Purpose

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.

Methods

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.

Results

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.

Conclusion

The pulsatile delivery of peptide the drug from the multilayer device with hyaluronic acid hydrogel and CPP-SA polymer alternative layers can be achieved.

中文翻译：

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旋涂法制备聚苯胺-水凝胶层的特立帕肽负载多层植入物的制备及其脉冲释放评价骨质疏松症

目的

特立帕肽（PTH（1-34））是经FDA批准的用于绝经后骨质疏松症治疗的合成代谢药物之一，在间歇给药中显示出合成代谢作用。在当前的研究中，通过旋涂和浸涂技术开发了多层可植入装置，以提供由聚合物和水凝胶层组成的特立帕肽的搏动性释放。

方法

合成了摩尔比为20:80和10:90的聚[1,3-双（对羧基苯氧基）丙烷-癸二酸]（CPP-SA）共聚物，并通过GPC，¹ HNMR和FTIR进行了表征。评估了透明质酸水凝胶的溶胀特性和体外药物释放。通过SEM图像评估聚合物层的降解行为和制造的植入物的形态。进行了体外释放研究以评估搏动释放模式。组织学评估旨在确定大鼠植入物的生物相容性。MTT法用于细胞毒性研究。通过体内研究获得血浆药物浓度和药代动力学数据。

结果

根据体内和体外数据，最佳制剂是浓度为20％的CPP-SA（10:90）。组织学评估显示轻度炎症。与正常剂量的药物相比，MTT分析显示无明显毒性。

结论

可以从具有透明质酸水凝胶和CPP-SA聚合物替代层的多层装置中实现药物的多肽脉冲式递送。