Core-Shell poly-(D,l-Lactide-co-Glycolide)-chitosan Nanospheres with simvastatin-doxycycline for periodontal and osseous repair

Po-Chun Chang; Wei-Chiu Tai; Hui-Ting Luo; Chern-Hsiung Lai; Hsu-Hsiang Lin; Zhi-Jie Lin; Ying-Chieh Chang; Bor-Shiunn Lee

doi:10.1016/j.ijbiomac.2020.04.183

Core-Shell poly-(D,l-Lactide-co-Glycolide)-chitosan Nanospheres with simvastatin-doxycycline for periodontal and osseous repair

Int J Biol Macromol. 2020 May 7:158:627-635. doi: 10.1016/j.ijbiomac.2020.04.183. Online ahead of print.

Authors

Po-Chun Chang¹, Wei-Chiu Tai², Hui-Ting Luo¹, Chern-Hsiung Lai³, Hsu-Hsiang Lin⁴, Zhi-Jie Lin⁴, Ying-Chieh Chang⁴, Bor-Shiunn Lee⁵

Affiliations

¹ Graduate Institute of Clinical Dentistry, School of Dentistry, National, Taiwan University; Division of Periodontics, Department of Dentistry, National, Taiwan University Hospital.
² Graduate Institute of Clinical Dentistry, School of Dentistry, National, Taiwan University.
³ College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Graduate Institute of Oral Biology, School of Dentistry, National, Taiwan University.
⁵ Graduate Institute of Clinical Dentistry, School of Dentistry, National, Taiwan University; Graduate Institute of Oral Biology, School of Dentistry, National, Taiwan University. Electronic address: leebs@ntu.edu.tw.

PMID: 32387616
DOI: 10.1016/j.ijbiomac.2020.04.183

Abstract

This study aimed to evaluated the potential of core-shell poly(D,l-lactide-co-glycolide)-chitosan (PLGA-chitosan) nanospheres encapsulating simvastatin (SIM) and doxycycline (DOX) for promoting periodontal and large-sized osseous defects. SIM, and/or DOX were encapsulated in PLGA-chitosan nanospheres using double emulsion technique and were delivered to sites of experimental periodontitis and large-sized mandibular osseous defects of rats for 1-4 weeks. The resultant nanospheres were ~ 200 nm diameter with distinct core-shell structure and released SIM and DOX sustainably for 28 days. DOX and SIM-DOX nanospheres significantly inhibited P. gingivalis and S. sanguinis. In experimental periodontitis sites, SIM-DOX nanospheres significantly down-regulated IL-1b and MMP-8 and significantly reduced bone loss. In mandibular osseous defects, VEGF was up-regulated, and osteogenesis was significantly augmented with SIM nanospheres treatment. In conclusion, core-shell PLGA-chitosan nanospheres released SIM and DOX sustainably. SIM-DOX and SIM nanospheres could be considered to promote the repair of infected periodontal sites and non-infected osseous defects respectively.

Keywords: Chitosan; Models, animal; Osteogenesis; Periodontitis; Polylactic acid-polyglycolic acid copolymer; Wound healing.