Hypericin-loaded oil-in-water nanoemulsion synthesized by ultrasonication process enhances photodynamic therapy efficiency

Author(s)

Ma, Hui Ling ^{[1, 2]} ; Varanda, Laudemir Carlos ^[1] ; Perussi, Janice Rodrigues ^[1] ; Carrilho, Emanuel ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

^[2] Inst Nacl Ciencia & Tecnol Bioanalit INCTBio, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY; v. 223, OCT 2021.
• Web of Science Citations: 0

Abstract

Hypericin (Hy) is a hydrophobic photosensitizer used in photodynamic therapy for cancer therapeutic. In this study, Hy-loaded oil-in-water (O/W) nanoemulsions (NEs) were produced by the ultrasonication method combing different biocompatible oils and surfactants to enhance Hy aqueous solubility and bioavailability. Experimental parameters were optimized by the characterization of droplet size, zeta potential, and physicochemical properties. In vitro studies based on the release profile, cytotoxicity, cell morphology, and Hy intracellular accumulation were assayed. Hy at 100 mg L-1 was incorporated into the low viscosity (similar to 0.005 Pa s) NEs with spherical droplets averaging 20-40 nm in size and polydispersity index <0.02. Hy release from the NE was significantly higher (4-fold) than its suspension (p < 0.001). The NEs demonstrated good physical stability during storage at 5 degrees C for at least six months. The Hy-loaded NEs exhibited an IC50 value 6-fold lower than Hy suspension during PDT against breast cancer cell lines (MCF-7). Cell microscopy imaging confirmed the increased cytotoxic effects of Hy-loaded NEs, showing damaged and apoptotic cells. Confocal laser scanning microscopy evidenced greater Hy delivery through NE into MCF-7 cells followed by improved intracellular ROS generation. Our results suggest that the Hy-loaded NEs can improve hypericin efficacy and assist Hy-PDT's preclinical development as a cancer treatment. (AU)

• FAPESP's process: 13/01284-2 - Theranostic nanoparticles based in superparamagnetic iron oxide for skin cancer therapy by magnetic hyperthermia
• Grantee: Laudemir Carlos Varanda
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07276-1 - CEPOF - Optics and Photonic Research Center
• Grantee: Vanderlei Salvador Bagnato
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants