Formation and characterization of silk fibroin/hyaluronic acid complexes and their use in iontophoretic drug delivery

Abstract

This study aimed the investigation of the pH-induced complexation of silk fibroin (SF) and hyaluronic acid (HA), and the potential use of the films casted from the aqueous mixtures of the SF-HA complexes in iontophoretic drug delivery applications.In the present study, SF-HA complex coacervation was investigated by turbidimetric, conductometric, gravimetric and viscosimetric analysis with respect to changes in total biopolymer concentration and biopolymer weight ratio. SF-HA complexes were formed within the pH-window of 2.5-3.5 regardless of the totalbiopolymer concentration, biopolymer ratio or mixing order.SF-HA aqueous complex mixtures, prepared under previously determined conditions, were casted and dried under controlled conditions. The resultant insoluble and transparent films were subjected to instrumental analysis such as DSC, XRD, FT-IR,SEM and AFM. Swelling kinetics of the films was studied for pH window of 2.5-7.4 and cyclic swelling test was performed to determine the pH-responsiveness of the films. It was shown that films swelled more in alkaline conditions and responded to the changes in pH of the medium. The permeability of the films were tested with modified-diffusion-vessels method at pH 2.5 and 7.4 and it was demonstrated that the complex films had higher permeability in alkaline condition. Eventually, iontophoretically assisted drug permeation and release studies were performed with a custom-made diffusion cell under both passive condition and electric field applied in pulsatile fashion.In conclusion, SF-HA complex films were found promising for the iontophoretic delivery of high molecular weight and charged drugs for a membrane-permeation controlled formulation. In this study, timolol maleate (TM) was used as the model drug.