Biodegradable Thermo-sensitive Hydrogels For Controlled Delivery Of PTH (1-34)

Objective:Implant denture as "human third dentition" has become the first choice ofrepairing missing teeth for more patients. During the implant restoration, bonequantity and quality of the implant site become the key factors of the primarystability of dental implant, but many patients have problems of lack ofperi-implant bone mass, so they need planting the early stage of implantation orcontemporaneous various bone incremental technologies, thus making theperi-implant bone healing time prolonged, the final repair time later.PTH can increase the activity and the numbers of osteoblasts, promotebone formation, increase bone density and reduce the occurrence of fractures.2002, PTH1-34was approved by the U.S. FDA as a treatment drug ofosteoporosis. PTH1-34enormous contribution in the clinical treatment ofosteoporosis has aroused the attention of scholars of the field of oralimplantology. In the past, PTH1-34as a drug for promoting the peri-implantbone healing in experimental studies, mostly limited to small doses ofintermittent systemic administration of the way, but PTH1-34exists a series ofclinical application defects, such as volatility, short half life, expensive, sobrings patients the inconvenience and economic burden, but also limits itsapplication in oral implantology areas. Developed a carrier to control thePTH1-34slow-release to improve its bioavailability and applied to bone defectaround the implant, by local administration, to achieve its superior osteogenesisin oral imlantology areas has good prospects for clinical application.The temperature sensitivity of poly N-isopropyl acrylamide (PNIPAAm)hydrogel is currently the most widely studied temperature sensitive hydrogel. There is a lower critical solution temperature (LCST)(32℃). This article isintended to N-isopropyl acrylamide as monomer, compose a temperaturesensitivity of a biodegradable hydrogel network by free radicalcopolymerization, this hydrogel loads PTH1-34, to achieve the PTH1-34controlled release, improve the efficiency of its bioavailability.Methods:Carbon-carbon double bond at both ends with a polycaprolactone forbio-degradable cross linker, N-isopropyl acryl amide monomer by free radicalcopolymerization of a biodegradable temperature-sensitive hydrogel network,and its structure was characterized by the swelling ratio of this hydrogel systemat different temperatures, the temperature responsiveness of the hydrogelsystem studied by transmittance test and the lower critical solution temperature(LCST) of the hydrogel was determined, observed the morphology of thehydrogel by scanning electron microscopy. In addition, this hydrogel systemstudied as a carrier containing a small amount of hydrophilic polymethacrylatesegments and do not contain hydrophilic polymethacrylate segments, two kindsof poly N-isopropylacrylamide amide temperature sensitive hydrogels loadedPTH1-34in vitro drug release behavior at different temperatures and the drugloading.Results:With a Carbon-carbon double bond at both ends with a polycaprolactonefor bio-degradable cross linker, N-isopropyl acryl amide monomer, thebiodegradable temperature-sensitive hydrogel was synthesized successfully byfree radical copolymerization. Gel2contained a small amount of hydrophilicpolymethacrylate segments, so that LCST increased above60℃. While Gel1did not contain hydrophilic polymethacrylate segments, the LCST decreased toabout27℃or so. Drug loading rate of Gel1is2.41%, and drug loading rate ofGel2is10.78%. Observed by scanning electron microscopy (SEM), PNIPAAm temperature sensitive hydrogels showed the porous structure of the rules. TheGel2LCST is higher than37℃, it is in a swelling state in37℃, and thus thegel package contained PTH1-34release faster, and about90percent of drugreleased within three days. The gel1LCST is around27℃, the hydrogel in20℃is in the swelling state as same, and thus the package contained PTH1-34within one day and released about90%. Gel1loaded PTH1-34in37℃, thehydrogel hydrophobic contraction pores smaller, PTH1-34from the sustainedrelease of the gel up to13days. Thus, the temperature-sensitive hydrogel-Gel1has a well long-term sustained release of PTH1-34at physiological temperature,with a potential application.Conclusion:1The lower critical solution temperature (LCST) of PNIPAAmtemperature sensitive hydrogels can be increased by adding hydrophilicpolymethacrylate segments, do not contain methyl methacrylate hydrogelcomponents, its LCST is about27℃.2Observed by scanning electron microscopy (SEM), PNIPAAmtemperature sensitive hydrogels showed the porous structure of the rules.3Under the condition of37℃，the PNIPAAm temperature sensitivehydrogels loaded PTH1-34can be achieved on the PTH1-34up to13days ofsustained release, has a good potential application in the field of oralimplantology.