Designing Jasmine Lactone Copolymer Micelles for Drug Delivery: Influence of Ionic Group Density and Chain Length

Abstract

Functionalized amphiphilic polymers have been widely applied as drug delivery vehicles due to their ability to self-assemble into micelles that enhance the solubility, stability, and bioavailability of poorly water-soluble drugs. Among these, poly jasmine lactone (PJL), a recently developed amphiphilic copolymer, offers the opportunity to functionalize with versatile functional groups via facile thiol-ene chemistry. In this study, we synthesized and compared anionic functionalized block copolymers of PJL (mPEG-b-PJL-COOH) having varying numbers of the -COOH groups to assess the effect on the encapsulation efficiency, particle size, drug release behavior, and cytotoxicity. Our results demonstrate that increasing the number of anionic groups did not improve the encapsulation efficiency of model drugs but sustained the drug release profile. Ex-vivo hemolytic studies were also performed to evaluate pH-dependent cell lysis as an indirect indicator of endosomal escape capabilities of prepared micelles. Coarse-grained molecular dynamics simulations also revealed that increasing the number of -COOH groups altered the structural properties of the lipid bilayer. Moreover, the aggregation of -COOH units within the lipid bilayer may represent the molecular mechanism underlying the higher cytotoxicity observed with a greater number of COOH groups.