Polymeric drug delivery systems: Lidocaine microspheres for prolonged and localized in vivo anesthetic effects and light-induced drug release from polymeric device mediated by bacteriorhodopsin

Polymers have been studied in controlling drug release for decades. They can be used to encapsulate drugs for the purpose of sustaining drug release or achieving intelligent drug release. In this dissertation, we explored both applications of the polymer system. First, we fabricated poly(lactide-co-glycolide) (PLGA)-based microspheres loaded with lidocaine in an attempt to prolong anesthetic effects locally at the site of surgical operation to relieve pain. Current treatment protocol for postoperative pain is to infuse anesthetic solution around nerves or into the epidural space. This clinical practice is beset by the short duration of the anesthetic effect unless the continuous infusion is adopted. A continuous infusion, however, requires hospitalization of the patients, thereby increasing associated medical costs. In addition, it may also cause systemic accumulation of the drug, leading to toxic effects. In the first part of dissertation, we demonstrated the extended in vivo anesthetic effects using PLGA-based lidocaine microspheres. The in vivo effects were assessed in a rat model using sciatic nerve blockade. The formulated microspheres loaded with lidocaine achieved a five-hour anesthetic effect compared to that of only one hour by lidocaine solution. To further prolong the effects, we formulated microspheres with poloxamer 407, a thermal sensitive material that gelled at physiological temperature but remained as a solution at cold temperatures such as 4°C. With this microsphere-gel system, the in vivo anesthetic effects were further extended to 8 hours using the same lidocaine dose.; The second part of this dissertation is to fabricate an intelligent polymer-based drug delivery system that releases drugs in response to external stimuli such as light. Polymers responsive to pH changes have been extensively investigated but have limited applicability due to the constancy of physiological pH. Herein we presented the use of bacteriorhodopsin (bR), a transmembrane protein from Halobacterium halobium that transports proton across the cell membrane upon light illumination around 569nm, to induce environmental pH changes upon light exposure. Combining this bR system with a pH-sensitive polymer that swells to release drugs upon the environmental pH changes, light-induced drug release from a one-compartment device made of the pH sensitive polymer was demonstrated.