PMID- 30342306 OWN - NLM STAT- MEDLINE DCOM- 20190420 LR - 20240229 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 97 DP - 2019 Jan TI - Topical application of phenytoin or nifedipine-loaded PLGA microspheres promotes periodontal regeneration in vivo. PG - 42-51 LID - S0003-9969(18)30216-4 [pii] LID - 10.1016/j.archoralbio.2018.10.002 [doi] AB - OBJECTIVES: Gingival recession and alveolar bone loss are common manifestations of periodontitis. Periodontal regeneration is the ideal strategy for rehabilitating periodontal tissue defects and preventing tooth loss. The present study examined whether localized, topical application of gingival overgrowth-inducing drugs, phenytoin, nifedipine or cyclosporine, induces periodontal regeneration. METHODS: Polylactic-co-glycolic acid (PLGA) was used as the carrier for preparation of phenytoin, nifedipine or cyclosporine-loaded PLGA microspheres, using an oil-in-water emulsification technique. The drug-loaded microspheres were delivered to periodontal defects created on alveolar ridges mesial to the first maxillary molars of Sprague-Dawley rats. After eight weeks, the operation area in each rat, including the maxillary molars and periodontal tissues, was harvested and evaluated by micro-computed tomography, histochemical and immunohistochemical analyses. RESULTS: Physical parameters representative of periodontal regeneration, including the length of new alveolar bone (p < 0.01) and the area of new alveolar bone (p < 0.01) were significantly improved in the phenytoin group. Compared to other groups, the phenytoin group demonstrated increased expression of COL-1, VEGF-A, osteoblast and osteoclast markers (BMP-2, TGF-beta1, OCN and TRAP staining), as well as decreased expression of MMP-8. CONCLUSIONS: Results of the present study provided new evidence that localized, controlled release of phenytoin confers therapeutic benefits toward gingival recession and alveolar bone loss. Phenytoin appears to be a promising drug that promotes periodontal regeneration. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Zhao, Xiao-Heng AU - Zhao XH AD - State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China. FAU - Tay, Franklin R AU - Tay FR AD - College of Graduate Studies, Augusta University, Augusta, GA, USA. FAU - Fang, Yan-Jun AU - Fang YJ AD - State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China. FAU - Meng, Liu-Yan AU - Meng LY AD - State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China. Electronic address: mengliuyan@whu.edu.cn. FAU - Bian, Zhuan AU - Bian Z AD - State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, PR China. Electronic address: bianzhuan@whu.edu.cn. LA - eng PT - Journal Article DEP - 20181006 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 RN - 0 (Biomarkers) RN - 83HN0GTJ6D (Cyclosporine) RN - 0 (Drug Carriers) RN - I9ZF7L6G2L (Nifedipine) RN - 6158TKW0C5 (Phenytoin) RN - 459TN2L5F5 (poly(lactide)) RN - 0 (Polyesters) SB - IM MH - Animals MH - Male MH - Rats MH - Administration, Topical MH - *Alveolar Bone Loss/drug therapy MH - Biomarkers/analysis MH - Cyclosporine/administration & dosage MH - *Drug Carriers/administration & dosage MH - *Gingival Recession/drug therapy MH - Immunohistochemistry MH - *Microspheres MH - *Nifedipine/administration & dosage MH - *Phenytoin/administration & dosage MH - *Polyesters/administration & dosage MH - Random Allocation MH - Rats, Sprague-Dawley MH - Single-Blind Method MH - X-Ray Microtomography OTO - NOTNLM OT - Alveolar bone loss OT - Anti-epileptics OT - Bone remodeling OT - Drug delivery OT - Gingival overgrowth EDAT- 2018/10/21 06:00 MHDA- 2019/04/20 06:00 CRDT- 2018/10/21 06:00 PHST- 2018/06/04 00:00 [received] PHST- 2018/09/13 00:00 [revised] PHST- 2018/10/02 00:00 [accepted] PHST- 2018/10/21 06:00 [pubmed] PHST- 2019/04/20 06:00 [medline] PHST- 2018/10/21 06:00 [entrez] AID - S0003-9969(18)30216-4 [pii] AID - 10.1016/j.archoralbio.2018.10.002 [doi] PST - ppublish SO - Arch Oral Biol. 2019 Jan;97:42-51. doi: 10.1016/j.archoralbio.2018.10.002. Epub 2018 Oct 6.