Formulazione di nanoparticelle contenenti doxorubicina mediante microfluidica

Nanotechnology has revolutionized the field of drug delivery with higher efficacy, improved bioavailability and safety. Several methods to prepare nanoparticles (NPs) have been studied. However, microfluidics represents a promising technique due to high reproducibility, fine parameters control, reduced reagents consumption and production steps. The work here presented provides insights over a biodegradable polymeric nanosystem for doxorubicin (DOX) encapsulation through a microfluidic approach. The possibility to obtain monodisperse NPs using water soluble polyelectrolytes, namely A and B, was firstly studied. Blank and DOX-loaded NPs obtained were characterized by a size of around 200 nm and negative zeta potential (-30 mV). NPs were then produced varying DOX concentration, polymer A concentration as well as the pressure imposed on the two phases. In particular, NPs prepared with 3.75 mg/mL concentration of polymer A, 2.75 mg/mL of polymer B and 1 mg/mL of DOX resulted in an average hydrodynamic diameter of 158 nm with a zeta potential value of around -34 mV, when the applied pressure was set at 400, 600 or 1000 mbar. Polymer A at the concentration of 2.5 and 3.75 mg/mL, and polymer B at 2.5 mg/mL concentration, successfully assembled in NPs with a hydrodynamic diameter ranging between 100 and 400 nm, and encapsulating DOX at the concentration of 0.4 or 1 mg/mL. The statistical analysis allowed to identify the relevance of each variable on NPs zeta potential, encapsulation efficiency (EE%) and drug loading (DL%). It was demonstrated that increasing polymer A and DOX concentration led to strongly negative zeta potential (from -25 to -40 mV), and promoted the loading capacity of the NPs (from 3 to 13%). Besides, DOX-loaded NPs freeze-dried with maltose and trehalose as cryoprotectants maintained their integrity after reconstitution in water, retaining their EE of around 80% and a high DL (4% or 10%, depending on DOX concentration). Overall, the proposed approach can represent a tool for the production of biodegradable polymer NPs for drug delivery.