Characterisation of cytotoxicity and immunomodulatory effects of glycolipid biosurfactants on human keratinocytes.

Skin irritation and allergic reactions associated with the use of skincare products formulated with synthetically derived surfactants such as sodium lauryl ether sulphate (SLES) have encouraged the search for naturally derived and biocompatible alternatives. Glycolipid biosurfactants such as sophorolipids (SL) and rhamnolipids (RL) offer a potential alternative to SLES. However, most studies on the bioactive properties of microbial glycolipids were determined using their mixed congeners, resulting in significant inter-study variations. This study aims to compare the effects of highly purified SL (acidic and lactonic) and RL (mono-RL and di-RL) congeners and SLES on a spontaneously transformed human keratinocyte cell line (HaCaT cells) to assess glycolipids' safety for potential skincare applications. Preparations of acidic SL congeners were 100% pure, lactonic SL were 100% pure, mono-RL were 96% pure, and di-RL were 97% pure. Cell viability using XTT assays, cell morphological analyses, and immunoassays revealed that microbial glycolipids have differing effects on HaCaT cells dependent on chemical structure. Compared with SLES, acidic SL and mono-RL have negligible effects on cell viability, cell morphology, and production of pro-inflammatory cytokines. Furthermore, at non-inhibitory concentrations, di-RL significantly attenuated IL-8 production and CXCL8 expression while increasing IL-1RA production and IL1RN expression in lipopolysaccharide-stimulated HaCaT cells. Although further studies would be required, these results demonstrate that as potential innocuous and bioactive compounds, microbial glycolipids could provide a substitute to synthetic surfactants in skincare formulations and perform immunopharmacological roles in topical skin infections such as psoriasis. KEY POINTS: • Purified glycolipid congeners have differing effects on human keratinocytes. • Compared with SLES, acidic sophorolipids and mono-rhamnolipids have innocuous effects on keratinocytes. • Di-rhamnolipids and mono-rhamnolipids modulate cytokine production in lipopolysaccharide stimulated human keratinocytes.

Glycolipid Biosurfactants in Skincare Applications: Challenges and Recommendations for Future Exploitation.

The 21st century has seen a substantial increase in the industrial applications of glycolipid biosurfactant technology. The market value of the glycolipid class of molecules, sophorolipids, was estimated to be USD 409.84 million in 2021, with that of rhamnolipid molecules projected to reach USD 2.7 billion by 2026. In the skincare industry, sophorolipid and rhamnolipid biosurfactants have demonstrated the potential to offer a natural, sustainable, and skin-compatible alternative to synthetically derived surfactant compounds. However, there are still many barriers to the wide-scale market adoption of glycolipid technology. These barriers include low product yield (particularly for rhamnolipids) and potential pathogenicity of some native glycolipid-producing microorganisms. Additionally, the use of impure preparations and/or poorly characterised congeners as well as low-throughput methodologies in the safety and bioactivity assessment of sophorolipids and rhamnolipids challenges their increased utilisation in both academic research and skincare applications. This review considers the current trend towards the utilisation of sophorolipid and rhamnolipid biosurfactants as substitutes to synthetically derived surfactant molecules in skincare applications, the challenges associated with their application, and relevant solutions proposed by the biotechnology industry. In addition, we recommend experimental techniques/methodologies, which, if employed, could contribute significantly to increasing the acceptance of glycolipid biosurfactants for use in skincare applications while maintaining consistency in biosurfactant research outputs.

Biosurfactants as Anticancer Agents: Glycolipids Affect Skin Cells in a Differential Manner Dependent on Chemical Structure.

Melanomas account for 80% of skin cancer deaths. Due to the strong relationship between melanomas and U.V. radiation, sunscreens have been recommended for use as a primary preventative measure. However, there is a need for targeted, less invasive treatment strategies. Glycolipids such as sophorolipids and rhamnolipids are microbially derived biosurfactants possessing bioactive properties such as antimicrobial, immunomodulatory and anticancer effects. This study aimed to ascertain the differing effects of glycolipids on skin cells. Highly purified and fully characterized preparations of sophorolipids and rhamnolipids were used to treat spontaneously transformed human keratinocyte (HaCaT) and the human malignant melanocyte (SK-MEL-28) cell lines. Cell viability and morphological analyses revealed that glycolipids have differential effects on the skin cells dependent on their chemical structure. Lactonic sophorolipids and mono-rhamnolipids were shown to have a significantly detrimental effect on melanoma cell viability compared to healthy human keratinocytes. These glycolipids were shown to induce cell death via necrosis. Additionally, sophorolipids were shown to significantly inhibit SK-MEL-28 cell migration. These findings suggest that glycolipids could be used as bioactive agents with selective inhibitory effects. As such, glycolipids could be a substitute for synthetically derived surfactants in sunscreens to provide additional benefit and have the potential as novel anti-skin-cancer therapies.

Mono-Rhamnolipid Biosurfactants Synthesized by Pseudomonas aeruginosa Detrimentally Affect Colorectal Cancer Cells.

Over the past 15 years, glycolipid-type biosurfactant compounds have been postulated as novel, naturally synthesized anticancer agents. This study utilized a recombinant strain of Pseudomonas aeruginosa to biosynthesize a preparation of mono-rhamnolipids that were purified via both liquid and solid-phase extraction, characterized by HPLC-MS, and utilized to treat two colorectal cancer cell lines (HCT-116 and Caco2) and a healthy colonic epithelial cell line CCD-841-CoN. Additionally, the anticancer activity of these mono-rhamnolipids was compared to an alternative naturally derived anticancer agent, Piceatannol. XTT cell viability assays showed that treatment with mono-rhamnolipid significantly reduced the viability of both colorectal cancer cell lines whilst having little effect on the healthy colonic epithelial cell line. At the concentrations tested mono-rhamnolipids were also shown to be more cytotoxic to the colorectal cancer cells than Piceatannol. Staining of mono-rhamnolipid-treated cells with propidium iodine and acridine orange appeared to show that these compounds induced necrosis in both colorectal cancer cell lines. These data provide an early in vitro proof-of-principle for utilizing these compounds either as active pharmaceutical ingredient for the treatment of colorectal cancer or incorporations into nutraceutical formulations to potentially prevent gastrointestinal tract cancer.

Microbial Biosurfactants in Cosmetic and Personal Skincare Pharmaceutical Formulations.

Cosmetic and personal care products are globally used and often applied directly on the human skin. According to a recent survey in Europe, the market value of cosmetic and personal care products in Western Europe reached about 84 billion euros in 2018 and are predicted to increase by approximately 6% by the end of 2020. With these significant sums of money spent annually on cosmetic and personal care products, along with chemical surfactants being the main ingredient in a number of their formulations, of which many have been reported to have the potential to cause detrimental effects such as allergic reactions and skin irritations to the human skin; hence, the need for the replacement of chemical surfactants with other compounds that would have less or no negative effects on skin health. Biosurfactants (surfactants of biological origin) have exhibited great potential such as lower toxicity, skin compatibility, protection and surface moisturizing effects which are key components for an effective skincare routine. This review discusses the antimicrobial, skin surface moisturizing and low toxicity properties of glycolipid and lipopeptide biosurfactants which could make them suitable substitutes for chemical surfactants in current cosmetic and personal skincare pharmaceutical formulations. Finally, we discuss some challenges and possible solutions for biosurfactant applications.