PLGA-g-PVP-based nanocarriers for the controlled delivery of antimalarial and antitumour drugs

Purpose of this piece of work was to establish the best formulation technologies to transform PLGA-g-PVP copolymers into nanosized carriers, namely nanoparticles (NPs) and lipid nanocapsules (NCaps), for the delivery of antitumour and antimalarial drugs, respectively. PLGA-PVP copolymers were used to prepare stable NPs loaded with doxorubicin in base (DoxB) and salt (Dox) forms, using the solvent displacement technique. Nanoparticles were characterized in terms of average diameter; polydispersity, zeta potential, morphology pH and osmolarity were also evaluated. The effect of the drug incorporation on their properties was also studied. In vitro release studies showed that after 24 h drugs were retained by PLGA-PVP NPs in blood physiological condition (pH= 7.4). In contrast, initial burst followed by a sustained drug releases were typical at pH 5.5 (tumour cytoplasmic pH). Antitumoural efficiency was evaluated by MTT test on mice (4T1) and human (MDA-MB231 and CRL-2335) breast cancer cell lines. Dox-loaded PLGA-PVP10:2 NPs highly affected cancer cell proliferation, allowed an inhibition activity of about 65-95 % at 0.02 M, instead of 25 % of free Dox. Simultaneously, PLGA-g-PVP copolymers were used as coatings of lipid nanocapsules for the delivery of curcumin and artemisinin as antimalarials. Drug loaded-lipid micro-dispersions were first prepared by oil in water emulsion. The lipid drops were converted into nanometric ones by high-pressure homogenization and finally surface coated. The physico-chemical properties of nanoparticles were evaluated. In vitro cytotoxicity studies were performed on Plasmodium Falciparum infected red blood cell (p-RBC) (3D7 culture lines). From preliminary growth inhibition assays, a significant parasitemia reduction was observed in the case of curcumin-loaded PLGA-PVP NCaps treatments (IC50 = 0.4-0.5 μM) with respect to free curcumin (IC50 = 8.0 μM). Artemisinin-loaded PLGA-PVP NCaps presented similar activities of free artesimin, thus they were not further analysed. No haemolytic activity was detected after 24 h for PLGA-PVP NCaps at concentrations used for parasitemia inhibition assay. In conclusion, PLGA-PVP nanocarriers were demonstrated to be effective as drug carriers for both antimalarial and antitumour applications.