Hydrogels as Drug Delivery System in Dental Applications by Photocrosslinking with Visible Light

Abstract

Over the past few decades, advances in hydrogel technologies have spurred development in many biomedical applications e.g. controlled drug delivery for proteins. Poly (2-hydroxyethyl methacrylate) (PHEMA) is one of the most frequently synthetic polymers which are used in biomedical applications. Biocompatibility and biodegradability of that polymer have been proven by many published reports. In this work, dextran and hydroxyethyl starch have been used as important starting polymer materials for developing new hydrogels by modification with HEMA as drug delivery system hydrogels. The degree of substitution (DS) of synthesized polymers was controlled during the coupling reaction in the polymer synthesis stage. Equilibrium swelling behavior of the gels was studied as one of the widely used methods to determine the average molecular weight between two adjacent crosslinks (Mc), the crosslinking density (Px), and the mesh size (?) of the hydrogel network. HES-HEMA, Dex-HEMA and HES-PEGMA hydrogels were successfully synthesized by in-situ hydrogelation via photocrosslinking based on visible light-irradiation, to avoid the risks which are arising from photocrosslinking by the use of UV-irradiation. The visible-light crosslinking method which is used in this study so far is mainly used in dentistry. However, the absorption wavelength of the photosensitizer and its efficiency has to be taken into account in the crosslinking process. Therefore, camphorquinone (CQ) was used in this study as a common photosensitizer in visible-light initiating system. In order to improve the insufficient mechanical properties of virgin hydrogels; nano-filler clays were introduced into the hydrogels particularly montmorillonite and Laponite-RD as model of natural and synthetic clays respectively. Additionally, hydroxyapatite nanoparticles have been investigated as biodegradable nanoparticles. The interactions between nanocomposite materials and polymer networks were evaluated by FTIR and XRD analysis. To overcome the poor solubility of CQ in water, carboxylated-camphorquinone (CQCOOH) was prepared. CQCOOH-amine-DPIC was evaluated to establish an innovative photoinitiating system, in terms of the crosslinking efficiency and the mechanical properties of the prepared hydrogels. HES-HEMA hydrogel which was crosslinked with CQCOOH-amine-DPIC system showed a very fast gelation time (~5 Sec.), more efficient crosslinking and more mechanically stable hydrogel than that was crosslinked with CQ-amine-DPIC. The biocompatibility of polymers and the components of photoinitiating system have been evaluated by MTT-assay using HGF cells. Photoinitiating system components e.g. CQCOOH, NPG, and L-arginine showed no toxic effect on HGF cell viability even in high concentrations.