Liposomal Avicequinone-B formulations: Aqueous solubility, physicochemical properties and apoptotic effects on cutaneous squamous cell carcinoma cells

Stephen Chu-Sung Hu; Yung-Shun Su; Yi-Chien Lai; Chih-Hua Tseng; Feng-Lin Yen

doi:10.1016/j.phymed.2019.152870

Liposomal Avicequinone-B formulations: Aqueous solubility, physicochemical properties and apoptotic effects on cutaneous squamous cell carcinoma cells

Phytomedicine. 2019 May:58:152870. doi: 10.1016/j.phymed.2019.152870. Epub 2019 Feb 18.

Authors

Stephen Chu-Sung Hu¹, Yung-Shun Su², Yi-Chien Lai³, Chih-Hua Tseng⁴, Feng-Lin Yen⁵

Affiliations

¹ Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Dermatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan.
³ Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. Electronic address: flyen@kmu.edu.tw.

PMID: 30903942
DOI: 10.1016/j.phymed.2019.152870

Abstract

Background: Avicequinone-B (Naphtho[2,3-b]furan-4,9-dione) is a furanonaphthoquinone derivative. It is a hydrophobic compound with poor aqueous solubility, which may restrict its potential pharmaceutical and biomedical applications.

Purpose: We synthesized different liposomal formulations of Avicequinone-B, and measured their particle size, aqueous solubility, and physicochemical properties. In addition, we investigated the anticancer activity of liposomal Avicequinone-B in human cutaneous squamous cell carcinoma (SCC) cells.

Methods: Liposomal Avicequinone-B formulations were synthesized using the thin-film hydration method. Drug yield, encapsulation efficiency and aqueous solubility were determined by high performance liquid chromatography. Particle size and polydispersity index were measured by submicron particle size analyzer, and ultrastructural morphology was visualized by transmission electron microscopy. Thermal transitions were determined by differential scanning calorimetry. Anti-skin cancer activity was determined in HSC-1 cells (human cutaneous SCC cell line) using the MTS cytotoxicity assay, apoptosis was assessed by caspase-3/7 activity assay, mitochondrial membrane potential was determined by JC-10 assay, and signal transduction pathways were evaluated by Western blot analysis.

Results: Liposomal Avicequinone-B formulations showed adequate yield and high encapsulation efficiency. These liposomal formulations produced small, uniformly sized nanoparticles, and greatly increased the aqueous solubility of Avicequinone-B. Differential scanning calorimetry showed loss of thermal phase transitions. In addition, liposomal Avicequinone-B showed significant cytotoxic effect on HSC-1 cells, through reduction of mitochondrial membrane potential, increased cytosolic cytochrome-c level, increased cleaved caspase 8 level, and induction of apoptosis. This was mediated through activation of ERK, p38 and JNK signaling pathways.

Conclusion: Liposomal Avicequinone-B demonstrated improved aqueous solubility and physicochemical characteristics, and induced apoptosis in cutaneous SCC cells. Therefore, liposomal Avicequinone-B may have potential uses as a topical anti-skin cancer drug formulation in the future.

Keywords: Apoptosis; Avicequinone-B; Cutaneous squamous cell carcinoma; Liposome; Solubility.

MeSH terms

Apoptosis / drug effects*
Benzoquinones / chemistry*
Benzoquinones / pharmacology
Calorimetry, Differential Scanning
Carcinoma, Squamous Cell / drug therapy*
Caspase 8 / drug effects
Caspase 8 / metabolism
Cell Line, Tumor
Drug Compounding*
Humans
Liposomes / chemistry*
Nanoparticles / chemistry
Particle Size
Skin Neoplasms / drug therapy*
Solubility
Water / chemistry

Substances

Benzoquinones
Liposomes
Water
quinone
Caspase 8