Abstract
The selection of technological parameters for nanoparticle formulation represents a complicated development phase. Therefore, the statistical analysis based on Box–Behnken methodology is widely used to optimize technological processes, including poly(lactic-co-glycolic acid) nanoparticle formulation. In this study, we applied a two-level three-factor design to optimize the preparation of nanoparticles loaded with cobalt (CoTPP), manganese (MnClTPP), and nickel (NiTPP) metalloporphyrins (MeP). The resulting nanoparticles were examined by dynamic light scattering, X-ray diffraction, Fourier transform infrared spectroscopy, MTT test, and hemolytic activity assay. The optimized model of nanoparticle formulation was validated, and the obtained nanoparticles possessed a spherical shape and physicochemical characteristics enabling them to deliver MeP in cancer cells. In vitro hemolysis assay revealed high safety of the formulated MeP-loaded nanoparticles. The MeP release demonstrated a biphasic profile and release mechanism via Fick diffusion, according to release exponent values. Formulated MeP-loaded nanoparticles revealed significant antitumor activity and ability to generate reactive oxygen species. MnClTPP- and CoTPP-nanoparticles specifically accumulated in tissues, preventing wide tissue distribution caused by long-term circulation of the hydrophobic drug. Our results suggest that MnClTPP- and CoTPP-nanoparticles represent the greatest potential for utilization in in anticancer therapy due to their effectiveness and safety.
Highlights
The most widely known metalloporphyrins (MeP) are natural heme (Fe containing) and chlorophyll (Mg containing) [1,2]
Poly(lactic-co-glycolic acid) (PLGA)-based delivery systems represent an object of great interest in modern medicine
Thorough formulation process optimization followed by scrupulous NPs characterization revealed good Box–Behnken experimental design (BBD) applicability for the MeP-loaded NP design, especially in Mn- and Co-containing porphyrins
Summary
The most widely known metalloporphyrins (MeP) are natural heme (Fe containing) and chlorophyll (Mg containing) [1,2]. In addition to the application in chemotherapy, MeP are practiced in photodynamic therapy (PDT) as photosensitizers [15,16,17,18]. Another promising method for cancer treatment using MeP is a catalyst therapy, based on the interaction of MeP and substrate (e.g., ascorbic acid (AA)) [19]. MeP encapsulation into polymer nanocarriers is one of the methods for increasing its bioavailability [29,30,31]
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