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Targeted uptake of folic acid-functionalized polymeric nanoparticles loading glycoalkaloidic extract in vitro and in vivo assays

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Autor(es):
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Miranda, M. A. [1] ; Silva, L. B. [1] ; Carvalho, I. P. S. [1] ; Amaral, R. [1] ; de Paula, M. H. [1] ; Swiech, K. [1] ; Bastos, J. K. [1] ; Paschoal, J. A. R. [1] ; Emery, F. S. [1] ; dos Reis, R. B. [2] ; Bentley, M. V. L. B. [1] ; Marcato, P. D. [1]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Ribeirao Preto, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 192, AUG 2020.
Citações Web of Science: 0
Resumo

Solarium lycocarpum fruits contain two major glycoalkaloids (GAs), solamargine (SM) and solasonine (SS). These compounds are reported as cytotoxic. However, they have poor water solubility and low bioavailability. To overcome these disadvantages and getting an efficient formulation the current study aimed to develop, characterize, and WA the effectiveness of a nanotechnology-based strategy using poly(D,L-lactide) (PLA) nanoparticles functionalized with folate as delivery system of glycoalkaloidic extract (AE) for bladder cancer therapy. The strategic of adding folic acid into nanoformulations can increase the selectivity of the compounds to the cancer cells reducing the side effects. Our results revealed the successful preparation of AE-loaded folate-targeted nanoparticles (NP-F-AE) with particle size around 177 nm, negative zeta potential, polydispersity index < 0.20, and higher efficiency of encapsulation for both GAs present in the extract (> 85 %). To investigate the cellular uptake, the fluorescent dye coumarin-6 was encapsulated into the nanoparticle (NP-F-C6). The cell studies showed high uptake of nanoparticles by breast (MDA-MB-231) and bladder (RT4) cancer cells, but not for normal keratinocytes cells (HaCaT) indicating the target uptake to cancer cells. The cytotoxicity of nanoparticles was evaluated on RT4 2D culture model showing 2.16-fold lower IC 50 than the free AE. Furthermore, the IC50 increased on the RT4 spheroids compared to 2D model. The nanoparticles penetrated homogeneously into the urotheliumof porcine bladder. These results showed that folate-conjugated polymeric nanoparticles are potential carriers for targeted glycoalkaloidic extract delivery to bladder cancer cells. (AU)

Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
Beneficiário:Maria Vitória Lopes Badra Bentley
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 12/50762-1 - Estudo comparativo dos efeitos do imunomodulador P-MAPA encapsulado em nanopartículas poliméricas mucoadesivas versus imunoterapia com BCG na progressão do câncer de bexiga urinária: avaliação histopatológica e molecular
Beneficiário:Priscyla Daniely Marcato Gaspari
Linha de fomento: Auxílio à Pesquisa - Regular