Bifunctional Therapeutic Application of Low-Frequency Ultrasound Associated with Zinc Phthalocyanine-Loaded Micelles

Autor(es)

Martins, Yugo A. ^[1] ; Fonseca, V, Maria J. ; Pavan, Theo Z. ^[2] ; Lopez, V, Renata F.

Afiliação do(s) autor(es)

^[1] V, Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Av Do Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Philosophy Sci & Letters Ribeirao Preto, BR-14090900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 15, p. 8075-8095, 2020.
• Citações Web of Science: 0

Resumo

Purpose: Sonodynamic therapy (SDT) is a new therapeutic modality for the noninvasive cancer treatment based on the association of ultrasound and sonosensitizer drugs. Topical SDT requires the development of delivery systems to properly transport the sonosensitizer, such as zinc phthalocyanine (ZnPc), to the skin. In addition, the delivery system itself can participate in sonodynamic events and influence the therapeutic response. This study aimed to develop ZnPc-loaded micelle to evaluate its potential as a topical delivery system and as a cavitational agent for low-frequency ultrasound (LFU) application with the dual purpose of promoting ZnPc skin penetration and generating reactive oxygen species (ROS) for SDT. Methods: ZnPc-loaded micelles were developed by the thin-film hydration method and optimized using the Quality by Design approach. Micelles' influence on LFU-induced cavitation activity was measured by potassium iodide dosimeter and aluminum foil pits experiments. In vitro skin penetration of ZnPc was assessed after pretreatment of the skin with LFU and simultaneous LFU treatment using ZnPc-loaded micelles as coupling media followed by 6 h of passive permeation of ZnPc-loaded micelles. The singlet oxygen generation by LFU irradiation of the micelles was evaluated using two different hydrophilic probes. The lipid peroxidation of the skin was estimated using the malondialdehyde assay after skin treatment with simultaneous LFU using ZnPc-loaded micelles. The viability of the B16F10 melanoma cell line was evaluated using resazurin after treatment with different concentrations of ZnPc-loaded micelles irradiated or not with LFU. Results: The micelles increased the solubility of ZnPc and augmented the LFU-induced cavitation activity in two times compared to water. After 6 h ZnPc-loaded micelles skin permeation, simultaneous LFU treatment increased the amount of ZnPc in the dermis by more than 40 times, when compared to non-LFU-mediated treatment, and by almost 5 times, when compared to LFU pretreatment protocol. The LFU irradiation of micelles induced the generation of singlet oxygen, and the lipoperoxidation of the skin treated with the simultaneous LFU was enhanced in three times in comparison to the non-LFU-treated skin. A significant reduction in cell viability following treatment with ZnPc-loaded micelles and LFU was observed compared to blank micelles and non-LFU-treated control groups. Conclusion: LFU-irradiated mice can be a potential approach to skin cancer treatment by combining the functions of increasing drug penetration and ROS generation required for SDT. (AU)

• Processo FAPESP: 14/22451-7 - Sistemas de liberação sustentada e direcionada de fármacos para o tecido epitelial
• Beneficiário: Renata Fonseca Vianna Lopez
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/17442-7 - Avaliação do potencial do ultrassom de baixa frequência para a terapia sonodinâmica de tumores cutâneos
• Beneficiário: Yugo Araújo Martins
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático