 formulations, indicating PLGA erosion. Compression strength of the PLGA microsphere/CaP samples decreased siginificantly in time, the microporous sample remained constant. After 12 weeks both PLGA/CaP samples showed a structure of spherical micropores and had a compressive strength of 12.2 MPa (10:90) and 4.3 MPa (20:80). Signs of cement degradation were also found with the 20:80 formulation. In conclusion, all physical parameters were well within workable ranges with both 10:90 and 20:80 PLGA microsphere/CaP cements. After 12 weeks the PLGA was totally degraded and a highly porous, but strong scaffold remained. PMID:17094642

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

2006-01-01

25

Synergistic co-delivery of doxorubicin and paclitaxel by porous PLGA microspheres for pulmonary inhalation treatment.  

PubMed

PLGA porous microspheres loaded with doxorubicin (DOX) and paclitaxel (PTX) were developed for in situ treatment of metastatic lung cancer. The synergistic effect of the combined drugs was investigated against B16F10 cells to obtain the optimal prescription for in vivo studies. The combination therapy showed great synergism when DOX was the majority in the combination therapy, while they showed moderate antagonism when PTX is in major. The combination of DOX and PTX at a molar ratio of 5/1 showed the best synergistic therapeutic effect in the free form. However, the drugs exhibited more synergism in the PLGA microspheres at a molar ratio of 2/1, due to the difference in drug release rate. The in vivo study verified the synergism of DOX and PTX at the optimal molar ratio. These results suggested that dual encapsulation of DOX and PTX in porous PLGA microspheres would be a promising technology for long effective lung cancer treatment. PMID:25305583

Feng, Tianshi; Tian, Huayu; Xu, Caina; Lin, Lin; Xie, Zhigang; Lam, Michael Hon-Wah; Liang, Haojun; Chen, Xuesi

2014-11-01

26

A long acting biodegradable controlled delivery of chitosan microspheres loaded with tetanus toxoide as model antigen.  

PubMed

The chitosan microspheres formulated by emulsion cross-linking method were found to be smooth and spherical without aggregation. The particle size range was between 1 and 90?m. The particle sizes were found to be influenced by the concentration of the chitosan gel. Tetanus toxoide (TT) vaccine was loaded by passive adsorption from an aqueous solution into the preformed chitosan microspheres cross-linked with glutaraldehyde. The loaded TT on to microspheres was estimated by ELISA method. The loading capacity was found to be 40% with microspheres prepared with 1% chitosan gel, 43% for 2% and 46% for the mixed batch of microspheres prepared from 1% and 2% chitosan gel. The loading efficiency was found to decrease with increase in the concentration of chitosan gel. The in vitro release of the antigenic TT into the phosphate buffer at 37°C from different batch of microspheres was studied and release had a remarkable dependence on the size of micropsheres. The percentage release of TT from chitosan microspheres prepared from 1% chitosan gel was 2.7% in 120days and that from 2% chitosan gel was only 2%. The mixed batch of microspheres could release 2.3% in 120days. The antigen integrity was investigated by SDS-PAGE with brilliant blue staining. The SDS-PAGE analysis confirmed that the antigen integrity was not affected by passive adsorption of protein antigen to preformed chitosan microspheres. The study revealed that the cross-linked chitosan microspheres would be an interesting system for long-term delivery of macromolecules drugs. PMID:24051124

Varma, Sujith; Sadasivan, C

2014-03-01

27

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

PubMed Central

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

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

2014-01-01

28

Enhancing Alendronate Release from a Novel PLGA\\/Hydroxyapatite Microspheric System for Bone Repairing Applications  

Microsoft Academic Search

Purpose  The goal of this study was to exploit the multifunction of PLGA based microsphere as efficient alendronate delivery and also\\u000a as potential injectable cell carrier for bone-repairing therapeutics.\\u000a \\u000a \\u000a \\u000a Materials and Methods  Novel poly (lactic-co-glycolic acid) (PLGA)-hybridizing -hydroxyapatite (HA) microspheres loaded with bisphosphonate-based\\u000a osteoporosis preventing drugs, alendronate (AL), are prepared with solid\\/oil\\/water (s\\/o\\/w) or water\\/oil\\/water (w\\/o\\/w) technique.\\u000a Macrophage resistance was evaluated by

Xuetao Shi; Yingjun Wang; Li Ren; Yihong Gong; Dong-An Wang

2009-01-01

29

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

NASA Astrophysics Data System (ADS)

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

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

2014-02-01

30

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

Microsoft Academic Search

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

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

2009-01-01

31

Formulation optimization of serratiopeptidase-loaded PLGA microspheres using selected variables.  

PubMed

Serratiopeptidase-loaded poly (D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared using the modified double emulsion method. The effect of polymer concentration and external aqueous phase volume on microsphere size and entrapment efficiency was studied by 3(2) full factorial experiments. The results of analysis of variance test for measured responses indicated the test's significance (P < 0.05). The contribution of PLGA concentration on microsphere size and percentage yield was found to be higher than that of external aqueous phase volume, which produced a significant effect on entrapment efficiency. Microspheres demonstrated spherical particles in the size range of 19.08-41.14 microm and entrapment efficiency between 15.37 and 79.86%. The formulation using a medium level of polymer and a low level of external aqueous phase (PLGA: 300 mg; EAP: 100 mL) showed maximum entrapment (75.86 +/- 2.31%). The in vitro release profile of all formulations demonstrated a similar sustained release showing an initial burst followed by diffusion. The bioactivity of the peptide remained intact after microencapsulation as assayed by in vitro proteolytic activity. Response surface graphs are presented to examine the effects of independent variables on the responses studied. In conclusion, controlled-release serratiopeptidase-loaded PLGA microspheres demonstrating maximum entrapment were successfully prepared by an experimental design methodology with a minimum number of runs, representing an economical approach. PMID:19634349

Singh, Deependra; Dixit, V K; Saraf, Swarnlata; Saraf, S

2009-01-01

32

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

33

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

PubMed Central

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

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

2013-01-01

34

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

Microsoft Academic Search

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

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

2000-01-01

35

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

Microsoft Academic Search

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

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

1997-01-01

36

Development of andrographolide loaded PLGA microspheres: optimization, characterization and in vitro-in vivo correlation.  

PubMed

The purpose of this study was to develop a sustained-release drug delivery system based on the injectable PLGA microspheres loaded with andrographolide. The andrographolide loaded PLGA microspheres were prepared by emulsion solvent evaporation method with optimization of formulation using response surface methodology (RSM). Physicochemical characterization, in vitro release behavior and in vivo pharmacokinetics of the optimized formulation were then evaluated. The percent absorbed in vivo was determined by deconvolution using the Loo-Riegelman method, and then the in vitro-in vivo correlation (IVIVC) was established. Results showed that the microspheres were spherical with a smooth surface. Average particle size, entrapment efficiency and drug loading were found to be 53.18±2.11 ?m, 75.79±3.02% and 47.06±2.18%, respectively. In vitro release study showed a low initial burst release followed by a prolonged release up to 9 days and the release kinetics followed the Korsmeyer-Peppas model. After a single intramuscular injection, the microspheres maintained relatively high plasma concentration of andrographolide over one week. A good linear relationship was observed between the in vitro and in vivo release behavior (R(2)=0.9951). These results suggest the PLGA microspheres could be developed as a potential delivery system for andrographolide with high drug loading capacity and sustained drug release. PMID:25219858

Jiang, Yunxia; Wang, Fang; Xu, Hui; Liu, Hui; Meng, Qingguo; Liu, Wanhui

2014-11-20

37

Effects of dexamethasone-loaded PLGA microspheres on human fetal osteoblasts.  

PubMed

Integration of a drug delivery function into implantable medical devices enables local release of specific bioactives to control cells-surface interactions. One alternative to achieve this biofunctionality for bone implants is to incorporate particulate drug delivery systems (DDSs) into the rough or porous implant surfaces. The scope of this study was to assess the effects of a model DDS consisting of poly(D,L-lactide-co-glycolide) (PLGA) microspheres loaded with an anti-inflammatory drug, dexamethasone (DXM), on the response of Simian Virus-immortalized Human Fetal Osteoblast (SV-HFO) cells. The microspheres were prepared by the oil-in-water emulsion/solvent evaporation method, whereas cells response was investigated by Alamar Blue test for viability, alkaline phosphatase (ALP) activity for differentiation, and Alizarin Red staining for matrix mineralization. Cell viability was not affected by the presence of increased concentrations of polymeric microspheres in the culture media. Furthermore, in the cultures with DXM-loaded microspheres, ALP activity was expressed at levels similar with those obtained under osteogenic conditions, indicating that DXM released from the microsphere-stimulated cell differentiation. Matrix mineralization occurred preferentially around the DXM-loaded microspheres confirming that the released DXM could act as osteogenic supplement for the cells. These in vitro findings suggest that a particulate PLGA-DXM DDS may actually provide dual, anti-inflammatory and osteogenic functions when incorporated on the surface of bone implants. PMID:21862514

Dawes, G J S; Fratila-Apachitei, L E; Necula, B S; Apachitei, I; van Leeuwen, J P T M; Duszczyk, J; Eijken, M

2012-11-01

38

Controlled-release injectable containing terbinafine/PLGA microspheres for onychomycosis treatment.  

PubMed

Controlled-release drug delivery systems based on biodegradable polymers have been extensively evaluated for use in localized drug delivery. In the present study, intralesionally injectable poly (lactide-co-glycolide) (PLGA) microspheres for controlled release of terbinafine hydrochloride (TH) was developed for treating fungal toe/finger nail infections. TH-PLGA microspheres were formulated using O/W emulsification and modified solvent extraction/evaporation technique. Microspheres were evaluated for particle size and size distribution, encapsulation efficiency, surface, and morphology. The in vitro drug release profile was studied in aqueous media as well as in 1% agar gel. Microspheres system was also evaluated in excised cadaver toe model, and extent of TH accumulation in nail bed, nail plate, and nail matrix was measured at different time points. Microspheres were found to provide consistent and sustained TH release. Intralesional administration of controlled-release microspheres can be a potential alternative mode of treating fungus-infected toe and/or finger nails. PMID:24497012

Angamuthu, Muralikrishnan; Nanjappa, Shivakumar H; Raman, Vijayasankar; Jo, Seongbong; Cegu, Phaniraj; Murthy, S Narasimha

2014-04-01

39

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

PubMed

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

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

2005-09-20

40

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. PMID:24143094

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

2013-01-01

41

Highly porous large poly(lactic-co-glycolic acid) microspheres adsorbed with palmityl-acylated exendin-4 as a long-acting inhalation system for treating diabetes  

Microsoft Academic Search

A porous large poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) adsorbed with palmityl-acylated exendin-4 (Ex4-C16) was devised as an inhalation delivery system. The porous MS was prepared by a single o\\/w emulsification\\/solvent evaporation method using extractable Pluronic F68\\/F127, and its fabrication and formulation conditions were carefully optimized. Results show that the prepared MS was in the appropriate size range for inhalation and

Hyunuk Kim; Juho Lee; Tae Hyung Kim; Eun Seong Lee; Kyung Taek Oh; Kang Choon Lee; Yu Seok Youn

2011-01-01

42

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

NASA Astrophysics Data System (ADS)

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

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

2014-08-01

43

Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature  

PubMed Central

Injectable scaffolds are of interest in the field of regenerative medicine because of their minimally invasive mode of delivery. For tissue repair applications, it is essential that such scaffolds have the mechanical properties, porosity and pore diameter to support the formation of new tissue. In the current study, porous poly(dl-lactic acid-co-glycolic acid) (PLGA) microspheres were fabricated with an average size of 84 ± 24 ?m for use as injectable cell carriers. Treatment with ethanolic sodium hydroxide for 2 min was observed to increase surface porosity without causing the microsphere structure to disintegrate. This surface treatment also enabled the microspheres to fuse together at 37 °C to form scaffold structures. The average compressive strength of the scaffolds after 24 h at 37 °C was 0.9 ± 0.1 MPa, and the average Young’s modulus was 9.4 ± 1.2 MPa. Scaffold porosity levels were 81.6% on average, with a mean pore diameter of 54 ± 38 ?m. This study demonstrates a method for fabricating porous PLGA microspheres that form solid porous scaffolds at body temperature, creating an injectable system capable of supporting NIH-3T3 cell attachment and proliferation in vitro. PMID:25152354

Qutachi, Omar; Vetsch, Jolanda R.; Gill, Daniel; Cox, Helen; Scurr, David J.; Hofmann, Sandra; Müller, Ralph; Quirk, Robin A.; Shakesheff, Kevin M.; Rahman, Cheryl V.

2014-01-01

44

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

PubMed Central

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

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

2015-01-01

45

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

PubMed Central

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.

2013-01-01

46

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. PMID:22312307

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

2012-01-01

47

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

48

Insulin loaded PLGA microspheres: effect of zinc salts on encapsulation, release, and stability.  

PubMed

The purpose of this study was to investigate the effect of three zinc salts (i.e., zinc oxide, zinc carbonate, and zinc acetate) on insulin encapsulation efficiency (EE), stability, and in vitro release kinetics from poly(lactic-co-glycolic acid) (PLGA) microspheres. Microspheres were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation technique and characterized. Integrity of the encapsulated insulin and stability of the released insulin was assessed using a wide range of comprehensive analytical techniques. The EE of the formulation prepared without the addition of a zinc salt was 69%, the secondary structure of the encapsulated insulin in this formulation was found to be altered. Further, desamido insulin and aggregates were observed during in vitro release. When insulin was encapsulated with a zinc salt, EE increased significantly, secondary structure was unaltered, and no degradation or aggregation products were found. Initial burst release and release kinetics were markedly changed with the addition of zinc salts. More than 87% of the encapsulated insulin was released over a 2-week period with the addition of a zinc salt. In conclusion, zinc salts can be useful to increase the EE and stability of insulin in PLGA microspheres prepared by w/o/w technique. PMID:18548615

Manoharan, Chandrasekar; Singh, Jagdish

2009-02-01

49

Highly porous large poly(lactic-co-glycolic acid) microspheres adsorbed with palmityl-acylated exendin-4 as a long-acting inhalation system for treating diabetes.  

PubMed

A porous large poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) adsorbed with palmityl-acylated exendin-4 (Ex4-C(16)) was devised as an inhalation delivery system. The porous MS was prepared by a single o/w emulsification/solvent evaporation method using extractable Pluronic F68/F127, and its fabrication and formulation conditions were carefully optimized. Results show that the prepared MS was in the appropriate size range for inhalation and contained many surfaces and internal pores meaning low aerodynamic density. Ex4-C(16) was more efficiently adsorbed onto porous PLGA MSs than native exendin-4, and an approximately 5% loading of Ex4-C(16) onto this porous MS (RG504H) was achieved. This optimized porous MS was found to be efficiently deposited throughout the entire lungs of mice including alveoli region. Furthermore, this porous MS adsorbed with Ex4-C(16) (approx. 100 ?g/mouse) displayed much protracted hypoglycemic efficacy in non-fasted type 2 diabetic db/db mice. Porous PLGA MS with adsorbed Ex4-C(16) showed the dual-advantages of (i) sustained release and acceptable drug-loading due to strong hydrophobic interaction and (ii) longer in vivo pulmonary hypoglycemic duration due to albumin-binding by the palmityl group. We consider that this new prototype of porous PLGA MS has considerable pharmaceutical potential as a type 2 anti-diabetic inhalation treatment. PMID:21126761

Kim, Hyunuk; Park, Hongil; Lee, Juho; Kim, Tae Hyung; Lee, Eun Seong; Oh, Kyung Taek; Lee, Kang Choon; Youn, Yu Seok

2011-02-01

50

Coating and release of an anti-inflammatory hormone from PLGA microspheres for tissue engineering.  

PubMed

Many biomaterials used in tissue engineering cause a foreign body response in vivo, which left untreated can severely reduce the effectiveness of tissue regeneration. In this study, an anti-inflammatory hormone ?-melanocyte stimulating hormone (?-MSH) was physically adsorbed to the surface of biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres to reduce inflammatory responses to this material. The stability and adsorption isotherm of peptide binding were characterized. The peptide secondary structure was not perturbed by the adsorption and subsequent desorption process. The ?-MSH payload was released over 72 h and reduced the expression of the inflammatory cytokine, Tumor necrosis factor-? (TNF-?) in lipopolysaccharide activated RAW 264.7 macrophage cells, indicating that the biological activity of ?-MSH was preserved. ?-MSH coated PLGA microspheres also appeared to reduce the influx of inflammatory cells in a subcutaneous implantation model in rats. This study demonstrates the potential of ?-MSH coatings for anti-inflammatory delivery and this approach may be applied to other tissue engineering applications. PMID:22125254

Go, Dewi P; Palmer, Jason A; Gras, Sally L; O'Connor, Andrea J

2012-02-01

51

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

PubMed Central

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

Reinhold, Samuel E.

2014-01-01

52

Anti-VEGFR2-conjugated PLGA microspheres as an x-ray phase contrast agent for assessing the VEGFR2 expression  

NASA Astrophysics Data System (ADS)

The primary goal of this study was to evaluate the feasibility of using anti-vascular endothelial growth factor receptor 2 (VEGFR2)-conjugated poly(lactic-co-glycolic acid) (PLGA) microspheres as an x-ray phase contrast agent to assess the VEGFR2 expression in cell cultures. The cell lines, mouse LLC (Lewis lung carcinoma) and HUVEC (human umbilical vein endothelial cell), were selected for cell adhesion studies. The bound PLGA microspheres were found to better adhere to LLC cells or HUVECs than unbound ones. Absorption and phase contrast images of PLGA microspheres were acquired and compared in vitro. Phase contrast imaging (PCI) greatly improves the detection of the microspheres as compared to absorption contrast imaging. The cells incubated with PLGA microspheres were imaged by PCI, which provided clear 3D visualization of the beads, indicating the feasibility of using PLGA microspheres as a contrast agent for phase contrast CT. In addition, the microspheres could be clearly distinguished from the wall of the vessel on phase contrast CT images. Therefore, the approach holds promise for assessing the VEGFR2 expression on endothelial cells of tumor-associated vessels. We conclude that PLGA microsphere-based PCI of the VEGFR2 expression might be a novel, promising biomarker for future studies of tumor angiogenesis.

Tang, Rongbiao; Chai, Wei-Min; Ying, Weihai; Yang, Guo-Yuan; Xie, Honglan; Liu, Hui-Qiang; Chen, Ke-Min

2012-05-01

53

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

PubMed

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

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

2014-06-01

54

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:24211960

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

2014-01-01

55

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

PubMed Central

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

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

2013-01-01

56

Development of porous PLGA/PEI1.8k biodegradable microspheres for the delivery of mesenchymal stem cells (MSCs).  

PubMed

Multipotent mesenchymal stem cells (MSCs) promise a therapeutic alternative for many debilitating and incurable diseases. However, one of the major limitations for the therapeutic application of human MSC (hMSC) is the lengthy ex vivo expansion time for preparing a sufficient amount of cells due to the low engraftment rate after transplantation. To solve this conundrum, a porous biodegradable polymeric microsphere was investigated as a potential scaffold for the delivery of MSCs. The modified water/oil/water (W1/O/W2) double emulsion solvent evaporation method was used for the construction of porous microspheres. PEI1.8k was blended with poly(lactic-co-glycolic acid) (PLGA) to enhance electrostatic cellular attachment to the microspheres. The porous PLGA/PEI1.8k (PPP) particles demonstrated an average particle size of 290?m and an average pore size of 14.3?m, providing a micro-carrier for the MSC delivery. PPP particles allowed for better attachment of rMSCs than non-porous PLGA/PEI1.8k (NPP) particles and non-porous (NP) and porous PLGA (PP) microspheres. rMSC successfully grew on the PPP particles for 2weeks in vitro. Next, PPP particles loaded with 3 different amounts of hMSC showed increased in vivo engraftment rates and maintained the stemness characteristics of hMSC compared with hMSCs-alone group in rats 2weeks after intramyocardial administration. These customized PPP particles for MSC delivery are a biodegradable and injectable scaffold that can be used for clinical applications. PMID:25575866

Lee, Young Sook; Lim, Kwang Suk; Oh, Jung-Eun; Yoon, A-Rum; Joo, Wan Seok; Kim, Hyun Soo; Yun, Chae-Ok; Kim, Sung Wan

2015-05-10

57

Oligonucleotide decoy to NF-kappaB slowly released from PLGA microspheres reduces chronic inflammation in rat.  

PubMed

Nuclear factor-kappaB (NF-kappaB) plays a key role in the expression of several genes involved in the immune and inflammatory process. Previously, we demonstrated that NF-kappaB activation can be significantly inhibited by a double stranded oligodeoxynucleotide (ODN). Nevertheless, the therapeutic use of ODN requires a delivery system able to improve poor crossing of cell membranes and rapid in vivo enzymatic degradation. Poly(D,L-lactide-co-glycolide) (PLGA) microspheres can increase ODN stability in biological environment and release the encapsulated drug in long time frames. Here, we used a decoy ODN against NF-kappaB and we investigated its effect, when administered in naked form or when delivered by PLGA microspheres, in a rat model of chronic inflammation. The subcutaneous implant of lambda-carrageenin-soaked sponges caused leukocyte infiltration and formation of granulation tissue which were inhibited up to 15 days by co-injection of microspheres releasing decoy ODN whereas naked decoy ODN showed this effect only up to 5 days. Molecular analysis performed on granulation tissue demonstrated an inhibition of NF-kappaB activation correlated to a decrease of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expression. Our results suggest that microspheres could be an useful tool to improve pharmacokinetics of decoy ODN and may represent a strategy to inhibit NF-kappaB activation in chronic inflammation. PMID:19427583

De Stefano, Daniela; De Rosa, Giuseppe; Maiuri, Maria Chiara; Ungaro, Francesca; Quaglia, Fabiana; Iuvone, Teresa; Cinelli, Maria Pia; La Rotonda, Maria Immacolata; Carnuccio, Rosa

2009-07-01

58

Controlling Acute Inflammation with Fast Releasing Dexamethasone-PLGA Microsphere/PVA Hydrogel Composites for Implantable Devices  

PubMed Central

Background Continuous release of dexamethasone from PLGA microsphere/PVA hydrogel composites has been shown to suppress the inflammatory tissue reaction in response to subcutaneously implanted foreign material for a period of one month. The scope of the present work is to investigate whether suppressing the initial acute inflammatory phase with fast releasing dexamethasone-PLGA microsphere/PVA composites (that release the drug over a period of one week) would prevent the development of a foreign body reaction in response to implantation in the subcutaneous tissue using a rat model. Methods Dexamethasone loaded PLGA microspheres were prepared using the solvent evaporation method. In vitro release from microspheres was analyzed using USP apparatus 4 in phosphate buffered saline (PBS) at 37°C. Composites were fabricated in 18G needles by freeze-thaw cycling the PVA/microsphere dispersion. The composites were implanted in the subcutaneous tissue of anesthetized rats. The pharmacodynamic effect was evaluated by histological examination of the tissue surrounding the composites at pre-determined time points. Results In vitro release studies showed that most of the drug entrapped in the microspheres was released within one week. At days 3 and 8, these fast releasing dexamethasone containing composites suppressed the acute phase of inflammation but did not prevent the development of an inflammatory reaction after dexamethasone was completely released from the composites. By day 30, chronic inflammation and fibrosis were observed in the tissue surrounding the drug-containing composites. On days 3 and 8, the number of inflammatory cells in the vicinity of the dexamethasone containing composites was similar to that in normal tissue. However, the number of inflammatory cells was higher in drug-containing composites as compared to drug-free composites by day 30. This was due to the inflammation being in a more advanced stage in drug-free composites where a granulomatous reaction had already developed. Conclusion Fast release of dexamethasone from PLGA/PVA composites did not provide long-term protection against the foreign body reaction in response to implantation. It would appear that a sustained delivery of anti-inflammatory agents such as dexamethasone is necessary to suppress inflammation throughout the implant life-time. PMID:19888374

Bhardwaj, Upkar; Sura, Radhakrishna; Papadimitrakopoulos, Fotios; Burgess, Diane J.

2007-01-01

59

Protective efficacy of PLGA microspheres loaded with divalent DNA vaccine encoding the ompA gene of Aeromonas veronii and the hly gene of Aeromonas hydrophila in mice.  

