RESUMO
In general, colloids provide increased cutaneous permeation of drugs. Still, skin interaction and main pathways for drug diffusion may vary depending on system and formulation characteristics. The knowledge of how different colloidal systems interact with biological membranes and the formulation impact on delivery is especially relevant for drugs that can be encapsulated in multiple nanosystems, as voriconazole (VOR). In here, we compared VOR release and permeation profile from liposomes (LP) and nanostructured lipid carriers (NLC) in aqueous colloidal dispersions and in gel formulations. Despite the controlled drug release provided by gel formulations, formulation only had a significant impact on drug skin accumulation from LP. The reduced mobility in gel formulations compromised follicle deposition and drug retention in the skin. Such a hypothesis was confirmed by permeation experiments evaluating follicle pathway influence. Follicular route also had an influence on delivery from NLC, which was only significant for total drug that reached the acceptor medium. These differences could be attributed to the mechanisms of colloid interaction with the skin and subsequent drug release. Follicle LP deposition and slow drug release leads to higher cutaneous amounts whilst NLC interaction with skin and fast drug release leads to fast drug diffusion and deeper penetration. By the low MIC50 values encountered against Trichophyton rubrum (⼠0.001⯵g/mL), permeated amounts could inhibit fungal growth, regardless the system. In conclusion, both LP and NLC seem to be valuable systems for cutaneous VOR delivery. Fluidic formulations could provide better efficiency for cutaneous drug delivery from LP.
Assuntos
Antifúngicos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanoestruturas/química , Voriconazol/administração & dosagem , Administração Cutânea , Antifúngicos/química , Antifúngicos/farmacologia , Difusão , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Lipossomos/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de Superfície , Trichophyton/efeitos dos fármacos , Trichophyton/crescimento & desenvolvimento , Voriconazol/química , Voriconazol/farmacologiaRESUMO
Topotecan is an important cytotoxic drug that has gained broad acceptance in clinical use for the treatment of refractory ovarian and small-cell lung cancer. The lactone active form of topotecan can be hydrolyzed in vivo, decreasing the drug's therapeutic efficacy. Lipid encapsulation may promote in vivo stabilization by removing topotecan from aqueous media. Earlier reports of topotecan lipid nanoencapsulation have focused on liposomal encapsulation; however, the higher stability and cost-effectiveness of solid lipid nanoparticles (SLN) highlight the potential of these nanoparticles as an advantageous carrier for topotecan. The initial motivation for this work was to develop, for the first time, solid lipid nanoparticles and nanostructured lipid carriers (NLC) with a high drug loading for topotecan. A microemulsion technique was employed to prepare SLNs and NLCs and produced homogeneous, small size, negatively charged lipid nanoparticles with high entrapment efficiency and satisfactory drug loading. However, low recovery of topotecan was observed when the microemulsion temperature was high and in order to obtain high quality nanoparticles, and precise control of the microemulsion temperature is critical. Nanoencapsulation sustained topotecan release and improved its chemical stability and cytotoxicity. Surprisingly, there were no significant differences between the NLCs and SLNs, and both are potential carriers for topotecan delivery.