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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Docetaxel and Lidocaine Co-Loaded (NLC-in-Hydrogel) Hybrid System Designed for the Treatment of Melanoma
Author
de Moura, Ludmilla David 1   VIAFID ORCID Logo  ; Ribeiro, Lígia N M 2   VIAFID ORCID Logo  ; de Carvalho, Fabíola V 1   VIAFID ORCID Logo  ; Gustavo H Rodrigues da Silva 1   VIAFID ORCID Logo  ; Lima Fernandes, Priscila C 1 ; Brunetto, Sérgio Q 3 ; Ramos, Celso D 3 ; Velloso, Lício A 4 ; de Araújo, Daniele R 5   VIAFID ORCID Logo  ; Eneida de Paula 1   VIAFID ORCID Logo 

 Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil; [email protected] (L.D.d.M.); [email protected] (L.N.M.R.); [email protected] (F.V.d.C.); [email protected] (G.H.R.d.S.); [email protected] (P.C.L.F.) 
 Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas—UNICAMP, Campinas 13083-862, SP, Brazil; [email protected] (L.D.d.M.); [email protected] (L.N.M.R.); [email protected] (F.V.d.C.); [email protected] (G.H.R.d.S.); [email protected] (P.C.L.F.); Institute of Biotechnology, Federal University of Uberlândia—UFU, Uberlândia 38405-319, MG, Brazil 
 Radiology Department, University of Campinas—UNICAMP, Campinas 13083-887, SP, Brazil; [email protected] (S.Q.B.); [email protected] (C.D.R.) 
 Clinical Medicine Department, School of Medicine Science, University of Campinas—UNICAMP, Campinas 13083-887, SP, Brazil; [email protected] 
 Human and Natural Science Center, ABC Federal University—UFABC, Santo André 09210-580, SP, Brazil; [email protected] 
First page
1552
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
19994923
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2584453566
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.