Cyano-phycocyanin is one of the active pigments of the blue-green algae and is usually isolated from the filamentous cyanobacteria Arthrospira platensis Gomont (Spirulina). Due to its multiple physiological functions and non-toxicity, cyano-phycocyanin may be a potential substance for the topical treatment of various skin diseases. Considering that the conventional medicine faces drug resistance, insufficient efficacy and side effects, the plant origin compounds can act as an alternative option. Thus, the aim of this paper was to review the wound healing, antimicrobial, antioxidative, anti-inflammatory, antimelanogenic and anticancer properties and mechanisms of cyano-phycocyanin topical activities on human skin. Moreover, possible applications and biotechnological requirements for pharmaceutical forms of cyano-phycocyanin for the treatment of various skin diseases are discussed in this review.

Cyano-phycocyanin (C-PC) is a light-absorbing biliprotein found in cyanobacteria, commonly known as blue-green algae. Due to its antioxidative, anti-inflammatory, and anticancer properties, this protein is a promising substance in medicine and pharmaceuticals. However, cyanobacteria tend to bind heavy metals from the environment, making it necessary to ensure the safety of C-PC for the development of pharmaceutical products, with C-PC isolated from naturally collected cyanobacterial biomass. This study aimed to determine the content of the most toxic heavy metals, arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in C-PC isolated from different cyanobacterial biomasses collected in the Kaunas Lagoon during 2019–2022, and compare them with the content of heavy metals in C-PC isolated from cultivated Spirulina platensis (S. platensis). Cyanobacteria of Aphanizomenon flos-aquae (A. flos-aquae) dominated the biomass collected in 2019, while the genus Microcystis dominated the biomasses collected in the years 2020 and 2022. Heavy metals were determined using inductively coupled plasma mass spectrometry (ICP-MS). ICP-MS analysis revealed higher levels of the most investigated heavy metals (Pb, Cd, and As) in C-PC isolated from the biomass with the dominant Microcystis spp. compared to C-PC isolated from the biomass with the predominant A. flos-aquae. Meanwhile, C-PC isolated from cultivated S. platensis exhibited lower concentrations of As and Pb than C-PC isolated from naturally collected cyanobacterial biomass.

This study aimed to develop and evaluate cyano-phycocyanin (C-PC)-loaded enriched transfersomes for topical application, improved skin delivery, and antioxidant protection. The main objective was to overcome the limitations associated with C-PC's instability and poor skin permeability due to its high molecular weight and hydrophilicity. Six formulations were prepared using an organic solvent-free two-step method: glycerol-enriched transfersomes (Gly-transfersomes),glycerol and cholesterol-enriched transfersomes (Gly-chol-transfersomes),hyaluronate-enriched transfersomes (Hyal-transfersomes),hyaluronate and cholesterol-enriched transfersomes (Hyal-chol-transfersomes),glycerol and hyaluronate-enriched transfersomes (Hyal-gly-transfersomes), anda combination of all three (Hyal-gly-chol-transfersomes). Empty vesicles were prepared via direct sonication, then C-PC was gently loaded using mild sonication in a temperature-controlled ultrasonic bath. All formulations demonstrated properties suitable for skin delivery, with mean diameters <115 nm, polydispersity indexes <0.2, and zeta potential below -30 mV. Cryo- transmission electron microscopy confirmed spherical, unilamellar or oligolamellar morphology. Gly- and Gly-chol-transfersomes exhibited the highest encapsulation efficiency (∼52 %) and remained stable for up to 8 months at 4 °C. Antioxidant activity of C-PC (∼23-27 μmol TE/g of dry C-PC) was confirmed via DPPH assay. Biological tests on HaCaT cells exposed to H₂O₂-induced oxidative stress showed ∼80 % cell viability after treatment with C-PC formulations, compared to ∼60 % in untreated cells, indicating cytoprotective activity. Ex vivo skin penetration studies revealed significantly higher C-PC accumulation in the epidermis especially for Gly- and Gly-chol-transfersomes versus aqueous C-PC. These findings confirm the potential of enriched transfersomes as effective carriers to improve the skin delivery and bioactivity of C-PC in antioxidant skin care formulations.

Background: This study explored the most suitable materials for incorporating cyano-phycocyanin (C-PC) into hydrogels, focusing on maintaining the C-PC’s long-term structural integrity and stabilityNext, the release of C-PC from the hydrogels and its skin penetration were investigated. Methods: A series of 1% (w/w) C-PC hydrogels was prepared using various gelling agents and preservatives. Spectrophotometric measurements compared the amount of C-PC in the hydrogels to the initially added amount. After selecting the most suitable gelling agent and preservative, two C-PC hydrogels, with and without propylene glycol (PG) (Sigma-Aldrich, St. Louis, MO, USA), were produced for further testing. In vitro release studies utilized modified Franz-type diffusion cells, while ex vivo skin-permeation studies employed Bronaugh-type cells and human skin. Confocal laser scanning microscopy analyzed C-PC accumulation in the skin. Results: The findings demonstrated that sodium alginate (Sigma-Aldrich, St. Louis, MO, USA), hydroxyethyl cellulose (HEC) (Sigma-Aldrich, St. Louis, MO, USA), and Soligel^TM (Givaudan, Vernier, Switzerland) are effective biopolymers for formulating hydrogels while maintaining C-PC stability. After 6 h, C-PC release from the hydrogel containing PG was approximately 10% or 728.07 (±19.35) μg/cm², significantly higher than the nearly 7% or 531.44 (±26.81) μg/cm² release from the hydrogel without PG (p < 0.05). The ex vivo qualitative skin-permeation study indicated that PG enhances C-PC penetration into the outermost skin layer. Conclusion: PG’s ability to enhance the release of C-PC from the hydrogel, coupled with its capacity to modify the skin barrier ex vivo, facilitates the penetration of C-PC into the stratum corneum.

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) develops through inflammation-driven preneoplastic alterations characterized by epidermal hyperplasia, dysplasia, and increased proliferative activity. C-phycocyanin (C-PC) possesses antioxidant and anti-inflammatory properties; however, its topical potential to attenuate a tumour-promoting cutaneous microenvironment is limited by poor skin penetration. This study evaluated the effects of C-PC-loaded transfersomes in a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse model of skin carcinogenesis. Methods: Male BALB/c mice were assigned to six groups (n = 10 per group). Carcinogenesis was initiated with a single topical application of DMBA, followed by twice-weekly TPA application for 16 weeks. C-PC-loaded transfersomes (1 mg/mL or 10 mg/mL) were applied topically. Histopathological assessment included epidermal thickness, rete ridge depth, mitotic activity, mast cell density, and semi-quantitative scoring of hyperplasia, dysplasia, and inflammation. Ki-67 immunohistochemistry was used to evaluate basal and suprabasal proliferation. Results: Carcinogen exposure induced marked epidermal thickening, severe dysplasia, increased mitotic activity, elevated Ki-67 expression, and pronounced dermal inflammation. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness, rete ridge depth, mast cell density, mitotic counts, and suprabasal Ki-67 index. The 1 mg/mL concentration demonstrated the most consistent attenuation of dysplasia severity and inflammatory changes. No adverse histopathological alterations were observed in internal organs. Conclusions: These findings indicate that transfersome-mediated topical delivery of C-PC attenuates early inflammation-driven epidermal remodelling and tumour-promoting alterations in experimental skin carcinogenesis, supporting its potential as a topical preventive strategy.