Physicochemical and pharmacological investigations of polyvinylpyrrolidone - tetrahydroxyborate hydrogel containing the local anesthetic lidocaine

Abstract

The short time of action and systemic toxicity of local anesthetics limit their clinical application. The objective of this work was to develop a modified release system for the local anesthetic lidocaine (LDC), using polyvinylpyrrolidone-Tetrahydroxyborate (PVP-THB) hydrogel to improve the pharmacological properties of the drug and their anesthetic activities investigated. The mechanical properties, rheological, swelling ratio, and water content behavior of candidate formulations were investigated. An increase in THB concentrations increased the storage modulus (G') and the loss modulus (G″) but decreased the loss tangent (tan δ < 1). In vitro release of PVP and THB were assessed to evaluate potential clinical dosing of free species originating from the hydrogel structure. The profiles of PVP-THB/LDC showed that the release of associated LDC was slower than that of the free drug. Evaluating the cytotoxic effect of these hydrogels on an in vitro mouse fibroblast (L929) cells showed their good cytotoxic activity towards L929 prolonged its anesthetic action. Particles were characterized using a scanning electron microscope (SEM) and atomic force microscopy (AFM) analyses confirming the amorphous nature and the uniformity of LDC inclusion in the PVP-THB hydrogel. The continuous release of LDC from the PVP-THB hydrogel was observed for more than three days, without a remarkable initial burst, which is probably owing to the stable entrapment of LDC in the PVP-THB core of the hydrogel. We evaluated the analgesic effect of PVP-THB/LDC in the carrageenan-induced arthritis rats model. Results showed that PVP-THB/LDC has a stronger and longer analgesic effect when administered in inflamed areas. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics.