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

pH and lipase-responsive nanocarrier-mediated dual drug delivery system to treat periodontitis in diabetic rats.
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pH 和脂肪酶响应纳米载体介导的双重药物递送系统治疗糖尿病大鼠牙周炎。

DOI:
10.1016/j.bioactmat.2022.02.008
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发表时间:
2022-12
影响因子:
18.9
通讯作者:
Song J
Song J
中科院分区:
工程技术1区
文献类型:
--
作者:
Wang L;Li Y;Ren M;Wang X;Li L;Liu F;Lan Y;Yang S;Song J

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精确和受控的药物递送治疗糖尿病患者的牙周炎仍然是一个重大的临床挑战。基于纳米颗粒的药物递送系统提供了一种潜在的治疗策略;然而,传统纳米颗粒的低装载效率、无响应性和单一作用阻碍了其临床应用。本研究设计了一种新型的自组装、双重响应、双重载药的纳米载体系统,该系统由两部分组成:由1,2-二硬脂酰-sn-甘油基-3-磷酸乙醇胺-聚(乙二醇)(DSPE-PEG)负载α-硫辛酸(ALA);和包含静电吸附盐酸米诺环素(Mino)的聚(酰胺基胺)树枝状聚合物(PAMAM)的亲水性壳。这种独特的设计允许在牙周病原体的脂肪酶刺激下控制释放抗氧化剂/ALA,并在炎症微环境的低pH下控制释放抗菌剂/Mino。体内和体外研究证实,该双纳米载体在糖尿病病理条件下能抑制龈下微生物菌落的形成,同时促进细胞的成骨分化,改善牙周骨吸收。这种有效和通用的药物输送策略具有良好的潜在应用,以抑制糖尿病相关的牙周骨丢失。纳米载体对pH和脂肪酶敏感,用于控制药物释放。纳米载体通过抗菌剂/米诺和抗氧化剂/ALA的受控释放同时发挥抗菌、抗氧化、抗炎和成骨功能。纳米载体为治疗糖尿病条件下的牙周炎提供了一种有前途的策略。
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. The nanocarriers are pH and lipase sensitive for controlled drug release. The nanocarriers simultaneously exert antibacterial, antioxidant, anti-inflammatory, and osteogenic functions via the controlled release of antibacterial/Mino and antioxidant/ALA. The nanocarriers offer a promising strategy to treat periodontitis under DM conditions.
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DOI: 10.2147/dmso.s246062
发表时间: 2020
期刊: Diabetes, metabolic syndrome and obesity : targets and therapy
影响因子: --
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