Desenvolvimento de formulações semissólidas contendo topotecano encapsulado em carreadores lipídicos nanoestruturados para aplicação tópica
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Data
2015-09-30
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Universidade Federal de Goiás
Resumo
Topotecan (TPT) is a potent cytotoxic agent used in the treatment of various tumors, and
studies have reported its effectiveness in the treatment of melanoma. Local treatment of
melanoma with TPT appears to be a viable alternative since conventional treatments result in
scarring, pain, inflammation and possible recurrence. However, the permeation of hydrophilic
drugs such as TPT, is quite difficult. The encapsulation of the drug into nanostructured lipid
carriers (NLC) may facilitate TPT permeation to deeper skin layers. Therefore, the final
formulation shall provide appropriate viscosity for easy application and remain in the desired
location. Thus, the objective was to incorporate the CLN-TPT in hydrogels hydroxyethyl
cellulose (NLC-TPT-HEC) and chitosan (NLC-TPT-QUIT) and evaluate the skin permeation of
the merged formulations or not in gels. NLC were incorporated into the hydrogels and were
characterized as mean diameter, polydispersity index (PdI), zeta potential, drug recovery
(REC%) and encapsulation efficiency (EE%). The release profiles and in vitro permeation
studies were carried out in Franz-type diffusion cells using synthetic membrane and porcine
ear skin, respectively. To quantify the TPT, high-performance liquid chromatography (HPLC)
was used and a method for its extraction and quantitation in different skin layers was
developed. The NLC-TPT-HEC and NLC-TPT-QUIT obtained respectively mean diameters of
117.8 nm and 183.2 nm; PdI of 0.32 and 0.33 and zeta potential -12,0mV and 75,0mV.
Approximately 60% of TPT was recovered at the end of the preparation of formulations and
EE% remained higher than 85% after the incorporation of the particles in the gels. The NLCTPT-HEC and NLC-TPT-QUIT demonstrated a significantly lower drug release (p <0.05) than
the drug incorporated in the hydrogel and in NLC aqueous dispersion, demonstrating a
potentiation in controlling the release of TPT. The NLC-TPT formulations CLN-TPT-HEC and
CLN-TPT-QUIT increased respectively 1.93, 2.37 and 2.06 times the permeation of the drug
into the deeper layers of the skin, compared to unloaded drug in same formulations. The NLCTPT-HEC / QUIT showed a lower permeation of the drug into the deeper skin layers when
compared with the CLN-TPT dispersed in water. The controlled release resulted in a lower
amount of drug available for permeation. Thus, the formulations allow control of permeation
through the control of the drug release, which can meet different needs. The gel QUIT, for
example, decreased the amount of drug retained in the EC and increases the amount of TPT
permeated to the deeper layers. The developed formulations have potential use for topical
treatment of melanoma.
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Citação
GOMES, J. H. V. Desenvolvimento de formulações semissólidas contendo topotecano encapsulado em carreadores lipídicos nanoestruturados para aplicação tópica. 2015. 79 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2015.