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Title: Hydrogel matrix entrapping PLGA-paclitaxel microspheres: Drug delivery with near zero-order release and implantability advantages for malignant brain tumour chemotherapy
Authors: Ranganath, S.H. 
Kee, I.
Krantz, W.B. 
Chow, P.K.-H. 
Wang, C.-H. 
Keywords: Chemotherapy
Electrohydrodynamic atomization
Issue Date: Sep-2009
Citation: Ranganath, S.H., Kee, I., Krantz, W.B., Chow, P.K.-H., Wang, C.-H. (2009-09). Hydrogel matrix entrapping PLGA-paclitaxel microspheres: Drug delivery with near zero-order release and implantability advantages for malignant brain tumour chemotherapy. Pharmaceutical Research 26 (9) : 2101-2114. ScholarBank@NUS Repository.
Abstract: Purpose: To develop paclitaxel-delivering PLGA microspheres entrapped in a gel matrix with sustained drug release properties and implantability advantages for local glioma chemotherapy. Methods: Paclitaxel-loaded PLGA microspheres were fabricated using electrohydrodynamic atomization and entrapped by electrospray and gelation. The physicochemical characterizations were performed using scanning electron microscopy and differential scanning calorimetry. The influence of various parameters on the disintegration time was investigated. In vitro release of paclitaxel was quantified using high performance liquid chromatography. Cytotoxicity of the formulations was assessed by the quantification of IC50 and caspase-3 activity against C6 glioma cells in vitro. The formulations were tested against a subcutaneous C6 glioma tumour in mice. Results: Highly monodisperse gel beads containing a uniform microsphere distribution were obtained. Gelation using Ca2+ ions ensured entrapment of microspheres with high loading efficiency. With an increase in the gelation time, gelling bath concentration and decrease in microsphere loading, it was more difficult to disintegrate the beads and release the microspheres. The formulations demonstrated sustained drug release for more than 60 days at a near-constant rate and a low initial burst. Cell culture studies proved the cytotoxicity against C6 glioma and improved performance in comparison to Taxol®. The formulations could reduce subcutaneous tumour volume to a greater extent compared to Taxol® and the control. Conclusions: Paclitaxel-loaded PLGA microspheres entrapped in an alginate gel matrix could be potential local chemotherapy implants to treat malignant glioma with critical advantages of implantability and sustained drug release with low initial burst. © 2009 Springer Science+Business Media, LLC.
Source Title: Pharmaceutical Research
ISSN: 07248741
DOI: 10.1007/s11095-009-9922-2
Appears in Collections:Staff Publications

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