PubMed

In the present study, poly (lactic-co-glycolic) acid (PLGA) was used as a carrier for a divalent fusion DNA vaccine encoding the Aeromonas veronii outer membrane protein A (ompA) and Aeromonas hydrophila hemolysins (hly) protein. The recombinant pET-28a-ompA-hly was constructed by inserting the ompA gene and hly gene into a pET-28a expression vector. Loading of ompA-hly antigen module on PLGA microspheres were accomplished by water-in-oil-in-water (W/O/W) encapsulation. The molecular weight and specificity of pET-28a-ompA-hly were detected by dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The microspheres showed an average particle size of 100-150 ?m and a loading efficiency (LE) of 68.8%. Mice received ompA-hly antigen-loaded PLGA microspheres by intraperitoneal or intragastric administration mounted strong and sustained IgG response, which was significantly higher (p<0.05) than those achieved by pET-28a-ompA-hly antigen alone. OmpA-hly antigen-loaded PLGA microsphere vaccine uniquely conferred a long lasting (30 days) sterile immunity against challenge infection. Results indicated that ompA-hly antigen-loaded PLGA microsphere vaccine is a qualified candidate vector system for sterile protective immunity against A. hydrophila and A. veronii infections. PMID:24012571

Gao, Shanshan; Zhao, Na; Amer, Said; Qian, Mingming; Lv, Mengxi; Zhao, Yuliang; Su, Xin; Cao, Jieying; He, Hongxuan; Zhao, Baohua

2013-11-19

60

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

PubMed Central

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

Li, Hongli; Yuan, Mingwei; Yuan, Minglong

2014-01-01

61

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

62

Sustained Release of TGF?3 from PLGA Microspheres and Its Effect on Early Osteogenic Differentiation of Human Mesenchymal Stem Cells  

PubMed Central

Despite the widespread role of transforming growth factor-?3 (TGF?3) in wound healing and tissue regeneration, its long-term controlled release has not been demonstrated. Here, we report microencapsulation of TGF?3 in poly-d-l-lactic-co-glycolic acid (PLGA) microspheres and determine its bioactivity. The release profiles of PLGA-encapsulated TGF?3 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, radiofrequency 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, TGF?3 (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 TGF?3. This was confirmed by lower alkaline phosphatase activity (2.25 ± 0.57 mU/mL/ng DNA) than controls (TGF?3-free) at 5.8 ± 0.9 mU/mL/ng DNA (p < 0.05). Control-released TGF?3 bioactivity was further confirmed by lack of significant differences in alkaline phosphatase upon direct addition of 1.35 ng/mL TGF?3 to cell culture (p > 0.05). These findings provide baseline data for potential uses of microencapsulated TGF?3 in wound healing and tissue-engineering applications. PMID:16579687

MOIOLI, EDUARDO K.; HONG, LIU; GUARDADO, JESSE; CLARK, PAUL A.; MAO, JEREMY J.

2010-01-01

63

Hydrogel Matrix Entrapping PLGA-Paclitaxel Microspheres: Drug Delivery with Near Zero-Order Release and Implantability Advantages for Malignant Brain Tumour Chemotherapy  

Microsoft Academic Search

Purpose  To develop paclitaxel-delivering PLGA microspheres entrapped in a gel matrix with sustained drug release properties and implantability\\u000a advantages for local glioma chemotherapy.\\u000a \\u000a \\u000a \\u000a Methods  Paclitaxel-loaded PLGA microspheres were fabricated using electrohydrodynamic atomization and entrapped by electrospray and\\u000a gelation. The physicochemical characterizations were performed using scanning electron microscopy and differential scanning\\u000a calorimetry. The influence of various parameters on the disintegration time was investigated.

Sudhir Hulikal Ranganath; Irene Kee; William B. Krantz; Pierce Kah-Hoe Chow; Chi-Hwa Wang

2009-01-01

64

Development of antibiotic and debriding enzyme-loaded PLGA microspheres entrapped in PVA-gelatin hydrogel for complete wound management.  

PubMed

A biocompatible moist system was developed for effective and complete wound healing. Optimized PLGA microspheres of gentamicin (GM) and serratiopeptidase (STP) were incorporated into PVA-gelatin slurry and casted into films to prepare multiphase hydrogel. The prepared system was characterized by in vitro and in vivo studies. Results revealed the uniform dispersion of microspheres in three-dimensional matrix of the hydrogel. The in vitro release data showed a typical biphasic release pattern. All parameters such as wound contraction, tensile strength, histopathological and biochemical parameters were observed significant (p

Singh, Deependra; Singh, Manju Rawat

2012-10-01

65

Preparation and property of a novel bone graft composite consisting of rhBMP-2 loaded PLGA microspheres and calcium phosphate cement.  

PubMed

Calcium phosphate cement (CPC) is a highly promising bone substitute and an excellent carrier for delivering growth factors. Yet, the lack of macro-porosity and osteoinductive ability, limit its use. This study is aimed at developing a novel biodegradable biomaterial for bone repair with both highly osteoconductive and osteoinductive properties. RhBMP-2 loaded PLGA microspheres were incorporated into rhBMP-2/CPC for macropores for bone ingrowth. The compressive strength, crystallinity, microscopic structure, and bioactivity of the composites were investigated. The results showed that with the incorporation of rhBMP-2 loaded PLGA microspheres, the compressive strength was decreased from (29.48+/-6.42) MPa to (8.26+/-3.58) MPa. X-ray diffraction revealed that the crystallinity pattern of HA formed by CPC had no significant change. Inside the composite, the microspheres distributed homogeneously and contacted intimately with the HA matrix, as observed by scanning electron microscopy (SEM). When the PLGA microspheres dissolved after having been emerged in PBS for 56 days, macropores were created within the CPC. The rhBMP-2/PLGA/CPC composite, showing a 4.9% initial release of rhBMP-2 in 24 h, followed by a prolonged release for 28 days, should have a greater amount of rhBMP-2 released compared to the CPC delivery system. When rabbit marrow stromal cells were cocultured with the composite, the alkaline phosphatase (ALP) and osteocalcin (OC) showed a dose response to the rhBMP-2 released from the composite, indicating that the activity of rhBMP-2 was retained. This study shows that the new composite reveals more rhBMP-2 release and osteogenic activity. This novel BMP/PLGA/CPC composite could be a promising synthetic bone graft in craniofacial and orthopedic repairs. PMID:17701313

Fei, Zhengqi; Hu, Yunyu; Wu, Daocheng; Wu, Hong; Lu, Rong; Bai, Jianping; Song, Hongxun

2008-03-01

66

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

67

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.  

PubMed

Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (?-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. ?-MSH and bFGF were released in a sustained manner and the bioactivity of ?-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1849-1863, 2015. PMID:25203163

Go, Dewi P; Palmer, Jason A; Mitchell, Geraldine M; Gras, Sally L; O'Connor, Andrea J

2015-05-01

68

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. PMID:19669866

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

2009-01-01

69

FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres 1 An article of related interest has been published by Yang et al. in J. Pharm. Sci., 88(2), Feb. 1999, accepted Nov. 1998. 1  

Microsoft Academic Search

A commonly used technique for protein encapsulation in microspheres is the double-emulsion method wherein an initial water-in-oil (w\\/o) emulsion of protein and polymer is formed via sonication, and then a second emulsion (w\\/o)\\/w is formed by dispersion in an aqueous phase via homogenization. This approach is often used to produce microspheres of biodegradable poly(lactic-co-glycolic acid) (PLGA). The harsh processing associated

Karen Fu; Kai Griebenow; Lisa Hsieh; Alexander M Klibanov; Robert Langer

1999-01-01

70

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

PubMed

To investigate the antiangiogenic effect of sustained-release poly (lactic-co-glycolic acid) microspheres containing docetaxel (PMCD) in human hepatoma xenograft. PMCD were prepared by solvent evaporation method with an encapsulation efficiency of 98.7% and a release period of about 3 weeks in vitro. PMCD were intratumorally injected once for mice bearing a human hepatocellular carcinoma. On day 21 post-treatment, the inhibition rate of tumor growth was 72.7% in the high-dose group, indicating a significant antitumor activity. Meanwhile, excellent antiangiogenic effect was observed based on the contrast-enhanced ultrasonography as well as microvessel density determination. Additionally, the real-time fluorescence quantitative PCR revealed that the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang2) genes were down-regulated significantly. Interstitial chemotherapy using PMCD was highly effective and safe for the treatment of the human hepatoma xenograft and that decreasing angiogenesis could be one of the most important mechanisms involved in the antitumor activity. PMID:21136211

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

2012-03-01

71

Porous PLGA microspheres with BMP2 releasing polyphosphate-functionalized nano-hydroxyapatite for enhanced bone regeneration  

Microsoft Academic Search

We report on bone-regenerative porous microspheres surface-decorated with polyphosphate-functionalized nano-hydroxyapatite (n-HAp) that can controllably release bone morphogenetic protein-2 (BMP-2). n-HAp was immobilized onto the pore surface of microspheres and could control the loading and the release of BMP-2.

Ahn Na Koo; Sang Cheon Lee

2011-01-01

72

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

NASA Astrophysics Data System (ADS)

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

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

2014-02-01

73

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

PubMed Central

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

Chue, Pierre

2007-01-01

74

Microspheres  

NASA Technical Reports Server (NTRS)

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

1990-01-01

75

Drug Controlled Release and Biological Behavior of Poly(D,L-Lactide-Co-Glycolide) Microspheres  

Microsoft Academic Search

Poly(D,L-lactide-co-glycolide) (PLGA, 75\\/25) microspheres loaded with bovine serum albumin (BSA) were prepared using the W\\/O\\/W emulsification solvent evaporation technique. The cytotoxicity in vitro of PLGA microspheres was investigated and the BSA release from PLGA microspheres was also studied. Scanning electron micrographs showed that the PLGA microspheres were regular and the surface was smooth. BSA release typically began with an initial

Zeqiang He; Lizhi Xiong

2011-01-01

76

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

77

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

78

Stability of proteins within biodegradable microspheres  

E-print Network

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

Fu, Karen, 1967-

2000-01-01

79

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

PubMed

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

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

2014-12-01

80

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

81

Long-acting local anesthetics in dentistry.  

PubMed Central

Long-acting local anesthetics have proved to be effective for the suppression of both intraoperative and postoperative pain. They are useful for lengthy dental treatments and for prevention of severe pain following many types of surgical procedures. Although the currently available long-acting local anesthetics for dentistry have minimal side effects in the doses usually employed, there are potential problems. Bupivacaine, for example, can cause significant cardiac depressant and dysrhythmogenic responses. Etidocaine has less pronounced effects on the cardiovascular system, but its use may be associated with inadequate control of intraoperative bleeding. A new long-acting local anesthetic, ropivacaine, appears to offer advantages over either of the currently used long-acting agents. PMID:1308373

Sisk, A. L.

1992-01-01

82

Long-acting risperidone: Focus on safety  

Microsoft Academic Search

Background: Although atypical antipsychotics are generally regarded as having more favorable tolerability profiles than conventional antipsychotics, differences between specific atypical agents can be important when individualizing treatment. Long-acting risperidone (LAR), the first long-acting injectable atypical anti-psychotic, has been found to be effective in the treatment of schizophrenia and schizoaffective disorder.Objectives: This review summarizes clinical evidence for the tolerability profile of

Hans-Jürgen Möller

2006-01-01

83

Prevention of local tumor growth with paclitaxel-loaded microspheres  

E-print Network

Prevention of local tumor growth with paclitaxel- loaded microspheres Solomon M. Azouz, MS,a Joseph. The primary aim of this study was to assess the feasibility of a microsphere drug delivery system to locally resection margin. Methods: Poly-(D,L-lactic-co-glycolic acid) (PLGA) microspheres loaded

84

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

PubMed

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

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

2015-04-01

85

Release optimization of epidermal growth factor from PLGA microparticles.  

PubMed

The objective of this study was to prepare poly lactic-co-glycolic acid (PLGA)-based microparticles as potential carriers for recombinant human epidermal growth factor (rhEGF). In order to optimize characteristic parameters of protein-loaded microspheres, bovine serum albumin (BSA) was selected as the model protein. To reduce burst release as a common problem of microspheres, a proper alteration in the particle composition was used, such as addition of poly vinyl alcohol and changes in initial drug loading. The effects of these parameters on particle size, encapsulation efficiency and in vitro release kinetics of BSA in PLGA microspheres were investigated using a Box-Behnken response surface methodology. The biological activity of the released rhEGF was assessed using human skin fibroblasts cell proliferation assay. The prepared rhEGF-loaded microspheres had an average size of 6.44 ± 2.45 µm, encapsulation efficiency of 97.04 ± 1.13%, burst release of 13.06 ± 1.35% and cumulative release of 22.56 ± 2.41%. The proliferation of human skin fibroblast cells cultivated with rhEGF releasate of microspheres was similar to that of pure rhEGF, indicating the biological activity of released protein confirming the stability of rhEGF during microsphere preparation. These results are in agreement with the purpose of our study to prepare rhEGF-entrapped PLGA microparticles with optimized characteristics. PMID:23777385

Mirdailami, Omolbanin; Khoshayand, Mohammad Reza; Soleimani, Masoud; Dinarvand, Rassoul; Atyabi, Fatemeh

2014-08-01

86

Long-acting injectable formulations of antipsychotic drugs for the treatment of schizophrenia.  

PubMed

Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available. Haloperidol decanoate and fluphenazine decanoate are first-generation depot drugs, but the use of these medicines has declined since the advent of second-generation depot agents, such as long-acting risperidone, paliperidone palmitate, and olanzapine pamoate. The second-generation depot drugs are better tolerated and have fewer adverse neurological side effects. Long-acting injectable risperidone, the first depot formulation of an atypical antipsychotic drug, was prepared by encapsulating risperidone into biodegradable microspheres. Paliperidone palmitate is an aqueous suspension of nanocrystal molecules, and olanzapine pamoate is a microcrystalline salt of olanzapine and pamoic acid suspended in aqueous solution. This review summarizes the characteristics and recent research of formulations of each long-acting injectable antipsychotic drug. PMID:23543652

Park, Eun Ji; Amatya, Sarmila; Kim, Myung Sun; Park, Jong Hoon; Seol, Eunyoung; Lee, Heeyong; Shin, Young-Hee; Na, Dong Hee

2013-06-01

87

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

88

In vitro and in vivo evaluation of taxol release from poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate and degradation of the microspheres  

Microsoft Academic Search

This study describes the release and degradation profiles of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate (IPM), namely, Taxol-IPM-PLGA-MS, in vitro and in vivo. Incorporation of IPM into the PLGA microspheres effectively increased the release of taxol from the microspheres in vitro. The molecular weight (Mol. Wt.) and copolymer ratio of lactic acid (LA) and glycolic acid (GA) displayed obvious

Ya Min Wang; Hitoshi Sato; Isamu Horikoshi

1997-01-01

89

Long-acting hormonal contraceptives for women.  

PubMed

Following the development and widespread use of oral hormonal contraceptives, it became evident that alternative long-acting delivery systems would be required to improve contraceptive practice in some cultural settings where injectable or subdermal routes of administration are preferred. Nowadays, long-acting contraceptives constitute an important option in family planning services in many parts of the world. Indeed, two long-acting injectable contraceptives containing just a synthetic progestogen (depot-medroxyprogesterone acetate (DMPA) and norethisterone enantate (NET-EN)) have been in clinical practice for more than 20 years. The World Health Organization's (WHO) Special Programme of Research in Human Reproduction, in collaboration with the U.S. National Institute of Child Health and Human Development (NICHD) and universities primarily in developing countries undertook a synthesis programme aimed at producing an improved injectable preparation by developing new derivatives of known steroids. One such compound (levonorgestrel 17-butanoate) is now at the stage of Phase II clinical testing. In addition, the Special Programme has developed and improved once-a-month injectable formulations and assessed their safety and efficacy in different countries worldwide. After large scale clinical testing, at least two progestogen-estrogen combinations have reached the point of introductory trials. PMID:1958567

Garza-Flores, J; Hall, P E; Perez-Palacios, G

1991-01-01

90

Mechanical and rheological properties and injectability of calcium phosphate cement containing poly (lactic-co-glycolic acid) microspheres  

Microsoft Academic Search

To enhance tissue ingrowth and promote rapid resorption, efforts were made to build macropores into calcium phosphate cement (CPC); however, this led to a decrease in its mechanical properties. In this study, poly (lactic-co-glycolic acid) (PLGA) microspheres were incorporated into CPC to impart macroporosity and maintain early strength. The influences of the content of PLGA microspheres on the mechanical strength,

Xiaopeng Qi; Jiandong Ye

2009-01-01

91

Long-acting preparations of exenatide  

PubMed Central

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

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

2013-01-01

92

One-step preparation of rifampicin\\/poly(lactic-co-glycolic acid) nanoparticle-containing mannitol microspheres using a four-fluid nozzle spray drier for inhalation therapy of tuberculosis  

Microsoft Academic Search

We prepared rifampicin (RFP)\\/poly(lactic-co-glycolic acid) (PLGA) nanoparticle-containing mannitol (MAN) microspheres for inhalation therapy of tuberculosis using a four-fluid nozzle spray drier in one step. The RFP and PLGA acetone\\/methanol (2\\/1) solution and MAN aqueous solution were supplied through different liquid passages of the four-fluid nozzle spray drier to obtain MAN microspheres including RFP\\/PLGA nanoparticles. The mean diameter of RFP\\/PLGA nanoparticles

Katsuya Ohashi; Takahiro Kabasawa; Tetsuya Ozeki; Hiroaki Okada

2009-01-01

93

Polymeric microspheres  

DOEpatents

The invention features core-shell microsphere compositions, hollow polymeric microspheres, and methods for making the microspheres. The microspheres are characterized as having a polymeric shell with consistent shell thickness.

Walt, David R.; Mandal, Tarun K.; Fleming, Michael S.

2004-04-13

94

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

PubMed

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

Shah, Ronak B; Schwendeman, Steven P

2014-12-28

95

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

96

Apatite-Coated Porous Poly(lactic-co-glycolic acid) Microspheres as an Injectable Bone Substitute  

Microsoft Academic Search

Previously, we developed an apatite-coated non-porous poly(lactic-co-glycolic acid) (PLGA) microsphere (ANPM) as an injectable bone substitute. We hypothesized that an apatite-coated porous PLGA microsphere (APPM) would have enhanced osteogenic potential compared to that of an ANPM. To test the hypothesis, critical-sized bone defects were made in mouse calvaria, and APPMs and ANPMs were implanted in the defects for 8 weeks.

Tae-Jin Lee; Sun-Woong Kang; Suk Ho Bhang; Jin Muk Kang; Byung-Soo Kim

2010-01-01

97

The release profiles and bioactivity of parathyroid hormone from poly(lactic-co-glycolic acid) microspheres  

Microsoft Academic Search

Poly(lactic-co-glycolic acid) (PLGA) microspheres containing bovine serum albumin (BSA) or human parathyroid hormone (PTH)(1–34) were prepared using a double emulsion method with high encapsulation efficiency and controlled particle sizes. The microspheres were characterized with regard to their surface morphology, size, protein loading, degradation and release kinetics, and in vitro and in vivo assessments of biological activity of released PTH. PLGA5050

Guobao Wei; Glenda J. Pettway; Laurie K. McCauley; Peter X. Ma

2004-01-01

98

Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam  

Microsoft Academic Search

This work was aimed at evaluating the effects of ? irradiation on the stability of microspheres made of a poly(lactide-co-glycolide) copolymer (PLGA) and loaded with 15% w\\/w of clonazepam (CLO). The influence of CLO on PLGA radiolysis mechanisms and the identification of possible irradiation markers were also investigated. Microspheres were prepared by means of a spray-drying method. ? Irradiation was

L. Montanari; F. Cilurzo; L. Valvo; A. Faucitano; A. Buttafava; A. Groppo; I. Genta; B. Conti

2001-01-01

99

Bone response to fast-degrading, injectable calcium phosphate cements containing PLGA microparticles  

Microsoft Academic Search

Apatitic calcium phosphate cements (CPC) are frequently used to fill bone defects due to their favourable clinical handling and excellent bone response, but their lack of degradability inhibits complete bone regeneration. In order to render these injectable CaP cements biodegradable, hollow microspheres made of poly (d,l-lactic-co-glycolic) acid (PLGA) have been previously used as porogen since these microspheres were shown to

Rosa P. Félix Lanao; Sander C. G. Leeuwenburgh; Joop G. C. Wolke; John A. Jansen

2011-01-01

100

Subcritical CO2 Sintering of Microspheres of Different Polymeric Materials to Fabricate Scaffolds for Tissue Engineering  

PubMed Central

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

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

2013-01-01

101

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

E-print Network

. Keywords Sustained release; protein; microspheres; poly(lactic-co-glycolic acid) (PLGA); in vitro release, or by modifying the protein or the polymer. Alternatively, some strategies have aimed at avoiding the formation ..................................................................................... 16 2.1.5 Use of a more hydrophilic polymer

Paris-Sud XI, Université de

102

Functionalized PLGA-doped zirconium oxide ceramics for bone tissue regeneration.  

PubMed

Bone tissue engineering is an alternative approach to bone grafts. In our study we aim to develop a composite scaffold for bone regeneration made of doped zirconium oxide (ZrO2) conjugated with poly(lactic-co-glycolic acid) (PLGA) particles for the delivery of growth factors. In this composite, the PLGA microspheres are designed to release a crucial growth factor for bone formation, bone morphogenetic protein-2 (BMP2). We found that by changing the polymer's molecular weight and composition, we could control microsphere loading, release and size. The BMP2 released from PLGA microspheres retained its biological activity and increased osteoblastic marker expression in human mesenchymal stem cells (hMSCs). Uncapped PLGA microspheres were conjugated to ZrO2 scaffolds using carbodiimide chemistry, and the composite scaffold was shown to support hMSCs growth. We also demonstrated that human umbilical vein endothelial cells (HUVECs) can be co-cultured with hMSCs on the ZrO2 scaffold for future vascularization of the scaffold. The ZrO2 composite scaffold could serve as a bone substitute for bone grafting applications with the added ability of releasing different growth factors needed for bone regeneration. PMID:23893013

Lupu-Haber, Yael; Pinkas, Oded; Boehm, Stefanie; Scheper, Thomas; Kasper, Cornelia; Machluf, Marcelle

2013-12-01

103

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

PubMed

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

Gopalakrishna, Ganesh; Aggarwal, Arpit; Lauriello, John

2013-01-01

104

Open Macroporous Poly(lactic-co-glycolic Acid) Microspheres as an Injectable Scaffold for Cartilage Tissue Engineering  

Microsoft Academic Search

Non-porous poly(lactic-co-glycolic acid) (PLGA) microspheres have been previously proposed as an injectable scaffold for in vivo cartilage tissue engineering. In this study, we tested whether using open macroporous PLGA microspheres as an injectable scaffold for in vivo cartilage tissue engineering provides a larger surface area for cell adhesion and a larger void space for cartilage tissue regeneration and, thus, regeneration

Sun-Woong Kang; Wan-Geun La; Byung-Soo Kim

2009-01-01

105

Characterization of the initial burst release of a model peptide from poly( d,l-lactide-co-glycolide) microspheres  

Microsoft Academic Search

In order to study the mechanism of initial burst release from drug-loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres, a model peptide, octreotide acetate, was encapsulated in PLGA 50\\/50 (Mw?50,000) microspheres using a double emulsion–solvent evaporation method. A simple and accurate continuous monitoring system was developed to obtain a detailed release profile. After different incubation times in the release medium, the morphology and permeability

Juan Wang; Barbara M. Wang; Steven P. Schwendeman

2002-01-01

106

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). PMID:22405902

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

2012-01-01

107

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

NASA Astrophysics Data System (ADS)

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

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

2011-02-01

108

Preparation of microspheres by the solvent evaporation technique  

Microsoft Academic Search

The microencapsulation process in which the removal of the hydrophobic polymer solvent is achieved by evaporation has been widely reported in recent years for the preparation of microspheres and microcapsules based on biodegradable polymers and copolymers of hydroxy acids. The properties of biodegradable microspheres of poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) have been extensively investigated. The encapsulation of highly

Patrick B O'Donnell; James W McGinity

1997-01-01

109

Gamma irradiation effects and EPR investigation on poly(lactide-co-glycolide) microspheres containing bupivacaine  

Microsoft Academic Search

The effects of ? radiation on the stability of microspheres made of a polylactide-co-glycolide 50:50 copolymer (PLGA) and loaded with 40% bupivacaine (BU) were studied. The radiolysis mechanisms of BU and BU-loaded microspheres were investigated by using electronic paramagnetic resonance (EPR) analysis. Microspheres were prepared by means of a spray drying method. ? Irradiation was carried out in the open,

L. Montanari; F. Cilurzo; B. Conti; I. Genta; A. Groppo; L. Valvo; A. Faucitano; A. Buttafava

2002-01-01

110

Protein bioactivity and polymer orientation is affected by stabilizer incorporation for double-walled microspheres  

Microsoft Academic Search

Double-walled microspheres present an improved drug delivery technique for sustained release of encapsulated substrates. In this study, the release kinetics and biological activity of lysozyme was analyzed from microspheres comprised of poly(lactic-co-glycolic acid) (PLGA) and poly(L-lactide) (PLLA). In addition, coencapsulation of the anionic surfactant, docusate sodium salt (AOT), was investigated as a method of decreasing protein denaturation during microsphere fabrication.

