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

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Abstract

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.

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Funding

This research has been financially supported by Tehran University of Medical Sciences and Health Services (grant number 96-03-33-32293, 2016).

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Nooshafarin Amani & Hamid Akbari Javar

  2. Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran

    Farid Abedin Dorkoosh

  3. Department of Pharmaceutics, Biopharmaceutics and Pharmacokinetics Division, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Reza Rouini

  4. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mohsen Amini

  5. Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohsen Amini

  6. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Sharifzadeh

  7. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Shahin Boumi

Authors
  1. Nooshafarin Amani
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  2. Hamid Akbari Javar
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  3. Farid Abedin Dorkoosh
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Correspondence to Hamid Akbari Javar.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (the ethics committee of Tehran University of Medical Sciences in accordance with the Helsinki declaration and national ethical guideline for medical research, ethics approval code: IR.TUMS.REC.1394.1167).

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Amani, N., Javar, H.A., Dorkoosh, F.A. et al. Preparation and Pulsatile Release Evaluation of Teriparatide-Loaded Multilayer Implant Composed of Polyanhydride-Hydrogel Layers Using Spin Coating for the Treatment of Osteoporosis. J Pharm Innov 16, 337–358 (2021). https://doi.org/10.1007/s12247-020-09453-1

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