Development of biodegradable polymeric paste formulations for taxol: An in vitro and in vivo study |
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| Affiliation: | 1. Division of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver BC, Canada V6T IZ3;2. Connective Tissue Research Group, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ONT, Canada;3. Angiogenesis Technologies, Inc., Vancouver BC, Canada;1. Center for Chemical and Environmental Technology, Nuclear and Energy Research Institute, CQMA/IPEN-CNEN/SP, Sao Paulo, Brazil;2. Metallurgical and Materials Engineering Department, Polytechnic School, University of Sao Paulo, Sao Paulo, SP, Brazil;3. Hacettepe University, Department of Chemistry, Polymer Chemistry Division, Beytepe, Ankara, Turkey;1. Área Académica de Química, Universidad Autónoma del Estado de Hidalgo, km 4.5 Carretera Pachuca-Tulancingo, Mineral de la Reforma, Hidalgo 42184, Mexico;2. Área Académica de Medicina, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo 42090, Mexico;3. Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico City 07000, Mexico;1. Balikesir University, Faculty of Science and Literature, Department of Chemistry, Balikesir, Turkey;2. Jackson State University, Interdisciplinary Nanotoxicology Ctr., Jackson, MS, USA |
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| Abstract: | ![]()
Biodegradable polymeric paste formulations (‘surgical pastes’) for local delivery of taxol were developed and characterized. Taxol was mixed into melted poly(D,L-lactide)-block-poly(ethylene glycol)-block-poly(D,L-lactide) (PDLLA-PEG-PDLLA) copolymers and blends of low molecular weight poly(D,L-lactic acid) and poly-ϵ-caprolactone (PDLLA:PCL) to obtain the paste formulations. The release of taxol into PBS albumin buffer was measured by HPLC. The polymers and pastes were characterized by gel permeation chromatography (GPC), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM). Taxol was released in a sustained manner from the PDLLA-PEG-PDLLA paste over a period of 2 months by diffusion and polymer erosion. The release from the blend was mainly erosion controlled and consisted of a burst followed by a period of slow release. Efficacy of the pastes in inhibiting tumor growth in mice was evaluated. Molten, taxol loaded paste formulations were placed at subcutaneous tumor sites in mice (pastes harden at 37°C). After 16 days, the reduction in tumor weight was measured. Both the taxol loaded copolymer and 90:10 PDLLA:PCL blend formulations significantly inhibited tumor growth in mice. The pastes with faster in vitro release rates resulted in greater efficacy in inhibiting tumor growth. The results showed that biodegradable polymeric surgical pastes are promising formulations for the local delivery of taxol to inhibit tumor growth. |
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