The integration of nanotechnology in drug delivery has gained increasing interest over the past few decades, revolutionizing how drugs are formulated and delivered allowing effective delivery and targeting of diseased tissues and organs. Trigger-responsive carriers have attracted a lot of attention in recent years due to the ability 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 stimulus to which the nanoparticles are sensitive. In this way, a controlled release has been obtained with my research group through a magneto-nanomechanical approach without a temperature increase. Specifically, an intermittent signal generated by a non-thermal pulsed electromagnetic fields (PEMFs), generated by a commercial device yet used for medical applications, was applied to magnetoliposomes (MLs) entrapping hydrophilic or hydrophobic magnetic nanoparticles (MNPs) proving to be a potential PEMF-controlled drug delivery system. Despite the good results obtained, the principal problem, especially for MLs incorporating hydrophilic MNPs, is the reduced loading of hydrophilic drugs. Moreover, some classic limitations of first-generation liposomes such as the physicochemical stability, elevated systemic clearance and the payload leakiness could be overcome accomplishing a hybrid assembly able to act as a depot system and to interact with a triggering remote signal, such as the external magnetic field, allowing drug release only when it is necessary reducing possible collateral effects. Starting from these considerations, the innovative idea of this project is to incorporate MLs in a hydrogel, in order to further increase the hydrophilic and hydrophobic drug loading, since liposomes could load both, and efficiently control the local release.
The proposed research represents a contribution towards a novel drug delivery system, in particular as a depot system for a local controlled drug release. The concept of magneto-mechanical actuation of single-domain magnetic nanoparticles (MNPs), hydrophilic and hydrophobic, in non-heating magnetic fields and its possible use for remote control of drug release was already described by the research group of my supervisor (dott. Stefania Petralito). Furthermore, the preparation and characterization of hydrogels based on different type of biocompatible polymer was also described. For these reasons, we speculate that a design of magnetic liposomes-hydrogel could represent an important step forward in the field of stimuli responsive drug delivery systems and which could overcome some disadvantages typical of both MLs and hydrogels. In particular, hydrogels usually cannot encapsulate hydrophobic drugs, further hydrophilic drug release from hydrogels is usually fast and difficulty to control. Otherwise, magnetoliposomes are characterized by the possibility to encapsulating both hydrophilic and hydrophobic drugs and by the stimuli controlled release. Therefore, magnetoliposomes incorporation in a hydrogel structure could enhance its drug delivery capabilities, in particular for hydrophobic drugs [1]. Furthermore, their incorporation in a hydrogel could confer it a stimuli-responsive properties, in particular a magnetic field responsivity in order to obtain a remote-controlled release system. The inclusion of magnetoliposomes in hydrogel structure generally does not require particularly conditions. However, it is known that hydrogels present an internal micrometric porosity, unlike the nanometric size of magnetoliposomes. Probably, a diffusion of MLs out of the hydrogel could also occur, with consequently loss of stimuli responsivity efficacy. For this reason, we speculate that an intimal contact between magnetoliposomes and polymer could be necessary in order to avoid the magnetoliposomes diffusion outside the hydrogel. Therefore, a Layer-by-Layer technique could be optimal to cover the magnetoliposomes surface directly with the polymer which, after the gelation process, will form the hydrogel. The research activity of my research group is focused on the development of new polymer- and/or lipid-based systems for biomedical or pharmaceutical applications. It is structured into the following main research lines:1) Synthesis and characterization of novel biopolymers and matrices for application as modified drug delivery systems or as scaffold for tissue engineering 2) Design and development of polymeric thin films for drug delivery 3) Design and development of hybrid drug delivery systems, such as Gel-in-Liposome (GiL) systems -liposomes with a gelled internal core 4)Design and development of stimuli responsive nano-systems for ¿on demand¿ drug release triggered by electrical or magnetic stimuli.
[1] Veloso, S.R.S.; Andrade, R.G.D.; Ribeiro, B.C.; Fernandes, A.V.F.; Rodrigues, A.R.O.; Martins, J.A.; Ferreira, P.M.T.; Coutinho, P.J.G.; Castanheira, E.M.S. Magnetoliposomes Incorporated in Peptide-Based Hydrogels: Towards Development of Magnetolipogels. Nanomaterials 2020, 10, 1702. https://doi.org/10.3390/nano10091702