Hyperbranched Copolymers Forming Polymersome-like Structures Used for Encapsulation and Controlled Release of α-Tocopherol Succinate (TOS): Drug Transport Modeling.

Abstract

Trimesic acid (TMA) and ethyelene diamine (ED) were reacted in various molar proportions to yield several branched/hyperbranched copolymers which formed polymersome-like structures, and they were used for encapsulation and release of a model drug, α-tocopherol succinate (TOS). The branched topology of the copolymers was established from spectroscopy, viscometry, and rheological measurements. Hydrodynamic size and transmission electron microscopy revealed the self-aggregated polymersome-like features of the copolymers with a dense core. Zeta potential studies unveiled pH-sensitive features of the aggregates. Both hydrodynamic size and viscosity were found to decrease with more branching, whereas the encapsulation efficiency displayed a drastic increase from 68 to 89.5% from the least branched (30%) to mostly branched grade (68%). The hydrophobic drug was primarily accommodated within the macromolecular voids inside the core and was released slowly following the diffusion mechanism. An indigenous model was established to explain the release kinetics from such a pH-sensitive and highly branched core-shell matrix which yielded a unique parameter called effective diffusivity or ED that took account of those parameters affecting the release rate. The copolymers were found to be biologically viable through a series of in vitro tests, thus inviting in vivo trials for future experimentation.