Topical delivery of seriniquinone for treatment of skin cancer and fungal infections is enabled by a liquid crystalline lamellar phase

Author(s):Show less -

Miguel, Rodrigo dos A. ; Hirata, Amanda S. ; Salata, Giovanna C. ; Apolinario, Alexsandra C. ; Barroso, Vinicius M. ; Ishida, Kelly ; Clair, James J. La ; Fenical, William ; Martins, Tereza S. ; Costa-Lotufo, Leticia V. ; Lopes, Luciana B.

• Document type: Journal article
• Source: European Journal of Pharmaceutical Sciences; v. 192, p. 14-pg., 2023-11-24.

Abstract

Seriniquinone (SQ) was initially described by our group as an antimelanoma drug candidate and now also as an antifungal drug candidate. Despite its promising in vitro effects, SQ translation has been hindered by poor watersolubility. In this paper, we described the challenging nanoformulation process of SQ, which culminated in the selection of a phosphatidylcholine-based lamellar phase (PLP1). Liposomes and nanostructured lipid carriers were also evaluated but failed to encapsulate the compound. SQ-loaded PLP1 (PLP1-SQ) was characterized for the presence of sedimented or non-dissolved SQ, rheological and thermal behavior, and irritation potential with hen's egg test on the chorioallantoic membrane (HET-CAM). PLP1 influence on transepidermal water loss (TEWL) and skin penetration of SQ was assessed in a porcine ear skin model, while biological activity was evaluated against melanoma cell lines (SK-MEL-28 and SK-MEL-147) and C. albicans SC5314. Despite the presence of few particles of non-dissolved SQ (observed under the microscope 2 days after formulation obtainment), PLP1 tripled SQ retention in viable skin layers compared to SQ solution at 12 h. This effect did not seem to relate to formulation-induced changes on the barrier function, as no increases in TEWL were observed. No sign of vascular toxicity in the HET-CAM model was observed after cutaneous treatment with PLP1. SQ activity was maintained on melanoma cells after 48 h-treatment (IC50 values of 0.59-0.98 mu M) whereas the minimum inhibitory concentration (MIC) against C. albicans after 24 h-treatment was 32-fold higher. These results suggest that a safe formulation for SQ topical administration was developed, enabling further in vivo studies. (AU)

• FAPESP's process: 22/15832-0 - Assessment of seriniquinone delivery to melanoma cells by poly (D,L-lactic-co-glycolic) acid (PLGA) nanoparticles
• Grantee: Rodrigo dos Anjos Miguel
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/11612-0 - Investigation of the antifungal activity and mechanism of action of 2-aryloxazolines derivatives on Candida albicans
• Grantee: Vinicius de Morais Barroso
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 20/09270-4 - Development of albumin nanoparticles as a vehicle of seriniquinone
• Grantee: Rodrigo dos Anjos Miguel
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/06613-8 - Characterization of seriniquinone mechanism of action in vemurafenibe resistant Melanoma cells
• Grantee: Amanda Soares Hirata
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/26048-6 - Development and application of multifunctional nanocarriers for intraductal delivery of chemotherapy aiming at Breast Cancer treatment
• Grantee: Giovanna Cassone Salata
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/05133-8 - Role of collagen receptors DDR in mechanosignaling and therapeutic resistance in melanoma
• Grantee: Amanda Soares Hirata
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds
• Grantee: Leticia Veras Costa Lotufo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 19/08582-5 - Multi-User Equipment approved in grant 17/17844-8: thermal analyzer - TG/DTA model sta 2500 TG/DTA room temperature to 1100 °c
• Grantee: Tereza da Silva Martins
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 21/01279-5 - Investigation of new targets and antifungal molecules on Candida spp. and Cryptococcus spp.
• Grantee: Kelly Ishida
• Support Opportunities: Regular Research Grants