Lauren E. Kokai; Huaping Tan; Siddharth Jhunjhunwala; Steven R. Little; Jason W. Frank; Kacey G. Marra

2010-01-01

111

Antioxidant encapsulated porous poly(lactide-co-glycolide) microparticles for developing long acting inhalation system.  

PubMed

The purpose of this study was to fabricate porous poly(lactide-co-glycolide) (PLGA) microparticles for efficient pulmonary deposition and increased therapeutic duration of the antioxidant anthocyanin (ATH). These microparticles were prepared by a water-in-oil-in-water (W(1)/O/W(2)) multi-emulsion method with vaporizing ammonium bicarbonate (AB) as a porogen and starch as a viscous additive. High porosity achieved by the decomposition reaction of AB to the base of ammonia, carbon dioxide, and water vapor at 50°C enabled efficient deposition of ATH throughout the entire lung in BALB/c mice. In addition, the porous microparticles incorporating starch showed sustained ATH release characteristics (up to 5 days) and protracted antioxidant activity (up to 5 days) for 2,2-diphenyl-1-pikryl-hydrazyl (DPPH) radicals, which was comparable to that of the porous microparticles without starch which completely released ATH in 2h. Furthermore, these porous microparticles incorporating starch led to longer ATH residence (up to 20 days) in in vivo lung epithelium. We believe that this system has great pharmaceutical potential as a long-acting antioxidant for continuously relieving oxidative stress in pulmonary diseases like chronic obstructive pulmonary disease (COPD). PMID:21820282

Yoo, Na Young; Youn, Yu Seok; Oh, Nam Muk; Oh, Kyung Taek; Lee, Deok-Keun; Cha, Kyung-Hoi; Oh, Young Taik; Lee, Eun Seong

2011-11-01

112

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

PubMed

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

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

2003-06-18

113

PLGA microdevices for retinoids sustained release produced by supercritical emulsion extraction: continuous versus batch operation layouts.  

PubMed

Retinyl acetate (RA) was selected as a model compound to be entrapped in poly(lactic-co-glycolic)acid (PLGA) microspheres using supercritical emulsion extraction (SEE). Several oil-in-water emulsions prepared using acetone and aqueous glycerol (80% glycerol, 20% water) were processed using supercritical carbon dioxide (SC-CO2 ) to extract the oily phase and to induce microspheres formation. The characteristics of the microspheres obtained by conventional liquid emulsion extraction and SEE were also compared: SEE produced spherical and free flowing microspheres, whereas the conventional liquid-liquid extraction showed large intraparticles aggregation. Emulsion extraction by SC-CO2 technology was tested using two different operation layouts: batch (SEE-B) and continuous (SEE-C). SEE-C was performed using a packed tower to produce emulsion/SC-CO2 contact in countercurrent mode, allowing higher microsphere recovery and process efficiencies. Operating at 80 bar and 36°C, SEE-C produced PLGA/RA microspheres with mean sizes between 3.3 and 4.5??m with an excellent encapsulation efficiency of 80%-90%. Almost all the drug was released in about 6 days when charged at 2.7% (w/w), whereas only 40% and 10% of RA were released in the same period of time when the charge was 5.2% and 8.8% (w/w), respectively. Release kinetics constants calculated from the experimental data, using a mathematical model, were also proposed and discussed. PMID:21638283

Porta, Giovanna Della; Campardelli, Roberta; Falco, Nunzia; Reverchon, Ernesto

2011-10-01

114

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

115

Long-acting reversible contraceptives for teenagers: Primary care recommendations.  

PubMed

Long-acting reversible contraceptive (LARC) methods are underutilized in the adolescent population despite their superior efficacy over non-LARC methods. The purpose of this article is to discuss the barriers that lead to underutilization of these methods and present an evidence-based approach for the use of LARC methods among adolescents in the primary care setting. PMID:25642635

Atkin, Kathryn; Beal, Margaret W; Long-Middleton, Ellen; Roncari, Danielle

2015-03-12

116

Narcotic tapering in pregnancy using long-acting morphine  

PubMed Central

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

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

2015-01-01

117

A Heterogeneously Structured Composite Based on Poly(lactic-co-glycolic acid) Microspheres and Poly(vinyl alcohol) Hydrogel Nanoparticles for Long-Term Protein Drug Delivery  

Microsoft Academic Search

Purpose. To prepare a heterogeneously structured composite based on poly (lactic-co-glycolic acid) (PLGA) microspheres and poly(vinyl alcohol) (PVA) hydrogel nanoparticles for long-term protein drug delivery.

Nuo Wang; XueShen Wu; JiaKui Li

1999-01-01

118

Preparation and Characterization of Poly (D,L-Lactide-Co-Glycolide) Microspheres for Controlled Release of Poly(L-Lysine) Complexed Plasmid DNA  

Microsoft Academic Search

Purpose. To produce and characterize controlled release formulations of plasmid DNA (pDNA) loaded in poly (D,L-lactide-co-glycolide) (PLGA) microspheres both in free form and as a complex with poly (L-lysine).

Yilmaz Capan; Byung H. Woo; Sisay Gebrekidan; Shamim Ahmed; Patrick P. DeLuca

1999-01-01

119

Emerging role of long acting muscarinic antagonists for asthma  

PubMed Central

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

Lipworth, Brian J

2014-01-01

120

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

PubMed Central

Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery. PMID:25028546

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

2014-01-01

121

Long-acting medications for the hyperkinetic disorders  

Microsoft Academic Search

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

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

2006-01-01

122

Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly(lactide-co-glycolide) microspheres.  

PubMed

We have assessed the biocompatibility of a new composite bone graft consisting of calcium phosphate cement (CPC) and poly(lactide-co-glycolide) (PLGA) microspheres (approximate diameter of 0.18-0.36 mm) using cell culture techniques. CPC powder is mixed with PLGA microspheres and water to yield a workable paste that could be sculpted to fit the contours of a wound. The cement then hardens into a matrix of hydroxyapatite microcrystals containing PLGA microspheres. The rationale for this design is that the microspheres will initially stabilize the graft but can then degrade to leave behind macropores for colonization by osteoblasts. The CPC matrix could then be resorbed and replaced with new bone. In the present study, osteoblast-like cells (MC3T3-E1 cells) were seeded onto graft specimens and evaluated with fluorescence microscopy, environmental scanning electron microscopy and the Wst-1 assay (an enzymatic assay for mitochondrial dehydrogenase activity). Cells were able to adhere, attain a normal morphology, proliferate and remain viable when cultured on the new composite graft (CPC-PLGA) or on a control graft (CPC alone). These results suggest that our new cement consisting of CPC and PLGA microspheres is biocompatible. This is the first time that a 'polymer-in-mineral' (PLGA microspheres dispersed in a CPC matrix) cement has been formulated that is moldable, resorbable and that can form macropores after the cement has set. PMID:12038620

Simon, Carl G; Khatri, Chetan A; Wight, Scott A; Wang, Francis W

2002-05-01

123

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 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

2014-01-01

124

Patient and Health Care Provider Perspectives on Long Acting Injectable Antipsychotics in Schizophrenia and the Introduction of Olanzapine Long-Acting Injection  

PubMed Central

Olanzapine long acting injection has joined risperidone and paliperidone as the second generation long acting antipsychotic injection options for treatment of patients with schizophrenia. Long acting injections are important alternatives to oral medications for patients who have difficulty adhering to daily or multiple daily medication administrations, yet may be underutilized or not well understood. Patient perceptions, adherence, and preferences are important issues for health care providers to address when discussing treatment options with their patients. Reviewed here are overall patient and health care provider attitudes and perceptions regarding long acting injections and the details of olanzapine long acting injectable, the newest agent, and how it will fit in the marketplace. In addition, efficacy, safety, dosing and use data regarding this newest long acting agent are reviewed and compared to other available long acting agents. PMID:23293546

Wehring, Heidi J.; Thedford, Sheryl; Koola, Maju; Kelly, Deanna L.

2011-01-01

125

Stability of insulin during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres  

Microsoft Academic Search

In recent years, the acylation of peptides during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres has been described in the literature. To investigate whether insulin is prone to the covalent attachment of lactic or glycolic acid, insulin-loaded PLA and PLGA microspheres containing 5% bovine insulin were manufactured using a w\\/o\\/w multiple emulsion-solvent evaporation technique. Microspheres were characterized for

Mohamed Abbas Ibrahim; Ahmed Ismail; Mohamed Ihab Fetouh; Achim Göpferich

2005-01-01

126

Microspherical catalysts  

SciTech Connect

A catalyst which is a hollow microsphere comprising an outer shell in which there are feeder pores and an active ingredient arranged within the shell. The microsphere has a diameter ranging from 20 to 120 microns and the shell has a thickness ranging from 0.1 to 20.0 microns. The active ingredient fills 1.0% to 100% of the void space within the microsphere.

Hettinger, W. P.; Beck, H. W.

1985-10-22

127

A Qualitative Analysis of Long-Acting Reversible Contraception.  

PubMed

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

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

2014-11-26

128

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. PMID:23678347

Jeong, Hyun-Ghang

2013-01-01

129

Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes  

PubMed Central

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

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

2014-01-01

130

New PLGA-P188-PLGA matrix enhances TGF-?3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells.  

PubMed

The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGF?3, they allowed the sustained release of 70% of the incorporated TGF-?3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-?3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair. PMID:23648834

Morille, Marie; Van-Thanh, Tran; Garric, Xavier; Cayon, Jérôme; Coudane, Jean; Noël, Danièle; Venier-Julienne, Marie-Claire; Montero-Menei, Claudia N

2013-08-28

131

Polyacrolein microspheres  

NASA Technical Reports Server (NTRS)

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

Rembaum, Alan (Inventor)

1987-01-01

132

Polyacrolein microspheres  

NASA Technical Reports Server (NTRS)

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

Rembaum, Alan (Inventor)

1983-01-01

133

Polyacrolein microspheres  

NASA Technical Reports Server (NTRS)

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

Rembaum, Alan (Inventor)

1986-01-01

134

Long acting porous microparticle for pulmonary protein delivery.  

PubMed

This study investigated the porous-microparticle (PM) with low mass density and large size for pulmonary drug delivery. PM was prepared by the water-in-oil-in-water (W(1)/O/W(2)) multi-emulsion method with cyclodextrin derivative as a porogen and a stabilizer of peptide drugs. Herein, sucrose ethyl acetate (SAIB) was incorporated in PM for long acting protein release. In vitro release studies, the rapid release rate of proteins from PM was reduced due to the high viscosity of the added SAIB. As a result, BSA release from PM continued up to 7 days. This result suggests that PM having sustained release characteristics may be successfully applied for long-term pulmonary administration of protein or peptide drug. In addition, it is expected that these particles arrive at a deep lung epithelium due to low density (high porosity) and limit macrophage recognition because of big particle size (more than 5 microm). PMID:17296275

Kwon, Min Jung; Bae, Jun Ho; Kim, Jung Ju; Na, Kun; Lee, Eun Seong

2007-03-21

135

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

PubMed

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

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

2013-12-01

136

Controlled Delivery Systems for Proteins Based on Poly(Lactic\\/Glycolic Acid) Microspheres  

Microsoft Academic Search

This paper describes an investigation of the use of poly(lactic\\/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic\\/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55–95 µm and encapsulated more

Smadar Cohen; Toshio Yoshioka; Melissa Lucarelli; Lena H. Hwang; Robert Langer

1991-01-01

137

Poly(lactide-co-glycolide) microspheres containing bupivacaine: comparison between gamma and beta irradiation effects  

Microsoft Academic Search

The ?- and ?-irradiation effects on stability of microspheres made of poly(lactide-co-glycolide) 50:50 copolymer (PLGA) containing bupivacaine (BU) were studied. Microspheres containing 10, 25, and 40% w\\/w, respectively, of BU were prepared by spray drying and irradiated in air with ?- and ?-irradiation at a dose of 25 kGy. Morphology (atomic force microscopy, particle-size analysis), physico–chemical characteristics (DSC and FT-IR

L Montanari; F Cilurzo; F Selmin; B Conti; I Genta; G Poletti; F Orsini; L Valvo

2003-01-01

138

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

139

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

PubMed Central

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

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

2014-01-01

140

The effect of a single remote injection of statin-impregnated poly (lactic- co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia  

Microsoft Academic Search

The aim of this study was to evaluate the effects of newly developed injectable poly (lactic-co-glycolic acid) (PLGA) microspheres containing fluvastatin on osteogenesis around titanium implants in the rat tibia. After confirmation of the sustained-release profile of fluvastatin from the microspheres by an in vitro assay, the microspheres were administered to the back skin of the rats by a single

Tomohiro Masuzaki; Yasunori Ayukawa; Yasuko Moriyama; Yohei Jinno; Ikiru Atsuta; Yoichiro Ogino; Kiyoshi Koyano

2010-01-01

141

Assessment of PLGA-PEG-PLGA copolymer hydrogel for sustained drug delivery in the ear.  

PubMed

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

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

2014-01-01

142

Long-acting injectable antipsychotics: focus on olanzapine pamoate  

PubMed Central

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

Lindenmayer, JP

2010-01-01

143

Possible interaction between letrozole and long-acting injectable zuclopenthixol.  

PubMed

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

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

2015-01-01

144

Pharmacokinetics of olanzapine long-acting injection: the clinical perspective  

PubMed Central

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

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

2014-01-01

145

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

PubMed

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

Prescott, Gina M; Matthews, Christina M

2014-01-01

146

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

PubMed

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

Mohamed, Farahidah; van der Walle, Christopher F

2006-03-27

147

Fluorescent microspheres  

NASA Technical Reports Server (NTRS)

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

Rembaum, A.

1978-01-01

148

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. PMID:15170848

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

149

The Pharmacokinetics and Pharmacodynamics of Lidocaine-Loaded Biodegradable Poly(lactic-co-glycolic acid) Microspheres  

PubMed Central

The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(d,l-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34 ± 0.3 ?m. The poly disperse index was 0.21 ± 0.03, and the zeta potential was +0.34 ± 0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5% ± 4.3% and 11.2% ± 1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02–2.06-fold that of lidocaine injection (p < 0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency. PMID:25268618

Liu, Jianming; Lv, Xin

2014-01-01

150

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

151

Preparation and characterization of protein loaded microspheres based on a hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid)  

Microsoft Academic Search

The purpose of this study was to investigate the suitability of a novel hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA), as controlled release system for pharmaceutical proteins. Dextran Blue (as a macromolecular model compound) and lysozyme-loaded PLHMGA and PLGA (control formulation) microspheres were prepared by a solvent evaporation technique. The Dextran Blue and lysozyme loaded PLHMGA microspheres prepared with 10%

A. H. Ghassemi; M. J. van Steenbergen; H. Talsma; C. F. van Nostrum; W. Jiskoot; D. J. A. Crommelin; W. E. Hennink

2009-01-01

152

Study of gamma-irradiation effects on aciclovir poly( d, l-lactic-co-glycolic) acid microspheres for intravitreal administration  

Microsoft Academic Search

Gamma-irradiation effects on aciclovir poly(d,l-lactic-co-glycolic) acid (PLGA) microspheres, with gelatin as additive, were studied. Microspheres with a 2:2:10 aciclovir:gelatin:polymer ratio were prepared by the solvent evaporation method and sterilised by ?-irradiation at a dose of 25 kGy. Loading efficiency, morphology (particle size analysis, scanning electron microscopy (SEM)), physical chemistry (infrared (IR) absorption spectrophotometry, differential scanning calorimetry (DSC), X-ray diffraction and

Concepción Mart??nez-Sancho; Roc??o Herrero-Vanrell; Sof??a Negro

2004-01-01

153

Ethical use of long-acting medications in the treatment of severe and persistent mental illnesses  

Microsoft Academic Search

Mental illnesses are prevalent, cause great suffering, and are burdensome to society. Traditional “depot” antipsychotic agents are used to treat the most severely and persistently mentally ill individuals. They will soon be joined by new atypical antipsychotic medications in long-acting formulations. These long-acting medications pose special ethical issues, but may greatly benefit some people who suffer from severe and persistent

Laura Weiss Roberts; Cynthia M. A Geppert

2004-01-01

154

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.

155

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

156

Protein bioactivity and polymer orientation is affected by stabilizer incorporation for double-walled microspheres.  

PubMed

Double-walled microspheres present an improved drug delivery technique for sustained release of encapsulated substrates. In this study, the release kinetics and biological activity of lysozyme was analyzed from microspheres comprised of poly(lactic-co-glycolic acid) (PLGA) and poly(L-lactide) (PLLA). In addition, coencapsulation of the anionic surfactant, docusate sodium salt (AOT), was investigated as a method of decreasing protein denaturation during microsphere fabrication. Herein, we show that through the inclusion of AOT, the capacity for two chemically similar polymers to phase separate and form double-walled (DW) microspheres is impaired leading to unique protein release kinetics. Additionally, we present the time period over which our released enzyme, lysozyme, remains biologically active. The consequences of AOT on protein bioactivity are also assessed and provide strong implications for the importance of appropriate stabilizer analysis in future studies involving drug co-encapsulates in polymer based microsphere systems. PMID:19751780

Kokai, Lauren E; Tan, Huaping; Jhunjhunwala, Siddharth; Little, Steven R; Frank, Jason W; Marra, Kacey G

2010-01-25

157

A new preparation method for protein loaded poly( d, l-lactic-co-glycolic acid) microspheres and protein release mechanism study  

Microsoft Academic Search

A new method for encapsulating a model protein, lysozyme into hydrophilic uncapped poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres was developed using an oil\\/water (O\\/W) single emulsion technique. Lysozyme powder, which was prepared from lyophilization after adjusting a lysozyme solution pH at 3, was molecularly dissolved in a co-solvent system composed of dimethylsulfoxide (DMSO) and methylene chloride. The resulting organic solution containing PLGA

Tae Gwan Park; Hee Yong Lee; Yoon Sung Nam

1998-01-01

158

Fabrication of Nanostructured PLGA Scaffolds Using Anodic Aluminum Oxide Templates  

Microsoft Academic Search

PLGA (poly(lactic-co-glycolic acid)) is one of the most used biodegradable and biocompatible materials. Nanostructured PLGA even has great application potentials in tissue engineering. In this research, a fabrication technique for nanostructured PLGA membrane was investigated and developed. In this novel fabrication approach, an anodic aluminum oxide (AAO) film was use as the template; the PLGA solution was then cast on

Cheng-Chih Hsueh; Gou-Jen Wang; Shan-Hui Hsu; Huey-Shan Hung

2008-01-01

159

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

PubMed Central

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

Karner, Charlotta; Cates, Christopher J

2014-01-01

160

Effect of gamma-irradiation on peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) microspheres.  

PubMed

The effect of gamma-irradiation on the physicochemical properties of peptide-containing hydrophilic poly (d,l-lactide-co-glycolide) (PLGA) microspheres was evaluated. PLGA (50/50, Mw: 8,600) with free carboxylic end groups was used to make drug-loaded and placebo microspheres by a solvent extraction evaporation method. Both formulated and non-formulated microspheres were gamma-irradiated at 0, 1, 1.5, and 2.5 Mrad doses. HPLC analysis based on extraction of peptide from the microspheres showed that peptide content of the microspheres was lowered upon irradiation and the reduction was more pronounced in formulated microspheres. The in-vitro release in 0.033M phosphate buffer, pH 7.0 at 37 degrees C (based on extraction of residual peptide) showed that the initial and subsequent release of peptide was higher in gamma-irradiated microspheres during the first 20 days. The difference became insignificant during the erosional controlled release of the peptide. There was no difference in release between the formulated and non-formulated microspheres of the nonirradiated or irradiated forms. Molecular weights (Mw and Mn), determined by size exclusion chromatography, were reduced by gamma-irradiation for both formulated and non-formulated placebo microspheres. Differential scanning calorimetry showed a gradual reduction in Tg of placebo microspheres but no reduction in peptide-loaded microspheres. In-vivo evaluation of the nonirradiated and the 1.5 Mrad irradiated microspheres showed no marked differences through 28 days. Since irradiation caused a lowering of Mw and Mn with the appearance of a low amount of unidentified substances, seemingly catalyzed by the polymer and the formulation excipients, gamma-irradiation sterilization of these parenteral delivery systems requires careful investigation on an individual product basis. PMID:10754729

Shameem, M; Lee, H; Burton, K; Thanoo, B C; Deluca, P P

1999-01-01

161

Evaluation of PEGylated exendin-4 released from poly (lactic-co-glycolic acid) microspheres for antidiabetic therapy.  

PubMed

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

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

2015-01-01

162

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

Microsoft Academic Search

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

Yilmaz Capan; Byung H Woo; Sisay Gebrekidan; Shamim Ahmed; Patrick P DeLuca

1999-01-01

163

The effect of gamma irradiation on PLGA and release behavior of BCNU from PLGA wafer  

Microsoft Academic Search

The objectives of this study were to investigate the influence of gamma irradiation for sterilization on poly(D,L-lactide-co-glycolide) (PLGA) with different molecular weight and the effect of gamma irradiation on the release behavior of 1,3-bis(2-chloroethyl)-1-nitrosourea\\u000a (BCNU, carmustine) from PLGA wafer with various irradiation doses. The effect of gamma irradiation on PLGA was evaluated by\\u000a gel permeation chromatography (GPC), differential scanning calorimetry

Jin Soo Lee; Gang Soo Chae; Gilson Khang; Moon Suk Kim; Sun Hang Cho; Hai Bang Lee

2003-01-01

164

Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization.  

PubMed

Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres. All synthesized microspheres were spherical in shape, calibrated in the 300-500 ?m range, swelled in phosphate-buffered saline (PBS) and easily injectable through a microcatheter. Hydrolytic degradation experiments performed in PBS at 37 °C showed that all of the formulations tested were totally degraded in less than 2 days. The resulting degradation products were a mixture of low-molecular-weight compounds (PEG, lactic and glycolic acids) and water-soluble polymethacrylate chains having molecular weights below the threshold for renal filtration of 50 kg mol(-1) for the microspheres containing MDO. Both the microspheres and the degradation products were determined to exhibit minimal cytotoxicity against L929 fibroblasts. Additionally, in vivo implantation in a subcutaneous rabbit model supported the in vitro results of a rapid degradation rate of microspheres and provided only a mild and transient inflammatory reaction comparable to that of the control group. PMID:24321348

Louguet, Stéphanie; Verret, Valentin; Bédouet, Laurent; Servais, Emeline; Pascale, Florentina; Wassef, Michel; Labarre, Denis; Laurent, Alexandre; Moine, Laurence

2014-03-01

165

Microradiographic microsphere manipulator  

DOEpatents

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

Singleton, Russell M. (Livermore, CA)

1980-01-01

166

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

Microsoft Academic Search

Aim:To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats.Methods:The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method. Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti-rhEPO antibody in the serum was measured to

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

2012-01-01

167

Hybrid microspheres  

NASA Technical Reports Server (NTRS)

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

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

1985-01-01

168

Comparative efficacy and safety of long-acting risperidone and risperidone oral tablets  

Microsoft Academic Search

A double-blind study of long-acting injectable risperidone and oral risperidone tablets was conducted in 640 patients with schizophrenia. All patients received flexible doses of 1–6 mg of oral risperidone for 8 weeks. Doses were stable during weeks 5–8. At the end of week 8, symptomatically stable patients were randomly assigned to receive long-acting risperidone (active injections, dummy oral) or continued

Pierre Chue; Marielle Eerdekens; Ilse Augustyns; Bernard Lachaux; Peter Mol?an; Lars Eriksson; H. Pretorius; Anthony S. David

2005-01-01

169

Improvement of protein loading and modulation of protein release from poly(lactide-co-glycolide) microspheres by complexation of proteins with polyanions.  

