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Exploring the potential of functional polymer-lipid hybrid nanoparticles for enhanced oral delivery of paclitaxel

Asian Journal of Pharmaceutical Sciences 2021年第3期16卷 387-395页

作者： Lu Qin Haiyang Wu Enyu Xu Xin Zhang Jian Guan Ruizhi Zhao Shirui Mao School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Department of Forensic Toxicological Analysis School of Forensic MedicineChina Medical UniversityShenyang 110122China Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000China

Most biopharmaceutics classification system(BCS)class IV drugs,with poor solubility and inferior permeability,are also substrates of P-glycoprotein(P-gp)and cytochrome P450(CYP450),leading to their low oral bioavailability.The objective of this study is to explore the potential of using functional polymer-lipid hybrid nanoparticles(PLHNs)to enhance the oral absorption of BCS IV drugs.In this paper,taking paclitaxel(PTX)as a drug model,PTX-loaded PLHNs were prepared by a self-assembly method.Chitosan was selected to modify the PLHN to enhance its mucoadhesion and stability.Three P-gp inhibitors(D-α-tocopherol polyethylene glycol 1000 succinate,pluronic P123 and Solutol RHS15)were incorporated into selected PLHNs,and a CYP450 inhibitor(the extract of VBRB,BC0)was utilized to jointly promote the drug absorption.Properties of all the PLHNs were characterized systemically,including particle size,zeta potential,encapsulation efficiency,morphology,stability,in vitro drug release,mucoadhesion,in situ intestinal permeability and in vivo systemic exposure.It was found mucoadhesion of the CS-modified PLHNs was the strongest among all the formulations tested,with absolute bioavailability 21.95%.P-gp and CYP450 inhibitors incorporation further improved the oral bioavailability of PTX to 42.60%,8-fold increase compared with that of PTX itself(4.75%).Taken together,our study might shed light on constructing multifunctional PLHNs based on drug delivery barriers for better oral absorption,especially for BCS IV drugs.

关键词： polymer-lipid hybrid nanoparticles (PLHNs) Chitosan P-gp inhibitors CYP450 inhibitors Mucoadhesion Oral bioavailability

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