PLGA nanoformulation of Sparfloxacin enhanced antibacterial activity with photoprotective potential under ambient UV-R exposure

Publication date: Available online 17 February 2018 Source:International Journal of Pharmaceutics Author(s): Jyoti Singh, Ashish Dwivedi, Lipika Ray, Deepti Chopra, Divya Dubey, Ajeet K. Srivastva, Smita Kumari, Randheer Kumar, Saroj Kumar Amar, Chandana Haldar, Ratan Singh Ray Sparfloxacin (SPFX) is a broad spectrum antibiotic which inhibits bacterial DNA gyrase enzyme activity. However, photodegradation in the presence of UVA limits its antibacterial activity and induces phototoxicity. Thus, to encounter this problem, we have developed poly d,l-lactic-co- glycolic acid (PLGA) loaded SPFX nanoparticles. Here, we have performed a comparative antibacterial activity of SPFX and its nanoparticles (NPs) through molecular docking and plate sensitivity assay. Under environmental UVA exposure, photoexcited SPFX significantly generates ROS, DNA damage and mitochondrial mediated cell death in comparison to PLGA-SPFX-NPs (nano SPFX) in human skin cell line (HaCaT). In presence of UVA, bulk SPFX induced cell cycle arrest with appearance of sub-G1 peak showing apoptosis while nano SPFX did not show any change. SPFX triggered apoptosis via alteration in membrane integrity of mitochondria and lysosome in comparison to PLGA-SPFX-NPs. Involvement of mitochondrial mediated cell death was confirmed by down-regulation of anti-apoptotic Bcl-2 and procaspase-3 and upregulation of pro-apoptotic Bax, cytochrome-c and caspase-3 proteins expression. Specific caspase inhibitor, Z-VAD-FMK ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research