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Functionally modified gelatin microspheres as a growth factor’s delivery system: development and characterization

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Abstract

One of the advances in biotechnology has been the development of the capability to produce large quantities of highly purified polypeptides and proteins. Unfortunately, the circulatory half-lives of many of these agents are short, usually of the order of minutes and the time required for a response in tissues is usually long compared to the half-life. Hence, there is always demand for polymeric systems which can deliver the proteins for prolonged period and also to protect the molecules from degradation. The present work was attempted to develop heparin-functionalized gelatin microspheres (HMS) to deliver heparin-binding growth factors particularly for wound-healing applications. The heparin conjugation was carried out using EDC/NHS coupling protocol. Heparin-binding EGF-like growth factor (HB-EGF) was loaded in HMS and its in vitro release behaviour in an environment with or without proteases was studied. The bioactivity of the HB-EGF released from the microspheres was assessed using NIH 3T3 mouse embryonic fibroblast culture. The extent of heparin modification was found to be 1.97 μmol/g of HMS and demonstrated significant protection against enzymatic degradation and sustained release of HB-EGF for more than 10 days. The bioactivity of HB-EGF released from the HMS was retained during the observed release period. The HMS was also found to be non-toxic as determined by calcein AM fluorescent staining. The overall study suggests that the HMS could be used as a growth factor’s delivery component in tissue engineering scaffolds particularly for wound-healing applications.

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Acknowledgments

This work was supported by Department of Biotechnology, Ministry of Science and Technology, New Delhi, India (Grant No. BT/PR8203/MED/14/1237/2006). The authors thank the Director, CLRI, for giving us the opportunity and encouragement to carry out this work.

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Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology, KMCH College of Pharmacy, Kalapatti Road, Kovai Estate, Coimbatore, 641048, Tamil Nadu, India

    N. Adhirajan & R. Thanavel

  2. Bioproducts Division, Central Leather Research Institute, Chennai, Tamil Nadu, India

    N. Adhirajan, N. Naveen & T. S. Uma

  3. Biomaterials Division, Central Leather Research Institute, Adyar, Chennai, Tamin Nadu, India

    N. Adhirajan & Mary Babu

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  1. N. Adhirajan
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  2. R. Thanavel
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Correspondence to N. Adhirajan.

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Adhirajan, N., Thanavel, R., Naveen, N. et al. Functionally modified gelatin microspheres as a growth factor’s delivery system: development and characterization. Polym. Bull. 71, 1015–1030 (2014). https://doi.org/10.1007/s00289-014-1108-3

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  • DOI: https://doi.org/10.1007/s00289-014-1108-3

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