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At least 199 records · Page 11Linked to original sources
PubMed2006

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

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.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Effects of ethylene glycol-based graft, star-shaped, and dendritic polymers on solubilization and controlled release of paclitaxel.

New methods and pharmaceutical compositions were developed to increase the aqueous solubility of paclitaxel (PTX), a poorly water-soluble drug. Graft and star-shaped graft polymers consisting of poly(ethylene glycol) (PEG400) graft chains increased the PTX solubility in water by three orders of magnitude. Polyglycerol dendrimers (dendriPGs) dissolved in water at high concentrations without significantly increasing the viscosity and, at 80 wt.%, were found to increase the solubility of PTX 10,000-fold. The solubilized PTX was released from graft polymers, star-shaped graft polymers, and the dendriPGs into the surrounding aqueous solution. The release rate was a function of the star shape and the dendrimer generation. The availability of the new graft, star and dendritic polymers having ethylene glycol units should permit development of novel delivery systems for other poorly water-soluble drugs.

Animals↗