Niyaz Ahmad1, Md Aftab Alam2, Rizwan Ahmad3, Sadiq Umar4, Farhan Jalees Ahmad5. 1. a Department of Pharmaceutics, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University , Dammam , Kingdom of Saudi Arabia. 2. b Department of Pharmaceutics, School of Medical and Allied Sciences , Galgotias University , Greater Noida , India. 3. c Department of Natural Products and Alternative Medicine College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University , Dammam , Kingdom of Saudi Arabia. 4. d Division of Rheumatology, Department of Medicine, University of Illinois, Chicago , IL , USA. 5. e 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 < 0.01) whereas the permeability for IRN was found to be higher at a rate of 4.32 folds, across rat ileum. Furthermore, pharmacokinetic studies demonstrated marked improvement of 3.53 fold and 8.03 fold in Wistar rat's plasma as well as brain higher oral bioavailability through IRN-CS-PLGA-NPs when compared with IRN-S. A simple, rapid UPLC-ESI-Q-TOF-MS/MS method for the determination of IRN (CPT-11) and SN-38 in both plasma and brain (over a range: 1.00-25000.00 ng/ml) was also developed and successfully applied for pharmacokinetic study. DISCUSSION: CS-IRN-PLGA-NPs approach may be effectively utilised, to replace pre-existing intravenous therapy thus providing 'patient care at home.
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 humanbreast adenocarcinoma cell lines (MCF-7), confirmed the superiority of IRN-CS-PLGA-NPs over free IRN solution (IRN-S). Cellular transport conducted on humancolon 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 < 0.01) whereas the permeability for IRN was found to be higher at a rate of 4.32 folds, across rat ileum. Furthermore, pharmacokinetic studies demonstrated marked improvement of 3.53 fold and 8.03 fold in Wistar rat's plasma as well as brain higher oral bioavailability through IRN-CS-PLGA-NPs when compared with IRN-S. A simple, rapid UPLC-ESI-Q-TOF-MS/MS method for the determination of IRN (CPT-11) and SN-38 in both plasma and brain (over a range: 1.00-25000.00 ng/ml) was also developed and successfully applied for pharmacokinetic study. DISCUSSION: CS-IRN-PLGA-NPs approach may be effectively utilised, to replace pre-existing intravenous therapy thus providing 'patient care at home.
Entities:
Keywords:
CS-PLGA-NPs; Irinotecan; cellular uptake and cellular transport with intestinal transport; oral bioavailability; oral drug delivery; plasma and brain pharmacokinetic
Authors: Niyaz Ahmad; Rizwan Ahmad; Ridha Abdullah Alrasheed; Hassan Mohammed Ali Almatar; Abdullah Sami Al-Ramadan; Taysser Mohammed Buheazah; Hussain Salman AlHomoud; Hassan Ali Al-Nasif; Md Aftab Alam Journal: Saudi J Biol Sci Date: 2020-05-20 Impact factor: 4.219