PubMed

A novel method was proposed to incorporate and modulate protein release from poly(lactide-co-glycolide) (PLGA) microspheres by a modified w/o/w emulsion solvent evaporation technique with poly(methacrylic acid) (PMAA)/insulin complex suspension as the inner aqueous phase instead of the neat protein solution. It was found that a reversible, water-insoluble complex could be formed between PMAA and insulin by electrostatic interactions. A great increase in insulin entrapment efficiency was observed as the PMAA/insulin complex was adopted to prepare PLGA microspheres. A large number of the complex particles adsorbed at the surface of the microspheres, resulting in the more rapid insulin release. The complexation and microencapsulation processes have little effect on insulin bioactivity, which was revealed by examination of the plasma glucose levels of the diabetic rats administrated with the microspheres. PMID:15762319

Jiang, H L; Jin, J F; Hu, Y Q; Zhu, K J

2004-09-01

170

Fabrication, characterization and in vitro release of paclitaxel (Taxol ®) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid\\/cholesterol emulsifiers  

Microsoft Academic Search

Spray dry technique was applied to produce paclitaxel loaded microspheres of biodegradable poly (lactic-co-glycolic acid) (PLGA) as an alternative delivery system. Various emulsifiers such as l-?-dipalmitoyl-phosphatidylcholine (DPPC), cholesterol, polyvinyl alcohol (PVA), gelatin were incorporated in order to achieve high encapsulating efficiency of paclitaxel in the microspheres and desired properties for a sustained release. Atomic force microscopy (AFM) and scanning electron

L Mu; S. S Feng

2001-01-01

171

Protective immunity in rats by intranasal immunization with Streptococcus mutans glucan-binding protein D encapsulated into chitosan-coated poly(lactic-co-glycolic acid) microspheres  

Microsoft Academic Search

Recombinant Streptococcus mutans glucan-binding protein D (rGbpD) was incorporated into poly(lactic-co-glycolic acid) (PLGA) microspheres which then were surface-coated with chitosan. The microspheres, with a mean diameter of ca. 1.8 m, were intranasally administered in rats. There were elevated salivary immunoglobulin A and serum immunoglobulin G antibody responses to rGbpD, as well as lower molar caries scores in immunized animals as compared to

Hongping Zhao; Buling Wu; Hong Wu; Lingyun Su; Jianliang Pang; Tiehong Yang; Yanli Liu

2006-01-01

172

Pitch carbon microsphere composite  

NASA Technical Reports Server (NTRS)

Petroleum pitch carbon microspheres were prepared by flash heating emulsified pitch and carbonizing the resulting microspheres in an inert atmosphere. Microsphere composites were obtained from a mixture of microspheres and tetraester precursor pyrrone powder. Scanning electron micrographs of the composite showed that it was an aggregate of microspheres bonded together by the pyrrone at the sphere contact points, with voids in and among the microspheres. Physical, thermal, and sorption properties of the composite are described. Composite applications could include use as a honeycomb filler in elevated-temperature load-bearing sandwich boards or in patient-treatment tables for radiation treatment of tumors.

Price, H. L.; Nelson, J. B.

1977-01-01

173

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

PubMed

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

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

2015-05-01

174

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

PubMed Central

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

2013-01-01

175

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

PubMed

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

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

2014-10-01

176

The effect of formulation variables on the characteristics of insulin-loaded poly(lactic-co-glycolic acid) microspheres prepared by a single phase oil in oil solvent evaporation method  

Microsoft Academic Search

Biodegradable polymeric microspheres are ideal vehicles for controlled delivery applications of drugs, peptides and proteins. Amongst them, poly(lactic-co-glycolic acid) (PLGA) has generated enormous interest due to their favorable properties and also has been approved by FDA for drug delivery. Insulin-loaded PLGA microparticles were prepared by our developed single phase oil in oil (o\\/o) emulsion solvent evaporation technique. Insulin, a model

Hamed Hamishehkar; Jaber Emami; Abdolhossein Rouholamini Najafabadi; Kambiz Gilani; Mohsen Minaiyan; Hamid Mahdavi; Ali Nokhodchi

2009-01-01

177

A Review of Long-Acting Medications for ADHD in Canada  

PubMed Central

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

Hosenbocus, Sheik; Chahal, Raj

2009-01-01

178

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

PubMed

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

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

2015-03-30

179

[Preparation and properties of Talpha1 loaded injectable sustained release microspheres].  

PubMed

To prepare thymosin alpha-1 (Talpha) loaded injectable sustained release microspheres and to evaluate its release behavior, bioactivities in vitro as well as its pharmacodynamics in vivo, Talpha1 loaded microspheres was prepared with poly ( lactic-co-glycolic acid) (PLGA) as carrier material by double emulsion (W/O/W) method. Physical and chemical properties of microspheres, such as mean diameter, The release behavior and its influencing factors were morphology and drug loading were evaluated. evaluated by HPLC determination. The bioactivity of Talpha1 in the course of encapsulation process and in vitro release ware evaluated by CCK-8 method. The ratio of CD4+/CD8+ in blood was determined with flow cytometry and the pharmacodynamics of Ta, loaded microspheres was evaluated by the change of CD4+/ CD8+. Microspheres with good shape and dispersive quality were prepared. The drug entrapment efficiency of two optimizing prescriptions containing 5% NaCl and 10% glucose as outer water phase were 87. 8% and 90. 2% , respectively. The cumulated release in one month is up to 90%. The bioactivity of Talpha was conserved with glucose as outer water phase, but in the course of in vitro release, the specific activity of Talpha in the microspheres decreased a little. Talpha microspheres can increase significantly the immunity of immuno-suppressed rats. Talpha can be encapsulated in injectable microspheres to yield one-month continuous release when using biodegradable polymers PLGA as carrier material, and this technique will have a favorable perspective in the near future. PMID:17518054

Zhu, Yan; Lu, Ying; Zhong, Yan-qiang

2007-02-01

180

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

NASA Astrophysics Data System (ADS)

Herein, we envisage the possibility of preparing stable cationic poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating the iron oxide nanoparticles (IONPs; 8-12 nm). The IONPs are incorporated into PLGA in organic phase followed by microsphere formation and chitosan coating in aqueous medium via nano-emulsion technique. The average size of the microspheres, as determined by dynamic light scattering are about 310 nm, while the zeta potential for the composite remains near 35 mV at pH 4.0. These microspheres are electrophoretically deposited onto indium tin oxide (ITO)-coated glass substrate used as cathode and parallel platinum plate as the counter electrode. This platform is utilized to fabricate a DNA biosensor, by immobilizing a probe sequence specific to Escherichia coli. The bioelectrode shows a surface-controlled electrode reaction with the electron transfer coefficient (?) of 0.64 and charge transfer rate constant (ks) of 61.73 s-1. Under the optimal conditions, this biosensor shows a detection limit of 8.7 × 10-14 M and is found to retain about 81% of the initial activity after 9 cycles of use.Herein, we envisage the possibility of preparing stable cationic poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating the iron oxide nanoparticles (IONPs; 8-12 nm). The IONPs are incorporated into PLGA in organic phase followed by microsphere formation and chitosan coating in aqueous medium via nano-emulsion technique. The average size of the microspheres, as determined by dynamic light scattering are about 310 nm, while the zeta potential for the composite remains near 35 mV at pH 4.0. These microspheres are electrophoretically deposited onto indium tin oxide (ITO)-coated glass substrate used as cathode and parallel platinum plate as the counter electrode. This platform is utilized to fabricate a DNA biosensor, by immobilizing a probe sequence specific to Escherichia coli. The bioelectrode shows a surface-controlled electrode reaction with the electron transfer coefficient (?) of 0.64 and charge transfer rate constant (ks) of 61.73 s-1. Under the optimal conditions, this biosensor shows a detection limit of 8.7 × 10-14 M and is found to retain about 81% of the initial activity after 9 cycles of use. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr34355c

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

2013-04-01

181

Treatment Adherence with Early Prescription of Long-Acting Injectable Antipsychotics in Recent-Onset Schizophrenia  

PubMed Central

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

2012-01-01

182

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

2012-01-01

183

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

E-print Network

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

Zheng, Yufeng

184

Preparation, characterization, and in vivo evaluation of salmon calcitonin microspheres  

Microsoft Academic Search

Purpose. This study was done to prepare, characterize, and evaluate salmon calcitonin (sCT) microspheres (ms) in vivo using a low\\u000a molecular weight, hydrophilic 50?50 poly (D,L-lactide-co-glycolide) polymer (PLGA).Methods. sCT ms were prepared by a dispersion\\/solvent extraction\\/evaporation process and characterized for drug content, particle\\u000a size, surface morphology, and structural integrity of encapsulated peptide. Peptide stability and binding to the polymer was

Bhas A. Dani; Patrick P. DeLuca

2001-01-01

185

Effectiveness of long-acting injectable antipsychotics in delusional disorders with nonprominent hallucinations and without hallucinations.  

PubMed

The presence of nonprominent hallucinations in delusional disorder (DD) has been accepted by the current Diagnostic and Statistical Manual of Mental Disorders, 5th ed. A recent meta-analysis revealed that patients with schizophrenia treated with long-acting atypical antipsychotics showed a significant improvement in psychotic symptoms. However, little research has been conducted on DD. Our goal was to investigate demographic and clinical differences between two subgroups of DD patients, those with nonprominent hallucinations and those without hallucinations, and to determine treatment effectiveness of long-acting antipsychotics in these patients. We conducted a longitudinal observational study with a 6-month follow-up period in a clinical group of 45 DD outpatients. Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale, and Hamilton Rating Scale for Depression-17 (HRSD-17) were used for assessment. Age at onset of DD, scores in baseline assessment scales, and drug compliance were included in the analysis as potential confounders. When uncorrected for influencing factors, patients treated with long-acting antipsychotics showed lower scores in PANSS positive and negative subscales. There were no statistically significant clinical subgroup×treatment group interactions for any of the scores in assessment scales at 6 months. After adjustment, patients treated with long-acting antipsychotics showed lower scores in the PANSS negative subscale and a tendency toward improvement in scores in the PANSS positive subscale. Our study suggests that risperidone long-acting injection and paliperidone palmitate long-acting injection may be useful in the treatment of DD patients, specifically those with nonprominent hallucinations. PMID:24681811

González-Rodríguez, Alexandre; Molina-Andreu, Oriol; Penadés, Rafael; Bernardo, Miquel; Catalán, Rosa

2014-05-01

186

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

187

A protein delivery system: biodegradable alginate–chitosan–poly(lactic-co-glycolic acid) composite microspheres  

Microsoft Academic Search

In the present study we developed alginate–chitosan–poly(lactic-co-glycolic acid) (PLGA) composite microspheres to elevate protein entrapment efficiency and decrease its burst release. Bovine serum albumin (BSA), which used as the model protein, was entrapped into the alginate microcapsules by a modified emulsification method in an isopropyl alcohol-washed way. The rapid drug releases were sustained by chitosan coating. To obtain the desired

Cai-Hong Zheng; Jian-Qing Gao; Ye-Ping Zhang; Wen-Quan Liang

2004-01-01

188

Poly( d, l lactic- co-glycolic acid) microspheres as biodegradable microcarriers for pluripotent stem cells  

Microsoft Academic Search

The pluripotent nature and proliferative capacity of embryonic stem cells makes them an attractive cell source for tissue engineering and regeneration. In our study we investigated the use of poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres as biodegradable microcarriers of pluripotent cells and as delivery systems of bioactive factors, which influence cell differentiation. The pluripotent P19 embryonal carcinoma cell line was used as

Kimberley D Newman; Michael W McBurney

2004-01-01

189

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

190

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

191

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

192

Engineering of Crystalline Combination Inhalation Particles of a Long-Acting ? 2 -agonist and a Corticosteroid  

Microsoft Academic Search

Purpose  Engineering of inhalation particles incorporating, in each individual particle, a combination of a long-acting ?-agonist and\\u000a a glucocorticosteroid in a pre-determined and constant ratio for delivery via a dry powder inhaler (DPI).\\u000a \\u000a \\u000a \\u000a Methods  Individual crystalline particles containing both the glucocorticosteroid fluticasone propionate (FP) and long-acting ?-agonist\\u000a salmeterol (SX) were prepared, in a ratio of 10:1, using the solution atomization and crystallization

Chonladda Pitchayajittipong; Jagdeep Shur; Robert Price

2009-01-01

193

[Glycopyrronium bromide is a long-acting inhaled anticholinergic in the treatment of severe COPD.  

PubMed

Long-acting bronchodilators are central in the management of chronic obstructive pulmonary disease (COPD). This short review provides an overview of the studies evaluating the safety and efficacy of inhaled glycopyrronium, a long-acting muscarinic antagonist, in patients with COPD. Glycopyrronium has clinically important effects on the level of forced expiratory volume in the first second, use of rescue medication, daytime dyspnoea scores, and health status. Glycopyrronium also has beneficial effects on dynamic hyperinflation, exercise tolerance, and the rate of exacerbations. Glycopyrronium seems to have the potential for a significant role in the future management of COPD. PMID:23978116

Ulrik, Charlotte Suppli

2013-08-26

194

Magnetically responsive elastic microspheres  

NASA Astrophysics Data System (ADS)

We report the design, fabrication, and characterization of magnetically responsive elastic microspheres consisting of polydimethylsioxane (PDMS) and magnetic nano-/microparticles. The microspheres can have either core-shell or solid structure, fabricated by using a microfluidic technique. The mechanical characteristics are determined with a modified electronic balance, and the results show that the microspheres exhibit magnetostrictive effect. Such microspheres can in addition behave as a smart material controllable through an external magnetic field. Owing to the transparency, biocompatibility and nontoxicity of PDMS, the magnetically responsive elastic microspheres may have potential applications in drug delivery, biosensing, bioseparation, and medical diagnosis.

Peng, Suili; Zhang, Mengying; Niu, Xize; Wen, Weijia; Sheng, Ping; Liu, Zhengyou; Shi, Jing

2008-01-01

195

Treatment-completion rates with olanzapine long-acting injection versus risperidone long-acting injection in a 12-month, open-label treatment of schizophrenia: indirect, exploratory comparisons  

PubMed Central

Background Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia. Methods Indirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication’s effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study) with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a “sensitivity analysis,” using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates. Results Comparison of olanzapine long-acting injection data (931 patients) with the pooled data from the nine risperidone long-acting injection studies (3950 patients) provided almost identical 12-month treatment-completion rates (72.7% versus 72.4%; P = 0.87). When the two most similar studies were compared, the 12-month completion rate for olanzapine long-acting injection was significantly higher than for risperidone long-acting injection (81.3% versus 47.0%; P < 0.001). However, any conclusions drawn from this comparison may be limited by differences in the studies’ geographic catchment areas. Conclusion Using treatment-completion rates as a proxy measure of medication effectiveness, olanzapine long-acting injection did not differ significantly from risperidone long-acting injection when including all eligible studies. However, the findings of this exploratory analysis should be interpreted with caution, considering the methodological limitations of these indirect, cross-study comparisons. PMID:22615534

Ascher-Svanum, Haya; Montgomery, William S; McDonnell, David P; Coleman, Kristina A; Feldman, Peter D

2012-01-01

196

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

E-print Network

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

Paris-Sud XI, Université de

197

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

PubMed Central

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

Catalán, Rosa; Penadés, Rafael

2011-01-01

198

Use of Long-Acting Birth Control Rises Fivefold in A Decade: CDC  

MedlinePLUS

... page, please enable JavaScript. Use of Long-Acting Birth Control Rises Fivefold in a Decade: CDC IUDs ... 2015) Tuesday, February 24, 2015 Related MedlinePlus Pages Birth Control Women's Health TUESDAY, Feb. 24, 2015 (HealthDay ...

199

Treatment effectiveness and adherence in patients with schizophrenia treated with risperidone long-acting injection  

Microsoft Academic Search

This study investigated the variables related to the effectiveness and adherence to treatment with risperidone long-acting injection (RLAI) in patients with schizophrenia. We performed a retrospective medical chart review of 137 patients with schizophrenia who were prescribed RLAI between July 2004 and December 2006. Cox regression analysis showed that the effectiveness of treatment in patients treated with RLAI was affected

Chen-Lin Chang; Dong-Sheng Tzeng; For-Wey Lung

2010-01-01

200

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. PMID:22659176

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

201

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

PubMed

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

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

2014-01-01

202

Improved peripheral nerve regeneration with sustained release nerve growth factor microspheres in small gap tubulization  

PubMed Central

Objective: To evaluate the long-term results of the use of nerve growth factor (NGF)-loaded poly-D, L-lactide-co-glycolide (PLGA) microspheres for improve nerve regeneration with small gap tubulization. Methods: NGF microspheres were prepared by a modified W/O/W emulsion solvent evaporation method. Forty-eight male SD rats were separated into 4 groups and received a chitin conduit to bridge a sciatic nerve injury left a 2 mm gap. Saline (Group A), 20 ng/ml NGF solution (Group B), blank PLGA microspheres (Group C), or 40 ng/ml NGF-loaded microspheres (Group D) was injected in the gap. Each group had two study endpoints, 3 months subgroup and 1 year subgroup. Results: The myelinated fiber count at 2 mm distal to the conduit at 1 year was slightly less than at 3 months in all groups (P>0.05). However, the maturity of the myelinated nerves at 1 year was obviously improved. The fiber count, myelin sheath thickness, axon area of NGF microsphere group were significantly higher than the saline groups at 3 months (P=0.05, P<0.05, and P<0.05, respectively). The SFI was significantly improved in NGF microspheres group compared to the saline group and NGF solution group at 1 year (P<0.05, and P<0.05, respectively). Conclusions: The results demonstrated that the release of NGF microspheres in small gap tubulization benefit on peripheral nerve injury facilitated nerve regeneration histologically, especially for the maturity of early regenerative nerve fibers and also had an effect on functional recovery in the long term. PMID:25075258

Wang, Zhenwei; Han, Na; Wang, Jiancheng; Zheng, Hua; Peng, Jianping; Kou, Yuhui; Xu, Chungui; An, Shuai; Yin, Xiaofeng; Zhang, Peixun; Jiang, Baoguo

2014-01-01

203

Switching from risperidone long-acting injectable to paliperidone long-acting injectable or oral antipsychotics: analysis of a Medicaid claims database.  

PubMed

This report examines relapse risk following a switch from risperidone long-acting injectable (RLAI) to another long-acting injectable antipsychotic [paliperidone palmitate (PP)] versus a switch to oral antipsychotics (APs). Truven Health's MarketScan Multistate Medicaid Database compared relapses following switches from RLAI. New user cohorts for these two groups were created on the basis of first incidence of exposure to the 'switched to' drug. Groups were balanced using 1:1 propensity score matching. Time-to-event analysis assessed schizophrenia-related hospital/emergency department visits. A total of 188 patients switched from RLAI to PP, and 131 patients switched from RLAI to oral AP. Propensity score-matched cohort included 109 patients who switched to PP and 109 patients who switched to an oral AP. Patients who switched from RLAI to PP had fewer events (26 vs. 32), longer time to an event (mean 70 vs. 47 days), and lower risk of relapse (hazard ratio, 0.54; 95% confidence interval, 0.32-0.92; P=0.024) compared with those who switched from RLAI to oral AP. Switching from RLAI to PP may be associated with a lower risk for relapse and longer duration of therapy compared with switching to oral AP. Given the limitations of observational studies, these results should be confirmed by other prospective evaluations. PMID:25730525

Voss, Erica A; Ryan, Patrick B; Stang, Paul E; Hough, David; Alphs, Larry

2015-05-01

204

Switching from risperidone long-acting injectable to paliperidone long-acting injectable or oral antipsychotics: analysis of a Medicaid claims database  

PubMed Central

This report examines relapse risk following a switch from risperidone long-acting injectable (RLAI) to another long-acting injectable antipsychotic [paliperidone palmitate (PP)] versus a switch to oral antipsychotics (APs). Truven Health’s MarketScan Multistate Medicaid Database compared relapses following switches from RLAI. New user cohorts for these two groups were created on the basis of first incidence of exposure to the ‘switched to’ drug. Groups were balanced using 1:1 propensity score matching. Time-to-event analysis assessed schizophrenia-related hospital/emergency department visits. A total of 188 patients switched from RLAI to PP, and 131 patients switched from RLAI to oral AP. Propensity score-matched cohort included 109 patients who switched to PP and 109 patients who switched to an oral AP. Patients who switched from RLAI to PP had fewer events (26 vs. 32), longer time to an event (mean 70 vs. 47 days), and lower risk of relapse (hazard ratio, 0.54; 95% confidence interval, 0.32–0.92; P=0.024) compared with those who switched from RLAI to oral AP. Switching from RLAI to PP may be associated with a lower risk for relapse and longer duration of therapy compared with switching to oral AP. Given the limitations of observational studies, these results should be confirmed by other prospective evaluations. PMID:25730525

Ryan, Patrick B.; Stang, Paul E.; Hough, David; Alphs, Larry

2015-01-01

205

Patient perspectives in the development and use of long-acting antipsychotics in schizophrenia: focus on olanzapine long-acting injection  

PubMed Central

Schizophrenia is a chronic mental disorder generally treated with antipsychotic medication. However, non-adherence and partial adherence to antipsychotic medication treatment is common and long-acting injectable “depot” preparations of antipsychotic medications have been used as an alternative to oral medication therapy for patients for whom adherence is a clinically significant problem, as well as for the sake of convenience and in response to patient preference. Olanzapine long-acting injection (OLAI) is a new treatment option and has been approved by several regulatory agencies for the treatment of schizophrenia. OLAI is a crystalline salt formulation of olanzapine and pamoic acid. Efficacy was established in 2 double-blind randomized clinical trials of OLAI for the treatment of acute schizophrenia and for the maintenance of response. The therapeutic OLAI dosages are 150 mg q2 weeks, 210 mg q2 weeks, 300 mg q2 weeks or q4 weeks, and 405 mg q4 weeks, administered by deep intramuscular gluteal injection with a 19-gauge needle. Injection volume ranges from 1 to 2.7 mL. OLAI has essentially the same general tolerability as that of oral olanzapine; however with the depot there is the additional risk of a post-injection delirium sedation syndrome occurring at a rate of 0.07% of injections, requiring a risk management plan that includes observing the patient for 3 hours post injection. PMID:20016798

Citrome, Leslie

2009-01-01

206

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. PMID:23990717

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

207

Hydrogen microsphere hazard evaluation  

NASA Astrophysics Data System (ADS)

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

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

1981-03-01

208

Combination of immune stimulating adjuvants with poly(lactide-co-glycolide) microspheres enhances the immune response of vaccines.  

PubMed

The development of vaccines that generate mixed humoral and cellular immune responses is a challenge in vaccinology. Poly(lactide-co-glycolide) microspheres are vaccine adjuvants which possess the advantage of allowing the coencapsulation of other adjuvants in addition to the antigen. Thus, we can stimulate the immune system from different ways and resemble the effects of a natural infection. In this study, we have coencapsulated BSA with monophosphoryl lipid A, polyinosinic-polycytidylic acid, ?-galactosylceramide and alginate into PLGA microspheres. All the microspheres have developed a higher humoral immune response, in terms of release of total IgG, in comparison to the administration of soluble antigen. In addition, they triggered a more balanced IgG1/IgG2a response. The combination of MPLA and ?-galactosylceramide within the microspheres developed the higher cellular response, confirming that combination of adjuvants with different action mechanisms is a good strategy to increase vaccines' immunogenicity. PMID:22119926

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

2012-01-11

209

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

210

[Intravenous regional anesthesia with long-acting local anesthetics. An update].  

