Characterization and biodistribution of bevacizumab TPGS-based nanomicelles: Preliminary studies

Bevacizumab is an FDA approved monoclonal antibody (anti VEGF) indicated in many cancers, mostly metastatic ones. D-α-tocopheryl polyethylene glycol succinate (TPGS) is the water-soluble form of vitamin E which usually forms micelles. This work aims to report preliminary results of the biodistribution of a TPGS based nano-micelle delivery system for bevacizumab in a gastric cancer xenograft model. Evaluation of the biodistribution of micelles/bevacizumab-99mTc was performed in Balb/c nude mice carrying MKN45 cell line xenograft. The nano-radiopharmaceutical (3.7 MBq/0.2 mL) was administered intraocularly and biodistribution was assesed 1 h post administration. The activity in each organ and blood was determined by a gamma counter. Mean size was 10 ± 1 nm for pure TPGS and 11 ± 1 nm for bevacizumab-TPGS respectively. Biodistribution showed that the highest uptake was found in both lungs and liver. Kidneys had also an important uptake. The tumor accumulated moderate to low radiolabeled nanomicelles, nevertheless tumor/blood ratio was very high. These preliminary results may help as a start point to continue evaluating the potential of radiolabeled bevacizumab-TPGS based nanomicelles to be used as a theranostic agent.Fil: Tesan, Fiorella Carla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cerqueira Coutinho, Cristal. Universidade Federal do Rio de Janeiro; BrasilFil: Salgueiro, María Jimena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Albernaz, Marta de Souza. Universidade Federal do Rio de Janeiro; BrasilFil: Pinto, Suyenne Rocha. Universidade Estadual da Zona Oeste; BrasilFil: Reis, Sara Rhaissa Rezende Dos. Universidade Estadual da Zona Oeste; BrasilFil: Bernardes, Emerson Soares. Instituto de Pesquisas Energéticas e Nucleares; BrasilFil: Chiapetta, Diego. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zubillaga, Marcela Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santos Oliveira, Ralph. Universidade Estadual da Zona Oeste; Brasi

Senescence and the Impact on Biodistribution of Different Nanosystems: the Discrepancy on Tissue Deposition of Graphene Quantum Dots, Polycaprolactone Nanoparticle and Magnetic Mesoporous Silica Nanoparticles in Young and Elder Animals

[EN] Purposes Senescence is an inevitable and irreversible process, which may lead to loss in muscle and bone density, decline in brain volume and loss in renal clearance. Although aging is a well-known process, few studies on the consumption of nanodrugs by elderly people were performed. Methods We evaluated three different nanosystems: i) carbon based nanosystem (Graphene Quantum Dots, GQD), ii) polymeric nanoparticles and mesoporous silica (magnetic core mesoporous silica, MMSN). In previous studies, our group has already characterized GQD and MMSN nanoparticles by dynamic light scattering analysis, atomic force microscopy, transmission electron microscopy, X-ray diffraction, Raman analysis, fluorescence and absorbance. The polymeric nanoparticle has been characterized by AFM and DLS. All the nanosystems were radiolabeled with 99 m-Tc by. The in vivo biodistribution/tissue deposition analysis evaluation was done using elder (PN270) and young (PN90) mice injected with radioactive nanosystems. Results The nanosystems used in this study were well-formed as the radiolabeling processes were stable. Biodistribution analysis showed that there is a decrease in the uptake of the nanoparticles in elder mice when compared to young mice, showing that is necessary to increase the initial dose in elder people to achieve the same concentration when compared to young animals. Conclusion The discrepancy on tissue distribution of nanosystems between young and elder individuals must be monitored, as the therapeutic effect will be different in the groups. Noteworthy, this data is an alarm that some specific conditions must be evaluated before commercialization of nano-drugs. Changes between younger and elderly individuals are undoubtedly, especially in drug tissue deposition, biodistribution and pharmacokinetics. The same thought should be applied to nanoparticles. A comprehensive analysis on how age discrepancy change the biological behavior of nanoparticles has been performed.Rezende Dos Reis, SR.; Rocha Pinto, S.; Duarte De Menezes, F.; Martínez-Máñez, R.; Ricci-Junior, E.; Rebelo Alencar, LM.; Helal-Neto, E.... (2020). Senescence and the Impact on Biodistribution of Different Nanosystems: the Discrepancy on Tissue Deposition of Graphene Quantum Dots, Polycaprolactone Nanoparticle and Magnetic Mesoporous Silica Nanoparticles in Young and Elder Animals. Pharmaceutical Research. 37(3):1-12. https://doi.org/10.1007/s11095-019-2754-911237