Abstract
Gemcitabine (dFdC) mediated cancer treatment faces obstacles, due to its high hydrophilicity. A valuable strategy was executed by synthesizing lipophilic fatty acid derivative of dFdC i.e., 4-(N)-stearoyl gemcitabine (C18dFdC), built-in into polymeric poly-lactic-co-glycolic acid nanoparticles (PLGA NPs) and compared with that of parent drug. Encapsulation of derivative within NPs was higher (68.24 +/- 3.64%) than dFdC and showed comparatively sustained drug release (19.87 +/- 1.73% within 12 hours), with a proof of increased biological half life. The cytotoxicity and flow cytometric analysis displayed enhanced MCF-7 cell inhibition by C18dFdC-NPs with higher uptake compared to dFdC-NPs. Interestingly, like gemcitabine, C18dFdC-NPs did not induce appreciable differences in blood parameters and in vivo tissue toxicity study demonstrating safe use of derivative at 40 mg/kg dose. In conclusion, the preclinical data obtained in vitro and in vivo demonstrate the C18dFdC-nanocarrier as an advantageous and promising delivery system for cancer treatment along with the potential to improve the clinical outcome of gemcitabine chemotherapy.
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