Microsistemi per il drug delivery attivato elettricamente e loro applicazione nel controllo del dolore post-operatorio

Abstract

Acute postoperative pain is a complex phenomenon characterized by occurrence of inflammatory events and pathophysiological alterations that can lead to the increase of post-operative morbidity, an increase in mortality and a delay in patient recovery. Nowadays, among the several approaches to manage postoperative pain, one of the most efficient strategies is the regional administration of local anaesthetics, in particular the continuous wound infusion. Since the wound is the fundamental source of the pain stimulus, by blocking the stimulus at its origin the analgesic efficacy could be improved and hence preventing at the same time the systemic effects induced by intravenous administration. On the other hand, the continuous wound infusion is carried out through the classic intralesional catheters that show several limits, such as the risk of infection, the reduction of the patients’ normal activities that influences their compliance, difficulty in administration and possible systemic toxicity. In this PhD thesis we have demonstrated the feasibility of a novel type of devices that could be fruitfully used in the post-operative pain treatment by delivering locally much reduced quantities of drugs. All the main features needed for a successful application of the envisaged devices have been demonstrated, including: the biocompatibility, both by using materials that have already been certified in literature and by tests in our labs; the ability of drug loading and sealing; the mechanism of delivery actuated by electrical signals that could be eventually easily controlled remotely. The different strategies that we explored to fabricate the final device are discussed in this thesis. We have demonstrated that we are able to load model agents both in form of crystals and liquids and we have developed various methods to seal the microcontainers. Finally, we have demonstrated for the first time the possibility of inducing the activation of the drug release by means of electric stimuli making it possible to control the drug administration remotely. We believe that the development of our new device can guarantee a safe, complete and effective administration contrasting the onset of both acute and chronic post-operative pain. We believe that all the research work carried out could have a much wider impact on the development in micro-nano medicine and in particular in local drug release methods.