In vitro and in vivo evaluation of polylactide and polylactide-co-glycolide microspheres of morphine for site-specific delivery

The aim of using opioid drugs such as morphine in chronic pain is optimal pain relief with a minimum of side effects. After the discovery that opioids could produce analgesia when administered intrathecally or extradurally, there has been particular interest in their administration by these routes and other site-specific routes. Controlled release systems of morphine are not currently available for parenteral routes. So, the design of a controlled release system for this analgesic was undertaken. To reach this goal, morphine-loaded microspheres (MLMs) made with polylactide and polylactide-co-glycolide polymers were prepared by the solvent evaporation process. MLMs were characterized by optical and scanning electron microscopy, by their drug contents and in vitro release kinetics. MLMs were then administered via subcutaneous injection in rabbits. The in vivo results, in accordance with the in vitro release studies, showed: (i) a controlled release of morphine avoiding high plasma levels; and (ii) an extended release of morphine.