Solvent-free nanoparticles synthesis for encapsulation of water-soluble compounds

The increasing concerns on green manufacturing practices with low environmental impact have put pressure on the pharmaceutical industry. Of particular concern is the large number of organic solvents used in a wide range of pharmaceutical products, posing a significant risk on human and environmental health. Recently, nanoparticles(NPs) emerged as advantageous drug-delivery systems with the potential to maximize drug efficacy and minimize side effects. Unfortunately, NPs synthesis processes are still environmentally unsustainable, due to the large amount of organic solvent involved. This contribution describes the synthesis and characterization of NPs encapsulating proteins or nucleic acids for metastatic melanoma treatment using alternative synthesis methods that replace organic solvents with water-based solutions. Two different green synthesis techniques have been investigated; (i)Ionic gelation was used to prepare chitosan(CS) NPs, exploiting the electrostatic interaction between the CS amino groups and tripolyphosphate(TPP), (ii)self-assembly technique to prepare siRNA/phosphate-poly(allylamine-hydrochloride)(PAH) NPs, exploiting the interactions between primary amines in the polymer and siRNAs to form stable complexes. CS and PAH NPs with the appropriate hydrodynamic diameters (~200 nm), polydispersity index, and Z potential for high cell internalization and tissue extravasation were obtained. Preliminary in vitro tests demonstrated that particles are well tolerated by human fibroblast which has shown high viability even when treated with the highest NPs concentration (viability ~85% at 48h from the treatment). Additional tests are currently ongoing to demonstrate the efficacy of the drug- loaded system on human fibroblasts. Carlotta Mattioda acknowledges PON "Ricerca e Innovazione" 2014-2020 Azione IV.R "dottorati su tematiche green" for co-financing her Ph.D scholarship.