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1.
Eur J Pharm Biopharm ; 200: 114328, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763329

RESUMO

Aggressive colon cancer treatment poses significant challenges. This study investigates the potential of innovative carbohydrate-based nanoparticles for targeted Capecitabine (CTB) delivery. CTB nanoparticles were synthesized by conjugating CTB with potato starch and chitosan using ultrasonication, hydrolysis, and ionotropic gelation. Characterization included drug loading, rheology, Surface-Enhanced Raman Spectroscopy (SERS), Fourier-Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Thermogravimetric Analysis (TGA). In vitro and in vivo antitumor activity was evaluated using HT-29 cells and N, N-dimethylhydrazine-induced Balb/c mice, respectively. Cellular assays assessed angiogenesis, migration, proliferation, and apoptosis. Nanoparticles exhibited a mean size of 245 nm, positive zeta potential (+30 mV), high loading efficacy (76 %), and sustained drug release (92 % over 100 h). CTB-loaded nanoparticles displayed superior colon histology, reduced tumour scores, and inhibited VEGD and CD31 expression compared to free CTB. Cellular assays confirmed significant antitumor effects, including reduced tube formation, migration, and proliferation, and increased apoptosis. This study demonstrates the promise of CTB-loaded potato starch-chitosan nanoparticles for aggressive colon cancer treatment. These findings highlight the potential of these nanoparticles for further evaluation in diverse cancer models.


Assuntos
Capecitabina , Quitosana , Neoplasias do Colo , Camundongos Endogâmicos BALB C , Nanopartículas , Solanum tuberosum , Amido , Animais , Quitosana/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Amido/química , Solanum tuberosum/química , Capecitabina/administração & dosagem , Capecitabina/farmacologia , Humanos , Camundongos , Nanopartículas/química , Células HT29 , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/química , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Proliferação de Células/efeitos dos fármacos , Masculino
2.
Int J Biol Macromol ; 253(Pt 1): 126716, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37673158

RESUMO

This research seeks to optimize a chitosan-stabilized Pickering emulsion (PE) containing 5-fluorouracil (5-FU) as a potential Squamous Cell Carcinoma therapy. The 5-Fluorouracil was also thoroughly analysed using UV spectrophotometry and RP-HPLC, demonstrating exceptional linearity, sensitivity, precision, and robustness. The techniques of characterization revealed Pickering emulsion (PE) morphology, solid-like gel properties, successful encapsulation, and promising anticancer effects. FTIR was used to validate the efficacy of encapsulation, and DSC was used to confirm the post-encapsulation drug stability. The 0.6 % chitosan-stabilized PE showed exceptional stability and drug loading efficiency. Anti-EGFR-5-FU-CS-PE gel was developed for sustained drug release in the treatment of Squamous Cell Carcinoma. Anti-EGFR-5-FU-CS-PE demonstrated potent anticancer effects in vitro, with a lower IC50 than 5-FU and 5-FU-CS-PE. Anti-EGFR-5-FU-PE Pickering emulsions based on chitosan were investigated for their rheological properties, cellular interactions, and therapeutic potential. Both emulsions and gel exhibited sustained in vitro drug release after successful encapsulation. Anti-EGFR-5-FU-CS-PE induced apoptosis, decreased mitochondrial membrane potential, and inhibited the migration of cancer cells. Wistar mice were tested for safety and tumour growth inhibition. All formulations exhibited exceptional six-month stability. Anti-EGFR-5-FU-CS-PE emerges as a viable therapeutic option, necessitating additional research.


Assuntos
Carcinoma de Células Escamosas , Quitosana , Nanopartículas , Ratos , Camundongos , Animais , Fluoruracila/farmacologia , Ratos Wistar , Emulsões
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