Research

Thesis title: "Bolalipids as new class of penetration enhancers in dermal products"

Thesis outline:
Introduction: In recent years, bolalipids have emerged as a novel excipient with promising potential for various pharmaceutical applications. Bolalipids are amphiphilic molecules characterised by two hydrophilic head groups separated by one or two hydrophobic alkyl chains, which can be further modified. These surfactants have the unique ability to self-assemble into diverse structures, including micelles, vesicles, nanotubes, and nanofibres, driven by weak non-covalent forces. Natural bolalipids, such as tetraether lipids (TELs), are found in Archaea cell membranes, endowing these microorganisms with remarkable stability under extreme environmental conditions.

Pharmaceutical applications: The stability provided by bolalipids in Archaea has been harnessed in pharmaceutical contexts, particularly in stabilising liposomal formulations. These bolalipid stabilised liposomes have demonstrated excellent tolerability following both oral and intravenous administration.

Hypothesis: We hypothesize that the bolalipid surfactants may enhance drug penetration, as they exhibit superior emulsifying properties compared to traditional phospholipids. Their biocompatibility makes them potentially valuable in the development of dermal products, either for liposome production or as solubilising agents for hydrophobic drugs. However, the impact of micellar bolalipid formulations on skin barrier function has not been investigated in the scientific literature. Therefore, it is essential to gain deeper insights into the interactions between bolalipids and skin, especially considering the availability of bolalipids with various chemical structures, such as different alkyl chain lengths.

Objectives: The main objectives of this study are as follows: 1.) To investigate the use of synthetic bolalipids at different concentrations in dermal products. 2.) To examine their impact on the skin penetration of model drugs. 3.) To assess their influence on skin physiology.

Methodology: To address these objectives, this research will employ a combination of in vitro, ex vivo and in vivo experiments:

In vitro experiments: 

• In vitro tape stripping, NIR‐densitometry, and fluorescence spectroscopy will be utilised to assess skin permeation using porcine skin as a surrogate for human skin.
• Permeation studies using Franz diffusion cells will be conducted, comparing porcine skin with synthetic membranes to evaluate the influence of different membrane types on drug permeation.

Additional ex vivo tests:

• The effect of bolalipids on skin barrier function will be examined using confocal Raman spectroscopy and ATR‐FTIR spectroscopy in combination with tape stripping on porcine ears.

In vivo experiments: 

• Human volunteers will be involved to measure skin barrier properties following the application of bolalipid formulations. These experiments will provide critical information on the behaviour of bolalipids on human skin and assess their effectiveness, efficiency, suitability, and safety for dermal products.

Comparison: The data generated will be compared with reference formulations consisting of conventional ionic and non‐ionic surfactants, including sodium dodecyl sulfate, polyethylene glycol 12‐ hydroxystearate, and a conventional lecithin. Water will be used as a negative control, and sodium fluorescein will serve as a hydrophilic model permeant for comparative analysis. In conclusion, this doctoral thesis aims to provide valuable insights into the potential of bolalipid surfactants in dermal products and their impact on skin penetration and physiology. The proposed research combines a comprehensive methodology involving both in vitro and in vivo studies, which will contribute to a better understanding of bolalipids' applicability in pharmaceutical formulations.

Supervisors: Lea Ann Dailey, Victoria Klang

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