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KMID : 0369820140440040265
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Jorunal of Korean Pharmaceutical Sciences
2014 Volume.44 No. 4 p.265 ~ p.272
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Formulation and evaluation of pH sensitive hydrogel of camptothecin with enhanced solubility by using β-cyclodextrin
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Kushwaha Swatantra Kumar Singh
Rai Awani Kumar
Singh Satyawan
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Abstract
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The use of a novel injectable biocompatible and biodegradable camptothecin (CPT) formulation for controlled intra-tumoral release of CPT is described. The drug delivery vehicle is an autogelling pH sensitive formulation, which is based on the natural biopolymer chitosan. The formulation was prepared by Crosslinking methods. The formulations were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, gelation time and viscosities were investigated for controlled release hydrogel formulation. The formulation, containing homogeneously dispersed CPT, was studied by MTT assay on tumor cell MCF-7. The effectiveness of treatment was measured in terms of percentage control tumor growth inhibition (TGI). The hydrogel formulation of CPT showed good release profile with polymer [chitosan (C)/glyceryl monooleate (GMO)/β-cyclodextrin (β-CD)] compare to without polymer. The gelation pH of the formulation PF, PF4, PF6, PF10 and PF12 were found to be 6.58, 7.42, 7.20, 6.98 and 7.30 respectively and calculated values of viscosity in centipoises of the formulation PF, PF4, PF6, PF10 and PF12 were 3,413.3, 5,843.1, 6,948.8, 5,212.6 and 6,972.6 respectively at 25 °C. It was found that cumulative percentage drug release for formulations prepared PF, PF4, PF6, PF10 and PF12 were released 48.48, 76.92, 83.72, 78.97 and 59.23 % respectively. The formulation PF6 showed maximum cumulative percentage drug release which has 3 % w/v chitosan, 3 % w/v GMO and 1.5 % w/v β-CD. The TGI was found that for formulations CPT, PF, PF4, PF6, PF10 and PF12 were 10.2 ± 1.22, 10.4 ± 0.85, 14.92 ± 1.06, 16.42 ± 1.11, 13.58 ± 1.21 and 11.71 ± 1.14 % respectively. The formulation PF6 showed maximum TGI in comparison to other formulation. The system formulated with CPT was found to be stable and the release profiles of a formulation with chitosan, GMO and β-CD showed all most effective release kinetics. These findings show chitosan/GMO/β-CD hydrogel to be a safe, effective, homogeneous, injectable and stable formulation for delivery of CPT and this approach represents an attractive technology platform for the delivery of other clinically important hydrophobic drugs.
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KEYWORD
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Chitosan, Hydrogel, β-Cyclodextrin, MCF-7, Camptothecin
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