Exploiting supramolecular interactions to produce bevacizumab-loaded nanoparticles for potential mucosal delivery

Autor: Denis Ricardo Martins de Godoi, Thiago V. Seraphim, Júlio César Borges, Natália Noronha Ferreira, Charlene P. Kiill, Hilde Harb Buzzá, Leonardo M.B. Ferreira, Maria Palmira Daflon Gremião, Douglas de Britto, Jovan D. Alonso, Odilio B. G. Assis
Přispěvatelé: Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
Popis: Made available in DSpace on 2018-12-11T16:52:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-01 Monoclonal antibody (mAb) delivery is gaining importance for local, systemic, and route-specific targeting. The mucus constitutes the main barrier for this type of delivery. In the present study, we aimed to develop a drug delivery platform by integrating mucus penetrating and mucoadhesive agents into a single system. Our hypothesis is that by combining these opposing functions, this system could have its properties modulated according to specific purposes. Self-assembly studies were conducted using three classes of building blocks: the protein drug bevacizumab (BVZ), mucus-penetrating polyanion dextran sulfate (DS), mucoadhesive polycations trimethylchitosan (TMC) and chitosan oligosaccharides (COS). We obtained two types of nanoparticles by manipulating supramolecular interactions between the components. Binary protein-polyanion (BVZ/DS) nanoparticles showed size of approximately 150 nm and a negative zeta potential. Ternary protein-polyanion-polycation (BVZ/DS/COS) nanoparticles were obtained using COS and exhibited 350 nm and a positive zeta potential. Assisted by calorimetric information, we demonstrated that building stable ternary nanoparticles carrying positive charges were not possible using the polycation TMC due to its thermodynamic constraints. Furthermore, spectroscopy analysis and CAM assay indicated that BVZ continued structurally and functionally stable after its incorporation into the nanoparticles. These two types of nanoparticles exhibited different behaviors when interacting with mucin, as shown by DLS and AFM studies. While the negatively charged particles promoted dispersion of the mucin network, suggesting a mucus penetrating effect of DS, the positively charged particles formed aggregates, probably caused by the mucoadhesive effect of COS. These results highlight the importance of understanding the role of supramolecular interactions, responsible for forming drug delivery systems containing complex molecules, such as proteins and polymers. School of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 1 Institute of Chemistry of Araraquara São Paulo State University UNESP Biophotonics Laboratory São Carlos Institute of Physics University of São Paulo (USP) EMBRAPA, Semi-Arid, Rodovia BE-428, Km 152, P.O. Box 23 EMBRAPA Instrumentation Rua XV de Novembro, 1.452, P.O. Box 741 Institute of Chemistry of São Carlos University of São Paulo USP School of Pharmaceutical Science São Paulo State University UNESP, Rodovia Araraquara/Jaú Km 1 Institute of Chemistry of Araraquara São Paulo State University UNESP
Databáze: OpenAIRE
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