PubMed

Intravenous regional anesthesia is a widely used technique for brief surgical interventions, primarily on the upper limbs and less frequently, on the lower limbs. It began being used at the beginning of the 20th century, when Bier injected procaine as a local anesthetic. The technique to accomplish anesthesia has not changed much since then, although different drugs, particularly long-acting local anesthetics, such as ropivacaine and levobupivacaine in low concentrations, were introduced. Additionally, drugs like opioids, muscle relaxants, paracetamol, neostigmine, magnesium, ketamine, clonidine, and ketorolac, have all been investigated as adjuncts to intravenous regional anesthesia, and were found to be fairly useful in terms of an increased onset of operative anesthesia and longer lasting perioperative analgesia. The present article provides an overview of current knowledge with emphasis on long-acting local anesthetic drugs. PMID:24156887

Atanassoff, P G; Lobato, A; Aguilar, J L

2014-02-01

211

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

PubMed Central

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

El-Hage, Wissam; Surguladze, Simon A

2010-01-01

212

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

PubMed Central

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

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

2008-01-01

213

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

2013-08-16

214

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

215

Short and long-acting oral nitrates for stable angina pectoris  

Microsoft Academic Search

Nitroglycerin (NTG) spray and sublingual tablets rapidly relieve an established attack of angina, and their infrequent use is not associated with the development of tolerance. Although, following a suitable nitrate-free interval, the first dose of oral, long-acting nitrates produces significant hemodynamic effects, increases angina free walking, and decreases exercise-induced ischemia, during continued long-term therapy tolerance limits their usefulness. Appropriate dosing

Udho Thadani; Raymond J. Lipicky

1994-01-01

216

Lysozyme release and polymer erosion behavior of injectable implants prepared from PLGA-PEG block copolymers and PLGA/PLGA-PEG blends  

PubMed Central

Purpose We evaluated the controlled release lysozyme from various poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50-polyethylene glycol (PEG) block copolymers relative to PLGA 50/50. Methods Lysozyme was encapsulated in cylindrical implants (0.8 mm diameter) by a solvent extrusion method. Release studies were conducted in phosphate buffered saline + 0.02 % Tween 80 (PBST) at 37°C. Lysozyme activity was measured by a fluorescence-based assay. Implant erosion was evaluated by kinetics of polymer molecular weight decline, water uptake, and mass loss. Results Lysozyme release from an AB15 di-block copolymer (15% 5 kDa PEG, PLGA 28 kDa) was very fast, whereas an AB10 di-block copolymer (with 10% 5 kDa PEG, PLGA 45 kDa) and ABA10 tri-block copolymer (with 10% 6 kDa PEG, PLGA 27kDa) showed release profiles similar to PLGA. We achieved continuous lysozyme release for up to 4 weeks from AB10 and ABA10 by lysozyme co-encapsulation with the pore- forming and acid-neutralizing MgCO3, and from AB15 by co-encapsulation of MgCO3 and blending AB15 with PLGA. Lysozyme activity was mostly recovered during four weeks. Conclusions These block co-polymers may have utility either alone or as PLGA blends for the controlled release of proteins. PMID:23959854

Milacic, Vesna; Schwendeman, Steven P.

2013-01-01

217

Controlled Delivery of the Anti-VEGF Aptamer EYE001 with Poly(lactic-co-glycolic)Acid Microspheres  

Microsoft Academic Search

PURPOSE. To develop a controlled-drug delivery system for the long-term inhibition of vascular endothelial growth factor (VEGF) and its mediated responses. METHODS. Poly(lactic-co-glycolic)acid (PLGA) microspheres containing anti-VEGF RNA aptamer (EYE001) formulations in the solid-state were developed by an oil-in-oil solvent evapora- tion process. In vitro experiments were performed to charac- terize the release profiles. Stability and bioactivity of the re-

Karen G. Carrasquillo; Joseph A. Ricker; Ioannis K. Rigas; Joan W. Miller; Evangelos S. Gragoudas; Anthony P. Adamis

2003-01-01

218

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

219

Making Polymeric Microspheres  

NASA Technical Reports Server (NTRS)

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

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

1989-01-01

220

Production of hollow aerogel microspheres  

DOEpatents

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

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

1993-01-01

221

Polyurethane Microspheres as Drug Carriers  

Microsoft Academic Search

Polyurethane microspheres were prepared by reacting polyethylene glycol [PEG] (of different molecular weights) with different mole ratios of tolylene diisocyanate. A conventional drug was incorporated into the microspheres. The polyurethane microspheres were characterized by FTIR, optical microscopy and particle size analysis. The equilibrium fluid content of microspheres was determined in suitable buffer media. The release pattern of the drug entrapped

P. V. Siva Reddy; G. N. Mahesh; S. Ramesh; P. A. Sivakumar; Ganga Radhakrishnan

1995-01-01

222

Production of hollow aerogel microspheres  

SciTech Connect

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

223

Metabolism of proteinoid microspheres  

NASA Technical Reports Server (NTRS)

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

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

1987-01-01

224

Metabolism of proteinoid microspheres  

NASA Technical Reports Server (NTRS)

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

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

1987-01-01

225

Improved injectability and in vitro degradation of a calcium phosphate cement containing poly(lactide-co-glycolide) microspheres.  

PubMed

An injectable calcium phosphate cement (CPC) containing 30 wt.% poly(lactide-co-glycolide) (PLGA) microspheres was developed in the present study. Sodium citrate solution was used as the cement liquid phase. The effects of sodium citrate concentration on the injectability, rheological properties, mechanical strength and self-setting properties of CPC containing PLGA microspheres were systematically investigated. The in vitro degradation behavior of the composite during immersion in phosphate buffer solution was also studied. With an increase in sodium citrate concentration, the viscosity and yield stress of the paste were reduced, thereby improving the injectability. At a sodium citrate concentration of 15%, the injectability of the paste reached 95%. The compressive strength of the specimen was also enhanced by the addition of sodium citrate. The specimens had a compressive strength of 32.24+/-2.72 MPa at 15% sodium citrate concentration, compared to 22.15+/-3.60 MPa for the specimen without sodium citrate. The in vitro degradation results demonstrate that incorporated PLGA microspheres can provide the required high strength to CPC in the early stage, which would gradually degrade to create macropores for bone ingrowth. In conclusion, an in situ macropore-generable CPC exhibited excellent injectability and high early strength, and should be a promising material for bone repair and bone reconstruction. PMID:18555756

Qi, Xiaopeng; Ye, Jiandong; Wang, Yingjun

2008-11-01

226

Recombinant interferon-alpha2b poly(lactic-co-glycolic acid) microspheres: pharmacokinetics-pharmacodynamics study in rhesus monkeys following intramuscular administration  

Microsoft Academic Search

Aim:Investigation into pharmacokinetic-pharmacodynamic properties of inter-feron-alpha (IFN-?)2b-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) in rhesus monkey primates.Method:IFN-?2b was loaded with biodegradable PLGA with 3 inherent viscosities using a double emulsion and solvent evaporation method. The particle size, surface morphology, and in vitro release profiles were investigated. Two groups of rhesus monkeys (n=3) were injected intramuscularly with either 3 MlU\\/kg commercial IFN-?2b

Yong-ming Zhang; Fan Yang; Yi-qun Yang; Feng-lan Song; An-long Xu

2008-01-01

227

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. PMID:22512527

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

2012-01-01

228

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.?? PMID:11502617

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

2001-01-01

229

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

PubMed Central

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

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

2006-01-01

230

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

231

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

PubMed Central

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

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

2014-01-01

232

Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum.  

PubMed

Drug delivery to the peritoneum is hampered by rapid clearance, and could be improved by application of controlled release technology. We investigated the suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co-glycolic) acid (PLGA), a biodegradable polymer with generally excellent biocompatibility commonly used for controlled drug release. We injected 90 kDa PLGA microparticles, 5-250 microm in diameter, into the murine peritoneum, in dosages of 10-100 mg (n=3-5 per group). We found a high incidence of polymeric residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-microm microparticles caused adhesions in 83% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles>5 microm in diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma irradiated) caused fewer adhesions (16.7%) with a similar incidence of residue. Nanoparticles (265 nm) of 90 kDa PLGA also caused much fewer adhesions (6.3% of animals), possibly because they were cleared from the peritoneum within 2 days, and sequestered in the spleen and liver, where foamy macrophages were noted. The effect of sterilization technique on the incidence of adhesion formation is also studied. PMID:16425240

Kohane, Daniel S; Tse, Julie Y; Yeo, Yoon; Padera, Robert; Shubina, Maria; Langer, Robert

2006-05-01

233

Generational PipeLined Genetic Algorithm (PLGA) using Stochastic Selection  

E-print Network

Generational PipeLined Genetic Algorithm (PLGA) using Stochastic Selection Malay K. Pakhira and Rajat K. De Abstract-- In this paper, a pipelined version of genetic algorithm, called PLGA, and a corresponding hardware platform are described. The basic operations of conventional GA (CGA) are made pipelined

De, Rajat Kumar

234

Microsphere Insulation Panels  

NASA Technical Reports Server (NTRS)

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

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

2006-01-01

235

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

2012-08-01

236

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. PMID:23533090

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

2014-02-01

237

Organic aerogel microspheres  

DOEpatents

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

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

1999-06-01

238

Organic aerogel microspheres  

DOEpatents

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

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

1999-01-01

239

Compartmentalization in proteinoid microspheres  

NASA Technical Reports Server (NTRS)

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

Brooke, S.; Fox, S. W.

1977-01-01

240

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

PubMed Central

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

Karner, Charlotta; Cates, Christopher J

2014-01-01

241

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

PubMed Central

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

2011-01-01

242

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

243

Comparative Effectiveness of Risperidone Long-Acting Injectable vs First-Generation Antipsychotic Long-Acting Injectables in Schizophrenia: Results From a Nationwide, Retrospective Inception Cohort Study.  

PubMed

Objective: To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). Methods: Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician's/patient's choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. Results: Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87-1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86-1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86-1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78-1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. Conclusions: In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second-generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects/patient centered outcomes. In future, head-to-head trials and additional nationwide database studies including other SGA-LAIs is needed. PMID:25180312

Nielsen, Jimmi; Jensen, Signe O W; Friis, Rasmus B; Valentin, Jan B; Correll, Christoph U

2014-09-01

244

Surface characteristics of PLA and PLGA films  

NASA Astrophysics Data System (ADS)

Surface segregation and restructuring in polylactides (poly( D, L-lactide) and poly( L-lactide)) and poly( D,L-lactide-co-glycolide) (PLGA) films of various thicknesses were investigated using both attenuated total reflection FTIR (ATR-FTIR) and contact angle relaxation measurements. In case of poly( D,L-lactide) (DLPLA), it was observed that the surface segregation and the surface restructuring of methyl side groups are influenced by the polymer film thickness. This result has been confirmed by X-ray photoelectron spectroscopy (XPS). In the same way, PLGA thick films were also characterized by an extensive surface segregation of methyl side groups. Finally, surface restructuring was investigated by dynamic contact angle measurements and it was observed when film surface comes into contact with water. In parallel, we also found that poly( L-lactide) (PLLA) thin and clear films with thickness ˜15 ?m undergo conformational changes on the surface upon solvent treatment with certain solvents. The solvent treated surface of PLLA becomes hazy and milky white and its hydrophobicity increases compared to untreated surface. FTIR spectroscopic analysis indicated that polymer chains at the surface undergo certain conformational changes upon solvent treatment. These changes are identified as the restricted motions of C-O-C segments and more intense and specific vibrations of methyl side groups. During solvent treatment, the change in water contact angle and FTIR spectrum of PLLA is well correlated.

Paragkumar N, Thanki; Edith, Dellacherie; Six, Jean-Luc

2006-12-01

245

Efficacy and safety of long acting injectable atypical antipsychotics: a review.  

PubMed

Schizophrenia is a chronic, severe and recurrent brain disorder that requires continuous, long-term treatment with antipsychotic medication to minimize relapse and provide clinical benefit to patients. For patients with schizophrenia, non-adherence to medication is a major risk factor for relapse and re-hospitalization. Long-acting injectable formulations of second-generation antipsychotics (SGAs-LAIs) provide constant medication delivery and the potential for improved adherence. Currently, three drugs are available for the treatment of schizophrenia, risperidone longacting injectable, olanzapine pamoate and paliperidone palmitate. Several studies have also demonstrated efficacy and safety of such drugs in patients with acute schizophrenia. In the present paper the literature on LAI atypical antipsychotics will be reviewed and practical advice will be given concerning the use of these drugs in the clinical practice. PMID:23343445

De Berardis, Domenico; Marini, Stefano; Carano, Alessandro; Lang, Antonella Padovan; Cavuto, Marilde; Piersanti, Monica; Fornaro, Michele; Perna, Giampaolo; Valchera, Alessandro; Mazza, Monica; Iasevoli, Felice; Martinotti, Giovanni; Di Giannantonio, Massimo

2013-08-01

246

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

PubMed Central

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

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

2014-01-01

247

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

PubMed Central

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

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

2011-01-01

248

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

PubMed

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

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

2014-06-15

249

Polypyrrole-Coated Electrospun PLGA Nanofibers for Neural Tissue Applications  

PubMed Central

Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Electrical stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40–50% longer neurites and 40–90% more neurite formation compared to unstimulated cells on the same scaffolds. In addition, stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of electrical stimulation and topographical guidance and the potential use of these scaffolds for neural tissue applications. PMID:19501901

Lee, Jae Young; Bashur, Chris A.; Goldstein, Aaron S.; Schmidt, Christine E.

2009-01-01

250

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

PubMed

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

Crocq, M-A

2015-02-01

251

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

PubMed

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

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

2013-06-01

252

Microsphere contrast agents for OCT  

E-print Network

409 CHAPTER 29 Microsphere contrast agents for OCT Stephen A Boppart Kenneth S Suslick INTRODUCTION in achieving this goal for OCT15 , with the development of contrast agents such as microspheres16 describes the fabrication, characterization and application of a new class of engineered protein microsphere

Suslick, Kenneth S.

253

Thermal Transpiration in Microsphere Membranes  

Microsoft Academic Search

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

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

2003-01-01

254

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

Microsoft Academic Search

Orntide acetate, a novel luteinizing hormone-releasing hormone (LHRH) antagonist, was prepared and evaluated in vivo in 30-day\\u000a and 120-day sustained delivery formulations using a rat animal model. Orntide poly(d,l- lactide-co-glycolide) (PLGA) and poly(d,l-\\u000a lactide) (PLA) microspheres were prepared by a dispersion method and administered subcutaneously in a liquid vehicle to rats\\u000a at 2.2 mg Orntide\\/kg of body weight (30-day forms)

Janusz W. Kostanski; Bhas A. Dani; George-Ann Reynolds; Cyril Y. Bowers; Patrick P. DeLuca

2000-01-01

255

Encapsulation of antigen in poly( d, l-lactide-co-glycolide) microspheres protects from harmful effects of ?-irradiation as assessed in mice  

Microsoft Academic Search

During the last two decades, synthetic polymers such as poly(lactide-co-glycolide) (PLGA) have been investigated for the development of nano- or microparticles as adjuvants or antigen vehicles. To enable transfer of this technology to human settings, the issue of sterilisation is of central importance. Since most polymers are heat-sensitive, sterilisation of polymeric microspheres for parenteral administration is assured either by costly

Deepa Mohanan; Bruno Gander; Thomas M. Kündig; Pål Johansen

256

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

257

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

258

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

259

Controlled release of the hammerhead ribozyme from biodegradable PLGA encapsulation  

E-print Network

applications. PLGA (Poly-Lactide-co-Glyolide) is an FDA approved and extensively characterized biodegradable controlled release system for drug delivery. These copolymer systems are preferred over conventional modes as they release the drug at a constant rate...

Sethuraman, Deepa

2001-01-01

260

Doppler cooling a microsphere  

E-print Network

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

P. F. Barker

2010-04-08

261

Doppler cooling a microsphere  

E-print Network

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

Barker, P F

2010-01-01

262

Long-acting beta-agonists and their association with inhaled corticosteroids in COPD.  

PubMed

Inhaled bronchodilators, including beta(2)-agonists and antimuscaric receptor antagonists, are the mainstay of pharmacotherapy in chronic obstructive pulmonary disease (COPD). The short-acting beta(2)-agonists, including salbutamol, and fenoterol, have a rapid onset of action, a bronchodilating effect for 3-6 h and are used on demand. The long-acting beta(2)-agonists (LABAs), including salmeterol and formoterol, have 12-hour duration of action and are used with a twice-daily dosing regimen for long-term COPD treatment. Unlike salmeterol, formoterol has a rapid onset of action. Pharmacological characteristics required by novel inhaled LABAs include 24 h bronchodilator effect in vivo which would make them suitable for once daily administration (ultra-LABA), high potency and selectivity for beta(2)-adrenoceptors, rapid onset of action, low oral bioavailability (< 5%) after inhalation, and high systemic clearance. Indacaterol, which has been approved for long-term treatment of COPD in Europe and in the USA, has a 24-h duration of action and a once-daily dosing regimen. Newer ultra-LABAs, including olodaterol, vilanterol, milveterol, carmoterol, and abediterol, are in development. Combination with ICS (fluticasone/salmeterol, budesonide/formoterol, beclomethasone/formoterol) appears to provide an additional benefit over the monocomponent therapy, although the extent of this benefit is variable and often not clinically significant in all the endpoints assessed. In patients with COPD, treatment with ICS is associated with increased risk of pneumonia which should be carefully considered when assessing the risk/benefit ratio of ICS/LABA combinations. Subphenotyping of patients with COPD (e.g., frequent exacerbations, sputum eosinophilia, mixed asthma/COPD phenotype) might help identify those patients who are most likely to benefit from addition of ICS to bronchodilating treatment. Ultra-LABA/ long-acting muscarinic receptor antagonist (LAMA) combination treatment is under development and is likely to become a standard pharmacological strategy for COPD. Dual-pharmacology inhaled muscarinic antagonist-beta(2) agonist (MABA) molecules provide a new approach to the treatment of COPD. PMID:23409722

Fuso, L; Mores, N; Valente, S; Malerba, M; Montuschi, P

2013-01-01

263

Evaluation of Mucoadhesive PLGA Microparticles for Nasal Immunization  

Microsoft Academic Search

In this study, hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared\\u000a and coated with chitosan and trimethyl chitosan (TMC) to evaluate the effect of coating material for nasal vaccine delivery.\\u000a The developed formulations were characterized for size, zeta potential, entrapment efficiency, and mucin adsorption ability.\\u000a Plain PLGA microparticles demonstrated negative zeta potential. However, coated microparticles showed

Dilip Pawar; Amit K. Goyal; Sharad Mangal; Neeraj Mishra; Bhuvaneshwar Vaidya; Shailja Tiwari; Arvind K. Jain; Suresh P. Vyas

2010-01-01

264

Paclitaxel release from micro-porous PLGA disks  

Microsoft Academic Search

Micro-porous biodegradable polymeric foams have potential applications in tissue engineering and drug delivery systems. A two-stage fabrication process combining spray drying and supercritical gas foaming is presented for the encapsulation of paclitaxel in micro-porous PLGA (poly lactic glycolic acid) foams. Encapsulation of paclitaxel in the PLGA polymer matrix was achieved and these foams have potential application as a new type

Lai Yeng Lee; Sudhir Hulikal Ranganath; Yilong Fu; Jasmine Limin Zheng; How Sung Lee; Chi-Hwa Wang; Kenneth A. Smith

2009-01-01

265

Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility.  

PubMed

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

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

2013-11-01

266

Combined corticosteroid and long-acting beta2-agonist in one inhaler versus long-acting beta2-agonists for chronic obstructive pulmonary disease  

PubMed Central

Background Both inhaled steroids (ICS) and long-acting beta2-agonists (LABA) are used in the management of chronic obstructive pulmonary disease (COPD). This updated review compared compound LABA plus ICS therapy (LABA/ICS) with the LABA component drug given alone. Objectives To assess the efficacy of ICS and LABA in a single inhaler with mono-component LABA alone in adults with COPD. Search methods We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search was November 2011. Selection criteria We included randomised, double-blind controlled trials. We included trials comparing compound ICS and LABA preparations with their component LABA preparations in people with COPD. Data collection and analysis Two authors independently assessed study risk of bias and extracted data. The primary outcomes were exacerbations, mortality and pneumonia, while secondary outcomes were health-related quality of life (measured by validated scales), lung function, withdrawals due to lack of efficacy, withdrawals due to adverse events and side-effects. Dichotomous data were analysed as random-effects model odds ratios or rate ratios with 95% confidence intervals (CIs), and continuous data as mean differences and 95% CIs. We rated the quality of evidence for exacerbations, mortality and pneumonia according to recommendations made by the GRADE working group. Main results Fourteen studies met the inclusion criteria, randomising 11,794 people with severe COPD. We looked at any LABA plus ICS inhaler (LABA/ICS) versus the same LABA component alone, and then we looked at the 10 studies which assessed fluticasone plus salmeterol (FPS) and the four studies assessing budesonide plus formoterol (BDF) separately. The studies were well-designed with low risk of bias for randomisation and blinding but they had high rates of attrition, which reduced our confidence in the results for outcomes other than mortality. Primary outcomes There was low quality evidence that exacerbation rates in people using LABA/ICS inhalers were lower in comparison to those with LABA alone, from nine studies which randomised 9921 participants (rate ratio 0.76; 95% CI 0.68 to 0.84). This corresponds to one exacerbation per person per year on LABA and 0.76 exacerbations per person per year on ICS/LABA. Our confidence in this effect was limited by statistical heterogeneity between the results of the studies (I2 = 68%) and a risk of bias from the high withdrawal rates across the studies. When analysed as the number of people experiencing one or more exacerbations over the course of the study, FPS lowered the odds of an exacerbation with an odds ratio (OR) of 0.83 (95% CI 0.70 to 0.98, 6 studies, 3357 participants). With a risk of an exacerbation of 47% in the LABA group over one year, 42% of people treated with LABA/ICS would be expected to experience an exacerbation. Concerns over the effect of reporting biases led us to downgrade the quality of evidence for this effect from high to moderate. There was no significant difference in the rate of hospitalisations (rate ratio 0.79; 95% CI 0.55 to 1.13, very low quality evidence due to risk of bias, statistical imprecision and inconsistency). There was no significant difference in mortality between people on combined inhalers and those on LABA, from 10 studies on 10,680 participants (OR 0.92; 95% CI 0.76 to 1.11, downgraded to moderate quality evidence due to statistical imprecision). Pneumonia occurred more commonly in people randomised to combined inhalers, from 12 studies with 11,076 participants (OR 1.55; 95% CI 1.20 to 2.01, moderate quality evidence due to risk of bias in relation to attrition) with an annual risk of around 3% on LABA alone compared to 4% on combination treatment. There were no significant differences between the results for either exacerbations or pneumonia from trials adding different doses or types of inhaled corticosteroid. Secondary outcomes ICS/LABA was more effective than LABA alone in improving health-related quality of life measured by the St George’s Resp

Nannini, Luis Javier; Lasserson, Toby J; Poole, Phillippa

2014-01-01

267

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. PMID:23983926

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

268

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

PubMed Central

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

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

2014-01-01

269

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

270

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. PMID:22966439

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

2012-01-01

271

Long-acting paliperidone palmitate – interim results of an observational study of its effect on hospitalization  

PubMed Central

Paliperidone palmitate (PP) is a recently introduced long-acting atypical, or second-generation, antipsychotic. Published data on PP are currently limited to controlled trials and case reports. In this observational study, we followed up 200 consecutive patients prescribed PP in normal practice. After 1 year, 65% of patients were still receiving PP. The number of admissions to hospital in the year following PP initiation was 0.49/patient compared with 0.69/patient/year, 3 years before initiation (P=0.0001). The mean number of bed days fell from 38.78 to 23.09/patient/year over the corresponding period (P=0.0001). The median number of bed days 3 years before PP initiation was 21.50/year and in the year following PP initiation, it was 0. Outcomes were numerically but not statistically better in those continuing PP than in those who ceased PP within a year of initiation. PP was effective and well-tolerated and, given its positive effect on hospital bed days, broadly cost-effective. PMID:24419004

Olofinjana, Olubanke

2014-01-01

272

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

273

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. PMID:23983974

McGlennon, Deirdre

2012-01-01

274

Long-acting paliperidone palmitate - interim results of an observational study of its effect on hospitalization.  

PubMed

Paliperidone palmitate (PP) is a recently introduced long-acting atypical, or second-generation, antipsychotic. Published data on PP are currently limited to controlled trials and case reports. In this observational study, we followed up 200 consecutive patients prescribed PP in normal practice. After 1 year, 65% of patients were still receiving PP. The number of admissions to hospital in the year following PP initiation was 0.49/patient compared with 0.69/patient/year, 3 years before initiation (P=0.0001). The mean number of bed days fell from 38.78 to 23.09/patient/year over the corresponding period (P=0.0001). The median number of bed days 3 years before PP initiation was 21.50/year and in the year following PP initiation, it was 0. Outcomes were numerically but not statistically better in those continuing PP than in those who ceased PP within a year of initiation. PP was effective and well-tolerated and, given its positive effect on hospital bed days, broadly cost-effective. PMID:24419004

Taylor, David; Olofinjana, Olubanke

2014-07-01

275

Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size.  

