title: Facilitation of transcutaneous drug delivery and vaccine immunization by a safe laser technology.
abstract: Full-surface laser ablation has been shown to efficiently disrupt stratum corneum and facilitate transcutaneous drug delivery, but it is frequently associated with skin damage that hampers its clinic use. We show here that a safer ablative fractional laser (AFL) can sufficiently facilitate delivery of not only patch-coated hydrophilic drugs but also protein vaccines. AFL treatment generated an array of self renewable microchannels (MCs) in the skin, providing free paths for drug and vaccine delivery into the dermis while maintaining integrity of the skin by quick healing of the MCs. AFL was superior to tape stripping in transcutaneous drug and vaccine delivery as a much higher amount of sulforhodamine B (SRB), methylene blue (MB) or a model vaccine ovalbumin (OVA) was recovered from AFL-treated skin than tape-stripped skin or control skin after patch application. Following entry into the MCs, the drugs or OVA diffused quickly to the entire dermal tissue via the lateral surface of conical-shaped MCs. In contrast, a majority of the drugs and OVA remained on the skin surface, unable to penetrate into the dermal tissue in untreated control skin or tape stripping-treated skin. Strikingly, OVA delivered through the MCs was efficiently taken up by epidermal Langerhans cells and dermal dendritic cells in the vicinity of the MCs or transported to the draining lymph nodes, leading to a robust immune response, in sharp contrast to a weak, though significant, immune response elicited in tape stripping group or a basal immune response in control groups. These data support strongly that AFL is safe and sufficient for transcutaneous delivery of drugs and vaccines.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital Department of Dermatology, Harvard Medical School, 50 Blossom St., Boston, MA 02114, United States.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Dilip
authors.initials: D
authors.lastname: Shah
authors.forename: Garuna
authors.initials: G
authors.lastname: Kositratna
authors.forename: Dieter
authors.initials: D
authors.lastname: Manstein
authors.forename: Richard R
authors.initials: RR
authors.lastname: Anderson
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D007114:Immunization / Q000295:instrumentation / Q000379:methods*; D053685:Laser Therapy / Q000379:methods*; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage; D012235:Rhodamines / Q000008:administration & dosage; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014612:Vaccines
chemical_list: D000941:Antigens; D012235:Rhodamines; D014612:Vaccines; C022027:lissamine rhodamine B; D010047:Ovalbumin; D008751:Methylene Blue