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정화준Hwajun Jeong

경희대학교

Chem. Eng. J., Volume 505, 1 February 2025, 159405 | https://doi.org/10.1016/j.cej.2025.159405 Conjugated polymer of Multi-arm-PEG and dimethylsiloxane (CPMD) for the effective transdermal delivery of deoxycholic acid for fat reduction

Hwajun Jeong ^a,1, Hye-Lin Kim^b,1, Harim Kim ^b, Min-Suk Lee ^c, Jae-Min Cho ^c, Chan Lee Park ^c, Hyo In Kim ^d, Jinbong Park ^b, Dokyoung Kim ^{a,e,f,g,h,i,j}

^aMedical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Core Research Institute (CRI), Kyung Hee University, Seoul 02447 Republic of Korea
^bDepartment of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447 Republic of Korea
^cDDS Research Team, Huons Co. Ltd, Gyeonggi-do 15588, Republic of Korea
^dDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
^eDepartment of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
^fDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
^gCenter for Converging Humanities, Kyung Hee University, Seoul 02447, Republic of Korea
^hKHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea
ⁱUC San Diego Materials Research Science and Engineering Center, La Jolla, CA 92093, USA
^jDepartment of Precision Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea

¹These authors contributed equally.
Corresponding authors : Hyo In Kim, Jinbong Park, Dokyoung Kim

Abstract

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.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-01-13)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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