Emulsion-based multi-responsive microspheres for the delivery of lipophilic Ozoile

Natural and biodegradable polymers with pH-responsive properties, such as alginate and chitosan, are widely exploited for drug delivery applications, most notably in the form of biocompatible microspheres. In addition, thermo-responsive poly(N-isopropyl-acrylamide) (PNIPAM) is often added to biomedical delivery systems due to its lower critical solution temperature close to human physiological conditions. In this work, multi-responsive microspheres (MRMs) consisting of a hydrogel matrix made of alginate, chitosan, and PNIPAM were successfully prepared by extrusion dripping and proposed as delivery system for Ozoile (Stable Ozonides) derived from biological olive oil. Ozoile acts as a biological inducer, regulating the main metabolic pathways and stimulating the endogenous defence system. The MRMs containing Ozoile were prepared from alginate/NIPAM emulsions integrating the lipophilic bioactive principle. The MRMs were further optimised with a chitosan coating to improve their stability and control the degradation behaviour of the hydrogel matrix, with subsequent release of Ozoile. Results in terms of chemical composition from Fourier transform infrared (FTIR) spectroscopy, thermoresponsive properties from differential scanning calorimetry (DSC) analysis, swelling and degradation behaviour were used to establish the potential use of the MRMs for the therapeutic release of Ozoile at specific inflammatory sites.