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

Autor(es)

de Moura, Ludmilla David ^[1] ; Ribeiro, Ligia N. M. ^{[1, 2]} ; de Carvalho, Fabiola V. ^[1] ; Rodrigues da Silva, Gustavo H. ^[1] ; Lima Fernandes, Priscila C. ^[1] ; Brunetto, Sergio Q. ^[3] ; Ramos, Celso D. ^[3] ; Velloso, Licio A. ^[4] ; de Araujo, Daniele R. ^[5] ; de Paula, Eneida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, BR-13083862 Campinas, SP - Brazil

^[2] Fed Univ Uberlandia UFU, Inst Biotechnol, BR-38405319 Uberlandia, MG - Brazil

^[3] Univ Campinas UNICAMP, Dept Radiol, BR-13083887 Campinas, SP - Brazil

^[4] Univ Campinas UNICAMP, Sch Med Sci, Dept Clin Med, BR-13083887 Campinas, SP - Brazil

^[5] ABC Fed Univ UFABC, Human & Nat Sci Ctr, BR-09210580 Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICS; v. 13, n. 10 OCT 2021.
• Citações Web of Science: 0

Resumo

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 NLCDTX 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 NLCDTX and HGel-NLCDTX. Addition of LDC to the hybrid system (HGel-NLCDTX-LDC) increased cell death in tumor and normal cells. In vivo tests on C57BL/6J mice with B16-F10-induced melanoma indicated that LDC, NLCDTX, HGel-NLCDTX-LDC and NLCDTX + 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 NLCDTX or the hybrid system. These results confirm the adjuvant antitumor effect of lidocaine and endorse HGel-NLCDTX-LDC as a promising formulation for the topical treatment of melanoma.</p> (AU)

• Processo FAPESP: 19/17784-0 - Análise farmacocinética e de distribuição local no tecido-alvo de fármacos encapsulados em sistemas carreadores baseados em lipídios
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Regular