pH and lipase-responsive nanocarrier-mediated dual drug delivery system to treat periodontitis in diabetic rats

Autor: Lu Wang, Yuzhou Li, Mingxing Ren, Xu Wang, Lingjie Li, Fengyi Liu, Yiqing Lan, Sheng Yang, Jinlin Song
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Bioactive Materials, Vol 18, Iss , Pp 254-266 (2022)
Druh dokumentu: article
ISSN: 2452-199X
DOI: 10.1016/j.bioactmat.2022.02.008
Popis: Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge. Nanoparticle-based drug delivery systems offer a potential therapeutic strategy; however, the low loading efficiency, non-responsiveness, and single effect of conventional nanoparticles hinder their clinical application. In this study, we designed a novel self-assembled, dual responsive, and dual drug-loading nanocarrier system, which comprised two parts: the hydrophobic lipid core formed by 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG) loaded with alpha-lipoic acid (ALA); and a hydrophilic shell comprising a poly (amidoamine) dendrimer (PAMAM) that electrostatically adsorbed minocycline hydrochloride (Mino). This unique design allows the controlled release of antioxidant/ALA under lipase stimulation from periodontal pathogens and antimicrobial/Mino under the low pH of the inflammatory microenvironment. In vivo and in vitro studies confirmed that this dual nanocarrier could inhibit the formation of subgingival microbial colonies while promoting osteogenic differentiation of cells under diabetic pathological conditions, and ameliorated periodontal bone resorption. This effective and versatile drug-delivery strategy has good potential applications to inhibit diabetes-associated periodontal bone loss.
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