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Release of human growth hormone from an in-situ implant modulated by poly(ethylene glycol) dimethyl ether and tris(hydroxymethyl) aminomethane

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Abstract

A patient-friendly delivery system to release human growth hormone (hGH) is very desirable. In situ forming implant systems (ISIs) can provide a long acting and effective protein delivery. In these systems, solvents and additives play major roles in drug release. In this study, four groups of PLGA-based ISIs containing hGH were prepared in N-methyl-2-pyrrolidone (NMP) and poly(ethylene glycol) dimethyl ether (PEG-DME) as solvents with and without tris(hydroxymethyl) aminomethane (Tris) as stabilizer. Several analyses were used to investigate the implants, which include release profile, viscosity, contact angle, gel permeation chromatography (GPC), scanning electron microscopy (SEM), hGH and IGF-1 serum measurements and histopathology. In in vitro release experiments, the hGH cumulative release from PEG-DME system was twice that from NMP system during 14 days, and hGH release was tripled in the presence of Tris. With the addition of Tris to the ISIs containing PEG-DME, the water penetration, interconnectivity of pores and inner channels, surface pores and hydrophilicity were increased. Moreover, the effect of Tris on the hGH stabilization synergized its positive effects and increased the hGH final cumulative release. Results of the ISIs containing PEG-DME and Tris injection in rabbits demonstrated a reduced tissue inflammation. Moreover, the 14-days serum levels of the hGH and IGF-1 of this system in recipient rabbits were comparable to those of the commercial daily injection samples.

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Acknowledgements

This work was supported by Royan institute and Iran Polymer and Petrochemical institute that provided the funding.

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Authors and Affiliations

  1. Department of Genetics, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

    Siyavash Mirzaei & Hamid Gourabi

  2. Department of Novel Drug Delivery Systems, Iran Polymer and Petrochemical Institute, P.O. Box: 14965/115, Tehran, Iran

    Hamid Mobedi & Sakine Khezli

  3. Medical Genetics Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

    Mohammad Hossein Sanati

  4. College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA

    Hamid Omidian

  5. Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Science (TUMS), Tehran, Iran

    Sima Sadrai

Authors
  1. Siyavash Mirzaei
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  2. Hamid Mobedi
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  3. Hamid Gourabi
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  4. Mohammad Hossein Sanati
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  5. Sakine Khezli
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Correspondence to Hamid Mobedi.

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Mirzaei, S., Mobedi, H., Gourabi, H. et al. Release of human growth hormone from an in-situ implant modulated by poly(ethylene glycol) dimethyl ether and tris(hydroxymethyl) aminomethane. Iran Polym J 29, 1019–1029 (2020). https://doi.org/10.1007/s13726-020-00857-x

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  • DOI: https://doi.org/10.1007/s13726-020-00857-x

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