PMID- 35156499 OWN - NLM STAT- MEDLINE DCOM- 20220223 LR - 20220223 IS - 1521-0464 (Electronic) IS - 1071-7544 (Print) IS - 1071-7544 (Linking) VI - 29 IP - 1 DP - 2022 Dec TI - Construction and performance of exendin-4-loaded chitosan-PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats. PG - 548-560 LID - 10.1080/10717544.2022.2036873 [doi] AB - 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. FAU - Shi, Shaojie AU - Shi S AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. AD - Department of Oral Surgery, 920th Hospital of Joint Logistics Support Force, Kunming, China. FAU - Song, Shuang AU - Song S AD - Department of Implant Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Liu, Xiangdong AU - Liu X AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. FAU - Zhao, Guoqiang AU - Zhao G AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. FAU - Ding, Feng AU - Ding F AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. FAU - Zhao, Wenshuang AU - Zhao W AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. FAU - Zhang, Sijia AU - Zhang S AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. FAU - Song, Yingliang AU - Song Y AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. FAU - Ma, Wei AU - Ma W AD - Department of Oral Implants, School of Stomatology, State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, The Fourth Military Medical University, Xi'an, China. LA - eng PT - Journal Article PL - England TA - Drug Deliv JT - Drug delivery JID - 9417471 RN - 0 (Delayed-Action Preparations) RN - 0 (Drug Implants) RN - 0 (Hypoglycemic Agents) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 9P1872D4OL (Exenatide) SB - IM MH - Animals MH - Cell Proliferation/drug effects MH - Chemistry, Pharmaceutical MH - Delayed-Action Preparations MH - Diabetes Mellitus, Experimental/*drug therapy MH - Drug Implants/*chemistry MH - Drug Liberation MH - Exenatide/administration & dosage/*pharmacology MH - Hypoglycemic Agents/administration & dosage/*pharmacology MH - Male MH - *Microspheres MH - Osseointegration/*drug effects MH - Particle Size MH - Polylactic Acid-Polyglycolic Acid Copolymer/chemistry MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Surface Properties PMC - PMC8856071 OTO - NOTNLM OT - Type 2 diabetes mellitus OT - chitosan OT - exendin-4 OT - microspheres OT - osseointegration OT - poly(lactic-co-glycolic acid) COIS- The authors report no conflicts of interest related to this study. EDAT- 2022/02/15 06:00 MHDA- 2022/02/24 06:00 PMCR- 2022/02/14 CRDT- 2022/02/14 08:52 PHST- 2022/02/14 08:52 [entrez] PHST- 2022/02/15 06:00 [pubmed] PHST- 2022/02/24 06:00 [medline] PHST- 2022/02/14 00:00 [pmc-release] AID - 2036873 [pii] AID - 10.1080/10717544.2022.2036873 [doi] PST - ppublish SO - Drug Deliv. 2022 Dec;29(1):548-560. doi: 10.1080/10717544.2022.2036873.