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Injectable Supramolecular Hydrogel from Insulin-Loaded Triblock PCL-PEG-PCL Copolymer and γ-Cyclodextrin with Sustained-Release Property

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Abstract

Supramolecular hydrogels formed by cyclodextrins and polymers have been widely investigated as a biocompatible, biodegradable and controllable drug delivery system. In this study, a supramolecular hydrogel based on biodegradable poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL-PEG-PCL) triblock copolymers and γ-cyclodextrin (γ-CD) was prepared through inclusion complexation as an injectable, sustained-release vehicle for insulin. The triblock copolymer PCL-PEG-PCL was synthesised by the ring-opening polymerisation method, using microwave irradiation. The polymerisation reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The supramolecular hydrogel was prepared in aqueous solution by blending an aqueous γ-CD solution with an aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. In vitro insulin release through the hydrogel system was studied. The relative surface hydrophobicity of standard and released insulin from the SMGel was estimated using 8-anilino-1-naphthalene sulfonic acid (ANS). Results of 1HNMR and gel permeation chromatography revealed that microwave irradiation is a simple and reliable method for synthesis of PCL-PEG-PCL copolymer. Gelation occurred within a minute. The supramolecular hydrogel obtained by mixing 10.54% (w/v) γ-CD and 2.5% (w/v) copolymer had an excellent syringeability. Insulin was released up to 80% over a period of 20 days. Insulin kept its initial folding after formulating and releasing from SMGel. A supramolecular hydrogel based on complexation of triblock PCL-PEG-PCL copolymer with γ-cyclodextrin is a suitable system for providing sustained release of therapeutic proteins, with desirable flow behaviour.

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Acknowledgments

This project was supported by a grant from Vice Chancellor of Research, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran. The results described in this paper were part of a Pharm D student thesis proposal related to Zinat Heidari.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Elham Khodaverdi, Zinat Heidari, Sayyed A. Sajadi Tabassi & Mohsen Tafaghodi

  2. Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Tehran, Iran

    Elham Khodaverdi, Zinat Heidari & Sayyed A. Sajadi Tabassi

  3. Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 9196773117, Mashhad, Iran

    Mona Alibolandi & Farzin Hadizadeh

  4. Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Farnaz Sadat Mirzazadeh Tekie

  5. Department of Drug Control, School of Pharmacy, Students Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

    Bahman Khameneh

Authors
  1. Elham Khodaverdi
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  2. Zinat Heidari
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  3. Sayyed A. Sajadi Tabassi
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  4. Mohsen Tafaghodi
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  5. Mona Alibolandi
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  6. Farnaz Sadat Mirzazadeh Tekie
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  7. Bahman Khameneh
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  8. Farzin Hadizadeh
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Corresponding authors

Correspondence to Sayyed A. Sajadi Tabassi or Farzin Hadizadeh.

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Khodaverdi, E., Heidari, Z., Tabassi, S.A.S. et al. Injectable Supramolecular Hydrogel from Insulin-Loaded Triblock PCL-PEG-PCL Copolymer and γ-Cyclodextrin with Sustained-Release Property. AAPS PharmSciTech 16, 140–149 (2015). https://doi.org/10.1208/s12249-014-0198-4

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  • DOI: https://doi.org/10.1208/s12249-014-0198-4

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