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A novel hydrogel of poloxamer 407-chitosan-hyaluronic acid as possible wound healing in skin and mucosa
* 1 , 1 , 2 , 3 , * 1 , 3
1  Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
2  Department of Biology, Healthcare and the Environment, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
3  Department of Pharmacy, Pharmaceutical Technology and Physical-chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.

Abstract:

Background: The use of hydrogels in the treatment of wound healing is becoming an increasingly routine. Hydrogels are materials that protect wound healing, avoiding and/or controlling infection, and providing moisture for the irregular wound environment. Poloxamer 407 (P407), chitosan (CH) and hyaluronic acid (HA) are biomaterials investigated to promote wound repair. P407 has thermoreversible properties and promotes wound contraction1. CH presents inherent analgesic, hemostatic and microbial effects2. HA, interacts directly with cells through its cell surface receptors resulting in fibroblast proliferation and protein synthesis3.

Purpose: The aim of this work was to develop and characterize a hydrogel (HG) prepared from a physical mixture of P407, CH and AH for the treatment of skin and mucosal wounds.

Methods: 0.5% CTS was dispersed in 0.5% acetic acid. Previously prepared 0.2% HA solution was added to the previous solution. The final HG was made by adding P407 (18 %) using the cold method with continuous stirring for 24 h. The HG was characterized by the following methods: swelling test, microbiological and in vivo studies. Swelling rate was assessed by a gravimetric method in phosphate buffer saline (PBS) at 32 ± 0.5 ºC for pH 5.5 and 37 ± 0.5 ºC for pH 7.4. The antimicrobial activity was evaluated through a Kirby-Bauer Disk Diffusion Susceptibility Test4 against Gram-negative bacteria, Gram-positive bacteria and fungi. The wound healing efficacy of the HG was evaluated in burn inducted mice. The formulation was applied topically once a day during 14 days. 2 groups were evaluated, hydrogel and reference formulation.

Results and Discussion: The swelling behavior in wound healing could help to absorb exudates and provides mechanical resiliency to the delivery system at the biological site of action4. Our results showed high swelling rates, being the best value at pH = 5.5. The HG provides an important improvement on antimicrobial properties and showed similar activity to reference. The wound healing in animals treated with HG was similar to Silvederma®.

Conclusions: The HG exhibited important antimicrobial and biological effects. Thus this hydrogel could be proposed as a suitable vehicle for new therapies for wound healing and infections on skin and mucosa.

References:

1Leyva-Gómez et al. Materials Science and Engineering C 74: 36-46, 2017.

2 Zhao X. et al. Biomaterials, 122:34-47, 2017.

3Hodgkinson and Bayat. J Appl Biomater Funct Mater 14(1): e9-e18, 2016.

4Gao et al. Colloids Surf. B Biointerfaces 167: 448–456, 2018.

Keywords: Hydrogel; Poloxamer; Chitosan; Hyaluronic acid; Wound healing
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