Paclitaxel delivery from PLGA foams for controlled release in post-surgical chemotherapy against glioblastoma multiforme.
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.
Ong
Benjamin Y S
BY
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
Ranganath
Sudhir H
SH
Lee
Lai Yeng
LY
Lu
Fan
F
Lee
How-Sung
HS
Sahinidis
Nikolaos V
NV
Wang
Chi-Hwa
CH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D003692:Delayed-Action Preparations; D004353:Drug Evaluation, Preclinical; D004343:Drug Implants; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004343:Drug Implants; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel