Effect of drug type on the degradation rate of PLGA matrices

Siegel, Steven J.; Kahn, Jonathan B.; Metzger, Kristina B.; Winey, Karen I.; Werner, Kathryn; Dan, Nily

doi:10.1016/j.ejpb.2006.06.009

Cited by 179 publications

(133 citation statements)

References 29 publications

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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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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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“…A need for lasting medication systems has already been expressed in several fields, including treatments for cardiovascular disease (Chui et al 2003), diabetes (Boccuzzi et al 2001), cancer (Natsugoe et al 1997) and HIV/AIDS (Andrews and Friedland 2000;Melbourne et al 1999;Tucker et al 2003). Accordingly, the ability of surgically implantable long-term delivery systems to incorporate other medications for the treatment of psychiatric and non-psychiatric illnesses has been further explored in complimentary studies associated with our group (Siegel et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and behavioral characterization of a long-term antipsychotic delivery system in rodents and rabbits

et al. 2006

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. Pharmacokinetic and behavioral characterization of a longterm antipsychotic delivery system in rodents and rabbits. Retrieved from http://repository.upenn.edu/mse_papers/122Pharmacokinetic and behavioral characterization of a longterm antipsychotic delivery system in rodents and rabbits AbstractRationale: Non-adherence with medication remains the major correctable cause of poor outcome in schizophrenia. However, few treatments have addressed this major determinant of outcome with novel longterm delivery systems.Objectives: The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits.Materials and methods: Implantable formulations of haloperidol were created using biodegradable polymers. Implants were characterized for in vitro release and in vivo behavior using prepulse inhibition of startle in rats and mice, as well as pharmacokinetics in rabbits.Results: Behavioral measures demonstrate the effectiveness of haloperidol implants delivering 1 mg/kg in mice and 0.6 mg/kg in rats to block amphetamine (10 mg/kg) in mice or apomorphine (0.5 mg/kg) in rats. Additionally, we demonstrate the pattern of release from single polymer implants for 1 year in rabbits. Conclusions:The current study suggests that implantable formulations are a viable approach to providing longterm delivery of antipsychotic medications in vivo using animal models of behavior and pharmacokinetics. In contrast to depot formulations, implantable formulations could last 6 months or longer. Additionally, implants can be removed throughout the delivery interval, offering a degree of reversibility not available with depot formulations. AbstractRationale Non-adherence with medication remains the major correctable cause of poor outcome in schizophrenia. However, few treatments have addressed this major determinant of outcome with novel long-term delivery systems. Objectives The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits. Materials and methods Implantable formulations of haloperidol were created using biodegradable polymers. Implants were characterized for in vitro release and in vivo behavior using prepulse inhibition of startle in rats and mice, as well as pharmacokinetics in rabbits. Results Behavioral measures demonstrate the effectiveness of haloperidol implants delivering 1 mg/kg in mice and 0.6 mg/kg in rats to block amphetamine (10 mg/kg) in mice or apomorphine (0.5 mg/kg) in rats. Additionally, we demonstrate the pattern of release from single polymer implants for 1 year in rabbits. Conclusions The current study suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications in vivo using animal models of behavior and pharmacokinetics. In contrast to depot formulations, implantable formulations could last 6 months or longer. Additionally, implants can be removed throughout the delivery interval, offering a ...

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“…However, in relation to M n and according not only to the specific polymer characteristics but their subsequent use as biodegradable scaffold in controlled drug release, it is not necessary to achieve its maximum value. Authors [22][23][24][25] use a wide variety of values of PLGA molecular weight for this purpose, although molecules of PLGA with molecular weight values around 20000 seem to be suitable for their use in controlled drug release [26,27]. So as long as a temperature of 160ºC is selected, this target value is reached and any value of MC ratio or IC ratio would be appropriate.…”

Section: Global Optimization Of the Polymerizationmentioning

confidence: 99%

Optimizing the bulk copolymerization of D,L-lactide and glycolide by response surface methodology

Cabezas¹,

Mazarro

Gracia³

et al. 2013

Express Polym. Lett.

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Poly(D,L-lactide-co-glycolide), PLGA, is a biodegradable polyester with high interest in medical industry, especially when zinc (II) 2-ethylhexanoate (ZnOct2) is used as catalyst substitute in polymerization processes as a substitute of the toxic tin (II) 2-ethylhexanoate (SnOct2) together an initiator such as methanol to improve the reaction rate. This article shows the optimization of the bulk copolymerization method by using a factorial design approach on three experimental parameters: temperature (T), molar ratio monomers/catalyst (MC ratio) and molar ratio initiator/catalyst (IC ratio). Their influence on mass conversion (X) and number-average molecular weight (Mn) was also discussed. Also it provides a useful tool to select in a fast way the proper experimental conditions for the obtaining of this polymer as a previous stage in the synthesis and impregnation of biodegradable scaffolds. This analysis revealed that the most relevant variable in the process is the temperature, being desirable to use the high value (160ºC) in order to obtain high values of conversion and molecular weight

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Effect of drug type on the degradation rate of PLGA matrices

Cited by 179 publications

References 29 publications

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

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

Pharmacokinetic and behavioral characterization of a long-term antipsychotic delivery system in rodents and rabbits

Optimizing the bulk copolymerization of D,L-lactide and glycolide by response surface methodology

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