Preclinical Evaluation of Polymeric Nanocomposite Containing Pregabalin for Sustained Release as Potential Therapy for Neuropathic Pain
Rafaela Figueiredo Rodrigues, Juliana Barbosa Nunes, Sandra Barbosa Neder Agostini, Paloma Freitas dos Santos, Juliana Cancino‐Bernardi, Rodrigo Vicentino Plácido, Thamyris Reis Moraes, Jennifer Tavares Jacon Freitas, Gislaine Ribeiro Pereira, Flávia Chiva Carvalho, Giovane Galdino, Vanessa Bergamin Boralli
Abstract
This study offers a novel oral pregabalin (PG)-loaded drug delivery system based on chitosan and hypromellose phthalate-based polymeric nanocomposite in order to treat neuropathic pain (PG-PN). PG-PN has a particle size of 432 ± 20 nm, a polydispersity index of 0.238 ± 0.001, a zeta potential of +19.0 ± 0.9 mV, a pH of 5.7 ± 0.06, and a spherical shape. Thermal and infrared spectroscopy confirmed nanocomposite generation. PG-PN pharmacokinetics was studied after a single oral dose in male Wistar rats. PG-PN showed greater distribution and clearance than free PG. The antinociceptive effect of PG-PN in neuropathic pain rats was tested by using the chronic constriction injury model. The parameter investigated was the mechanical nociceptive threshold measured by the von Frey filaments test; PG-PN showed a longer antinociceptive effect than free PG. The rota-rod and barbiturate sleep induction procedures were used to determine adverse effects; the criteria included motor deficit and sedative effects. PG-PN and free PG had plenty of motors. PG-PN exhibited a less sedative effect than free PG. By prolonging the antinociceptive effect and decreasing the unfavorable effects, polymeric nanocomposites with pregabalin have shown promise in treating neuropathic pain.