The development of novel PVA hydrogel for biomedical and drug delivery applications

Abstract

Hydrogels have been used widely in biomaterial applications, mainly due to their low interfacial tension, useful swelling properties and high lubricity. In addition to their promising biocompatibility characteristics, certain hydrogels are desirable in the biomedical field due to their sensitivity to the physiological or biological environment where they are used. There are many current applications for hydrogels, and this includes 8,000 different kinds of medical devices and 40,000 different pharmaceutical preparations. This research aims to develop and characterise the physically cross-linked PVA hydrogels with different sizes range from centi- to micro- to nano- meter in macroscopic, microscopic and nanoscopic viewpoint for drug delivery applications (Figure 1). Freeze-thawing and thermal annealing were the physical crosslinking methods used to prepare the PVA hydrogels. Water-soluble drugs (i.e. caffeine, doxorubicin hydrochloride, propolis extract) and poorly water-soluble drugs (i.e. ciprofloxacin, clarithromycin) were incorporated into these PVA hydrogels to study their drug release kinetics. In the macro point of view, although freeze-thawed hydrogels have been deeply studied in the literature, uniaxial stretching hydrogels in between freeze-thawing cycles could further improve its mechanical properties. It suggested that the orientated PVA hydrogel provided an immediate full caffeine release in 15-20 min. Furthermore, PVA hydrogel was made into spheres to increase its surface area. The PVA spheres provide an immediate full ciprofloxacin or caffeine release within 60 min. Both orientated PVA hydrogels and PVA spheres followed Hixson-Crowell release kinetics and were found to be non-toxic to NIH 3T3 fibroblast cells. The field of biomedical applications for hydrogels required the development of nanostructures with specific controlled diameter and mechanical properties. Nanofibres were ideal candidates for these advanced requirements, and one of the easiest techniques that can produce nanostructured materials in fibrous form was the electrospinning process. Electrospinning demonstrated extreme versatility, allowing the use of different polymers for tailoring properties and applications. The thermal annealed PVA/PAA bilayer nanofibres gave a dual drug delivery of clarithromycin and doxorubicin hydrochloride for osteosarcoma treatment. The U2OS osteosarcoma cells viability was effectively decreased with the combination of both drugs. Furthermore, the freeze-thawed PVA+propolis nanofibres showed a bi-phasic drug release with an initial burst drug release in first 30 min and followed by a much slower release for 8 h. Finally, all these novel hydrogels have the potential to be produced as new commercialise products in biomedical area mainly in drug delivery applications because of their tunable hydrogel preparation process, intrinsic biocompatible and non-toxic characteristics.