Investigation of physical methods associated with drug delivery systems in the local immune and antimicrobial response

Abstract

Intelligent drug delivery systems, which release the drug as a function of a specific change in pH or the presence of an enzyme, are increasingly being studied to reduce adverse effects and increase the efficiency of treatments. Activation of this release by physical stimuli, and not only chemical or biological, provides greater control of drug release, which is well documented in the literature. In addition to this release control, the physical stimulus potential to modulate the delivery system absorption and intracellular traffic, the immune response, and the microbiota close to the site of the physical stimulus application need to be better understood and investigated. This project aims to examine the physical, chemical, and biological implications of the association of delivery systems, including nanoparticles, with electrical, sound, light, and magnetic stimuli in the treatment mainly of skin, eye, and lung disorders. Evaluating the interactions among the physical method, the delivery system, the biological environment, and the responses triggered by them is, therefore, the mainline of this proposal. Membranes, matrices, and nanoparticles will be designed depending on the application site characteristics and the treatment condition. The impact of electric current, ultrasound, light, or magnetism on the interactions of the delivery system with the epithelia under study will be evaluated, in vitro and in vivo, as a function of drug release rate, cellular uptake, intracellular traffic, specific interactions with the target tissue, stimulation of the immune response and local antimicrobial activity. These studies are expected to target the release of drugs to specific sites of the studied epithelium after topical application, increase the efficiency of treatments, and understand at the cellular and molecular level the mechanisms involved in the cure of the disorders studied in the face of the applied physical stimulus. Together, the results may contribute to developing more effective treatment strategies. Finally, modulating the release of drugs from the delivery systems and understanding how the physical stimuli in question interact with these systems and with the tissues can help in the development of formulations that are increasingly targeted to the epithelium site to be treated, in the reduction of adverse effects and increased treatment efficacy. (AU)