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Temozolomide-loaded PLGA nanoparticles to treat glioblastoma cells: a biophysical and cell culture evaluation
Temozolomide-loaded PLGA nanoparticles to treat glioblastoma cells: a biophysical and cell culture evaluation NEUROLOGICAL RESEARCH Ananta, J. S., Paulmurugan, R., Massoud, T. F. 2016; 38 (1): 51-59Abstract
Current chemotherapies for brain glioblastoma do not achieve sufficient drug concentrations within tumors. Polymeric nanoparticles have useful physicochemical properties that make them promising as nanoparticle platforms for glioblastoma drug delivery. Poly[lactic-co-glycolic acid] (PLGA) nanoparticles encapsulating temozolomide (TMZ) could improve localized delivery and sustained drug release to glioblastomas.We investigated three different procedures to encapsulate TMZ within PLGA nanoparticles. We studied the biophysical features of optimized nanocarriers, including their size, shape, surface properties, and release characteristics of TMZ. We evaluated the antiproliferative and cytotoxic effects of TMZ-loaded PLGA nanoparticles on U87 MG glioblastoma cells.A single emulsion technique using a TMZ saturated aqueous phase produced nanoparticles =200 nm in size allowing a maximal drug loading of 4.4% w/w of polymer. There was a bi-phasic drug release pattern, with 80% of TMZ released within the first 6 h. Nanoparticles accumulated in the cytoplasm after effective endocytosis. There was no significant difference in cytotoxic effect of TMZ encapsulated within PLGA nanoparticles and free TMZ.PLGA nanoparticles are not suitable as carriers of TMZ for glioblastoma drug delivery on account of the overall high IC50 values of glioblastoma cells to TMZ and poor loading and encapsulation efficiencies. Further biotechnological developments aimed at improving the loading of TMZ in PLGA nanoparticles or co-delivery of small molecule sensitizers to improve the response of human glioblastoma cells to TMZ are required for this approach to be considered and optimized for future clinical translation.
View details for DOI 10.1080/01616412.2015.1133025
View details for PubMedID 26905383