Catiúscia P Oliveira1,2, Willian A Prado3, Vladimir Lavayen3, Sabrina L Büttenbender3, Aline Beckenkamp4, Bruna S Martins3, Diogo S Lüdtke3, Leandra F Campo3, Fabiano S Rodembusch3, Andréia Buffon4, Adalberto Pessoa5, Silvia S Guterres4, Adriana R Pohlmann6,7,8. 1. Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, 90610-000, RS, Brazil. catipadilha@yahoo.com.br. 2. Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, 91501-970, RS, Brazil. catipadilha@yahoo.com.br. 3. Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, 91501-970, RS, Brazil. 4. Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, 90610-000, RS, Brazil. 5. Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Prof. Lineu Prestes, 580, São Paulo, 05434-070, SP, Brazil. 6. Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, 90610-000, RS, Brazil. adriana.pohlmann@ufrgs.br. 7. Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, 91501-970, RS, Brazil. adriana.pohlmann@ufrgs.br. 8. Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, 91501-970, RS, Brazil. adriana.pohlmann@ufrgs.br.
Abstract
PURPOSE: This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors. METHODS: Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined. RESULTS: Bro-MLNC-Zn had z-average diameter of 135 nm and zeta potential of +23 mV. The complex is formed by a Zn-N chemical bond and a chelate with hydroxyl and carboxyl groups. Bromelain complexed at the nanocapsule surface maintained its proteolytic activity and showed anti-proliferative effect against human breast cancer cells (MCF-7) (72.6 ± 1.2% at 1.250 μg mL-1 and 65.5 ± 5.5% at 0.625 μg mL-1). Comparing Bro-MLNC-Zn and bromelain solution, the former needed a dose 160-folds lower than the latter for a similar effect. Tripan blue dye assay corroborated the results. CONCLUSIONS: The surface functionalization approach produced an innovative formulation having a much higher anti-proliferative effect than the bromelain solution, even though both in vitro proteolytic activity were similar, opening up a great opportunity for further studies in nanomedicine.
PURPOSE: This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors. METHODS: Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined. RESULTS:Bro-MLNC-Zn had z-average diameter of 135 nm and zeta potential of +23 mV. The complex is formed by a Zn-N chemical bond and a chelate with hydroxyl and carboxyl groups. Bromelain complexed at the nanocapsule surface maintained its proteolytic activity and showed anti-proliferative effect against humanbreast cancer cells (MCF-7) (72.6 ± 1.2% at 1.250 μg mL-1 and 65.5 ± 5.5% at 0.625 μg mL-1). Comparing Bro-MLNC-Zn and bromelain solution, the former needed a dose 160-folds lower than the latter for a similar effect. Tripan blue dye assay corroborated the results. CONCLUSIONS: The surface functionalization approach produced an innovative formulation having a much higher anti-proliferative effect than the bromelain solution, even though both in vitro proteolytic activity were similar, opening up a great opportunity for further studies in nanomedicine.
Entities:
Keywords:
MCF-7 human breast cancer cells; bromelain; lipid-core nanocapsules; metal-chitosan complex; surface-functionalized nanoparticles
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