Innovative nanofabrication methodologies for the preparation of drug delivery systems

In recent years, novel nanofabrication approaches have attracted the growing interest of researchers in the biomedical field. Nanomaterials are highly versatile tools that can interact with cells in general, including bacteria, animal and plant cells. When used as drug carriers, NPs can afford improved circulation and biodistribution, in addition to high drug loading and controlled release rates, as well as protection from degradation that may occur both in vitro and in vivo. Biopolymers have been extensively explored in recent years for biomedical applications thanks to their properties such as biocompatibility and biodegradability. Our research group has been designing biopolymeric nanovectors for the controlled delivery of bioactive molecules by using different nanoprecipitation approaches. Conventional methods such as ionotropic gelation have been used for the development of positively charged chitosan-based NPs for the delivery of nucleic acids (plasmid DNA, siRNA) or antibiotics for bacterial biofilm management1. Moreover, we have patented a methodology based on the use of semipermeable membranes to fabricate polymeric NPs by exploiting their solution properties at the interface in different media. Size modulation can be obtained by changing experimental conditions such as temperature, polymer concentration and solvent polarity. The NPs obtained are free of contaminants such as surfactants, initiator residues, and their decomposition products. More recently, we have assembled a novel and versatile capillary-based microfluidic system for the reproducible production of stabilized polymeric NPs with low polydispersion and diameters ranging between 35 and 350 nm. This system also allowed the synthesis of dexamethasone (DXM) -loaded poly-(lactic-co-glycolic) acid (PLGA) NPs in a one-step procedure2. These methodologies that allow to prepare in one step drug-loaded NPs were used for the production of DXM-loaded biopolymeric NPs that were able to induce human gingival fibroblasts to acquire an osteogenic phenotype3. Also, we developed stable PLGA NPs loaded with doxorubicin (DOX). We tested these preparations on human breast cancer cells and we found that the uptake efficiency of DOX was dramatically increased when loaded in PLGA NPs, that improved the antitumor efficacy with a reduced toxicity in cell cultures. 1. L. Chronopoulou, E.G. Di Domenico, F. Ascenzioni, C. Palocci, J. Nanopart. Res. 2016, 18, 308. 2. L. Chronopoulou, C. Sparago, C. Palocci, J. Nanopart. Res. 2014, 16, 2703. 3. L. Chronopoulou, G. Nocca, A. Amalfitano, C. Callà, A. Arcovito, C. Palocci, Biotechnol. Prog. 2015, 31, 1381