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Temperature Responsive and Biodegradable Dendronized Copolymer for Controlled Release of Therapeutic Agents across the Blood Brain Barrier (Bbb)

Eun Seok Gil, Department of Surgery, Pennsylvania State University, 500 University Drive, Hershey, PA 17033 and Tao Lu Lowe, Departments of Surgery, Bioengineering, and Materials Science and Engineering, Pennsylvania State University, 500 University Drive, Hershey, PA 17033.

We have developed a novel temperature responsive and biodegradable dendronized copolymer, which composed of biodegradable poly-L-lactic acid (PLLA) branches, temperature responsive poly (N-isopropyl acrylamide) (PNIPAAm), and poly-L-lysine (PLL) dendrons. We synthesize the dendronized copolymer by using combination of solid phase peptide synthesis (SPPS), ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) techniques. The objective of this study is to develop this temperature responsive and biodegradable dendronized copolymer as effective controlled drug delivery systems for proteins and anticancer drugs across the blood brain barrier (BBB). BBB is a selective protective barrier composed of a tightly packed capillary endothelial cell monolayer, which prevents the passage of many substances, but it poses a problem for cerebral drug delivery. In the present work, we study the effect of the molecular structures and charge properties of the dendronized copolymer on the in vitro cytotoxicity and the permeability of the polymer towards bovine brain microvascular endothelial cells (BBMVECs) monolayer, an in vitro BBB model.