Sanyog Jain1, Neha Bhankur2, Nitin K Swarnakar2, Kaushik Thanki2. 1. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S., Nagar (Mohali), Punjab, 160062, India. sanyogjain@niper.ac.in. 2. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S., Nagar (Mohali), Punjab, 160062, India.
Abstract
PURPOSE: The present work focuses on design and development of surface functionalized LCNPs for improving tumor delivery of DTX. METHODS: Phytantriol based "stealth" LCNPs were prepared using hydrotrope method and optimized. The potential of developed formulation was further assessed using cell culture experiments, in vivo pharmacokinetics, in vivo pharmacodynamics and toxicity studies. RESULTS: A biphasic drug release pattern was observed with sustained release of drug till 72 h. In vitro cell culture experiments revealed efficient internalization within MCF-7 cells with 25.80-fold decrease in IC50 value for PEG-LCNPs as compared to free DTX. Mechanistic insights demonstrated preferential co-localization of LCNPs in the vicinity of the nucleus. Furthermore, in vivo pharmacokinetic studies revealed 14.45-fold enhancement in circulation half-life of PEG-LCNPs as compared to marketed formulation Taxotere®. In vivo efficacy studies PEG-LCNPs in DMBA induced breast cancer model revealed ~81% reduction in the tumor burden compared to Taxotere® which caused/achieve only 47% reduction or showed only 47% decrease. Furthermore, safety profile was noted for PEG-LCNPs as compared to Taxotere®, measured as a function of hepato- and nephro-toxicity. CONCLUSIONS: Surface functionalization of LCNPsis a viable approach for improving the therapeutic potential of DTX.
PURPOSE: The present work focuses on design and development of surface functionalized LCNPs for improving tumor delivery of DTX. METHODS:Phytantriol based "stealth" LCNPs were prepared using hydrotrope method and optimized. The potential of developed formulation was further assessed using cell culture experiments, in vivo pharmacokinetics, in vivo pharmacodynamics and toxicity studies. RESULTS: A biphasic drug release pattern was observed with sustained release of drug till 72 h. In vitro cell culture experiments revealed efficient internalization within MCF-7 cells with 25.80-fold decrease in IC50 value for PEG-LCNPs as compared to free DTX. Mechanistic insights demonstrated preferential co-localization of LCNPs in the vicinity of the nucleus. Furthermore, in vivo pharmacokinetic studies revealed 14.45-fold enhancement in circulation half-life of PEG-LCNPs as compared to marketed formulation Taxotere®. In vivo efficacy studies PEG-LCNPs in DMBA induced breast cancer model revealed ~81% reduction in the tumor burden compared to Taxotere® which caused/achieve only 47% reduction or showed only 47% decrease. Furthermore, safety profile was noted for PEG-LCNPs as compared to Taxotere®, measured as a function of hepato- and nephro-toxicity. CONCLUSIONS: Surface functionalization of LCNPsis a viable approach for improving the therapeutic potential of DTX.
Entities:
Keywords:
DMDA model; PEGylation; docetaxel; in vivo antitumor efficacy; liquid crystalline nanoparticles (LCNPs); surface functionalization
Authors: Justas Barauskas; Camilla Cervin; Marija Jankunec; Marija Spandyreva; Kristina Ribokaite; Fredrik Tiberg; Markus Johnsson Journal: Int J Pharm Date: 2010-03-07 Impact factor: 5.875