Topical Codelivery of an Antibiotic and a Protein from in Situ Forming Chitosan-Peg Hydrogel for Wound Healing Applications

Sharma, P. K., IIT Ropar
Singh, Y., IIT Ropar
Effective wound healing requires accelerated tissue regeneration and simultaneous inhibition of infection at the wound site. In situ forming hydrogels can be explored as candidates for wound management because of their viscoelastic characteristics, which translates into ease of application and ability to deliver multiple therapeutic agents, each with a discrete release kinetics1. In addition, the hydrogel-based wound care formulation must possess the ability to provide a moist environment and absorb dead cell debris and tissue exudates2. Chitosan has been extensively explored in variety of wound management devices, owing to its hemostatic and anti-infectious characteristics3. Chitosan also possesses skin adhesion properties, which facilitates robust and stable application of the formulation onto the skin surface. Wound healing processes can be synergized by a faster release of antibiotics at early stages of injury to neutralize opportunistic bacterial infections, followed by a sustained release of growth factors to accelerate cell proliferation in later stages. Chitosan hydrogels, for wound healing applications, have been conventionally prepared using small molecule crosslinkers like glutaraldehyde and glyoxal, which are associated with the risk of toxicity and poor swelling capabilities. Therefore, a new glyoxylic aldehyde-containing homobifunctional PEG crosslinker was prepared to obtain chitosan-PEG hydrogels, crosslinked through biodegradable glyoxylic imine linkages4. The hydrogels were prepared by mixing different concentrations of the crosslinker (3, 6, 9, and 12%, w/v) with chitosan (1%, w/v) in buffer at room temperature. A linear inverse relationship between concentration and curing kinetics for the hydrogel was observed from the time sweep rheology data. The viscoelastic characterization was conducted using small amplitude oscillatory rheometry and maximum value of G’ was found to be 6.24, 40.602, 104, and 165.47 Pa for hydrogels prepared using 3, 6, 9, and 12% (w/v) of crosslinker. The swelling and degradation data overall indicated improved swelling capacity of hydrogels, with maximum swelling reaching to 120%. Resulting from increased hydrolytic stability, a maximum degradation time of 10 days was observed for these hydrogels. The hydrogels were injectable and exhibited self-healing characteristics along with pH-responsive sol-to-gel transition. The in vitrodrug delivery studies revealed a faster diffusion driven release for the antibiotic, for up to 24 h, and a degradation driven slow and sustained release of the model protein, for up to 6 days. These scaffolds might be of potential application in wound care management.

Acknowledgements: Authors acknowledge financial assistance from the CSIR, New Delhi [grant # 02(0245)/15/EMR-II] and PKS is thankful to IIT Ropar for the institute fellowship.


(1) Griffin, D. R.; Weaver, W. M.; Scumpia, P. O.; Di Carlo, D.; Segura, T. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks. Nat. Mater. 2015, 14, 737–744

(2) Bolton, L.; Fattu, A. J. Topical agents and wound healing. Clin. Dermatol. 1994, 12, 95–120

(3) Ueno, H.; Mori, T.; Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv. Drug. Deliv. Rev. 2001, 52, 105–15

(4) Singh, Y.; Defrancq, E.; Dumy, P. New method to prepare peptide-oligonucleotide conjugates through glyoxylic oxime formation. J. Org. Chem. 2004, 69, 8544–8546