The integration of nanotechnology in drug delivery has gained increasing interest over the past few decades. The clever use of nanoparticles has revolutionized how drugs are formulated and delivered allowing effective delivery and targeting of diseased tissues and organs. One of the crucial aspects of the success of nanoparticle-based drug delivery system is its ability to specifically respond to internal triggers or to an external one in order to make the nanocarrier leaky. Trigger-responsive carriers have the potential to act as "remote switches" that can turn on or off the therapeutic effects of the nanoparticles, based on the presence or absence of the trigger. The development of smart, stimuli-responsive nanoparticles offers the possibility of controlling the response of the therapeutic agent precisely and specifically. External triggers can be easily controlled and do not have variability problems that may be associated with internal triggers. Recently, a pilot study has demonstrated the feasibility of a smart controlled delivery through a magnetic field with intensity significantly lower than the usual ones reported in literature. In this way, a controlled release has been obtained through a magneto-mechanical approach without a macroscopic temperature increase. Specifically, an intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFs) was applied to high-transition temperature magnetoliposomes (high-Tm MLs) entrapping hydrophilic magnetic nanoparticles (MNPs) that have been proven to be a potential biomaterial to PEMF-controlled drug delivery system. Starting from these considerations, the innovative idea of this project is to demonstrate that the preferential location of the MNPs next to the liposomal bilayer could result in the enhancement of the PEMF actuation. For this purpose MLs will be prepared in presence of hydrophobic coated MNPs to allow their entrapment within the lipid bilayer membrane.
The proposed research represents a contribution towards a novel drug delivery approaches. The concept of magneto-mechanical actuation of single-domain magnetic nanoparticles (MNPs) in low amplitude alternating magnetic fields (AMFs) and pulsed magnetic field (PEMFs) and its possible use for remote control of drug release was already described by the research group of my supervisor (dott. Stefania Petralito). The application of this approach for remote actuation of drug release was discussed in comparison to conventional strategies employing magnetic hyperthermia.
With respect to hyperthermia, the absence of heating allowed by the concept of magneto-mechanical actuation, offers substantial benefits because it limits damage and secondary effects to the surrounding tissues due to both the temperature increase and to magnetically induced eddy currents. Inclusion of nanoparticles in the bilayer, instead of in the aqueous core of liposomes, could represents an improvement of the stimuli responsive nanosystem. In fact, the risk that nanoparticles will flow outside the vesicle during the application of the stimulus is limited. This represent an advantage for the applicability of the stimulus during time and in term of safety because nanoparticles will be eliminated from the human body embedded within the liposomes rather than circulating in the body. Once demonstrated that PEMFs fields can trigger a response from the membrane bilayer of liposomal vesicles, releasing their content outside it, one can think to the possibility to translate such laboratory experimental activity to the clinics. In particular, PEMFs has been demonstrated to exert an anti-inflammatory effect resulted in early pain control and enhanced functional recovery in the knee diseases, reducing knee osteoarthritic lesion progression with long term positive benefits for patients [1]. At the same time, it is well known that a single-dose intra-articular administration of liposomes within a synovial joint, can be used to treat the inflammatory process [2]. Therefore, a novel concept of enhanced localized treatments could be proposed combining the functionalities of the magneto-mechanical actuation and the healing properties of a non-thermal magnetic field. Both approaches could work in close synergy with drug-loaded nanocarriers, able to control drug release by application of a remote magnetic field. In this way, the efficiency of anti-inflammatory therapies can be maximized in future medical applications.
[1] Veronesi F., et al., [2014] J. Orthop. Res. 32:677-685
[2] Chuang S.Y., et al., [2018]. Nanomaterials 8:42-58.