Archaeosomes facilitate storage and oral delivery of cannabidiol

Cannabidiol (CBD) has received great scientific interest due to its numerous therapeutic applications. Degradation in the gastrointestinal (GI) tract, first-pass metabolism, and low water solubility restrain bioavailability of CBD to only 6% in current oral administration. Lipid-based nanocarriers are delivery systems that may enhance accessibility and solubility of hydrophobic payloads, such as CBD. Conventional lecithin-derived liposomes, however, have limitations regarding stability in the GI tract and long-term storage. Ether lipid-based archaeosomes may have the potential to overcome these problems due to chemical and structural uniqueness.

In this study, we compared lecithin-derived liposomes with archaeosomes in their applicability as an oral delivery system of CBD. We evaluated drug load, storage stability, stability in a simulated GI tract, and in vitro particle uptake in Caco-2 cells. Loading capacity was 6-fold higher in archaeosomes than conventional liposomes while providing a stable formulation over six months after lyophilization. In a simulated GI tract, CBD recovery in archaeosomes was 57 ± 3% compared to only 34 ± 1% in conventional liposomes and particle uptake in Caco-2 cells was enhanced up to 6-fold. Our results demonstrate that archaeosomes present an interesting solution to tackle current issues of oral CBD formulations due to improved stability and endocytosis.

Highlights

Oral CBD administration is currently limited by a bioavailability of only 6%.

Lecithin-based liposomes have limitations regarding stability.

Archaeosomes enable 6-fold increased payload compared to liposomes.

Lyophilization allows storage of CBD archaeosomes for over six months.

Accelerated and enhanced in vitro particle uptake of archaeosomes in Caco-2 cells.

Chemicals and reagents

Archaeal lipid extract was provided by NovoArc GmbH (Austria). It consists of a mixture of diether- and tetraether lipids with various headgroups, mainly inositol phosphate and mono- and dihexoses (Quehenberger et al., 2020). CBD was acquired from PhytoLab (Germany) in solid form with a purity of > 99%, and Phospholipon® 90 G (SPC) was kindly supplied by Lipoid (Germany). Cholesterol and 1,2-dipalmitoyl-sn-glycerol-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (ammonium salt) (16:0 Liss Rhod PE) were purchased from Avanti Polar Lipids, Inc (USA). RGE-15 (rabbit gastric extract) was obtained from LipolyTech (France). All solvents (ethanol, 2-propanol, dimethyl sulfoxide), pancreatin, and bile salts were obtained from Sigma Aldrich (USA) or Roth (Germany). Solvents for HPLC analysis were purchased from PanReac AppliChem ITW Reagents (Germany).

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Viktor Sedlmayr, Christina Horn, David Johannes Wurm, Oliver Spadiut, Julian Quehenberger,
Archaeosomes facilitate storage and oral delivery of cannabidiol,
International Journal of Pharmaceutics,
Volume 645, 2023, 123434, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2023.123434.