Development of nitrosyl ruthenium complex-loaded lipid carriers for topical administration: improvement in skin stability and in nitric oxide release by visible light irradiation.
The prominent nitric oxide (NO) donor [Ru(terpy)(bdqi)NO](PF(6))(3) has been synthesized and evaluated with respect to noteworthy biological effects due to its NO photorelease, including vascular relaxation and melanoma cell culture toxicity. The potential for delivering NO in therapeutic quantities is tenable since the nitrosyl ruthenium complex (NRC) must first reach the "target tissue" and then release the NO upon stimulus. In this context, NRC-loaded lipid carriers were developed and characterized to further explore its topical administration for applications such as skin cancer treatment. NRC-loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers were prepared via the microemulsification method, with average diameters of 275+/-15 nm and 211+/-31 nm and zeta potentials of -40.7+/-10.4 mV and -50.0+/-7.5 mV, respectively. In vitro kinetic studies of NRC release from nanoparticles showed sustained release of NRC from the lipid carriers and illustrated the influence of the release medium and the lyophilization process. Stability studies showed that NO is released from NRC as a function of temperature and time and due to skin contact. The encapsulation of NRC in SLN followed by its lyophilization, significantly improved the complex stability. Furthermore, of particular interest was the fact that in the NO photorelease study, the NO release from the NRC-loaded SLN was approximately twice that of just NRC in solution. NRC-loaded SLN performs well enough at releasing and protecting NO degradation in vitro that it is a promising carrier for topical delivery of NO.
Marquele-Oliveira
Franciane
F
Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto, SP, Brazil.
Santana
Danielle Cristine de Almeida
DC
Taveira
Stephânia Fleury
SF
Vermeulen
Deise Mirella
DM
de Oliveira
Anderson Rodrigo Moraes
AR
da Silva
Roberto Santana
RS
Lopez
Renata Fonseca Vianna
RF
D000287:Administration, Topical; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D008027:Light; D008055:Lipids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000737:chemistry*; D010777:Photochemistry; D017975:Ruthenium Compounds / Q000008:administration & dosage / Q000737:chemistry*; D012878:Skin Neoplasms / Q000188:drug therapy; D013552:Swine
D004337:Drug Carriers; D008055:Lipids; D020030:Nitric Oxide Donors; D017975:Ruthenium Compounds; D009569:Nitric Oxide