Enhancement of oral bioavailability of salmon calcitonin through chitosan modified dual-drug loaded nanoparticles
作者单位：Institute of Pharmaceutics College of Pharmaceutical Sciences Zhejiang University The First Affiliated Hospital College of Medicine Zhejiang University College of Pharmaceutical Sciences Zhejiang Chinese Medical University
会议名称：《2018年浙江省医学会临床药学分会学术年会》
会议日期：2018年
学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学]
摘 要：Since numerous challenges limiting effective oral delivery of protein and peptide drugs, a promising strategy for oral administration, salmon calcitonin(sCT) combined with puerarin(PR) as digestive enzymes inhibitor, was performed and the oral delivery property was evaluated. A chitosan(CS) modified dual-drug loaded nanoparticles(NPs) simultaneously containing sCT and PR(CS-sCT/PR-NPs) was prepared by optimized double emulsification solvent evaporation method to achieve particles sized at(190.32±2.65) nm and Zeta potential of(16.5±1.08) mV. This oral delivery system showed efficient encapsulation of sCT(75.7%) and PR(50.9%), protection for encapsulated sCT and PR from releasing too fast in SGJ(pH 1.2), and sustained-release behavior in PBS(pH=7.4). Moreover, CS-sCT/PRNPs had a capability of sequential drug release that PR was partially released prior to sCT, providing a possibility for PR to play a role of enzyme inhibitor before sCT release. The in vitro stability studies indicated that CS-sCT/PRNPs were more stable than CS-sCT-NPs in simulated intestinal ·uid in the absence of pancreatinum. An in vitro cell evaluation demonstrated that the internalization of FITC-sCT by Caco-2 cells was increased when incorporated into NPs, either sole drug loaded or dual drug loaded, compare with free sCT. In vivo, the developed sCT loaded NPs showed increased elimination half-life compared with i.v. sCT solution in rats. Notably, a significant increase of AUC of sCT in the CS-sCT/PR-NPs group was observed compared to that in the CS-sCT-NPs group, and the oral absolute bioavailability of sCT in CS-sCT/PR-NPs of 12.52 ± 1.83% was approximately 1.74-fold higher than that in NPs without co-loaded with PR. In conclusion, the CS based NPs and the introduction of PR as a protease inhibitor improve the oral bioavailability of sCT and have the potential for the oral delivery of peptide drug.