In Vitro Cutaneous Application of ISCOMs on Human Skin Enhances Delivery of Hydrophobic Model Compounds Through the Stratum Corneum
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 4
Abstract
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.
Authors and Affiliations
Henriette Baun Madsen, Peter Ifversen, Flemming Madsen, Birger Brodin, Ingrid Hausser, Hanne Mørck Nielsen
Keywords
Related Articles
- EP ID EP681515
- DOI 10.1208/s12248-009-9149-5
- Views 82
- Downloads 0
Levy G, Hayes B, “Physiochemical Basis of the Buffered Acetylsalicylic Acid Controversy New Engl. J. Med. 262:1053–1058 (1960)”—The Backstory
Dr. Levy is retired and can be reached through email.
Ocular Drug Delivery
Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aq...
Evaluation of Mucoadhesive PLGA Microparticles for Nasal Immunization
In this study, hepatitis B surface antigen (HBsAg) loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared and coated with chitosan and trimethyl chitosan (TMC) to evaluate the effect of coating material...
Targeted lipidomics: Discovery of new fatty acyl amides
The discovery of endogenous fatty acyl amides such asN-arachidonoyl ethanolamide (anandamide),N-oleoyl ethanolamide (OEA), andN-arachidonoyl dopamine (NADA) as important signaling molecules in the central and peripheral...
Theoretical Considerations and Practical Approaches to Address the Effect of Anti-drug Antibody (ADA) on Quantification of Biotherapeutics in Circulation
Continuous improvement in bioanalytical method development is desired in order to ensure the quality of the data and to better support pharmacokinetic (PK) and safety studies of biotherapeutics. One area that has been ge...