PubMed

The main purpose of this study was to develop and compare the pharmacokinetic behavior of two paliperidone palmitate (PP) nanosuspensions with different particle size after intramuscular (i.m.) administration. PP nanosuspensions were prepared by wet media milling method and the mean particle size of nanosuspension was controlled as 1,041 ± 6 nm (A) and 505 ± 9 nm (B), respectively. The morphology of nanosuspensions was observed by scanning electron microscope (SEM). Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) confirmed the crystallinity of PP in nanosuspensions. The physical and chemical stabilities of nanosuspensions A and B were investigated by particle analyzer and HPLC after storage for 2 months at 25°C, 4°C and mechanical shaking condition. No obvious change in particle size and chemical degradation of drug were observed. Following single-dose i.m. administration to beagle dogs, the release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A and B was 6 (d) and 10 (d). The AUC0-t and Cmax of nanosuspensions A was 2.0-fold and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with a larger particle size performed better than nanosuspension B. As a result, it is important to design appropriate particle size of nanosuspensions for i.m. administration in order to produce larger therapeutic effect. PMID:24882037

Leng, Donglei; Chen, Hongming; Li, Guangjing; Guo, Mengran; Zhu, Zhaolu; Xu, Lu; Wang, Yongjun

2014-09-10

276

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

PubMed

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

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

2014-03-01

277

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

PubMed Central

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

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

2014-01-01

278

PEGylated recombinant human interferon-? as a long-acting antiviral agent: structure, antiviral activity and pharmacokinetics.  

PubMed

Recombinant human interferon-? (rhIFN-?) exhibits a potent antiviral activity. Because of poor pharmacokinetics (PK) of rhIFN-?, frequent dosing of rhIFN-? is necessitated to achieve the sustained antiviral efficacy. PEGylation can efficiently improve the PK of rhIFN-? while substantially decrease its bioactivity. The structure, antiviral activity and PK of the PEGylated rhIFN-? were measured to establish their relationship with PEGylation sites, polyethylene glycol (PEG) mass and PEG structure. Accordingly, N-terminus and the lysine residues were selected as the PEGylation sites. PEGs with Mw of 20kDa and 40kDa were used to investigate the effect of PEG mass. Linear and branched PEGs were used to investigate the effect of PEG structure. PEGylation decreased the antiviral activity of rhIFN-? and improved its PK. The PEGylation sites determine the bioactivity of the PEGylated rhIFN-? and the conjugated PEG mass determines the PK. N-terminally PEGylated rhIFN-? with 40kDa linear PEG maintains 21.7% of the rhIFN-? antiviral activity with a half-life of 139.6h. Thus, N-terminally PEGylated rhIFN-? with linear 40kDa PEG is a potential antiviral agent for long-acting treatment of the viral diseases. PMID:24936771

Yu, Weili; Yu, Changming; Wu, Ling; Fang, Ting; Qiu, Rui; Zhang, Jinlong; Yu, Ting; Fu, Ling; Chen, Wei; Hu, Tao

2014-08-01

279

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

2013-12-01

280

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

PubMed Central

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

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

2013-01-01

281

Cost of unintended pregnancy in Norway: a role for long-acting reversible contraception  

PubMed Central

Objectives The objective of this study was to quantify the cost burden of unintended pregnancies (UPs) in Norway, and to estimate the proportion of costs due to imperfect contraceptive adherence. Potential cost savings that could arise from increased uptake of long-acting reversible contraception (LARC) were also investigated. Methods An economic model was constructed to estimate the total number of UPs and associated costs in women aged 15–24?years. Adherence-related UP was estimated using ‘perfect use’ and ‘typical use’ contraceptive failure rates. Potential savings from increased use of LARC were projected by comparing current costs to projected costs following a 5% increase in LARC uptake. Results Total costs from UP in women aged 15–24?years were estimated to be 164 million Norwegian Kroner (NOK), of which 81.7% were projected to be due to imperfect contraceptive adherence. A 5% increase in LARC uptake was estimated to generate cost savings of NOK 7.2 million in this group. Conclusions The cost of UP in Norway is substantial, with a large proportion of this cost arising from imperfect contraceptive adherence. Increased LARC uptake may reduce the UP incidence and generate cost savings for both the health care payer and contraceptive user. PMID:25537792

Henry, Nathaniel; Schlueter, Max; Lowin, Julia; Lekander, Ingrid; Filonenko, Anna; Trussell, James; Skjeldestad, Finn Egil

2015-01-01

282

The future of the long-acting beta-adrenergic bronchodilators in the treatment of asthma.  

PubMed

The combination of long-acting beta-agonist (LABA) bronchodilators with inhaled corticosteroids (ICSs) has been shown to be an extremely effective treatment for asthma. Use of LABA as monotherapy for asthma is associated with increased adverse events including exacerbations and asthma deaths. However, intensive evaluation of the combined LABA-ICS therapy provided no signals of increased risk. LABA appears to potentiate the effects of ICS. This provides the opportunity for use a of lower ICS dose for asthma control with less risk of steroid side effects. The combination of formoterol and budesonide used as both maintenance and relief medications may offer superior asthma control with less medication use. The recent introduction of 24-hour LABA, which are in clinical trials, makes possible the concept of very effective once-daily combinations of LABA and ICS, which would be expected to increase patient adherence and improve asthma outcomes. The 24-hour LABA will likely be combined with a 24-hour anticholinergic to treat chronic obstructive pulmonary disease. Whether this dual combination with ICS will enhance our treatment of more severe asthma remains an exciting hypothesis to be tested. PMID:18430306

Mansfield, Lyndon E

2008-01-01

283

Polyvinyl pyridine microspheres  

NASA Technical Reports Server (NTRS)

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

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

1979-01-01

284

Microsphere insulation systems  

NASA Technical Reports Server (NTRS)

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

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

2005-01-01

285

Polyvinyl pyridine microspheres  

NASA Technical Reports Server (NTRS)

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

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

1980-01-01

286

Fusion microsphere targets  

SciTech Connect

It was shown that a microsphere within the structure limitations is hydrodynamically stable. To insure its perfect formation, the initial chemical compositions must have a blowing capability, more important, the resultant liquid compositions must also have sufficient surface tension and low viscosity.

Koo, J.C.

1980-07-28

287

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

E-print Network

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 ...

Mieszawska, Aneta J.

288

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

PubMed Central

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

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

2013-01-01

289

The relationship between prepulse inhibition and general psychopathology in patients with schizophrenia treated with long-acting risperidone.  

PubMed

Patients with schizophrenia exhibit impairments in prepulse inhibition (PPI) of the startle response. Available data suggest that atypical antipsychotics may be more effective than typical antipsychotics in improving PPI deficits in schizophrenia. However, previous studies have used between-subjects rather than longitudinal within-subjects designs to demonstrate superiority of particular atypical antipsychotics over typical antipsychotics in improving PPI in patients with schizophrenia. This longitudinal within-subjects test-retest study was designed to evaluate changes in PPI and clinical symptoms in patients with schizophrenia after switching from the conventional antipsychotic zuclopenthixol to long-acting injectable risperidone. PPI was measured in 45 chronic male patients with schizophrenia treated with zuclophentixol depot (session T1), and 12 weeks after switching to long-acting injectable risperidone (session T2). Thirty-six healthy control subjects were also evaluated. Patients with schizophrenia showed a significant improvement in PPI after changing to long-acting risperidone. Improvement of PPI deficits between T1 and T2 assessments correlated significantly with improvements in PANSS general psychopathology subscale scores. Our findings indicate that long-acting risperidone improves PPI deficits in subjects with chronic schizophrenia. These results also suggest that the PPI-restoring effect of risperidone may be related to improvement in symptoms other than positive and negative symptoms. PMID:19846280

Martinez-Gras, Isabel; Rubio, Gabriel; del Manzano, Blanca Alvarez; Rodriguez-Jimenez, Roberto; Garcia-Sanchez, Fernando; Bagney, Alexandra; Leza, Juan Carlos; Borrell, José

2009-12-01

290

Treatment Outcomes with Long Acting Octreotide in Inoperable Hepatocellular Carcinoma: a Local Experience and Review of Literature  

Microsoft Academic Search

Objective: To determine the efficacy of long acting octreotide (LAR) in the treatment of inoperable hepatocellu- lar carcinoma; as well as to estimate the improvement in the quality of life. Methods: This study was carried out at the Shifa International Hospital, Islamabad between February and September 2003. Patients were recruited after an informed consent. There were 22 patients who decided

Muzaffar Lateef Gill; Muslim Atiq; Syma Sattar; Nasir Khokhar

291

Use of long-acting somatostatin analog SMS 201-995 in patients with pancreatic islet cell tumors  

Microsoft Academic Search

Natural somatostatin reduces plasma concentrations of many peptides, and is of short term benefit in patients with islet cell tumors, but has to be given as a continuous intravenous infusion. We review the published experience with the long acting synthetic somatostatin analogue SMS 201-995 in patients with islet cell tumors. Fifteen of 18 patients with vasoactive intestinal peptide-producing tumors, 8

Paul N. Maton; Jerry D. Gardner; Robert T. Jensen

1989-01-01

292

Nonstationary nonlinear effects in optical microspheres  

E-print Network

Nonstationary nonlinear effects in optical microspheres Alexey E. Fomin and Michael L. Gorodetsky produce oscillatory instability in optical microspheres. We experimentally demon- strate this instability observed slow and irreversible thermo-optical processes in microspheres. © 2005 Op- tical Society

293

Electrospinning growth factor releasing microspheres into fibrous scaffolds.  

PubMed

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

Whitehead, Tonya J; Sundararaghavan, Harini G

2014-01-01

294

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

PubMed

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

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

2014-07-01

295

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

PubMed Central

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

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

2014-01-01

296

Loss of Asthma Control in Pediatric Patients after Discontinuation of Long-Acting Beta-Agonists  

PubMed Central

Recent asthma recommendations advocate the use of long-acting beta-agonists (LABAs) in uncontrolled asthma, but also stress the importance of stepping down this therapy once asthma control has been achieved. The objective of this study was to evaluate downtitration of LABA therapy in pediatric patients who are well-controlled on combination-inhaled corticosteroid (ICS)/LABA therapy. Clinical and physiologic outcomes were studied in children with moderate-to-severe persistent asthma after switching from combination (ICS/LABA) to monotherapy with ICS. Of the 54 patients, 34 (63%) were determined to have stable asthma after the switch, with a mean followup of 10.7 weeks. Twenty (37%) had loss of asthma control leading to addition of leukotriene receptor antagonists, increased ICS, or restarting LABA. There were 2 exacerbations requiring treatment with systemic steroids. In patients with loss of control, there was a statistically significant decline in FEV1 (?8% versus ?1.9%, P = 0.03) and asthma control test (?3.2 versus ?0.5, P = 0.03). This did not approach significance for FEF25-75%, exhaled nitric oxide, lung volumes or airway reactivity. No demographic, asthma control measures, or lung function variables predicted loss of control. Pediatric patients with moderate-to-severe persistent asthma who discontinue LABA therapy have a 37% chance of losing asthma control resulting in augmented maintenance therapies. Recent recommendations of discontinuing LABA therapy as soon as control is achieved should be evaluated in a prospective long-term study. PMID:22966431

R. O'Hagan, Adrian; Morton, Ronald; Eid, Nemr

2012-01-01

297

Comparison of SGA Oral Medications and a Long-Acting Injectable SGA: The PROACTIVE Study.  

PubMed

Until relatively recently, long-acting injectable (LAI) formulations were only available for first-generation antipsychotics and their utilization decreased as use of oral second-generation antipsychotics (SGA) increased. Although registry-based naturalistic studies show LAIs reduce rehospitalization more than oral medications in clinical practice, this is not seen in recent randomized clinical trials. PROACTIVE (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) relapse prevention study incorporated efficacy and effectiveness features. At 8 US academic centers, 305 patients with schizophrenia or schizoaffective disorder were randomly assigned to LAI risperidone (LAI-R) or physician's choice oral SGAs. Patients were evaluated during the 30-month study by masked, centralized assessors using 2-way video, and monitored biweekly by on-site clinicians and assessors who knew treatment assignment. Relapse was evaluated by a masked Relapse Monitoring Board. Differences between LAI-R and oral SGA treatment in time to first relapse and hospitalization were not significant. Psychotic symptoms and Brief Psychiatric Rating Scale total score improved more in the LAI-R group. In contrast, the LAI group had higher Scale for Assessment of Negative Symptoms Alogia scale scores. There were no other between-group differences in symptoms or functional improvement. Despite the advantage for psychotic symptoms, LAI-R did not confer an advantage over oral SGAs for relapse or rehospitalization. Biweekly monitoring, not focusing specifically on patients with demonstrated nonadherence to treatment and greater flexibility in changing medication in the oral treatment arm, may contribute to the inability to detect differences between LAI and oral SGA treatment in clinical trials. PMID:24870446

Buckley, Peter F; Schooler, Nina R; Goff, Donald C; Hsiao, John; Kopelowicz, Alexander; Lauriello, John; Manschreck, Theo; Mendelowitz, Alan J; Miller, Del D; Severe, Joanne B; Wilson, Daniel R; Ames, Donna; Bustillo, Juan; Mintz, Jim; Kane, John M

2015-03-01

298

Inverse association of long-acting natriuretic peptide with metabolic syndrome in congestive heart failure patients  

PubMed Central

Aims Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) pro-hormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the metabolic syndrome (MetS) among congestive heart failure (CHF) patients. Methods Fasting blood samples were obtained from 186 patients with normal renal function in cardiac clinic outpatients. CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Results Ninety-eight patients (52.7%) had CHF. There was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased (p?=?0.002). Forty-six of the CHF patients (46.9%) had MetS. Fasting LANP level negatively correlated with MetS among CHF patients (p?

2013-01-01

299

Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage.  

PubMed

The inflammatory response plays a pivotal role in propagating injury of intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with antidiabetic effect and may also have antiinflammatory properties. Despite consensus that the glucoregulatory action is mediated by the GLP-1 receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation, neurobehavior, and inflammatory parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic deficit following ICH, which were partially reversed by GLP-1R inhibitor and AMPK phosphorylation inhibitor. Liraglutide-mediated AMPK phosphorylation was unaffected by GLP-1R inhibitor, and was found to be induced by GLP-1(9-36)a. GLP-1(9-36)a showed salutary effects on primary outcomes that were reversed by AMPK phosphorylation inhibitor but not by GLP-1R inhibitor. Liraglutide and DPP-4 inhibitor co-administration reversed liraglutide-mediated AMPK phosphorylation and antiinflammatory effects. Liraglutide exerted duals actions and the antiinflammatory effects are partially mediated by its metabolite in a phosphorylated AMPK-dependent manner. Therapies that inhibit GLP-1 degradation may weaken the metabolite-mediated effects. PMID:22968320

Hou, Jack; Manaenko, Anatol; Hakon, Jakob; Hansen-Schwartz, Jacob; Tang, Jiping; Zhang, John H

2012-12-01

300

A randomized trial of paliperidone palmitate and risperidone long-acting injectable in schizophrenia.  

PubMed

Paliperidone palmitate (PP) is a recently (USA) approved injectable new-generation antipsychotic. This 53-wk, Phase-III double-blind study was designed to assess the non-inferiority of PP to risperidone long-acting injectable (RIS-LAI) in schizophrenia treatment. Acutely symptomatic patients (n=749), with a Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomly allocated to gluteal injections of either (a) PP: 50 mg eq. on days 1 and 8, and flexible dosing [25-100 mg eq. (i.e. 39-156 mg USA dosing)] once-monthly; or (b) RIS-LAI: bi-weekly injections of 25 mg on days 8 and 22, and flexible dosing (25-50 mg) starting from day 36, with allowed oral supplementation. Patients (n=747) were 59% men, 92% white, mean (s.d.) age of 41 (11.95) yr and 45% (n=339) completed the study. Mean (s.d.) change from baseline to endpoint in PANSS total score was: -11.6 (21.22) PP; and -14.4 (19.76) RIS-LAI (per-protocol analysis set, primary measure); least-squares means difference was -2.6 (95% CI -5.84 to 0.61), with a prespecified 5-point non-inferiority margin. PP's suboptimal dosing regimen (<150 mg eq. initial dose) resulted in lower median plasma levels of the active moiety in PP-treated vs. RIS-LAI-treated patients. Insomnia was the most common treatment-emergent adverse event, with a similar incidence in both groups (15%). PP did not demonstrate comparable efficacy to RIS-LAI, which may be attributable to the initiation dosing strategy employed. Tolerability of both treatments was comparable to previous studies, with no new safety signals detected. PMID:21777507

Fleischhacker, W Wolfgang; Gopal, Srihari; Lane, Rosanne; Gassmann-Mayer, Cristiana; Lim, Pilar; Hough, David; Remmerie, Bart; Eerdekens, Marielle

2012-02-01

301

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

PubMed Central

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

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

2014-01-01

302

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

2011-03-01

303

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

PubMed Central

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

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

2012-01-01

304

Pharmacokinetics and Disposition of Rilpivirine (TMC278) Nanosuspension as a Long-Acting Injectable Antiretroviral Formulation?  

PubMed Central

The next-generation human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) was administered in rats and dogs as single intramuscular (IM) or subcutaneous (SC) injections, formulated as a 200-nm nanosuspension. The plasma pharmacokinetics, injection site concentrations, disposition to lymphoid tissues, and tolerability were evaluated in support of its potential use as a once-monthly antiretroviral agent in humans. Rilpivirine plasma concentration-time profiles showed sustained and dose-proportional release over 2 months in rats and over 6 months in dogs. The absolute bioavailability approached 100%, indicating a complete release from the depot, in spite of rilpivirine concentrations still being high at the injection site(s) 3 months after administration in dogs. For both species, IM administration was associated with higher initial peak plasma concentrations and a more rapid washout than SC administration, which resulted in a stable plasma-concentration profile over at least 6 weeks in dogs. The rilpivirine concentrations in the lymph nodes draining the IM injection site exceeded the plasma concentrations by over 100-fold 1 month after administration, while the concentrations in the lymphoid tissues decreased to 3- to 6-fold the plasma concentrations beyond 3 months. These observations suggest uptake of nanoparticles by macrophages, which generates secondary depots in these lymph nodes. Both SC and IM injections were generally well tolerated and safe, with observations of a transient inflammatory response at the injection site. The findings support clinical investigations of rilpivirine nanosuspension as a long-acting formulation to improve adherence during antiretroviral therapy and for preexposure prophylaxis. PMID:20160045

van ?t Klooster, Gerben; Hoeben, Eva; Borghys, Herman; Looszova, Adriana; Bouche, Marie-Paule; van Velsen, Frans; Baert, Lieven

2010-01-01

305

Short Term Effects of Tiotropium on COPD Patients Treated with Long Acting Bronchodilators  

PubMed Central

Background The results of bronchodilator therapy in chronic obstructive pulmonary disease (COPD) are not satisfactory and because of this, many drugs are administered for treatment of disease. We examined the short-term additive bronchodilator effects of tiotropium in patients with stable COPD already treated with salmeterol twice daily. Materials and Methods In a double-blind, double-dummy randomized study we evaluated the acute bronchodilator efficacy of a single 18 µg dose of tiotropium in patients with COPD under chronic treatment with a long acting beta-adrenergic (salmeterol 50µg twice a day). Measurements of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and six-minute walking test (6 MWT) as indicator of daily activities were made before and after giving the drug. A total of 129 outpatients with stable COPD (Gold level 2 -3- 4) were enrolled and 92 completed the study. Results Tiotropium elicited a significantly greater bronchodilation than the placebo. The action of the drug was elicited as increase in FEV1 (p ? 0.001) and FVC (p ? 0.001); 6-MWT increased 35 meters in patients treated with tiotropium compared to 2.5 meters in those receiving placebo (p ? 0.001). Conclusion Addition of tiotropium to chronic administration of a beta-adrenergic drug such as salmeterol induced an increase in pulmonary function parameters and in exercise capacity suggesting that association of the two drugs can be more efficient for treatment of disease and improvement of daily living activities than beta-adrenergics alone. PMID:25191397

2012-01-01

306

Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage  

PubMed Central

The inflammatory response plays a pivotal role in propagating injury of intracerebral hemorrhage (ICH). Glucagon-like-peptide-1 (GLP-1) is a hormone with antidiabetic effect and may also have antiinflammatory properties. Despite consensus that the glucoregulatory action is mediated by the GLP-1 receptor (GLP-1R), mechanisms in the brain remain unclear. We investigated the effect of a long-acting GLP-1 analog, liraglutide, and its truncated metabolite, GLP-1(9-36)a from dipeptidyl peptidase-4 (DPP-4) cleavage in ICH-induced brain injury. Primary outcomes were cerebral edema formation, neurobehavior, and inflammatory parameters. GLP-1(9-36)a, GLP-1R inhibitor, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation inhibitor and DPP-4 inhibitor were administered to examine the mechanisms of action. Liraglutide suppressed neuroinflammation, prevented brain edema and neurologic deficit following ICH, which were partially reversed by GLP-1R inhibitor and AMPK phosphorylation inhibitor. Liraglutide-mediated AMPK phosphorylation was unaffected by GLP-1R inhibitor, and was found to be induced by GLP-1(9-36)a. GLP-1(9-36)a showed salutary effects on primary outcomes that were reversed by AMPK phosphorylation inhibitor but not by GLP-1R inhibitor. Liraglutide and DPP-4 inhibitor co-administration reversed liraglutide-mediated AMPK phosphorylation and antiinflammatory effects. Liraglutide exerted duals actions and the antiinflammatory effects are partially mediated by its metabolite in a phosphorylated AMPK-dependent manner. Therapies that inhibit GLP-1 degradation may weaken the metabolite-mediated effects. PMID:22968320

Hou, Jack; Manaenko, Anatol; Hakon, Jakob; Hansen-Schwartz, Jacob; Tang, Jiping; Zhang, John H

2012-01-01

307

Production of hollow aerogel microspheres  

SciTech Connect

A process is described for preparing hollow aerogel microspheres, comprising the steps of: reacting metal alkoxide with water and base catalyst in alcohol solvent until a viscous alcogel is attained; forming a drop of viscous alcogel; injecting inert gas and base catalyst into the drop, at the time of drop formation, to form a hollow alcogel microsphere; blowing the hollow alcogel microsphere free of the viscous alcogel to fall into an atmosphere of inert gas and base catalyst; capturing said hollow alcogel microsphere on foam; and subjecting said hollow alcogel microsphere to supercritical drying to form a hollow aerogel microsphere of 800-1,200 [mu]m diameter with a wall thickness of 100-300 [mu]m and a wall density of 0.03 to 0. 3 g/cm[sup 3].

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

1993-07-13

308

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

NASA Astrophysics Data System (ADS)

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

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

2014-09-01

309

Microspheres and nanoparticles from ultrasound  

Microsoft Academic Search

Improved preparations of various examples of monodispersed, porous, hollow, and core-shell metal and semiconductor nanoparticles or nanowires have been developed. Now titania microspheres and nanoparticles and silica microspheres can be synthesized using an inexpensive high frequency (1.7 MHz) ultrasonic generator (household humidifier; ultrasonic spray pyrolysis; USP). Morphology and pore size of titania microspheres were controlled by the silica to Ti(IV)

Won Hyuk Suh

2006-01-01

310

Porous microsphere and its applications  

PubMed Central

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

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

2013-01-01

311

Mesenchymal stem cells attenuated PLGA-induced inflammatory responses by inhibiting host DC maturation and function.  

