Controlled and time-scheduled drug delivery: Polyanhydride-based nanoparticles as ocular medication carriers

Nanoparticles offer an ideal opportunity for the efficient local anesthetic drug delivery required during and after ocular procedures. Currently available local anesthetic drugs are short acting, which may prevent adequate ocular pain control. Therefore, development of sustained controlled release anesthetic devices for pain control over a relatively short period (up to 48 h) potentially meets various opthalmological analgesic requirements. This study presents preliminary findings for drug delivery using poly(sebacic acid) (PSA) nanoparticles for tetracaine and lidocaine administration. Tetracaine- or lidocaine-loaded PSA nanoparticles were prepared using a double emulsion methodology. Release profiles were similar for both formulations, with 50% cumulative release achieved after 17 h and 23 h for tetracaine and lidocaine, respectively. The release profiles were studied, and data obtained from in vitro experiments were fit to different mathematical models. Based on mathematical models used in this study, drug release from all PSA-based formulations was diffusion-controlled, best described by the Higuchi model. Based on preliminary experiments, a hybrid formulation providing a burst effect was designed to counter the fast adsorption of drug expected in the physiological system. This was achieved by coating the lidocaine-loaded PSA nanoparticles with a gelatin/lidocaine layer. The coating provided accelerated lidocaine release, with 50% cumulative release obtained as early as 7 h compared to 23 h for uncoated nanoparticles. This formulation provided a triphasic release that can treat different pain levels at predetermined timelines. Our results provide new insight into the benefits of using polyanhydrides as a platform for drug delivery in ophthalmology.