Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma

Pharmaceutics

Lício A. Velloso¹  Priscila C. Lima Fernandes²  Gustavo H. Rodrigues da Silva²  Ludmilla David de Moura²  Lígia N. M. Ribeiro²  Fabíola V. de Carvalho²  Eneida de Paula²  Daniele R. de Araújo³  Sérgio Q. Brunetto⁴  Celso D. Ramos⁴ 

[1] Clinical Medicine Department, School of Medicine Science, University of Campinas—UNICAMP, Campinas 13083-887, SP, Brazil;Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil;Human and Natural Science Center, ABC Federal University—UFABC, Santo André 09210-580, SP, Brazil;Radiology Department, University of Campinas—UNICAMP, Campinas 13083-887, SP, Brazil;

关键词: nanostructured lipid carriers;    hydrogel;    lidocaine;    docetaxel;    melanoma;   

DOI  :  10.3390/pharmaceutics13101552

来源: DOAJ

【 摘 要 】

Melanoma is the most aggressive skin carcinoma and nanotechnology can bring new options for its pharmacological treatment. Nanostructured lipid carriers (NLC) are ideal drug-delivery carriers for hydrophobic drugs, such as the antineoplastic docetaxel (DTX), and hybrid (NLC-in-hydrogel) systems are suitable for topical application. This work describes a formulation of NLC_DTX in xanthan-chitosan hydrogel containing lidocaine (LDC) with anticancer and analgesia effects. The optimized nanoparticles encapsulated 96% DTX and rheological analysis revealed inherent viscoelastic properties of the hydrogel. In vitro assays over murine fibroblasts (NIH/3T3) and melanoma cells (B16-F10), human keratinocytes (HaCaT) and melanoma cells (SK-MEL-103) showed reduction of docetaxel cytotoxicity after encapsulation in NLC_DTX and HGel-NLC_DTX. Addition of LDC to the hybrid system (HGel-NLC_DTX-LDC) increased cell death in tumor and normal cells. In vivo tests on C57BL/6J mice with B16-F10-induced melanoma indicated that LDC, NLC_DTX, HGel-NLC_DTX-LDC and NLC_DTX + HGel-LDC significantly inhibited tumor growth while microPET/SPECT/CT data suggest better prognosis with the hybrid treatment. No adverse effects were observed in cell survival, weight/feed-consumption or serum biochemical markers (ALT, AST, creatinine, urea) of animals treated with NLC_DTX or the hybrid system. These results confirm the adjuvant antitumor effect of lidocaine and endorse HGel-NLC_DTX-LDC as a promising formulation for the topical treatment of melanoma.

【 授权许可】

Unknown