Paclitaxel-loaded microparticles and implants for the treatment of brain cancer: Preparation and physicochemical characterization

Elkharraz, K. and Faisant, N. and Guse, C. and Siepmann, F. and Arica-Yegin, B. and Oger, J. M. and Gust, R. and Goepferich, A. and Benoit, J. P. and Siepmann, J. (2006) Paclitaxel-loaded microparticles and implants for the treatment of brain cancer: Preparation and physicochemical characterization. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 314 (2). pp. 127-136. ISSN 0378-5173, 1873-3476

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Abstract

The aim of this study was to prepare different types of paclitaxel-loaded, PLGA-based microparticles and lipidic implants, which can directly be injected into the brain tissue. Releasing the drug in a time-controlled manner over several weeks, these systems are intended to optimize the treatment of brain tumors. The latter is particularly difficult because of the blood-brain barrier (BBB), hindering most drugs to reach the target tissue upon systemic administration. Especially paclitaxel (being effective for the treatment of ovarian, breast, lung and other cancers) is not able to cross the BBB to a notable extent since it is a substrate of the efflux transporter P-glycoprotein. Both, biodegradable microparticles as well as small, cylindrical, glycerol tripalmitate-based implants (which can be injected using standard needles) were prepared with different paclitaxel loadings. The effects of several formulation and processing parameters on the resulting drug release kinetics were investigated in phosphate buffer pH 7.4 as well as in a diethynicotinamide (DENA)/phosphate buffer mixture. Using DSC, SEM, SEC and optical microscopy deeper insight into the underlying drug release mechanisms could be gained. The presence of DENA in the release medium significantly increased the solubility of paclitaxel, accelerated PLGA degradation, increased the mobility of the polymer and drug molecules and fundamentally altered the geometry of the systems, resulting in increased paclitaxel release rates. (c) 2006 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: POLY(LACTIC-CO-GLYCOLIC ACID) MICROSPHERES; BIODEGRADABLE MICROSPHERES; INTERSTITIAL CHEMOTHERAPY; ISOPROPYL MYRISTATE; ACCELERATED RELEASE; SUSTAINED DELIVERY; TARGETED DELIVERY; MALIGNANT GLIOMA; P-GLYCOPROTEIN; DRUG-DELIVERY; paclitaxel; microparticle; implant; controlled release; brain tumor
Subjects: 600 Technology > 615 Pharmacy
Divisions: Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 Feb 2021 07:51
Last Modified: 15 Feb 2021 07:51
URI: https://pred.uni-regensburg.de/id/eprint/34536

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