A transformable and biocompatible polymer series using ring-opening polymerization of cyclic silane for more effective transdermal drug delivery

Abstract

Transdermal drug delivery system (TDDS) has drawn attention in clinical and translational medicine for its advantages such as painless and facile drug administration and the first-pass metabolism avoidance. We disclosed a new siloxane-based polymer series (named PDDS) prepared using the ring-opening polymerization of cyclic silane (2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane) using acidic initiators (acetic acid, citric acid, trifluoroacetic acid, and hydrochloric acid). The properties of the PDDS polymer series including molecular weight, viscosity, and the surface wettability were controlled by (i) acidity of the initiators, (ii) molar ratio of monomer and initiator, and (iii) polymerization temperature. Hydrophobic-/hydrophilic-substrates were successfully encapsulated into the polymers when the polymerization was initiated, and the polymerization condition readily controlled their encapsulation efficiency and release profile. Among the series, the C2 polymer (initiator: citric acid) showed the lowest toxicity and excellent biocompatibility in vivo among the others. In addition, the C2 polymer showed significantly enhanced drug permeation efficacy through the skin and improved considerably therapeutic efficacy relative to the free drug in melanoma xenograft model mice. This study presents a new series of biocompatible polymers that can be used in TDDS as a promising carrier with skin permeation and therapeutic ability.