Design and characterization of polymer-based nanoparticles loaded with zinc phthalocyanine for use in photodynamic therapy

Abstract

Zinc phthalocyanine (ZnPc) is a promising second-generation photosensitizer (PS) that exhibits advantageous properties that include low toxicity, high chemical and photochemical stability, strong absorption in the red region of the spectrum in which the tissue exhibits optimal transparency, high triplet quantum yields, long-lived triplet excited state, high singlet oxygen quantum yields and satisfactory therapeutic effects. The main obstacle for ZnPc to be used as a drug in photodynamic therapy (PDT) is the low level of physiological acceptance due to its highly hydrophobic nature, resulting in poor solubility in body fluid and consequently low bioavailability and aggregation. To overcome these drawbacks, the third-generation of PS, which is composed of a second-generation PS conjugated or encapsulated in biodegradable/biocompatible nanoparticles (NP) have successfully emerged. Thus, the main of this work was to develop two new nanocarriers for ZnPc: carboxymethyl chitosan/ionic liquid imidazolium (ZnPc@CMC/IL) and maltoheptaose-b-polystyrene block glycopolymer (ZnPc@MH-b-PS), and evaluate their physicochemical properties, photodynamic activity, encapsulation efficiencies and drug release profile for use in PDT. The ZnPc@CMC/IL nanoparticles showed values of hydrodynamic radius (Rh) in the range of 67 - 76 nm, low polydispersity index, negative zeta potential, high drug loading and encapsulation efficiencies higher than 98%. The ZnPc@MH-b-PS nanoparticles showed Rh values in the range of 22 - 139 nm, suitable values of drug loading and encapsulation efficiency, a cleavable and redox-responsive profile and have been shown to be non-toxic towards Caenorhabditis elegans. Both nanocarriers showed spherical morphology and the ability to produce cytotoxic singlet oxygen (1O2) with values of singlet oxygen quantum yields appropriated for application in PDT. Concerning the drug release profile, the ZnPc@CMC/IL nanoparticles exhibits a diffusion-controlled sustained release profile being described by Higuchi model, while for ZnPc@MH-b-PS NPs showed a biexponential release profile, with a burst effect in the early stage, followed by a diffusion-controlled sustained release profile (Fickian behavior) in the late stage. The results showed that these bio-based NPs are appropriate as drug delivery systems and are a promising strategy to be employed in PDT.