Hypericin supramolecular assembles: A way to increase the skin availability and photodynamic efficiency in tumor cells

•Supramolecular assembly containing HY presented a better hydrophilic aspect (log P).•HY presented better cellular uptake after complexation with β-CD.•Two-time drug release was achieved after the complexation of HY into β-CD.•β-CDHY presented greater skin permeation compared to HY.•Higher phototoxicity is achieved with β-CDHY, proving its higher uptake into tumor cells. Cyclodextrins (CDs) are molecules approved by the FDA and show promise in increasing the solubility of hydrophobic molecules and making them more available to the skin. These CDs have been used to form complexes with some photosensitizers for Photodynamic Therapy (PDT), such as Hypericin (HY). HY is a lipophilic photosensitizer known for its exceptional fluorescence and singlet oxygen quantum yield generation of over 20 % under 590 nm irradiation. In this study, we found a six-fold increase in the release of HY in vitro after complexation with β-CD. The β-CDHY assembly also demonstrated better skin retention, which is crucial for the topical application of this photosensitizer. Furthermore, the β-CD complexation led to a significant increase in the phototoxicity of HY at three different light doses (3, 6, and 10 J cm−2) due to its improved water solubility and higher in vitro accumulation (approximately two times compared with free HY) in HeLa and Vero cell lines. [Display omitted]