Liquid crystalline nanogel targets skin cancer via low-frequency ultrasound treatment

Tatiana Aparecida Pereira; Danielle Nishida Ramos; Lays Martin Sobral; Yugo Araújo Martins; Raquel Petrilli; Márcia de Abreu Carvalho Fantini; Andréia Machado Leopoldino; Renata Fonseca Vianna Lopez

doi:10.1016/j.ijpharm.2023.123431

Liquid crystalline nanogel targets skin cancer via low-frequency ultrasound treatment

Int J Pharm. 2023 Nov 5:646:123431. doi: 10.1016/j.ijpharm.2023.123431. Epub 2023 Sep 20.

Authors

Tatiana Aparecida Pereira¹, Danielle Nishida Ramos², Lays Martin Sobral³, Yugo Araújo Martins⁴, Raquel Petrilli⁵, Márcia de Abreu Carvalho Fantini⁶, Andréia Machado Leopoldino⁷, Renata Fonseca Vianna Lopez⁸

Affiliations

¹ School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil. Electronic address: tatiana.pereira@uniube.br.
² School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil. Electronic address: ramos.dnr@gmail.com.
³ School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil. Electronic address: lays.martinsobral@cuanschutz.edu.
⁴ School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil. Electronic address: yugomartins@usp.br.
⁵ School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil; Institute of Health Sciences, University of International Integration of the Afro-Brazilian Lusophony, Redenção, Brazil. Electronic address: petrilliraquel@unilab.edu.br.
⁶ Institute of Physics, University of São Paulo, Rua do Matão 1371, 05508-090 São Paulo-SP, Brazil. Electronic address: mfantini@if.usp.br.
⁷ School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil. Electronic address: andreiaml@usp.br.
⁸ School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Av. Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil. Electronic address: rvianna@fcfrp.usp.br.

PMID: 37739094
DOI: 10.1016/j.ijpharm.2023.123431

Abstract

The potential of low-frequency ultrasound (LFU) combined with nanotechnology-based formulations in improving skin tumors topical treatment was investigated. The impact of solid lipid nanoparticles (SLN) and hydrophilic nanogels as coupling media on LFU-induced skin localized transport regions (LTR) and the penetration of doxorubicin (DOX) in LFU-pretreated skin was evaluated. SLN were prepared by the microemulsion technique and liquid crystalline nanogels using Poloxamer. In vitro, the skin was pretreated with LFU until skin resistivity of ∼1 KΩ.cm² using the various coupling media followed by evaluation of DOX penetration from DOX-nanogel and SLN-DOX in skin layers. Squamous cell carcinoma (SCC) induced in mice was LFU-treated using the nanogel with the LFU tip placed 5 mm or 10 mm from the tumor surface, followed by DOX-nanogel application. LFU with nanogel coupling achieved larger LTR areas than LFU with SLN coupling. In LFU-pretreated skin, DOX-nanogel significantly improved drug penetration to the viable epidermis, while SLN-DOX hindered drug transport through LTR. In vivo, LFU-nanogel pretreatment with the 10 mm tip distance induced significant tumor inhibition and reduced tumor cell numbers and necrosis. These findings suggest the importance of optimizing nanoparticle-based formulations and LFU parameters for the clinical application of LFU technology in skin tumor treatment.

Keywords: Doxorubicin; Low frequency ultrasound; Skin cancer therapy; Sonophoresis; Topical treatment.