Polymeric films based on chitosan, hyaluronic acid and acyclovir for topical treatment of herpes

VALENZUELA-OSES, JOHANNA; GARCÍA, MÓNICA C

Lima

Encuentro; Encuentro Científico Internacional (ECI); 2018

Skin wounds caused by Herpesvirus represent a serious problem worldwide1. Creams and ointments are used for the treatment of this disease; however, they have some disadvantages, such us lack of residence time, improper dosification and thermodynamic unstability2. The aim of this research was to develop and characterize polymeric films loaded with acyclovir for the topical treatment of herpes. Interpolyelectrolyte-drug complexes (DIPEC) based on chitosan (Ch), hyaluronic acid (HA) and acyclovir (ACI) were develop by ionic interaction in aqueous dispersions, using a sufficient amount of ACI and HA to neutralize 50% and 10%of amine groups of Ch respectively. DIPEC with the formula Ch- ACI50-HA10 were obtained. Hydrodynamic diameter (Dh) and zeta potential (ZP) of the DIPEC dispersions were analyzed by photon correlation spectroscopy (DLS). DIPEC loaded and unloaded with ACI showed sizes of 834.3±59 and 662.3±29 nm, respectively. ZP of the DIPEC showed values of 59.6±0.79. Ionic displacement by the addition of 0.9% NaCl showed a slight change in pH with NaCl due to ionic exchange with the conjugated base of the drug. In contrast, the addition of 5% glucose did not produce changes since this is a non-electrolyte. This result confirm the ionic interaction between the drug and polymer matrix. Differential exploratory calorimetry and thermogravimetric analysis (TGA) revealed the absence of fusion peak at 250 °C of the ACI showing evidence that there is no free drug. TGA showed that Ch, HA, ACI and DIPEC exhibited thermal stability at high temperatures compared to the physical mixture (simple mix of the powders of polymers and drug in the same proportion that in the DIPEC). X-ray diffraction and optical microscopy revealed that polymers and DIPEC are amorphous solids since they did not showed peaks in the diffractogram and no birefringent phenomenon was observed under the effect of polarized light in the microscope, which indicate absence of free drug. Films showed adequate drug uniformity content with variations less than 5%, which indicated that the process for obtaining the films is reproducible and the drug was distributed homogeneously throughout the film. In vitro release studies showed controlled release of ACI from the films. Films also exhibited bioadhesive properties and swelling behavior. Films show promising biopharmaceutical properties and they would be therapeutic alternatives for the topical treatment of herpes.