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

作者全名："Wang, Lu; Li, Yuzhou; Ren, Mingxing; Wang, Xu; Li, Lingjie; Liu, Fengyi; Lan, Yiqing; Yang, Sheng; Song, Jinlin"

作者地址："[Wang, Lu; Li, Yuzhou; Wang, Xu; Liu, Fengyi; Yang, Sheng; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Wang, Lu; Ren, Mingxing; Lan, Yiqing; Yang, Sheng; Song, Jinlin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Li, Yuzhou; Ren, Mingxing; Wang, Xu; Li, Lingjie; Lan, Yiqing; Yang, Sheng; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing, Peoples R China"

通信作者："Yang, S; Song, JL (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China."

来源：BIOACTIVE MATERIALS

ESI学科分类：　

WOS号：WOS:000788759800002

JCR分区：Q1

影响因子：18.9

年份：2022

卷号：18

期号：　

开始页：254

结束页：266

文献类型：Article

关键词：Diabetes mellitus; Periodontitis; Bone loss; PAMAM; Drug delivery

摘要："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-Disteamyl-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."

基金机构："National Natural Science Foundation of China [82171010, 81771082, 31971282, 82001103]; Basic Research and Frontier Exploration Grant of Chongqing Science and Technology Commission [cstc2021jcyj-jqX0028, cstc2019jcyj-msxmX0366, cstc2019jcyj-bshX0005]; ""Associate Doctoral Supervisor"" Cultivation Fund of the Stomatological Hospital of Chongqing Medical University [KQFBD002]; Project of the Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201900441]; Chongqing Graduate Tutor Team [dstd201903]"

基金资助正文："This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 82171010, 81771082, 31971282, 82001103) ; the Basic Research and Frontier Exploration Grant of Chongqing Science and Technology Commission (Grant Nos. cstc2021jcyj-jqX0028, cstc2019jcyj-msxmX0366, cstc2019jcyj-bshX0005) ; the ""Associate Doctoral Supervisor"" Cultivation Fund of the Stomatological Hospital of Chongqing Medical University (Grant No. KQFBD002) ; the Project of the Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN201900441) ; and the Chongqing Graduate Tutor Team (Grant No. dstd201903) ."