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

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 diethylnicotinamide (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.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Elkharraz K,Faisant N,Guse C,Siepmann F,Arica-Yegin B,Oger JM,Gust R,Goepferich A,Benoit JP,Siepmann J

doi

10.1016/j.ijpharm.2005.07.028

keywords:

subject

Has Abstract

pub_date

2006-05-18 00:00:00

pages

127-36

issue

2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(06)00093-7

journal_volume

314

pub_type

杂志文章

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