A Microfluidic Co-Flow Route for Human Serum Albumin-Drug-Nanoparticle Assembly

Autor(es)

Hakala, Tuuli A. ^[1] ; Davies, Sarah ^[1] ; Toprakcioglu, Zenon ^[1] ; Bernardim, Barbara ^[1] ; Bernardes, Goncalo J. L. ^{[1, 2]} ; Knowles, Tuomas P. J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW - England

^[2] Univ Lisbon, Fac Med, Inst Med Mol, Ave Prof Egas Moniz, P-1649028 Lisbon - Portugal

• Tipo de documento: Artigo Científico
• Fonte: CHEMISTRY-A EUROPEAN JOURNAL; v. 26, n. 27 APR 2020.
• Citações Web of Science: 0

Resumo

Nanoparticles are widely studied as carrier vehicles in biological systems because their size readily allows access through cellular membranes. Moreover, they have the potential to carry cargo molecules and as such, these factors make them especially attractive for intravenous drug delivery purposes. Interest in protein-based nanoparticles has recently gained attraction due to particle biocompatibility and lack of toxicity. However, the production of homogeneous protein nanoparticles with high encapsulation efficiencies, without the need for additional cross-linking or further engineering of the molecule, remains challenging. Herein, we present a microfluidic 3D co-flow device to generate human serum albumin/celastrol nanoparticles by co-flowing an aqueous protein solution with celastrol in ethanol. This microscale co-flow method resulted in the formation of nanoparticles with a homogeneous size distribution and an average size, which could be tuned from approximate to 100 nm to 1 mu m by modulating the flow rates used. We show that the high stability of the particles stems from the covalent cross-linking of the naturally present cysteine residues within the particles formed during the assembly step. By choosing optimal flow rates during synthesis an encapsulation efficiency of 75 +/- 24 % was achieved. Finally, we show that this approach achieves significantly enhanced solubility of celastrol in the aqueous phase and, crucially, reduced cellular toxicity. (AU)

• Processo FAPESP: 15/07509-1 - Modificação específica de proteínas via reação de Horner-Wadsworth-Emmons seguida de rearranjo de Wolff
• Beneficiário: Barbara Bernardim de Souza
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 17/13168-8 - Construção de conjugados anticorpo-droga quimicamente definidos utilizando reagentes carbonilacrílicos
• Beneficiário: Barbara Bernardim de Souza
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado