Development of biobased polymeric nanoparticles containing active pharmaceutical ingredients for anticancer application

Abstract

Vegetable oils are potential substitutes for petroleum derivatives, as they present themselves as a clean and environmentally friendly alternative and are available in high quantities at relatively low prices. Biomass-derived chemicals can be converted into monomers with unique structures, generating materials with new properties. Methyl 10-undecenoic acid, a castor oil derived, was shown to be a suitable starting material for the preparation of esters with alkene groups that can be lead in biodegradable polymers. The main objective of this research work is the study of the synthesis and physical, chemical, and biological characterization of polymeric particles derived from renewable sources, containing the active pharmaceutical ingredients (APIs) zinc phthalocyanine (ZnPc) and full-spectrum Cannabis extract (CN), both with promising action against cancer. At the first step of the work, the encapsulation of zinc phthalocyanine in poly(thioether-ester) (PTEe) nanoparticles via thiol-ene miniemulsion polymerization using a biobased α-ω-diene diester monomer (derived from castor oil) was obtained. Two different thiols were employed as comonomers. ZnPc loaded PTEe nanoparticles presented an average diameter of around 122 -145 nm and high encapsulation efficiency (> 95%) of ZnPc for both thiols. FTIR and thermal analyses showed that there was no significant interaction between the drug and the polymer, indicating that ZnPc is molecularly dispersed in the polymeric matrix. The ZnPc release profile in the nanoparticles showed an initial burst effect followed by a slowrelease rate. Cytotoxicity studies showed that nanoparticles do not cause hemolytic damage and showed phototoxic effect in breast cancer cells at low concentrations of ZnPc. In second step, full-spectrum Cannabis extract was encapsulated in PTEe nanoparticles synthesized by thiolene in situ miniemulsion and solvent evaporation with the biobased monomer (1,3-propylene diundec-10-enoate). The Full-spectrum Cannabis extract was analyzed by physicochemical characterizations and also by biological in vitro studies such as cytotoxicity assay, hemolysis assay, apoptosis, and membrane potential to investigate the potential of nanoparticles for anticancer therapy treatments. With high encapsulation efficiency (> 97%) and an average diameter between 91 - 229 nm, the encapsulation of full-Cannabis extract in biobased nanoparticles was efficient to stimulate a cytotoxic effect on cancer cells line.