The effect of sterol and surfactant substitution on the ability of non-ionic surfactant vesicles to reduce IL-6 production by murine macrophages stimulated with LPS

Student thesis: Master's Thesis

Abstract

Intro: Non-ionic surfactant vesicles (NISV) have previously been used widely in drug delivery and vaccines, with NISV containing mono palmitoyl glycerol (MPG) and cholesterol conferring an anti-inflammatory effect when delivered without a payload in vivo. This formulation was able to reduce production of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumour necrosis factor α (TNFα), which are commonly involved in pathology of sepsis and toxoplasma gondii infection. Methods: new NISV formulations based on those containing MPG and cholesterol were produced with the surfactant component replaced (hexadecanoylglyceroyl (HG) instead of MPG), or the sterol component replaced (ergosterol or stigmasterol instead of cholesterol) at the same molar ratio as previous NISV. Macrophages were stimulated with NISV formulations alone or with NISV and LPS for 24hrs and cellular viability assessed with alamarblue assay. ELISA for IL-6 was performed on supernatants from these cells to determine degree of anti-inflammatory effect after 24hr stimulation. RESULTS: Individual components contributed to cellular toxicity but had no anti-inflammatory effect when not formulated into vesicles. A reduction in IL-6 was found in NISV irrespective of whether the sterol was cholesterol or ergosterol. NISV containing HG instead of MPG retained the anti-inflammatory effect but exhibited greater toxicity at higher concentrations. Conclusions: Our findings widen the possible range of NISV formulations to include ergosterol or hexadecanoyl glycerol that could be used as an adjuvant treatment for inflammatory diseases like sepsis.
Date of Award4 Mar 2021
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde

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