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Article

Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles

1
N.M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, 119991 Moscow, Russia
2
JSC Russian Research Center for Molecular Diagnostics and Therapy, 117149 Moscow, Russia
3
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117198 Moscow, Russia
4
Chemistry Department, Lomonosov Moscow State University, 119234 Moscow, Russia
5
Lomonosov Institute of Fine Chemical Technologies, MIREA—Russian Technological University, 119454 Moscow, Russia
*
Authors to whom correspondence should be addressed.
Academic Editor: Alexander A. Kamnev
Int. J. Mol. Sci. 2021, 22(22), 12261; https://doi.org/10.3390/ijms222212261
Received: 8 October 2021 / Revised: 8 November 2021 / Accepted: 10 November 2021 / Published: 12 November 2021
(This article belongs to the Special Issue Nanoparticles: From Synthesis to Properties)
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. View Full-Text
Keywords: nanoparticles; PLGA; metalloporphyrins; Box–Behnken design; drug release; kinetics; binding constant; hemolytic activity; pharmacokinetics nanoparticles; PLGA; metalloporphyrins; Box–Behnken design; drug release; kinetics; binding constant; hemolytic activity; pharmacokinetics
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MDPI and ACS Style

Mollaeva, M.R.; Yabbarov, N.; Sokol, M.; Chirkina, M.; Mollaev, M.D.; Zabolotskii, A.; Seregina, I.; Bolshov, M.; Kaplun, A.; Nikolskaya, E. Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles. Int. J. Mol. Sci. 2021, 22, 12261. https://doi.org/10.3390/ijms222212261

AMA Style

Mollaeva MR, Yabbarov N, Sokol M, Chirkina M, Mollaev MD, Zabolotskii A, Seregina I, Bolshov M, Kaplun A, Nikolskaya E. Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles. International Journal of Molecular Sciences. 2021; 22(22):12261. https://doi.org/10.3390/ijms222212261

Chicago/Turabian Style

Mollaeva, Mariia R., Nikita Yabbarov, Maria Sokol, Margarita Chirkina, Murad D. Mollaev, Artur Zabolotskii, Irina Seregina, Mikhail Bolshov, Alexander Kaplun, and Elena Nikolskaya. 2021. "Optimization, Characterization and Pharmacokinetic Study of Meso-Tetraphenylporphyrin Metal Complex-Loaded PLGA Nanoparticles" International Journal of Molecular Sciences 22, no. 22: 12261. https://doi.org/10.3390/ijms222212261

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