Matrices of a hydrophobically functionalized hyaluronic acid derivative for the locoregional tumour treatment

Abstract

A hyaluronic acid (HA) derivative bearing octadecylamine and acylhydrazine functionalities has been here employed for the production of a paclitaxel delivering matrix for locoregional chemotherapy. Through a strategy consisting in a powder compression and a plasticization with a mixture water/ethanol, a physically assembled biomaterial, stable in solutions with physiologic ionic strengths, has been produced. Two different drug loading strategies have been adopted, by using paclitaxel as chemotherapic agent, and obtained samples have been assayed in terms of release in enhanced solubility conditions and in vitro and in vivo tumoural cytotoxicity. In particular sample with the best releasing characteristics was chosen for an in vivo evaluation against a HCT-116 xenograft on mice. Local tumour establishment and metastatic diffusion was assayed locally at the site of xenograft implantation and at the tributary lymph nodes. Obtained results demonstrated how loading procedure influenced paclitaxel crystallinity into the matrix and consequently drug diffusion and its cytoreductive potential. Chosen paclitaxel loaded matrix was able to drastically inhibit HCT-116 establishment and metastatic diffusion.

Keywords: Biomaterials; Hyaluronic acid; Locoregional tumour treatment; Paclitaxel.