Paclitaxel delivery from PLGA foams for controlled release in post-surgical chemotherapy against glioblastoma multiforme

Biomaterials. 2009 Jun;30(18):3189-96. doi: 10.1016/j.biomaterials.2009.02.030. Epub 2009 Mar 14.

Abstract

Paclitaxel loaded biodegradable poly-(DL-lactic-co-glycolic) acid (PLGA) foams with microporous matrix were fabricated by a novel pressure quenching approach to provide a sustained paclitaxel release. The foams with micropores provided increased surface area to volume ratio and were also implantable for post-surgical chemotherapy applications. The two formulations 5% (w/w) paclitaxel loaded PLGA 85:15 foam (F1) and 10% (w/w) paclitaxel loaded PLGA 50:50 foam (F2), were evaluated in vitro and in vivo. Both the foams were found to provide a paclitaxel release beyond a month in vitro with a near zero-order kinetics and with minimum burst release. Furthermore, apoptosis of C6 glioma cells in vitro demonstrated the benefits of sustained paclitaxel release by the foams in comparison to acute Taxol exposure. Both the foams exhibited continuous paclitaxel release in an in vivo (subcutaneous) environment up to a month which correlated well with the in vitro release profiles. Bio-distribution results in the rat brain showed paclitaxel penetration at therapeutic levels up to 3mm into the tissue from the site of foam implantation. Hence these foams could be employed as potential implants for post-surgical chemotherapy against malignant glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Chemotherapy, Adjuvant
  • Delayed-Action Preparations
  • Drug Evaluation, Preclinical
  • Drug Implants
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Glioblastoma / surgery
  • Lactic Acid*
  • Mice
  • Mice, Inbred BALB C
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / therapeutic use
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Porosity
  • Rats
  • Rats, Wistar
  • Tissue Distribution

Substances

  • Antineoplastic Agents, Phytogenic
  • Delayed-Action Preparations
  • Drug Implants
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Paclitaxel