A surface modification of clozapine-loaded nanocapsules improves their efficacy: A study of formulation development and biological assessment.
This work aimed to develop nanocapsules (NC) coated with polysorbate 80 (P80), cationic chitosan (CS) or polyethylene glycol (PEG) using clozapine (CZP) as the drug model. The zeta potential, pH and encapsulation efficiency were directly affected by the CS coating. Using the bag dialysis method, the in vitro CZP release from CS-coated nanocapsules was similar to the PEG-coated at pH 7.4. Nanocapsules coated with PEG and CS exhibited an increased action duration compared to the P80-coated nanocapsules in pseudo-psychosis induced by d,l-amphetamine in rats. When comparing both groups, the group administered CS-coated nanocapsules showed better activity than the PEG-coated nanocapsules at 6, 10 and 12h after d,l-amphetamine administration. The pharmacokinetic assessment in rats demonstrated that the observed half-lives were free CZP<P80-coated<PEG-coated ̴ CS-coated nanocapsules. Both the P80- and PEG-coated nanocapsules showed a statistically significant increase in their volume of distribution compared to free CZP. On the other hand, the cationic nanocapsules showed a decrease in total clearance. Together, these results indicate that the PEG and CS coatings are a promising delivery system for CZP in the treatment of schizophrenia.
Curso de Farmácia, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil.
Simone M
SM
Vieira
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil.
Luana R
LR
Michels
Programa de Pós-Graduação em Farmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Av. Roraima 1000, Prédio 21, Sala 5220, Santa Maria, CEP 97105-900 RS, Brazil.
Katiane
K
Roversi
Programa de Pós-Graduação em Farmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Av. Roraima 1000, Prédio 21, Sala 5220, Santa Maria, CEP 97105-900 RS, Brazil.
Vinícia G
VG
Metz
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil.
Barbra K S
BKS
Moraes
Curso de Farmácia, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil.
Eduarda M
EM
Piegas
Curso de Farmácia, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil.
Rodrigo J
RJ
Freddo
Campus Bagé, Universidade Federal do Pampa, Travessa 45, 1650 Bagé, CEP96413-170 RS, Brazil.
André
A
Gundel
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, CEP 90610-000 RS, Brazil.
Teresa Dalla
TD
Costa
Programa de Pós-Graduação em Farmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Av. Roraima 1000, Prédio 21, Sala 5220, Santa Maria, CEP 97105-900 RS, Brazil.
Marilise E
ME
Burger
Curso de Farmácia, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil; Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil.
Letícia M
LM
Colomé
Curso de Farmácia, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil; Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Pampa-UNIPAMPA, BR 472, Km 592, CP 118, CEP 97500-970 Uruguaiana, RS, Brazil. Electronic address: sandrahaas@unipampa.edu.br.
Sandra E
SE
Haas
D048271:Chitosan / Q000737:chemistry; D003024:Clozapine / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D053769:Nanocapsules / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry
D004337:Drug Carriers; D053769:Nanocapsules; D011136:Polysorbates; D011092:Polyethylene Glycols; D048271:Chitosan; D003024:Clozapine
Chitosan; Clozapine; Nanocapsules; Polyethylene glycol; Polysorbate 80