PubMed

The poly lactic-co-glycolic acid (PLGA) bio-scaffold is a biodegradable scaffold commonly used for tissue repair. However, implanted PLGA scaffolds usually cause serious inflammatory responses around grafts. To improve PLGA scaffold-based tissue repair, it is important to control the PLGA-mediated inflammatory responses. Recent evidence indicated that PLGA induce dendritic cell (DC) maturation in vitro, which may initiate host immune responses. In the present study, we explored the modulatory effects of mesenchymal stem cells (MSC) on PLGA-induced DCs (PLGA-DC). We found that mouse MSCs inhibited PLGA-DC dendrite formation, as well as co-stimulatory molecule and pro-inflammatory factor expression. Functionally, MSC-educated PLGA-DCs promoted Th2 and regulatory T cell differentiation but suppressed Th1 and Th17 cell differentiation. Mechanistically, we determined that PLGA elicited DC maturation via inducing phosphorylation of p38/MAPK and ERK/MAPK pathway proteins in DCs. Moreover, MSCs suppressed PLGA-DCs by partially inactivating those pathways. Most importantly, we found that the MSCs were capable of suppressing DC maturation and immune function in vivo. Also, the proportion of mature DCs in the mice that received MSC-PLGA constructs greatly decreased compared with that of their PLGA-film implantation counterparts. Additionally, MSCs co-delivery increased regulatory T and Th2 cells but decreased the Th1 and Th17 cell numbers in the host spleens. Histological analysis showed that MSCs alleviated the inflammatory responses around the grafted PLGA scaffolds. In summary, our findings reveal a novel function for MSCs in suppressing PLGA-induced host inflammatory response and suggest that DCs are a new cellular target in improving PLGA scaffold-based tissue repair. PMID:25890764

Zhu, Heng; Yang, Fei; Tang, Bo; Li, Xi-Mei; Chu, Ya-Nan; Liu, Yuan-Lin; Wang, Shen-Guo; Wu, De-Cheng; Zhang, Yi

2015-06-01

312

Effect of formulation factors on incorporation of the hydrophilic peptide dalargin into PLGA and mPEG-PLGA nanoparticles.  

PubMed

The objective of this study was to examine formulation factors that influence the incorporation of the hydrophilic peptide dalargin into poly(D, L-lactic-co-glycolic acid) (PLGA) and methoxy-polyethylene glycol (mPEG)-PLGA nanoparticles. In particular, the effect of ionic additives and nanoparticle method of preparation on the incorporation of dalargin and resultant nanoparticle properties was investigated. Biodegradable nanoparticles were prepared from mPEG-PLGA and PLGA by both solvent evaporation and solvent diffusion methods with inclusion of ionic additives of dextran sulphate (DS), sulfobutyl ether-beta-cyclodextrin (SB-CD), or sodium dodecyl sulfate (SDS). The resultant nanoparticles were analyzed for their mean particle size and size distribution, zeta-potential, peptide loading, yield, and morphology. The inclusion of ionic additives in the nanoparticle formulation significantly influenced dalargin entrapment efficiency (EE). For example, with the PLGA/SDS formulation EE increased from 13.3% to 91.2% and from 4.1% to 68.6% with the solvent diffusion and evaporation methods, respectively. The inclusion of ionic surfactant SDS has also lead to the formation of smaller size of nanoparticles. Isothermal titration microcalorimetry revealed a strong interaction between dalargin and DS, medium level interaction with SDS, and weak interaction with SB-CD. The results of this study suggest that a strong ionic interaction between peptides and additives may lead to enhanced peptide incorporation but also increased particle size. Intermediate ionic interaction, especially when it is associated with the formation of reversed micelles in a hydrophobic polymer solution, could be used to enhance the incorporation of hydrophilic peptides in PLGA and mPEG-PLGA nanoparticles. PMID:18459172

Chen, Y; Wang, F; Benson, H A E

2008-01-01

313

HDL-Mimetic PLGA Nanoparticle To Target Atherosclerosis Plaque Macrophages.  

PubMed

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

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

2015-03-18

314

In vivo biocompatibility of the PLGA microparticles in parotid gland  

PubMed Central

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

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

2013-01-01

315

Anticancer efficacy of perillyl alcohol-bearing PLGA microparticles  

PubMed Central

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

2012-01-01

316

In vitro Study on Biodegradable AZ31 Magnesium Alloy Fibers Reinforced PLGA Composite  

E-print Network

21 March 2013] AZ31 magnesium alloy fibers reinforced poly(lactic-co-glycolic acid) (PLGA) composites materials have never been reported to our knowledge. Poly(lactic-co-glycolic acid) (PLGA) is the copolymerIn vitro Study on Biodegradable AZ31 Magnesium Alloy Fibers Reinforced PLGA Composite Y.H. Wu1) , N

Zheng, Yufeng

317

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

E-print Network

have remained a problem. To achieve controlled drug release, paclitaxel (Ptx)-loaded poly(lactic-co- glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-NPs) were prepared by the emulsion-solvent evaporation methodA Novel Technique for Loading of Paclitaxel-PLGA Nanoparticles onto ePTFE Vascular Grafts Hyun Jung

Park, Jong-Sang

318

Functional magnetic microspheres  

NASA Technical Reports Server (NTRS)

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

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

1981-01-01

319

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

PubMed Central

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

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

2014-01-01

320

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

PubMed Central

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

2013-01-01

321

Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness  

PubMed Central

Background Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. Methods Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. Results LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. Recommendations for medication management when switching oral antipsychotics to LAI antipsychotics are proposed. Recommendations are also given for the use of LAI in specific populations. Conclusion In an evidence-based clinical approach, psychiatrists, through shared decision-making, should be systematically offering to most patients that require long-term antipsychotic treatment an LAI antipsychotic as a first-line treatment. PMID:24359031

2013-01-01

322

A comparative study of paliperidone palmitate and risperidone long-acting injectable therapy in schizophrenia.  

PubMed

This open-label, rater-blinded, parallel-group study was designed to evaluate noninferiority of paliperidone palmitate (PP), a once-monthly injectable atypical antipsychotic, to once-biweekly risperidone long-acting injectable (RIS-LAI) in adult Chinese patients with acute schizophrenia. Eligible Chinese adults (N=452) with schizophrenia were randomized (1:1) to either PP (N=229; deltoid injections on day 1 [150 mg eq.] and day 8 [100 mg eq.]; then once-monthly deltoid or gluteal injections, flexibly dosed [50, 100, or 150 mg eq.]), or RIS-LAI (N=223; once-biweekly gluteal injections, flexibly dosed [25, 37.5 or 50 mg]). RIS-LAI-treated patients received oral risperidone supplementation (1-6 mg/day) at initiation and with RIS-LAI dose increases. Mean (SD) Positive and Negative Syndrome Scale (PANSS) total score at baseline was 83.2 (12.44). Mean (SD) change from baseline to endpoint in PANSS total scores (primary efficacy measure) was: -23.6 (16.28) for PP group and -26.9 (15.43) for RIS-LAI group. PP was noninferior to RIS-LAI (least squares mean difference [95% CI]: -2.3 [-5.20; 0.63]; predetermined non-inferiority margin: -5.5). Mean (SD) change from baseline to endpoint in Clinical Global Impression-Severity scale score was: -1.5 (1.24; PP group), -1.7 (1.16; RIS-LAI group) and in Personal and Social Performance Scale scores was: 16.8 (14.76; PP group), 18.6 (13.92; RIS-LAI group). The incidence of treatment-emergent adverse events (TEAEs) was similar between the two groups (73% [PP]; 75% [RIS-LAI]). The most common TEAEs were akathisia, tremor, and insomnia. The study demonstrated the noninferiority of PP (50-150 mg eq., flexibly dosed, without oral paliperidone supplementation) to risperidone-LAI (25-50 mg, flexibly dosed, with oral risperidone supplementation) for the treatment of acute schizophrenia in adult Chinese patients. PP injections were generally tolerable, and no new safety signals were detected in this population. PMID:21315787

Li, Huafang; Rui, Qing; Ning, Xiaoping; Xu, Haiyan; Gu, Niufan

2011-06-01

323

Trading polymeric microspheres: Exchanging DNA molecules via microsphere interaction.  

PubMed

A new class of artificial molecular transport system is constructed by polymeric microspheres. The microspheres are prepared by self-assembly of poly(ethylene glycol)-block-poly(3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate), PEG-b-PDMAPS, by intermolecular dipole-dipole interaction of sulfobetaine side chains in water. Below the upper critical solution temperature (UCST) of PEG-b-PDMAPS, the microspheres (?1?m) interact with other microspheres by partial and transit fusion. In order to apply the interaction between microspheres, a 3'-TAMRA-labeled single-stranded DNA oligomer (ssDNA) is encapsulated into a PEG-b-PDMAPS microsphere by thermal treatment. The exchange of ssDNA between microspheres is confirmed by fluorescence resonance energy transfer (FRET) quenching derived from double-stranded formation with complementary 5'-BHQ-2-labeled ssDNA encapsulated in PEG-b-PDMAPS microspheres. The exchange rate of ssDNA is controllable by tuning the composition of the polymer. The contact-dependent transport of molecules can be applied in the areas of microreactors, sensor devices, etc. PMID:25731098

Morimoto, Nobuyuki; Muramatsu, Kanna; Nomura, Shin-Ichiro M; Suzuki, Makoto

2015-04-01

324

Fabrication of pillared PLGA microvessel scaffold using femtosecond laser ablation  

PubMed Central

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

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

2012-01-01

325

Microencapsulation of curcumin in PLGA microcapsules by coaxial flow focusing  

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

326

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. PMID:22754405

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

2012-01-01

327

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

PubMed Central

Background Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of mortality worldwide. Long-acting bronchodilators are considered first line therapies for patients with COPD but their effects on mortality are not well known. We performed a comprehensive systematic review and meta-analysis to evaluate the effects of long-acting bronchodilators on total mortality in stable COPD. Methods Using MEDLINE, EMBASE and Cochrane Systematic Review databases, we identified high quality randomized controlled trials of tiotropium, formoterol, salmeterol, formoterol/budesonide or salmeterol/fluticasone in COPD that had a follow-up of 6 months or longer and reported on total mortality. Two reviewers independently abstracted data from the original trials and disagreements were resolved by iteration and consensus. Results Twenty-seven trials that included 30,495 patients were included in the review. Relative risk (RR) for total mortality was calculated for each of the study and pooled together using a random-effects model. The combination of inhaled corticosteroid (ICS) and long-acting beta-2 agonist (LABA) therapy was associated with reduced total mortality compared with placebo (RR, 0.80; p = 0.005). Neither tiotropium (RR, 1.08; p = 0.61) nor LABA by itself (RR, 0.90; p = 0.21) was associated with mortality. Conclusions A combination of ICS and LABA reduced mortality by approximately 20%. Neither tiotropium nor LABA by itself modifies all-cause mortality in COPD. PMID:20459831

2010-01-01

328

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

PubMed Central

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

Addissie, Adamu

2014-01-01

329

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. PMID:24167680

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

2013-01-01

330

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

331

Advances in Microsphere Insulation Systems  

Microsoft Academic Search

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

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

2004-01-01

332

Phagocytosis of polymer microspheres by macrophages  

Microsoft Academic Search

This article reviews the phagocytosis of polymer microspheres by macrophages with respect to the size and the surface characteristics of the microspheres. Since few investigations have been carried out using well-characterized polymer microspheres, the authors have emphasized own experimental results. The findings provide useful information on the development of polymer microspheres as carriers for drug delivery systems.

Yasuhiko Tabata; Yoshito Ikada

333

Solar energy collector having hollow microspheres  

Microsoft Academic Search

Hollow glass microspheres made from a low heat conductivity glass composition containing a high vacuum and a thin metal coating deposited on the inner wall surface of the microspheres are described. The hollow glass microspheres are used to make superior insulation materials in the construction of highly efficient solar energy collectors. The hollow glass microspheres can also be made to

Torobin

1981-01-01

334

Metal containing polymeric functional microspheres  

NASA Technical Reports Server (NTRS)

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

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

1979-01-01

335

Daily Average Consumption of 2 Long-Acting Opioids: An Interrupted Time Series Analysis  

PubMed Central

Background Oxycodone controlled release (CR) and oxymorphone extended release (ER) are frequently prescribed long-acting opioids, which are approved for twice-daily dosing. The US Food and Drug Administration approved a reformulated crush-resistant version of oxycodone CR in April 2010. Objective To compare the daily average consumption (DACON) for oxycodone CR and for oxymorphone ER before and after the introduction of the reformulated, crush-resistant version of oxycodone CR. Methods This was a retrospective claims database analysis using pharmacy claims from the MarketScan database for the period from January 2010 through March 2011. The interrupted time series analysis was used to evaluate the impact of the introduction of reformulated oxycodone CR on the DACON of the 2 drugs—oxycodone CR and oxymorphone ER. The source of the databases included private-sector health data from more than 150 medium and large employers. All prescription claims containing oxycodone CR and oxymorphone ER dispensed to members from January 1, 2010, to March 31, 2011, were included in the analysis. Prescription claims containing duplicate National Drug Codes, missing member identification, invalid quantities or inaccurate days supply of either drug, and DACON values of <1 and >500 were removed. Results The database yielded 483,063 prescription claims for oxycodone CR and oxymorphone ER from January 1, 2010, to March 31, 2011. The final sample consisted of 411,404 oxycodone CR prescriptions (traditional and reformulated) dispensed to 85,150 members and 62,656 oxymorphone ER prescriptions dispensed to 11,931 members. Before the introduction of reformulated oxycodone CR, DACON values for the highest strength available for each of the 2 drugs were 0.51 tablets higher for oxycodone CR than for oxymorphone ER, with mean DACON values of 3.5 for oxycodone CR and 3.0 for oxymorphone ER (P <.001). The differences of mean DACON between the 2 drugs for all lower strengths were 0.46 tablets, with mean DACON values of 2.7 for oxycodone CR and 2.3 for oxymorphone ER (P <.001). After the introduction of the new formulation, the difference in mean DACON between the 2 drugs was slightly lower: 0.45 tablets for the highest-strength and 0.40 tablets for the lower-strength pairs. Regression analyses showed that the immediate and overall impact of the reformulation of oxycodone CR on the DACON of oxycodone CR was minimal, whereas no changes were seen in the DACON of oxymorphone ER. The estimated DACON for oxycodone CR decreased by 0.1 tablets, or 3.7% (P <.001), 6 months after the new formulation was introduced. Conclusion The mean DACON was 0.4 tablets per day higher for oxycodone CR compared with oxymorphone ER for all dosage strengths for the entire study period. After the introduction of the reformulated oxycodone CR, the DACON for this drug was slightly mitigated; however, there was a minimal impact on the mean differences between oxycodone CR and oxymorphone ER. PMID:24991311

Puenpatom, R. Amy; Szeinbach, Sheryl L.; Ma, Larry; Ben-Joseph, Rami H.; Summers, Kent H.

2012-01-01

336

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. PMID:21034447

2010-01-01

337

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

PubMed Central

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

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

2014-01-01

338

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

339

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

340

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

PubMed

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

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

2014-06-10

341

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

E-print Network

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

Walter, M.Todd

342

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

Microsoft Academic Search

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

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

2009-01-01

343

Gentamicin-loaded discs and microspheres and their modifications: characterization and in vitro release.  

PubMed

Osteomyelitis is an infection of the bone, and successful treatment involves local administration for about 6 weeks. Gentamicin is a very hydrophilic drug and tends to come out into the water phase when microspheres are fabricated using solvent evaporation method. Hence, spray drying is an option, and it was observed that the release rate tends to be fast when the particle size is small and large particles cannot be prepared by spray drying. In an effort to get better encapsulation efficiency and release rate, we have worked on the possibility of compressing the microspheres into discs and modifying the porosity of the discs by using biocompatible materials like polyethylene glycol (PEG) and calcium phosphates and also on the fabrication of double-walled and composite microspheres. In the case of microspheres, two methods of fabrication both based on solvent evaporation method were employed. The two polymers used are poly-L-lactide (PLLA) and copolymers of poly-DL-lactic-co-glycolic acid (PLGA). One method is based on the spreading coefficient theory for the formation of double-walled microspheres by using single solvent, while the other is based on the property of PLLA not being soluble in ethyl acetate (EA). Characterization to check if the microspheres formed are double-walled was performed. The fabrication method where two solvents, dichloromethane (DCM) and ethyl acetate, were used gave double-walled microspheres, while the other where only dichloromethane was used gave composites. The double-walled microspheres were smaller in size compared to the composites, which were in the range of 100-600 microm. This can be attributed to the difference in the fabrication procedure. We were able to achieve better encapsulation efficiencies of more than 50% and slower release rates, which lasted for about 15 days. It was observed that size played a major role in the encapsulation efficiency and release rates. The possibility of achieving better results by studying the effect of concentration of polymer in solvent and the effect of using different polymers was investigated. PMID:15653156

Naraharisetti, Pavan Kumar; Lew, Magdeleine Duan Ning; Fu, Yin-Chih; Lee, Duu-Jong; Wang, Chi-Hwa

2005-02-01

344

Chalcogenide glass microsphere laser.  

PubMed

Laser action has been demonstrated in chalcogenide glass microsphere. A sub millimeter neodymium-doped gallium lanthanum sulphide glass sphere was pumped at 808 nm with a laser diode and single and multimode laser action demonstrated at wavelengths between 1075 and 1086 nm. The gallium lanthanum sulphide family of glass offer higher thermal stability compared to other chalcogenide glasses, and this, along with an optimized Q-factor for the microcavity allowed laser action to be achieved. When varying the pump power, changes in the output spectrum suggest nonlinear and/or thermal effects have a strong effect on laser action. PMID:21165022

Elliott, Gregor R; Murugan, G Senthil; Wilkinson, James S; Zervas, Michalis N; Hewak, Daniel W

2010-12-01

345

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

PubMed

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

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

2015-02-01

346

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

PubMed Central

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

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

2014-01-01

347

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

PubMed Central

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

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

2014-01-01

348

Controlled release of dutasteride from biodegradable microspheres: in vitro and in vivo studies.  

PubMed

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

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

2014-01-01

349

Novel PLA microspheres with hydrophilic and bioadhesive surfaces for the controlled delivery of fenretinide.  

PubMed

Novel polylactide (PLA) microspheres endowed with hydrophilic and bioadhesive surfaces as injectable formulations for the controlled release of fenretinide were prepared, using a novel technique based on the co-precipitation of PLA with gelatin, at the interface of a liquid dispersion formed by the addition of N-methylpyrrolidone containing PLA and dextrin (DX), towards an aqueous solution of gelatin (G). The resulting PLA-G-DX microspheres were compared with others prepared by the same technique using polylactide-co-glycolide (PLGA), with or without DX, and with or without phosphatidylcholine. Of the different systems, the PLA-G-DX microspheres had the best morphological, dimensional and functional characteristics. They had the highest drug loading, and their drug release was the most efficient over time without any burst effect. Their in vitro anti-tumoural activity was strongly enhanced with respect to the pure fenretinide. This paralleled the increased drug concentration inside the cells due to their marked bioadhesion to the tumour cell membranes as indicated by scanning electron microscope images. PMID:23862726

Falconi, Mirella; Focaroli, Stefano; Teti, Gabriella; Salvatore, Viviana; Durante, Sandra; Nicolini, Benedetta; Orienti, Isabella

2014-01-01

350

Potential long-acting anticonvulsants. 1; Synthesis and activity of succinimides containing an alkylating group at the 2 position.  

PubMed

The synthesis of succinimide derivatives in which alkylating groups have been attached to the 2 positions of the ring or to the para position of the 2-phenyl substituent is described. The alkylating groups used were (a) alpha-haloacetyl, (b) alpha-haloacetamido, (c) maleimido, and (d) maleamyl. These compounds were prepared as potential long-acting anticonvulsants. Several of these derivatives exhibited activity against metrazole-induced seizures comparable to phensuximde, The maleimide 16 and the bromoacetamido derivative 23 exhibited a duration of action of at least 3.5 h. PMID:845873

Kornet, M J; Crider, A M; Magarian, E O

1977-03-01

351

Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone  

PubMed Central

Introduction Opioid-related mortality appears to be increasing in Canada. We examined the true extent of the problem and the impact of the introduction of long-acting oxycodone. Methods We examined trends in the prescribing of opioid analgesics in the province of Ontario from 1991 to 2007. We reviewed all deaths related to opioid use between 1991 and 2004. We linked 3271 of these deaths to administrative data to examine the patients’ use of health care services before death. Using time-series analysis, we determined whether the addition of long-acting oxycodone to the provincial drug formulary in January 2000 was associated with an increase in opioid-related mortality. Results From 1991 to 2007, annual prescriptions for opioids increased from 458 to 591 per 1000 individuals. Opioid-related deaths doubled, from 13.7 per million in 1991 to 27.2 per million in 2004. Prescriptions of oxycodone increased by 850% between 1991 and 2007. The addition of long-acting oxycodone to the drug formulary was associated with a 5-fold increase in oxycodone-related mortality (p < 0.01) and a 41% increase in overall opioid-related mortality (p = 0.02). The manner of death was deemed unintentional by the coroner in 54.2% and undetermined in 21.9% of cases. Use of health care services in the month before death was common: for example, of the 3066 patients for whom data on physician visits were available, 66.4% had visited a physician in the month before death; of the 1095 patients for whom individual-level prescribing data were available, 56.1% had filled a prescription for an opioid in the month before death. Interpretation Opioid-related deaths in Ontario have increased markedly since 1991. A significant portion of the increase was associated with the addition of long-acting oxycodone to the provincial drug formulary. Most of the deaths were deemed unintentional. The frequency of visits to a physician and prescriptions for opioids in the month before death suggests a missed opportunity for prevention. PMID:19969578

Dhalla, Irfan A.; Mamdani, Muhammad M.; Sivilotti, Marco L.A.; Kopp, Alex; Qureshi, Omar; Juurlink, David N.

2009-01-01

352

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

E-print Network

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

Park, Jong-Sang

353

CCMR: Characterization of Microsphere Lasers  

NSDL National Science Digital Library

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

Tsai, Tracy

2005-08-17

354

[Experimental study on application recombinant human bone morphogenetic protein 2(rhBMP-2)/poly-lactide-co-glycolic acid (PLGA)/fibrin sealant(FS) on repair of rabbit radial bone defect].  

PubMed

This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft. PMID:23198432

Fan, Zhongkai; Cao, Yang; Zhang, Zhe; Zhang, Mingchao; Lu, Wei; Tang, Lei; Yao, Qi; Lu, Gang

2012-10-01

355

Fiber-coupled microsphere laser  

Microsoft Academic Search

We demonstrate a 1.5-mm-wavelength fiber laser formed by placement of glass microsphere resonators along a fiber taper. The fiber taper serves the dual purpose of transporting optical pump power into the spheres and extracting the resulting laser emission. A highly doped erbium:ytterbium phosphate glass was used to form microsphere resonant cavities with large gain at 1.5 mm. Laser threshold pump

M. Cai; K. J. Vahala; P. C. Sercel

2000-01-01

356

Glass microsphere lubrication  

NASA Technical Reports Server (NTRS)

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

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

1991-01-01

357

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

358

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

2011-06-01

359

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

PubMed

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

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

2009-08-01

360

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

PubMed

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, and nucleotide therapeutics. According to the real-time bio-imaging of HA derivatives using quantum dots (QDot), HA-QDot conjugates with 35mol% HA modification maintaining enough binding sites for HA receptors were mainly accumulated in the liver, while those with 68mol% HA modification losing much of HA characteristics were evenly distributed to the tissues in the body. The results are well matched with the fact that HA receptors are abundantly present in the liver with a high specificity to HA molecules. Accordingly, slightly modified HA derivatives were used for target specific intracellular delivery of nucleotide therapeutics and highly modified HA derivatives were used for long-acting conjugation of peptide and protein therapeutics. HA has been also used as a novel depot system in the forms of physically and chemically crosslinked hydrogels for various protein drug delivery. This review will give you a peer overview on novel HA derivatives and the latest advances in HA-based drug delivery systems of various biopharmaceuticals for further clinical development. PMID:19758573

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

2010-01-01

361

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”. PMID:23991303

Dirican, Adem; Tuna, Tibel

2013-01-01

362

Fabrication of PLGA microvessel scaffolds with circular microchannels using soft lithography  

NASA Astrophysics Data System (ADS)

A simple micromolding method for fabricating PLGA (poly(lactic-co-glycolic acid)) microstructures made up of microchannels with a circular cross-section is presented. The thermal reflow technique is adopted to fabricate the semi-cylindrical photoresist master. The PLGA solution is prepared by dissolving PLGA polymer in acetone and then casting the solution onto the semi-cylindrical photoresist master to produce PLGA microstructures. Two PLGA membranes are bonded together to form microstructures consisting of circular microchannels. A microvessel scaffold suitable for tissue engineering was fabricated using the proposed method, and bovine endothelial cells were cultured into the scaffold by semi-dynamic seeding. The cell stain Calcein-AM was used to overcome the problem of the PLGA scaffolds becoming opaque, which in the past had made it difficult to effectively monitor the progress of cell seeding.

