Preparation and Pulsatile Release Evaluation of Teriparatide-Loaded Multilayer Implant Composed of Polyanhydride-Hydrogel Layers Using Spin Coating for the Treatment of Osteoporosis

Abstract

Teriparatide (PTH(1–34)), as one of the FDA-approved anabolic medications for postmenopausal osteoporosis treatment, shows anabolic effects in intermittent administration. In the current study, a multilayer implantable device was developed by spin-coating and dip-coating techniques for providing pulsatile pattern release of teriparatide, composed of polymeric and hydrogel layers. Copolymers of poly [1,3-bis (p-carboxyphenoxy) propane-sebasic acid] (CPP-SA) with molar ratios of 20:80 and 10:90 were synthesized and characterized by GPC, 1HNMR, and FTIR. Swelling property and in vitro drug release from hyaluronic acid hydrogel were evaluated. The degradation behavior of the polymer layer and the morphology of the fabricated implant was evaluated by SEM images. An in vitro release study was done for evaluating the pulsatile release pattern. Histology assessment aimed to determine the biocompatibility of implants in rats. MTT assay was applied for cell cytotoxicity study. Plasma drug concentration and pharmacokinetic data were achieved by in vivo study. According to in vivo and in vitro data, the best formulation was CPP-SA (10:90) with a concentration of 20%. Histology assessment showed mild inflammation. MTT assay showed no significant toxicity compared with control in normal doses of the drug. The pulsatile delivery of peptide the drug from the multilayer device with hyaluronic acid hydrogel and CPP-SA polymer alternative layers can be achieved.