Biodegradable Microspheres in Drug Delivery

Okada, Hiroaki; Toguchi, Hajime

doi:10.1615/critrevtherdrugcarriersyst.v12.i1.10

Cited by 363 publications

(159 citation statements)

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“…Poly(lactide-co-glycolide) microparticles (MPs) and nanoparticles (PLGA NPs) have been extensively studied as drug carriers based upon the properties of degradability and biocompatibility [1,2]. Small molecule and biomacromolecular therapeutics, e.g.…”

Section: Introductionmentioning

confidence: 99%

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Guo

Gemeinhart

2008

European Journal of Pharmaceutics and Biopharmaceutics

114

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Polyelectrolyte-coated nanoparticles or microparticles interact with bioactive molecules (peptides, proteins or nucleic acids) and have been proposed as delivery systems for these molecules. However, the mechanism of adsorption of polyelectrolyte onto particles remains unsolved. In this study, cationic poly(lactide-co-glycolide) (PLGA) nanoparticles were fabricated by adsorption of various concentrations of a biodegradable polysaccharide, chitosan (0-2.4 g/L), using oil-in-water emulsion and solvent evaporation techniques. The particle diameter, zeta-potential, and chitosan adsorption of chitosan coated PLGA nanoparticles confirmed the increase of polyelectrolyte adsorption. Five adsorption isotherm models (Langmuir, Freundlich, Halsey, Henderson and Smith) were applied to the experimental data in order to better understand the mechanism of adsorption. Both particle diameter and chitosan adsorption increased with chitosan concentration during adsorption. A good correlation was obtained between PLGA-chitosan nanoparticle size and adsorbed chitosan on the surface, suggesting the increased particle size was primarily due to the increased chitosan adsorption. The zeta-potential of chitosan-coated PLGA nanoparticles was positive and increased with chitosan adsorbed until a maximum value (+55 mV) was reached at approximately 0.4-0.6 g/L; PLGA nanoparticles had a negative zeta-potential (−20 mV) prior to chitosan adsorption. Chitosan adsorption on PLGA nanoparticles followed a multilayer adsorption behavior, although the Langmuir monolayer equation held at low concentrations of chitosan. The underlying reasons for adsorption of chitosan on PLGA nanoparticles were thought to be the cationic nature of chitosan, high surface energy and microporous non-uniform surface of PLGA nanoparticles.

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Section: Introductionmentioning

confidence: 99%

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Guo

Gemeinhart

2008

European Journal of Pharmaceutics and Biopharmaceutics

114

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“…To improve therapeutic efficacy while minimizing side effects, various drug delivery and targeting systems have been investigated such as synthetic polymer-drug conjugates (3), liposomes (4), micelles (5,6), nanogels (7), and micro-or nanosphere (8,9). Nano-sized delivery systems are able to passively accumulate drugs in solid tumors by an enhanced permeation and retention (EPR) effect (10).…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

Kim¹,

Lee²,

Park³

et al. 2008

Pharm Res

107

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Purpose-To evaluate pH-sensitive mixed micelles for multidrug resistant (MDR) ovarian tumor targeting and optical imaging of solid tumors.Method-Doxorubicin (DOX) encapsulated pH-sensitive mixed micelles composed of poly(Lhistidine) (MW 5K)-b-PEG(MW 2K) and poly(L-lactic acid)(3K)-b-PEG (2K)-folate (PHSM-f) were prepared. Folate receptor-mediated endocytosis, drug uptake, endosomal disruption and cell viability were investigated at the cellular level. For in vivo tumor growth inhibition tests, multidrug resistant ovarian A2780/DOX R xenografted nude mice were used. Optical imaging was performed by using a Cy5.5 fluorescence dye-labeled mixed micelle system. Cy5.5 fluorescence intensity at the tumor site was measured in KB epidermoid xenografted nude mice.Results-In vitro cell viability and drug distribution in the cytoplasm demonstrated the significantly superior efficacy of PHSM-f to free DOX and a control sample of DOX loaded pH-insensitive micelle composed of poly(L-lactic acid)(3K)-b-PEG(2K)/poly(L-lactic acid)(3K)-b-PEG(2K)-folate (80/20 wt/wt%) (PHIM-f). The mechanisms of these results were proved by folate receptor mediated endocytosis of micelle and endosomal disruption function by it. In addition, the optical imaging demonstrated the future application of the diagnositic area. PHSM-f inhibited the growth of multidrug resistant ovarian tumors efficiently in mice, with minimum weight loss.Conclusions-The pH-sensitive mixed micelle system demonstrates effective antitumor efficacy against the multidrug resistant ovarian tumor A2780/DOX R .

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“…PLGA implants are amenable to many compounds, including devices to control thyrotropinreleasing hormone in maintaining metabolism, deliver L-dopa in the treatment of Parkinson's disease, and manage sustained release of luteinizing hormone releasing hormone (LHRH) antagonist to treat prostate cancer (Du 2006;Okada 1995;Sabel et al 1990). Future studies could incorporate various agents to tests their applicability in long-term delivery.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo demonstration of risperidone implants in mice

Rabin

Liang

Ehrlichman

et al. 2008

Schizophrenia Research

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Background-Nonadherence with medication is a critical limitation in current long-term treatment of schizophrenia and a primary factor in poor quality-of-life outcomes. However, few treatments have addressed this shortcoming using an implantable drug delivery approach. The goal of this study was to provide in vitro and in vivo proof of concept for a long-term implantable risperidone delivery system in mice.

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Biodegradable Microspheres in Drug Delivery

Cited by 363 publications

References 0 publications

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Doxorubicin Loaded pH-sensitive Micelle: Antitumoral Efficacy against Ovarian A2780/DOXR Tumor

In vitro and in vivo demonstration of risperidone implants in mice

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