Wang, Gou-Jen; Hsueh, Cheng-Chih; Hsu, Shan-hui; Hung, Huey-Shan

2007-10-01

363

A subunit vaccine based on biodegradable microspheres carrying rHsp65 protein and KLK protects BALB/c mice against tuberculosis infection.  

PubMed

Of the hundreds of new tuberculosis (TB) vaccine candidates, some have therapeutic value in addition to their prophylactic properties. This is the case for the DNA vaccine encoding heat-shock protein 65 (DNAhsp65) from Mycobacterium leprae. However, there are concerns about the use of DNA vaccines in certain populations such as newborns and pregnant women. Thus, the optimization of vaccination strategies that circumvent this limitation is a priority. This study evaluated the efficacy of a single dose subunit vaccine based on recombinant Hsp65 protein against infection with M. tuberculosis H37Rv. The Hsp65 protein in this study was either associated or not with immunostimulants, and was encapsulated in biodegradable PLGA microspheres. Our results demonstrate that the protein was entrapped in microspheres of adequate diameter to be engulfed by phagocytes. Mice vaccinated with a single dose of Hsp65-microspheres or Hsp65+CpG-microspheres developed both humoral and cellular-specific immune responses. However, they did not protect mice against challenge with M. tuberculosis. By contrast, Hsp65+KLK-microspheres induced specific immune responses that reduced bacilli loads and minimized lung parenchyma damage. These data suggest that a subunit vaccine based on recombinant protein Hsp65 is feasible. PMID:21157178

dos Santos, Sandra Aparecida; Zárate-Bladés, Carlos Rodrigo; de Sá Galetti, Fábio Cícero; Brandão, Izaíra Tincani; Masson, Ana Paula; Soares, Edson Garcia; Araújo, Ana Paula Ulian; Silva, Celio Lopes

2010-12-01

364

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

PubMed Central

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

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

2013-01-01

365

The fabrication of PLGA microvessel scaffolds with nano-patterned inner walls  

Microsoft Academic Search

Poly (lactic-co-glycolic acid) (PLGA) is one of the most commonly used biodegradable, biocompatible materials. Nanostructured PLGA has immense\\u000a potential for application in tissue engineering. In this article we discuss a novel approach for the fabrication of PLGA microvessel\\u000a scaffolds with nanostructured inner walls. In this novel nano-patterning approach, the thermal reflow technique is first adapted\\u000a to fabricate a semi-cylindrical photoresist

Gou-Jen Wang; Yan-Cheng Lin; Shan-hui Hsu

2010-01-01

366

Culturing of skin fibroblasts in a thin PLGA–collagen hybrid mesh  

Microsoft Academic Search

A thin biodegradable hybrid mesh of synthetic poly(DL-lactic-co-glycolic acid) (PLGA) and naturally derived collagen was used for three-dimensional culture of human skin fibroblasts. The hybrid mesh was constructed by forming web-like collagen microsponges in the openings of a PLGA knitted mesh. The behaviors of the fibroblasts on the hybrid mesh and PLGA knitted mesh were compared. The efficiency of cell

Guoping Chen; Takashi Sato; Hajime Ohgushi; Takashi Ushida; Tetsuya Tateishi; Junzo Tanaka

2005-01-01

367

Design and Fabrication of PLGA Sandwiched Cell\\/Fibrin Constructs for Complex Organ Regeneration  

Microsoft Academic Search

A poly(DL-lactic-co-glycolic acid) (PLGA) sandwich fibrinogen\\/ adipose stem cell (ADSC) construct was fabricated to generate smooth muscle tissue. The mechanical properties and ADSC compatibility of PLGA, poly(ethylene glycol-1,6-hexamethyl diisocyanate-caprolactone) i.e. polyurethane (PU), gelatin, alginate, and fibrin composites were evaluated for vascular smooth muscle tissue generation. Synthetic PLGA and PU combined with natural gelatin, alginate, and fibrin for strength and cell

Xiaohong Wang; Shaochun Sui; Yongnian Yan; Renji Zhang

2010-01-01

368

Apatite Coating of Electrospun PLGA Fibers Using a PVA Vehicle System Carrying Calcium Ions  

Microsoft Academic Search

A novel method to coat electrospun poly(D,L-lactic-co-glycolic acid) (PLGA) fiber surfaces evenly and efficiently with low-crystalline carbonate apatite crystals using a poly(vinyl alcohol) (PVA) vehicle system carrying calcium ions was presented. A non-woven PLGA fabric was prepared by electrospinning: a 10 wt% PLGA solution was prepared using 1,1,3,3-hexafluoro-2-propanol as a solvent and electrospun under a electrical field of 1 kV\\/cm

In Ae Kim; Sang-Hoon Rhee

2010-01-01

369

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

PubMed

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

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

2015-02-01

370

Fabrication of PLGA nanoparticles with a fluidic nanoprecipitation system  

Microsoft Academic Search

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

Hui Xie; Jeffrey W Smith

2010-01-01

371

Dissolution behavior of biomimetic minerals on 3D PLGA scaffold  

Microsoft Academic Search

The bone-like carbonate apatite (BLCA) coatings have a great potential to apply in orthopaedic and dental implants due to their excellent biocompatibility and biodegradability. The BLCA layer can be coated biomimetically in the surfaces of polymers or inorganic materials using simulated body plasma. We have prepared 3D poly(lactic-co-glycolic acid) (PLGA) porous scaffolds by solvent casting\\/particulate leaching method. The BLCA was

A. Champa Jayasuriya; Malak Assad; Ahalapitiya H. Jayatissa; Nabil A. Ebraheim

2006-01-01

372

Surface functionalisation of PLGA nanoparticles for gene silencing  

Microsoft Academic Search

This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using benzyl alcohol. We demonstrate by x-ray photoelectron spectroscopy (XPS), 2.6 times higher surface presentation of amines using the cetyl derivative compared to non-cetylated-PEI

Morten Ø. Andersen; Agata Lichawska; Ayyoob Arpanaei; Stig Møller Rask Jensen; Harpreet Kaur; David Oupicky; Flemming Besenbacher; Peter Kingshott; Jørgen Kjems; Kenneth A. Howard

2010-01-01

373

Fabrication of glass microspheres with conducting surfaces  

DOEpatents

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

Elsholz, W.E.

1982-09-30

374

Fabrication of glass microspheres with conducting surfaces  

DOEpatents

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

Elsholz, William E. (Acampo, CA)

1984-01-01

375

Ultrafine palladium particles immobilized on polymer microspheres  

Microsoft Academic Search

Ultrafine palladium particles immobilized on submicrometer copolymer microspheres were prepared by reduction of palladium\\u000a ions in the presence of the copolymer microspheres. Copolymer microspheres with surface carboxylic or cyano functionality\\u000a were used. Transmission electron microscopy observation and X-ray diffraction analysis indicated that ultrafine palladium\\u000a particles of nanometer size were formed and were attached on the surface of the copolymer microspheres.

P. H. Wang; C.-Y. Pan

2001-01-01

376

Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition.  

PubMed

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

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

2003-06-01

377

UV curable polyurethane-based microspheres  

Microsoft Academic Search

Radiation curable polyurethane-based microspheres were prepared by modifying conventional procedures for preparing anionic polyurethane dispersions. Vinyl groups were introduced to the side chains and the ends of the polyurethane main chains. Photoinitiators and multifunctional acrylate oligomers were incorporated into each microsphere. The curing behavior of the films obtained from these microspheres under UV were studied. The MEK resistance of UV

Masakazu Hirose; Jianhui Zhou; Fumiyuki Kadowaki

1999-01-01

378

Fabrication of glass microspheres with conducting surfaces  

Microsoft Academic Search

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

Elsholz

1984-01-01

379

Hollow glass microsphere composites: preparation and properties  

Microsoft Academic Search

Composites consisting of bonded hollow glass microspheres are promising for constructions in which materials are needed that combine a high Young's modulus with a low density. The elastic properties of ideally bonded hollow glass microsphere composites are predicted theoretically. Heat-treated castings of quartz glass microspheres approach the theoretical Young's modulus from below. The best result achieved was a Young's modulus

H. Verweij; D. Veeneman

1985-01-01

380

Fabrication of glass microspheres with conducting surfaces  

Microsoft Academic Search

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

Elsholz

1982-01-01

381

Development of biodegradable co-poly( d,l-lactic\\/glycolic acid) microspheres for the controlled release of 5FU by the spray drying method  

Microsoft Academic Search

The water-soluble anti-cancer drug, 5-fluorouracil (5-fluoro-2,4-pyrimidinedione) (5-FU) is encapsulated into biodegradable co-poly (d,l-lactic\\/glycolic acid) (PLGA) using the spray drying method for the development of long-lasting controlled release systems. In this study, the effects of both polymeric composition and technological parameters on release profiles of 5-FU were investigated. The degradation of various microspheres was also investigated. The mixture of dichloromethane\\/chloroform\\/methanol (1:1:2

Ywu-Jang Fu; Shin-Shing Shyu; Fu-Hu Su; Pih-Chen Yu

2002-01-01

382

Short- and long-term effect of a long-acting somatostatin analogue, lanreotide (SR-L) on metastatic gastrinoma.  

PubMed

Medical treatment is the elective therapy for patients with gastrinoma when the tumor is not found at surgery or is unresectable or when there is a metastatic disease. H2-blockers and omeprazol are able to control gastric acid secretion and, in addition, somatostatin analogues decrease gastrin levels. A new long-acting and slow release formulation of a somatostatin analogue (lanreotide, SR-L) has been developed. We treated two patients suffering from gastrinoma, total gastrectomy and hepatic metastases with 30 mg intramuscular injections of SR-L every 15 and 10 days, respectively, for a seven-month period. After the treatment, gastrin levels decreased from 35,494 and 15,086 ng/l to 3,211 and 167 ng/l (92 and 98% below pre-treatment levels) in case 1 and 2 respectively, with a relief of symptoms and no side effects. PMID:10195383

Gaztambide, S; Vazquez, J A

1999-02-01

383

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

2013-10-01

384

Long-acting neuroleptics used in wildlife management do not impair thermoregulation or physical activity in goats (Capra hircus).  

PubMed

Long-acting neuroleptics commonly are used in wildlife management to decrease stress-related mortality in wild animals, but with possible effects on thermoregulation, which may contribute to residual morbidity and mortality. We investigated the effects of haloperidol (0.01, 0.1, 1 mg kg(-1), n=4), zuclopenthixol (0.1, 1, 10 mg kg(-1), n=4) and perphenazine (0.1, 1, 10 mg kg(-1), n=8), as well as control injections of sunflower oil, on body temperature and physical activity of laboratory goats under hot, cold and thermoneutral ambient temperatures. Implanted data loggers continuously recorded abdominal temperature, and data loggers attached externally on the foreleg recorded movement of unrestrained goats, in a climatic chamber at 35 degrees C, 10 degrees C and 22 degrees C. Cycling ambient temperature between 35 degrees C in daytime and 10 degrees C at night time caused a significant increase in amplitude of the circadian rhythm of body temperature in goats given sunflower oil (P=0.0012, unpaired t-test, n=8), but the administration of zuclopenthixol or perphenazine did not affect this change in amplitude (P>0.05, two-way ANOVA, n=4). Mean daily body temperature after administration of zuclopenthixol or perphenazine, and mean daily activity after zuclopenthixol administration, were not significantly different to those after control injections, at any ambient temperature, for the expected duration of drug activity (all P>0.05, two-way ANOVA, n=4). Thermal response indices, and mean activity, during heat, cold or thermoneutral exposure, of goats for 7 h after haloperidol injection, were not significantly different, at any dose or any ambient temperature, to those following control injections (all P>0.05, repeated measures ANOVA, n=4). Long-acting neuroleptics did not impair activity or thermoregulation of goats subjected to inescapable thermal challenges. PMID:17355912

Fick, Linda; Mitchell, Duncan; Fuller, Andrea

2007-06-01

385

Micro-porous Paclitaxel-Loaded PLGA Foams -- a New Implant Material for Controlled Release of Chemotherapeutic Agents  

E-print Network

Supercritical gas foaming using CO? was used to fabricate blank poly DL lactide-co-glycolide (PLGA) micro-porous foams. Paclitaxel-loaded PLGA foams were also produced for the first time using a modification of the ...

Lee, Lai Yeng

386

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

387

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

PubMed Central

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

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

2015-01-01

388

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

PubMed Central

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

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

2013-01-01

389

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

Microsoft Academic Search

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

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

2008-01-01

390

Modeling the Formation of Polyimide Microspheres  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

391

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

PubMed

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

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

2014-11-28

392

Combined effects of Ag nanoparticles and oxygen plasma treatment on PLGA morphological, chemical, and antibacterial properties.  

PubMed

The purpose of this study is to investigate the combined effects of oxygen plasma treatments and silver nanoparticles (Ag) on PLGA in order to modulate the surface antimicrobial properties through tunable bacteria adhesion mechanisms. PLGA nanocomposite films, produced by solvent casting with 1 wt % and 7 wt % of Ag nanoparticles were investigated. The PLGA and PLGA/Ag nanocomposite surfaces were treated with oxygen plasma. Surface properties of PLGA were investigated by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), static contact angle (CA), and high resolution X-ray photoelectron spectroscopy (XPS). Antibacterial tests were performed using an Escherichia coli RB (a Gram negative) and Staphylococcus aureus 8325-4 (a Gram positive). The PLGA surface becomes hydrophilic after the oxygen treatment and its roughness increases with the treatment time. The surface treatment and the Ag nanoparticle introduction have a dominant influence on the bacteria adhesion and growth. Oxygen-treated PLGA/Ag systems promote higher reduction of the bacteria viability in comparison to the untreated samples and neat PLGA. The combination of Ag nanoparticles with the oxygen plasma treatment opens new perspectives for the studied biodegradable systems in biomedical applications. PMID:23360180

Fortunati, Elena; Mattioli, Samantha; Visai, Livia; Imbriani, Marcello; Fierro, Josè Luis G; Kenny, Josè Maria; Armentano, Ilaria

2013-03-11

393

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

E-print Network

investigated 51 biodegradable polymers are poly(lactic-co-glycolic acid) (PLGA) and 52 its constituent polymers of avidin and palmitic acid can be used to modify poly(lactic-co-glycolic acid) (PLGA) particle 27surfaces in humans 54 and their degradation under physiologic conditions releases lactic 55 and/or glycolic acid

Fahmy, Tarek

394

Research Article PEGylated PLGA nanoparticles for the improved delivery of doxorubicin  

E-print Network

of cytotoxic chemotherapeutic agents in biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles may. 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

Fahmy, Tarek

395

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

PubMed Central

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

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

2014-01-01

396

PCL microparticle-dispersed PLGA solution as a potential injectable urethral bulking agent.  

PubMed

The PCL microparticle-dispersed PLGA solutions were prepared as a potential injectable urethral bulking agent. The mixture solutions were prepared by mixing polycarprolactone (PCL) microparticles (diameter, 100 approximately 200mum; fabricated by a temperature-induced phase transition method) and poly(dl-lactic-co-glycolic acid) (PLGA) solution (dissolved in tetraglycol to 10wt%) with different PCL microparticle to PLGA solution ratio. The mixture solution was solidified by the precipitation of PLGA when the solution was contact with water. In contact with water, the PCL microparticles exhibited a well-packed structure entrapped in a solidified porous PLGA matrix, which can effectively prevent the microparticle migration in the body and retain its initial volume even after PLGA matrix degradation. The PCL microparticle-dispersed PLGA solution (particle to solution ratio, 45/55 (w/v)) was easily injected through 18G needle into back of hairless mouse (subcutaneously) and stably located at the apply site. The surrounding tissue including blood vessel were gradually infiltrated into the implant up to 8 weeks without the initial injected volume change and with little inflammatory response. The PCL microparticle-dispersed PLGA solution may be a good candidate as an injectable bulking agent for the treatment of urinary incontinence owing to its good injectability, volume retention potential as well as biocompatibility. PMID:16221494

Oh, Se Heang; Lee, Ji Youl; Ghil, Sung Ho; Lee, Sang Sup; Yuk, Soon Hong; Lee, Jin Ho

2006-03-01

397

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

PubMed Central

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

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

2010-01-01

398

Production of monodisperse, polymeric microspheres  

NASA Technical Reports Server (NTRS)

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

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

1990-01-01

399

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

NASA Astrophysics Data System (ADS)

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

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

2014-09-01

400

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

PubMed

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

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

2012-01-01

401

Preparation of hollow hydroxyapatite microspheres.  

PubMed

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

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

2006-07-01

402

POROUS WALL, HOLLOW GLASS MICROSPHERES  

Microsoft Academic Search

Hollow Glass Microspheres (HGM) is not a new technology. All one has to do is go to the internet and Google{trademark} HGM. Anyone can buy HGM and they have a wide variety of uses. HGM are usually between 1 to 100 microns in diameter, although their size can range from 100 nanometers to 5 millimeters in diameter. HGM are used

2012-01-01

403

SRNL POROUS WALL GLASS MICROSPHERES  

Microsoft Academic Search

The Savannah River National Laboratory (SRNL) has developed a new medium for storage of hydrogen and other gases. This involves fabrication of thin, Porous Walled, Hollow Glass Microspheres (PW-HGMs), with diameters generally in the range of 1 to several hundred microns. What is unique about the glass microballons is that porosity has been induced and controlled within the thin, one

G Wicks; L Leung Heung; R Ray Schumacher

2008-01-01

404

The degradation of the three layered nano-carbonated hydroxyapatite\\/collagen\\/PLGA composite membrane in vitro  

Microsoft Academic Search

ObjectiveThe purpose of this paper was to investigate the in vitro biodegradation of a guided tissue regeneration composite membrane, nano-carbonated hydroxyapatite\\/collagen\\/poly(lactic-co-glycolic acid) (nCHAC\\/PLGA). Especially for periodontal therapy, the functional graded material (FGM) nCHAC\\/PLGA membrane was prepared that consisted of three layers with 8wt% nCHAC+PLGA\\/4wt% nCHAC+PLGA\\/PLGA, where one face of the membrane is porous, thereby allowing cell growth thereon and the

Susan Liao; Fumio Watari; Yuhe Zhu; Motohiro Uo; Tsukasa Akasaka; Wei Wang; Guofu Xu; Fuzhai Cui

2007-01-01

405

Microspheres and nanoparticles from ultrasound  

NASA Astrophysics Data System (ADS)

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

Suh, Won Hyuk

406

Preparation and Characterization of Microspheres of Albumin-Heparin Conjugates  

E-print Network

Preparation and Characterization of Microspheres of Albumin-Heparin Conjugates GLEN S. KWON,* YOU-heparinconjugatewascrosslinkedin a water-in-oilemulsionto formalbumin- heparin microspheres.The compositionofthe conjugatewas determinedby-heparin microspheres.Surfacesofalbumin-heparin and albumin microsphereswerecharacterizedby ESCA

Twente, Universiteit

407

Composite Tectocapsules Containing Porous Polymer Microspheres as Release Gates  

E-print Network

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

Hitchcock, Adam P.

408

21 CFR 522.1451 - Moxidectin microspheres for injection.  

Code of Federal Regulations, 2014 CFR

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

2014-04-01

409

Electrostatically Tuned Interactions in Silica Microsphere-Polystyrene Nanoparticle Mixtures  

E-print Network

Electrostatically Tuned Interactions in Silica Microsphere-Polystyrene Nanoparticle Mixtures Angel mechanism in binary mixtures of silica microspheres and polystyrene nanoparticles. By selectively tuning their electrostatic interactions, both the initial microsphere stability and the role of nanoparticle additions

Lewis, Jennifer

410

Recombinant human growth hormone poly(lactic-co-glycolic acid) microsphere formulation development 1 This manuscript is dedicated to the memory of Dr. Michael J. Cronin. Dr. Cronin was a brilliant endocrine scientist with an incredible ability to objectively evaluate any problem, no matter how complex. His spirit and knowledge contributed to the success of the work described herein and his wisdom continues to guide those of us fortunate enough to have known him. 1  

Microsoft Academic Search

The development of a sustained release formulation of recombinant human growth hormone (rhGH) has focused on a depot preparation using the biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), for microsphere production. These formulations have been designed to assure the maintenance of protein integrity both during the microencapsulation process and upon subsequent release in vitro and in vivo. In addition, animal models were

Jeffrey L Cleland; OluFunmi L Johnson; Scott Putney; Andrew J. S Jones

1997-01-01

411

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

PubMed Central

Objectives. Quantify changes in hospital resource use in Finland following initiation of risperidone long-acting injection (RLAI). Materials and Methods. A retrospective multi-center chart review (naturalistic setting) was used to compare annual hospital bed-days and hospital episodes for 177 schizophrenia patients (mean age 47.1 years, 52% female, 72% hospitalized) before and after initiation of RLAI (between January 2004 and June 2005) using the within-patient “mirror-image” study design. The base case analytical approach allocated hospital episodes overlapping the start date entirely to the preinitiation period. In order to investigate the impact of inpatient care ongoing at baseline, the change in bed-days was also estimated using an alternative analytical approached related to economic modelling. Results. In the conventional analysis, the mean annual hospitalisation costs declined by €11,900 and the number of bed-days was reduced by 40%, corresponding to 0.19 fewer hospital episodes per year. The reductions in bed-days per patient-year were similar for patients switched to RLAI as inpatients and as outpatients. In the modelling-based analysis, an 8% reduction in bed-days per year was observed. Conclusion. Despite uncertainty in the choice of analytic approach for allocating inpatient episodes that overlapping this initiation, consistent reductions in resource use are associated with the initiation of RLAI in Finland. PMID:22966445

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

2012-01-01

412

[Use of selective long-acting beta-blocker with vasodilating activity celiprolol in patients with essential hypertension].  

PubMed

Effects of 8 weeks therapy with long-acting selective b-blocker celiprolol (200 mg o.d.) on 24-hour blood pressure, central hemodynamics (oscillometry) and microcirculation (laser doppler flowmetry) were studied in 30 patients (17 women and 13 men, mean age 51.9 years), with stage I-II essential hypertension. Celiprolol lowered both systolic and diastolic blood pressure (BP) during all periods of 24-hour BP monitoring and improved BP circadian rhythm. Treatment with celiprolol was not associated with considerable heart rate decrease or changes of stroke volume and cardiac output. 24 hour monitoring of parameters of central hemodynamics during treatment with celiprolol revealed existence of significant direct correlation between mean BP and total peripheral vascular resistance. Thus, hypotensive effect of celiprolol was mostly attributed to its vasodilatory action. This activity of celiprolol was confirmed by its beneficial influence on parameters of microcirculation. After therapy normalization of peripheral blood flow was observed in 50%, and tendency to its improvement--in 83,3 % of patients. PMID:12494052

Podzolkov, V I; Mozharova, L G

2002-01-01

413

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

PubMed Central

We sought to evaluate the within-drug benefit-risk of olanzapine long-acting injection (LAI) using both quantitative and qualitative methods. Subjects included 1192 adult patients with schizophrenia or schizoaffective disorder who participated in clinical trials with the opportunity for at least two years of continuous treatment with olanzapine LAI (45–405?mg every two to four weeks). Using the Benefit Risk Action Team (BRAT) framework, we evaluated frequency versus duration of benefits and risks commonly observed with atypical antipsychotics. We then used the Transparent Uniform Risk/Benefit Overview (TURBO) method, which weighs the drug's two most medically serious and/or frequent adverse events versus its primary benefit (effectiveness) and an ancillary benefit. The most frequent events among all patients were remaining free of relapse (91.4% for an average of 306?days at one year, 88.4% for 546?days at two years) and symptomatic remission (81.7% for an average of 239?days at one year, 84.1% for 438?days at two years). One- and two-year incidence of ?7% weight gain was 33.3% and 41.7%. Incidences for sexual dysfunction, hyperprolactinemia, and post-injection delirium/sedation syndrome (PDSS) were <2%. TURBO ratings unanimously selected PDSS and weight gain as key risks and resulted in an average score in the acceptable benefit-risk balance range. PMID:24996038

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

2014-01-01

414

Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.  

PubMed

The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 ?m), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect. PMID:23542494

Wei, Xiao-Lan; Han, Ying-Rui; Quan, Li-Hui; Liu, Chun-Yu; Liao, Yong-Hong

2013-05-13

415