Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules
Cecilia B. Michalowski,
Marcelo D. Arbo,
Louise Altknecht,
Andréia N. Anciuti,
Angélica S. G. Abreu,
Luciana M. R. Alencar,
Adriana R. Pohlmann,
Solange C. Garcia,
Sílvia S. Guterres
Affiliations
Cecilia B. Michalowski
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, Brazil
Marcelo D. Arbo
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, Brazil
Louise Altknecht
Laboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegre 90610-000, Brazil
Andréia N. Anciuti
Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, Porto Alegre 90035-003, Brazil
Angélica S. G. Abreu
Laboratório de Microscopia Avançada, Departamento de Física, Universidade Federal do Ceara, Campus do Pici, Fortaleza 60455-900, Brazil
Luciana M. R. Alencar
Laboratório de Microscopia Avançada, Departamento de Física, Universidade Federal do Ceara, Campus do Pici, Fortaleza 60455-900, Brazil
Adriana R. Pohlmann
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, Brazil
Solange C. Garcia
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, Brazil
Sílvia S. Guterres
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752, Porto Alegr 90610-000, Brazil
Multi-wall lipid-core nanocapsule (MLNC) functionalized with captopril and nanoencapsulating furosemide within the core was developed as a liquid formulation for oral administration. The nanocapsules had mean particle size below 200 nm, showing unimodal and narrow size distributions with moderate dispersity (laser diffraction and dynamic light scattering). Zeta potential was inverted from −14.3 mV [LNC-Fur(0,5)] to +18.3 mV after chitosan coating. Transmission electron microscopy and atomic force microscopy showed spherical structures corroborating the nanometric diameter of the nanocapsules. Regarding the systolic pressure, on the first day, the formulations showed antihypertensive effect and a longer effect than the respective drug solutions. When both drugs were associated, the anti-hypertensive effect was prolonged. On the fifth day, a time effect reduction was observed for all treatments, except for the nanocapsule formulation containing both drugs [Capt(0.5)-Zn(25)-MLNC-Fur(0.45)]. For diastolic pressure, only Capt(0.5)-Zn(25)-MLNC-Fur(0.45) presented a significant difference (p < 0.05) on the first day. On the fifth day, both Capt(0.5)-MLNC-Fur(0.45) and Capt(0.5)-Zn(25)-MLNC-Fur(0.45) had an effect lasting up to 24 h. The analysis of early kidney damage marker showed a potential protection in renal function by Capt(0.5)-Zn(25)-MLNC-Fur(0.45). In conclusion, the formulation Capt(0.5)-Zn(25)-MLNC-Fur(0.45) proved to be suitable for hypertension treatment envisaging an important innovation.
