Construction and performance of exendin-4-loaded chitosan-PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats.
Construction and performance of exendin-4-loaded chitosan-PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats.
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DOI：
10.1080/10717544.2022.2036873
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发表时间：
2022-12
期刊：
影响因子：
6
通讯作者：
Ma W
中科院分区：
文献类型：
--
作者：
Shi S;Song S;Liu X;Zhao G;Ding F;Zhao W;Zhang S;Song Y;Ma W
药物递送系统的更新和优化对于改善药物的体内行为以及改善糖尿病患者受损的种植体骨整合至关重要。许多研究已经报道了exendin-4对糖尿病骨的益处，具有增强糖尿病骨整合的潜力。为构建一种以exendin-4为靶点的糖尿病种植体骨整合缓释系统，本研究以聚乳酸-羟基乙酸共聚物（PLGA）和壳聚糖为载体，制备了exendin-4缓释微球。考察了微球的形态、粒径、包封率和药物释放行为。研究载药微球对糖尿病骨髓基质细胞增殖和成骨分化的生物活性，探讨壳聚糖-PLGA微球负载exendin-4的药理作用。此外，使用2型糖尿病（T2 DM）大鼠种植体模型评价微球对骨整合的影响。4周后，通过放射学和组织学分析评估样品。体外实验结果表明，所制备的壳聚糖-PLGA微球具有良好的载药性能，壳聚糖的加入可提高微球的包封率和药物释放。此外，载exendin-4的微球可促进糖尿病BMSCs的增殖和成骨分化。体内实验结果显示，载exendin-4微球显著改善T2 DM大鼠种植体周围受损的骨整合和骨形成，而不影响血糖水平。因此，局部应用exendin-4-loaded chitosan-PLGA微球可能是一个有前途的治疗策略，以提高T2 DM患者的牙科种植体的疗效。
The updating and optimization of drug delivery systems is critical for better in vivo behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan–PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of in vitro experiments showed that the prepared exendin-4-loaded chitosan–PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of in vivo experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan–PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.
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作者：
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DOI：
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发表时间：
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期刊：
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons
影响因子：
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作者：
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