Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes

Springer Science and Business Media LLC - Tập 55 - Trang 948-957 - 2012
Yong Han1, XueYan Zhang2, E LingLing1, DongSheng Wang1, HongChen Liu1
1Institute of Stomatology, Chinese General Hospital of PLA, Beijing, China
2Chinese PLA 66400 Hospital, Beijing, China

Tóm tắt

Dental implantation is an effective standard treatment modality to restore missing teeth and maxillofacial defects. However, in diabetics there is an increased risk for implant failure due to impaired peri-implant osseous healing. Early topical insulin treatment was recently shown to normalize diabetic bone healing by rectifying impairments in osteoblastic activities. In this study, insulin/poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double-emulsion solvent evaporation method. Microspheres were then incorporated in fibrin gel to develop a local drug delivery system for diabetic patients requiring implant treatment. In vitro release of insulin from fibrin gel loaded with these microspheres was assessed, and sustained prolonged insulin release over 21 days ascertained. To assess the bioactivity of released insulin and determine whether slow release might improve impaired diabetic bone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP) activity, mineralized nodule formation, and ELISA (enzyme-linked immunosorbent assay) assays were performed. The insulin released from the drug delivery system stimulated cell growth in previously inhibited cells, and ameliorated the impaired bone-forming ability of human MG-63 cells under high glucose conditions. Fibrin gel loaded with insulin/PLGA microspheres shows potential for improving peri-implant bone formation in diabetic patients.

