Conjugated polymer of Multi-arm-PEG and dimethylsiloxane (CPMD) for the effective transdermal delivery of deoxycholic acid for fat reduction

Transdermal drug delivery systems (TDDS) have garnered significant interest within clinical and translational medicine due to their non-invasive nature, ease of drug administration, and ability to circumvent first-pass metabolism. Herein, we disclose the development of a novel conjugated polymer, X-CPMD, which combines multi-arm-PEG and dimethylsiloxane (X represents the number of arms, X = 1, 2, 4, and 8) and is designed to enhance transdermal delivery of deoxycholic acid (DCA). DCA, known for its lipolytic properties, disrupts adipocytes cell membranes and destroys fat cells. X-CPMD was synthesized through in situ ring-opening polymerization of multi-arm-PEG-COOH and dimethylsiloxane. The synergistic effects of the hydrophilic PEG and the lipophilic dimethylsiloxane of X-CPMD enable superior biocompatibility, high water solubility, drug encapsulation ability, and transdermal efficiency. Among the X-CPMD series, 4-arm-CPMD (4-CPMD) exhibited remarkable reproducibility in large-scale synthesis, high DCA encapsulation efficacy, high transdermal DCA delivery ability in Franz cell study (efficacy > 90 %), and excellent biocompatibility. 4-CPMD significantly enhanced the permeation of DCA through the skin and improved fat reduction compared to free DCA in a high-fat mouse model. In the DCA@4-CPMD treatment group, significant average weight loss was observed compare with non-treated control and free DCA treatment group. Additionally, 4-CPMD demonstrated potential for oral uptake and accelerated intestinal absorption. This study introduces an innovative approach to the design of conjugated polymers, establishing them as a promising carrier system in TDDS, with effective skin permeation and robust therapeutic efficacy.