Injectable bio-multifunctional hyaluronic acid-based hydrogels loaded with poly ADP-ribose polymerase inhibitors for ovarian cancer therapy.

Autor: Han X; Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China., Li G; Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao 266113, China., You S; Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China., Shen M; Department of Public Health, Qingdao University, Qingdao 266021, China., Xu Y; Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China., Yang H; School of Urology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China., Lu C; Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China., Zhang M; Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China., Fang J; Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Qingdao 266237, China., Zhou Q; Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao 266113, China. Electronic address: qihuizhou@uor.edu.cn., Yao Q; Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address: dr_yaoqin@qdu.edu.cn.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Jun; Vol. 270 (Pt 1), pp. 132275. Date of Electronic Publication: 2024 May 09.
DOI: 10.1016/j.ijbiomac.2024.132275
Abstrakt: The recent use of PARP inhibitors (PARPi) in the maintenance treatment of ovarian tumor has significantly improved the survival rates of cancer patients. However, the current oral administration of PARP inhibitors fails to realize optimal therapeutic effects due to the low bioavailability in cancerous tissues, and often leads to a range of systemic adverse effects including hematologic toxicities, digestive system reactions, and neurotoxicities. Therefore, the demand for an advanced drug delivery system that can ensure effective drug administration while minimizing these unfavorable reactions is pressing. Injectable hydrogel emerges as a promising solution for local administration with the capability of sustainable drug release. In this study, we developed an injectable hydrogel made from aminated hyaluronic acid and aldehyde-functionalized pluronic127 via Schiff base reaction. This hydrogel exhibits excellent injectability with short gelation time and remarkable self-healing ability, and is applied to load niraparib. The drug-loaded hydrogel (HP@Nir hydrogel) releases drugs sustainably as tested in vitro as well as displays significant anti-proliferation and anti-migratory properties on human epithelial ovarian cancer cell line. Notably, HP@Nir hydrogel effectively suppresses the growth of ovarian cancer, without significant adverse reactions as demonstrated in animal studies. Additionally, the developed hydrogel is gradually degraded in vivo for around 20 d, while maintaining good biocompatibility. Overall, the injectable hydrogel loaded with niraparib provides a secure and efficient strategy for the treatment and management of ovarian cancer.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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