Tài liệu tham khảo

Pjetursson B E, Bragger U, Lang N P, et al. Comparison of survival and complication rates of tooth-supported fixed dental prostheses (FDPs) and implant-supported FDPs and single crowns (SCs). Clin Oral Implants Res, 2007, 18: 97–113 Morris H F, Ochi S, Winkler S. Implant survival in patients with type 2 diabetes: placement to 36 months. Ann Periodontol, 2000, 5: 157–165 Moy P K, Medina D, Shetty V, et al. Dental implant failure rates and associated risk factors. Int J Oral Maxillofac Implants, 2005, 20: 569–577 Zupnik J, Kim S W, Ravens D, et al. Factors associated with dental implant survival: a 4-year retrospective analysis. J Periodontol, 2011, 82: 1390–1395 Eastman R C, Vinicor F. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care, 1997, 20: 1183–1197 Taylor G W, Burt B A, Becker M P, et al. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. J Periodontol, 1998, 69: 76–83 Lalla E, Lamster I B, Drury S, et al. Hyperglycemia, glycoxidation and receptor for advanced glycation endproducts: potential mechanisms underlying diabetic complications, including diabetes-associated periodontitis. Periodontol, 2000, 23: 50–62 Kaur G, Holtfreter B, Rathmann W, et al. Association between type 1 and type 2 diabetes with periodontal disease and tooth loss. J Clin Periodontol, 2009, 36: 765–774 Hasegawa H, Ozawa S, Hashimoto K, et al. Type 2 diabetes impairs implant osseointegration capacity in rats. Int J Oral Maxillofac Implants, 2008, 23: 237–246 Siqueira J T, Cavalher-Machado S C, Arana-Chavez V E, et al. Bone formation around titanium implants in the rat tibia: role of insulin. Implant Dent, 2003, 12: 242–251 Takeshita F, Murai K, Iyama S, et al. Uncontrolled diabetes hinders bone formation around titanium implants in rat tibiae. A light and fluorescence microscopy, and image processing study. J Periodontol, 1998, 69: 314–320 Beam H A, Parsons J R, Lin S S. The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus. J Orthop Res, 2002, 20: 1210–1216 Gandhi A, Beam H A, O’Connor J P, et al. The effects of local insulin delivery on diabetic fracture healing. Bone, 2005, 37: 482–490 Thrailkill K M, Lumpkin C K Jr., Bunn R C, et al. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab, 2005, 289: E735–745 Hough S, Avioli L V, Bergfeld M A, et al. Correction of abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetes mellitus in the rat by insulin therapy. Endocrinology, 1981, 108: 2228–2234 Pun K K, Lau P, Ho P W. The characterization, regulation, and function of insulin receptors on osteoblast-like clonal osteosarcoma cell line. J Bone Miner Res, 1989, 4: 853–862 Zhang W, Shen X, Wan C, et al. Effects of insulin and insulin-like growth factor 1 on osteoblast proliferation and differentiation: differential signalling via Akt and ERK. Cell Biochem Funct, 2012, 30: 297–302 Yang J, Zhang X, Wang W, et al. Insulin stimulates osteoblast proliferation and differentiation through ERK and PI3K in MG-63 cells. Cell Biochem Funct, 2010, 28: 334–341 Liu B, Dong Q, Wang M, et al. Preparation, characterization, and pharmacodynamics of exenatide-loaded poly(DL-lactic-co-glycolic acid) microspheres. Chem Pharm Bull, 2010, 58: 1474–1479 Zhang J X, Zhu K J, Chen D. Preparation of bovine serum albumin loaded poly (D, L-lactic-co-glycolic acid) microspheres by a modified phase separation technique. J Microencapsul, 2005, 22: 117–126 Manoharan C, Singh J. Insulin loaded PLGA microspheres: effect of zinc salts on encapsulation, release, and stability. J Pharm Sci, 2009, 98: 529–542 Hinds K D, Campbell K M, Holland K M, et al. PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis. J Controlled Release, 2005, 104: 447–460 Wang B, Song Y, Wang F, et al. Effects of local infiltration of insulin around titanium implants in diabetic rats. Br J Oral Maxillofac Surg, 2010, 49: 225–229 Wang F, Song Y L, Li C X, et al. Sustained release of insulin-like growth factor-1 from poly(lactide-co-glycolide) microspheres improves osseointegration of dental implants in type 2 diabetic rats. Eur J Pharmacol, 2010, 640: 226–232 Kaufman M R, Westreich R, Ammar S M, et al. Autologous cartilage grafts enhanced by a novel transplant medium using fibrin sealant and fibroblast growth factor. Arch Facial Plast Surg, 2004, 6: 94–100 Gwak S J, Kim S S, Sung K, et al. Synergistic effect of keratinocyte transplantation and epidermal growth factor delivery on epidermal regeneration. Cell Transplant, 2005, 14: 809–817 Spicer P P, Mikos A G. Fibrin glue as a drug delivery system. J Controlled Release, 2010, 148: 49–55 Jeon O, Kang S W, Lim H W, et al. Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel. Biomaterials, 2006, 27: 1598–1607 Zhou W, Zhao M, Zhao Y, et al. A fibrin gel loaded with chitosan nanoparticles for local delivery of rhEGF: preparation and in vitro release studies. J Mater Sci Mater Med, 2011, 22: 1221–1230 Lauterbach E C. Dextromethorphan as a potential rapid-acting antidepressant. Med Hypotheses, 2011, 76: 717–719 Zhang L, Li H, Hu X, et al. Glucocorticoid-induced p11 over-expression and chromatin remodeling: A novel molecular mechanism of traumatic stress? Med Hypotheses, 2011, 76: 774–777 Hill D J, Milner R D. Insulin as a growth factor. Pediatr Res, 1985, 19: 879–886 Sinha V R, Trehan A. Biodegradable microspheres for protein delivery. J Controlled Release, 2003, 90: 261–280 Branemark P I, Hansson B O, Adell R, et al. Osseointegrated implants in the treatment of the edentulous jaw. Experience from a 10-year period. Scand J Plast Reconstr Surg Suppl, 1977, 16: 1–132 Terada M, Inaba M, Yano Y, et al. Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells. Bone, 1998, 22: 17–23 Zhen D, Chen Y, Tang X. Metformin reverses the deleterious effects of high glucose on osteoblast function. J Diabetes Complicat, 2010, 24: 334–344 Wang W, Zhang X, Zheng J, et al. High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP/protein kinase A/extracellular signal-regulated kinase pathway. Mol Cell Biochem, 2010, 338: 115–122 Hrynyk M, Martins-Green M, Barron A E, et al. Sustained prolonged topical delivery of bioactive human insulin for potential treatment of cutaneous wounds. Int J Pharm, 2010, 398: 146–154 Shao P G, Bailey L C. Stabilization of pH-induced degradation of porcine insulin in biodegradable polyester microspheres. Pharm Devel Technol, 1999, 4: 633–642 Lian J B, Stein G S. Development of the osteoblast phenotype: molecular mechanisms mediating osteoblast growth and differentiation. Iowa Orthop J, 1995, 15: 118–140