In vitro cutaneous application of ISCOMs on human skin enhances delivery of hydrophobic model compounds through the stratum corneum.
This study aimed to investigate the effect of a novel kind of immune-stimulating complexes (ISCOMs) on human skin penetration of model compounds in vitro to evaluate their potential as a delivery system, ultimately for transcutaneous vaccination. Special focus was on elucidating the mechanisms of penetration. Preparation of ISCOMs was done by dialysis and subsequent purification in a sucrose density gradient. The penetration pathways of acridine-labeled ISCOMs were visualized using confocal laser scanning microscopy (CLSM). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural changes in the skin after application of the ISCOMs with or without hydration. Transcutaneous permeation of the model compound, methyl nicotinate, was evaluated in diffusion cells. The prepared ISCOMs were 42-52 nm in diameter as evaluated by dynamic light scattering with zeta potentials of -33 to -26.1 mV. TEM investigations verified the presence of ISCOM structures. Penetration of acridine into skin was greatly increased by incorporation into ISCOMs as visualized by CLSM. Permeation of methyl nicotinate was enhanced in the presence of ISCOMs. Ultrastructural changes of the intercellular space in the stratum corneum after exposure of ISCOMs were observed on micrographs, especially for hydrated skin. In conclusion, cutaneous application of ISCOMs leads to increased penetration of hydrophobic model compounds through human stratum corneum and thus shows potential as a transcutaneous delivery system. The increased penetration seems to be reflected by a change in the intercellular space between the corneocytes, and the effect is most likely caused by the components of the ISCOMs rather than intact ISCOMs.
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Henriette Baun
HB
Madsen
Peter
P
Ifversen
Flemming
F
Madsen
Birger
B
Brodin
Ingrid
I
Hausser
Hanne Mørck
HM
Nielsen
D000166:Acridines / Q000008:administration & dosage / Q000493:pharmacokinetics; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000287:Administration, Topical; D000465:Algorithms; D002626:Chemistry, Pharmaceutical; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D014867:Water
D000166:Acridines; D000276:Adjuvants, Immunologic; D009539:Nicotinic Acids; D004364:Pharmaceutical Preparations; D014867:Water; C008473:methyl nicotinate