RESUMEN
The objective of this study was to develop and characterize a biodegradable drug-loaded nerve guide for peripheral nerve regeneration. Sabeluzole, a nerve growth agent, was selected as model compound. Four biodegradable polymers were selected for this study: a copolymer of polylactic acid and polycaprolactone (PCL); a copolymer of polyglycolic acid and polycaprolactone PCL; a copolymer of PCL/polydioxanone (PDO) and PDO. Placebo and drug loaded nerve guides were obtained by melt compression and melt extrusion. It was observed that melt compression and melt extrusion are feasible techniques to prepare the nerve guides. Based on the physicochemical characterization, all samples show absence of crystalline sabeluzole, indicating the formation of an amorphous dispersion. The in vitro release measurements show that the release of sabeluzole is complete, reproducible and can be controlled by the proper selection of the polymer. The release mechanism for all samples follows Fickian release behaviour.
Asunto(s)
Implantes Absorbibles , Líquidos Corporales/química , Implantes de Medicamentos/química , Ácido Láctico/química , Piperidinas/administración & dosificación , Piperidinas/química , Poliésteres/química , Polímeros/química , Tiazoles/administración & dosificación , Tiazoles/química , Animales , Materiales Biocompatibles , Difusión , Estabilidad de Medicamentos , Análisis de Falla de Equipo , Humanos , Ensayo de Materiales , Factores de Crecimiento Nervioso/administración & dosificación , Factores de Crecimiento Nervioso/química , Regeneración Nerviosa/efectos de los fármacos , Traumatismos de los Nervios Periféricos , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/cirugía , Diseño de Prótesis , TemperaturaRESUMEN
Post-surgical adhesion formation has numerous deleterious side effects in a wide variety of surgical settings. Physical barriers used together with laparoscopy were developed to reduce tissue trauma seen with open procedures. However, despite surgeons' meticulous techniques and the use of such barriers, adhesion formation remains a serious clinical problem, creating complications that cost the health care system over $1 billion annually. Our laboratories have combined a previously marketed drug, Tranilast, with a sodium carboxymethylcellulose (NaCMC) gel in a sustained release formulation using poly(p-dioxanone) (PDO) to provide a locally delivered medicated device that significantly reduces adhesions. This paper describes the preparation of the gel and the sustained release formulation, its key physical properties, and its sustained release kinetics. Pre-clinical data on inhibition of adhesion formation by the sustained release poly(p-dioxanone)/sodium carboxymethylcellulose/Tranilast drug enhanced device are also presented.