title: 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin.
abstract: Although conventional vaccines have generated major successes in the control of infectious diseases, several obstacles remain in their development against chronic diseases (HIV, tuberculosis), against which no current candidate vaccines yet ensure protection. The transcutaneous route of vaccine administration appears to be a promising approach of targeting vaccines toward antigen-presenting cells (APCs) and thus improving immune responses. We investigated the suitability of nanoparticles in this approach. We found a high density of Langerhans cells (LCs) around hair follicles that, when sorted, readily internalized all size particles. However, flow cytometry after transcutaneous application of 40, 750, or 1,500 nm nanoparticles on human skin samples revealed that only 40 nm particles entered epidermal LC. Fluorescence and laser scan microscopies, which were carried out to identify the penetration pathway of transcutaneously applied nanoparticles, revealed that only 40 nm particles deeply penetrate into vellus hair openings and through the follicular epithelium. We conclude that 40 nm nanoparticles, but not 750 or 1,500 nm nanoparticles, may be efficiently used to transcutaneously deliver vaccine compounds via the hair follicle into cutaneous APCs.
authors.affiliation: Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Physiology, Charite-Universitätsmedizin Berlin, Berlin, Germany. annika.vogt@charite.de
authors.forename: Annika
authors.initials: A
authors.lastname: Vogt
authors.forename: Behazine
authors.initials: B
authors.lastname: Combadiere
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hadam
authors.forename: Karola M
authors.initials: KM
authors.lastname: Stieler
authors.forename: Juergen
authors.initials: J
authors.lastname: Lademann
authors.forename: Hans
authors.initials: H
authors.lastname: Schaefer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
mesh_terms: D000279:Administration, Cutaneous; D018949:Antigens, CD1 / Q000032:analysis; D001428:Bacterial Vaccines / Q000008:administration & dosage; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism*; D049329:Nanostructures; D010316:Particle Size; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012869:Skin Absorption; D014765:Viral Vaccines / Q000008:administration & dosage
chemical_list: D018949:Antigens, CD1; D001428:Bacterial Vaccines; C419393:CD1a antigen; D014765:Viral Vaccines