a Department of Pharmaceutics, College of Clinical Pharmacy , Imam Abdulrahman Bin Faisal University , Dammam , Kingdom of Saudi Arabia.
b Department of Pharmaceutics, School of Medical and Allied Sciences , Galgotias University , Greater Noida , India.
J Microencapsul. 2018 Jun;35(4):327-343. doi: 10.1080/02652048.2018.1485755. Epub 2018 Jul 9.
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.
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.
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.
CS-IRN-PLGA-NPs approach may be effectively utilised, to replace pre-existing intravenous therapy thus providing 'patient care at home.
伊立替康（IRN）（CPT-11）是一种喜树碱衍生物，由于肠道 P-糖蛋白（p-gp）受体的主动外排，其口服生物利用度较低。因此，迄今为止，还没有上市的 IRN 口服制剂，其口服摄入仍然是一个挑战。
本研究旨在开发一种纳米制剂，即壳聚糖（CS）包覆的 IRN 载多聚乳酸-乙醇酸共聚物（PLGA）纳米粒（CS-IRN-PLGA-NPs），以提高 IRN 的口服生物利用度。
所开发的制剂显示出粒径为 166.9±13.63nm、zeta 电位为 14.67±1.08mV 和药物含量（42.69±1.97μg/mg），具有球形和光滑的表面。对人乳腺癌腺癌细胞系（MCF-7）进行的细胞毒性研究证实，IRN-CS-PLGA-NPs 优于游离 IRN 溶液（IRN-S）。在人结肠腺癌细胞系（Caco-2）上进行的细胞转运研究表明，与 IRN-S 相比，IRN 通过 CS-IRN-PLGA-NPs 的通透性提高了 1.33 倍（p<0.01），而 IRN 的通透性则提高了 4.32 倍。此外，药代动力学研究表明，与 IRN-S 相比，Wistar 大鼠血浆中的 IRN 的口服生物利用度提高了 3.53 倍，脑内提高了 8.03 倍，通过 IRN-CS-PLGA-NPs。还开发并成功应用于药代动力学研究了一种用于同时测定血浆和脑（范围：1.00-25000.00ng/ml）中 IRN（CPT-11）和 SN-38 的简单、快速的 UPLC-ESI-Q-TOF-MS/MS 方法。
CS-IRN-PLGA-NPs 方法可能有效地用于替代现有的静脉治疗，从而提供“家庭患者护理”。
