报告题目：Design of efficient delivery system for biopharmaceutical products based on self-assembly technology
报 告 人：石凯 博士（沈阳药科大学）
Kai Shi, Ph.D. is the Professor in Department of Pharmaceutics, School of Pharmacy at Shenyang Pharmaceutical University. Dr. Shi’s research has been in the area of biological therapy and target drug delivery. His current work centers on nano self-assembled vectors for gene transfer in tumors. He serves as a Young director for Chinese Society of Particuology (CSP) and Under-Secretary-General for special committee on biological particles of CSP. He is also the editorial board for Journal of Shenyang Pharmaceutical University, Asian Journal of Pharmaceutical Sciences (SCI journal) and the referee for international peer-reviewed journals related to pharmaceutical sciences. He was a prize-winner for the youth biopharmaceutical award of China Pharmaceutical Association in 2013. He has published more than 40 research papers on the effective delivery of biotechnology drugs, with nearly 100 influencing factors. In addition, his teaching courses involve industrial pharmaceutics and pharmacokinetics for undergraduates and graduates.
The efficient and controlled delivery of therapeutic biomacromolecules (such as protein, peptide and genes) without generation of new molecular entities provides us with a promising alternative and significant clinical benefit. However, the poor stability of these drugs in vivo, as well as high clearance and low cellular membrane permeability limit their wide range of clinical applications. To this end, we aim to construct a series of biomimetic self-assembly delivery systems driven by metal coordination that enable satisfactory drug loading and controllable delivery. One of the projects we show here is that the therapeutic protein of rhIFN can self-assemble into a three-dimensional ordered structure with spherical semi-crystalline features under certain crystallization conditions and the guidance of additives. The plasma pharmacokinetics suggested that s.c. administration of the self-assemblies offered a significant prolonged duration time of rhIFN blood levels up to seven days, which efficacy is comparable to the long-acting preparations already on the market. Another project demonstrated is the biomimetic self-assembly of low-density lipoprotein (LDP) directed by the inorganic kernel of calcium phosphate. The reconstituted LDP nanovehicles serve as a “Trojan horse” for targeted delivery of STAT3-decoy oligonucleotides into tumor cells, and reverse their TRAIL resistance through blocking STAT3 signaling and consequent expression of downstream anti-apoptotic genes.