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Preparation of thermo-responsive and injectable hydrogels based on hyaluronic acid and poly(N-isopropylacrylamide) and their drug release behaviors

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Abstract

Copolymers composed of hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PNIPAAm) were prepared to create temperature-sensitive injectable gels for use in controlled drug delivery applications. Semi-telechelic PNIPAAm, with amino groups at the end of each main chain, was synthesized by radical polymerization using 2-aminoethanethiol hydrochloride (AESH) as the chain transfer agent, and was then grafted onto the carboxyl groups of HA using carbodiimide chemistry. The result of the thermo-optical analysis revealed that the phase transition of the PNIPAAm-grafted HA solution occurred at around 30∼33°C. As the graft yield of PNIPAAm onto the HA backbone increased, the HA-g-PNIPAAm copolymer solution exhibited sharper phase transition. The short chain PNIPAAm-grafted HA (M w =6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA (M w = 13,100). PNIPAAm-grafted HA exhibited an increase in viscosity above 35°C, thus allowing the gels to maintain their shape for 24 h afterin vivo administration. From thein vitro riboflavin release study, the HA-g-PNIPAAm gel showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased. In addition, BSA released from the PNIPAAm-g-HA gels showed a maximum concentration in the blood 12 h after being injected into the dorsal surface of a rabbit, followed by a sustained release profile after 60 h.

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Authors and Affiliations

  1. School of Chemical Engineering, College of Engineering, Hanyang University, 133-791, Seoul, Korea

    Dong In Ha, Sang Bong Lee, Moo Sang Chong & Young Moo Lee

  2. Nanomaterials Application Division, Korea Institute of Ceramic Engineering and Technology, 153-801, Seoul, Korea

    So Yeon Kim

  3. Department of Polymer Engineering, Sunchon National University, 540-742, Jeonnam, Korea

    Young Hoon Park

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  1. Dong In Ha
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  2. Sang Bong Lee
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  3. Moo Sang Chong
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Correspondence to Young Moo Lee.

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Ha, D.I., Lee, S.B., Chong, M.S. et al. Preparation of thermo-responsive and injectable hydrogels based on hyaluronic acid and poly(N-isopropylacrylamide) and their drug release behaviors. Macromol. Res. 14, 87–93 (2006). https://doi.org/10.1007/BF03219073

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  • DOI: https://doi.org/10.1007/BF03219073

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