Paclitaxel delivery from PLGA foams for controlled release in post-surgical chemotherapy against glioblastoma multiforme |
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Authors: | Benjamin YS Ong Sudhir H Ranganath Lai Yeng Lee Fan Lu How-Sung Lee Nikolaos V Sahinidis Chi-Hwa Wang |
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Institution: | 1. Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium;2. Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium;3. MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, France;4. Pharmacy Department, UFR Santé, Université Bretagne Loire, Angers, France |
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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 3 mm 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. |
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