Improvement of oral efficacy of Irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations |
| |
| Authors: | Niyaz Ahmad Md Aftab Alam Rizwan Ahmad Sadiq Umar Farhan Jalees Ahmad |
| |
| Affiliation: | 1. Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia;2. Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Greater Noida, India;3. Department of Natural Products and Alternative Medicine College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia;4. Division of Rheumatology, Department of Medicine, University of Illinois, Chicago, IL, USA;5. Nanomedicine Lab, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India |
| |
| Abstract: | Background: Irinotecan (IRN) (CPT-11) is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein (p-gp) receptors. Hence, no oral formulation is marketed for IRN till date and its oral ingestion continues to remain a challenge.Aim of study: The study aims to develop a nanoformulation i.e. Chitosan (CS)-coated-IRN-loaded-poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) (CS-IRN-PLGA-NPs)in order to enhance oral bioavailability of IRN.Results: Developed formulation revealed particle size, 166.9?±?13.63?nm, zeta potential, 14.67?±?1.08?mV and drug content (42.69?±?1.97 µg/mg), with spherical shape and smooth surface. Cytotoxicity studies, performed against human breast adenocarcinoma cell lines (MCF-7), confirmed the superiority of IRN-CS-PLGA-NPs over free IRN solution (IRN-S). Cellular transport conducted on human colon adenocarcinoma cell line (Caco-2) exhibited a higher permeability of 1.33 folds for IRN through CS-IRN-PLGA-NPs as compared to IRN-S (p?Discussion: CS-IRN-PLGA-NPs approach may be effectively utilised, to replace pre-existing intravenous therapy thus providing ‘patient care at home. |
| |
| Keywords: | Irinotecan CS-PLGA-NPs oral drug delivery cellular uptake and cellular transport with intestinal transport oral bioavailability plasma and brain pharmacokinetic |
|
|
