Sustained release of a water-soluble GP IIb/IIIa antagonist from copoly(dl-lactic/glycolic)acid microspheres

Takada, Shigeyuki; Kurokawa, Tomofumi; Miyazaki, Keiko; Iwasa, Satoru; Ogawa, Yutaka

doi:10.1016/s0378-5173(96)04780-1

Cited by 17 publications

(4 citation statements)

References 16 publications

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“…With the exception of solvent‐diffusion‐controlled morphology, there existed differences between the formulations with various Hb loadings. Consistent with the viewpoints of Gorner et al28 and Takada et al,29 when a relatively high content of Hb was initially available to be accommodated in the same size of nanoparticles, it would prone to forming a heterogeneous matrix. So, from this viewpoint, with the increasing of the Hb concentration from 100 to 300 mg/mL, the internal structure became more compact and dense.…”

Section: Discussionsupporting

confidence: 73%

Porosity and semipermeability of hemoglobin‐loaded polymeric nanoparticles as potential blood substitutes

et al. 2009

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Porosity and semipermeability, allowing life-sustaining small molecules to penetrate, but hemoglobin (Hb) and other enzymes to cut off, predominantly affect the functionalities of the Hb-loaded polymeric nanoparticles (HbPNPs) as blood substitutes. In this article, HbPNPs formulated in the size range of 110-122 nm were prepared by a modified double-emulsion method with poly(lactic acid) (PLA)-based polymers. The influences of the main preparation conditions, including solvent composition, stirring speed, Hb concentration and polymer matrix, on the porosity were investigated in details. To evaluate the porosity of HbPNPs, a novel nondestructive testing method based on molecular weight cut-off (MWCO) was developed, and an effusion approach was applied to investigate the pore size in the particle shells with poly(ethylene glycol)s (PEGs) of different molecular weights (PEG200, PEG400, PEG600) as probes. Moreover, in vitro diffusion behaviors of ascorbic acid and reduced glutathione from HbPNPs fabricated with various polymer matrices were studied. The MWCO of HbPNPs by changing solvent composition, stirring speed, Hb concentration, and polymer composition varied from 200 to 600, especially the PEGylation of the polymer, which exhibited obvious influence on the MWCO of HbPNPs. Ascorbic acid with molecular weight 176.1 could diffuse into PEGylated nanoparticles with mPEG content of 5-30 wt % freely, while reduced glutathione with molecular weight 307.3 could not penetrate when mPEG content reached 30 wt %. These results suggest that the HbPNPs optimized with MWCO between 400 and 600 can facilitate the transport of all those life-sustaining small molecules.

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Section: Discussionsupporting

confidence: 73%

Porosity and semipermeability of hemoglobin‐loaded polymeric nanoparticles as potential blood substitutes

et al. 2009

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“…Indeed, research has shown that these therapeutic agents have varying physicochemical properties that could alter polymer degradation and thereby alter drug release profiles [12][13][14][15][16]. This highlights the need to investigate the effect of a drug on polymer degradation as it can be critical with respect to product performance, as cited by several authors [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Degradation of Lactide-co-Glycolide Polymer with Basic Nucleophilic Drugs

D’Souza

Faraj

Dorati

et al. 2015

Advances in Pharmaceutics

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The purpose of this study was to examine the degradative effect of weakly basic nucleophilic drugs on a lactide-co-glycolide (PLGA) polymer in a microsphere formulation. Biodegradable PLGA microspheres of two second-generation atypical antipsychotics, Risperidone and Olanzapine, were manufactured using a solvent extraction/evaporation technique. The effect of drug content, buffer pH and temperature on polymer molecular weight and degradation, were examined via a series of experiments and compared against a control (Placebo PLGA microspheres). In comparison to Placebo microspheres, significant polymer molecular weight reduction was observed upon encapsulation of varying levels of either Risperidone or Olanzapine. There was excellent correlation between the extent of molecular weight reduction during manufacture and the amount of encapsulated drug in the microspheres. Subsequent studies on polymer degradation showed: the following (a) the Placebo and Olanzapine microspheres followed pseudo first order kinetics, (b) Risperidone microspheres exhibited biphasic degradation profiles, and (c) polymer degradation was dependent on temperature, not pH. The findings of these studies show that encapsulation of weakly basic nucleophile type drugs into PLGA can accelerate the biodegradation of the PLGA and have major implications on the design of polymeric microsphere drug delivery systems.

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“…Drug release from PLGA microcapsules is initiated by hydration with the surrounding aqueous media, and then the drug dissolves and diOE uses through aqueous-® lled pores within the particles, and subsequently the polymer degrades by hydrolysis associated with drug release (Ogawa 1997). PLGA has accordingly been used to achieve a sustained release not only of insulin, but also of other drugs (Okada et al 1994 ;Takada et al 1995Takada et al , 1997aYanai et al 1995 ;Ogawa 1997 ;Barichello et al 1999a, b ;Lam et al 2000).…”

Section: Discussionmentioning

confidence: 99%

A novel insulin formulation can keep providing steady levels of insulin for much longer periods in-vivo

Takenaga

Yamaguchi

Kitagawa

et al. 2002

Journal of Pharmacy and Pharmacology

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We have recently succeeded in preparing insulin-loaded microcapsules that release the insulin in a strictly controlled manner with little initial rapid release in-vitro or in-vivo. We show here the superiority of the best formulation prepared with co-poly(D,L-lactic/glycolic) acids (PLGA) (mean MW 5800, L/G ratio 50:50) with a main diameter of 15 approximately 30 microm in-vivo. When 3.2 % insulin-loaded PLGA microcapsules were subcutaneously given as a single dose to streptozotocin-induced hyperglycaemic rats (250 U kg(-1)), plasma insulin levels gradually increased and constant levels (30.3-94.1 microU mL(-1)) were sustained. Rats receiving the formulation once a week showed not only steady plasma insulin levels, but also gained weight at a similar speed to normal rats. Meanwhile, daily treatment with Humulin U (25 U kg(-1)) caused a transient high insulin level (2723.9 microU mL(-1) at 1 h) in plasma, but the body weight of the rats was little changed. A pharmacological study in female Cynomolgus monkeys also revealed that the microcapsular formulation provided a flat release of insulin for longer periods and showed no immunogenic activity. In the near future, therefore, this insulin formulation could become very beneficial as a provider of basal insulin levels for insulin-dependent diabetic patients.

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Sustained release of a water-soluble GP IIb/IIIa antagonist from copoly(dl-lactic/glycolic)acid microspheres

Cited by 17 publications

References 16 publications

Porosity and semipermeability of hemoglobin‐loaded polymeric nanoparticles as potential blood substitutes

Porosity and semipermeability of hemoglobin‐loaded polymeric nanoparticles as potential blood substitutes

Enhanced Degradation of Lactide-co-Glycolide Polymer with Basic Nucleophilic Drugs

A novel insulin formulation can keep providing steady levels of insulin for much longer periods in-vivo

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