Performance studies of a conical nozzle designed for the macromolecular skin delivery.

Human skin is an attractive site for the delivery of protein and peptide-based macromolecular drugs for the treatment of topical and systemic diseases as well as for DNA immunisation. However, the delivery of those macromolecules in or across the skin is undesirably limited due to its permeation property. To expand the number of macromolecules to be delivered to specific targeting tissue/cells, a unique biomedical device, the handheld powdered injection system, has been developed.

Characteristics of a micro-biolistic system for murine immunological studies.

With an advanced computational fluid dynamics (CFD) technique, we have numerically developed and examined a micro-biolistic system for delivering particles to murine target sites. The micro-particles are accelerated by a high speed flow initiated by a traveling shock wave, so that they can attain a sufficient momentum to penetrate in to the cells of interest within murine skin (or mucosa). In immunization application, powdered vaccines are directly delivered into the antigen presenting cells (APCs) within the epidermis/dermis of the murine skin with a narrow and highly controllable velocity range (e.

Femtosecond two-photon high-resolution 3D imaging, spatial-volume rendering and microspectral characterization of immunolocalized MHC-II and mLangerin/CD207 antigens in the mouse epidermis.

Langerhans cells (LCs) play a sentinel role by initiating both adaptive and innate immune responses to antigens pertinent to the skin. With the discovery of various LCs markers including antibodies to major histocompatibility complex class II (MHC-II) molecules and CD1a, intracellular presence of racket-shaped "Birbeck granules," and very recently Langerin/CD207, LCs can be readily distinguished from other subsets of dendritic cells. Femtosecond two-photon laser scanning microscopy (TPLSM) in recent years has emerged as an alternative to the single photon-excitation based confocal laser scanning microscope (CLSM), particularly for minimally-invasive deep-tissue 3D and 4D vital as well as nonvital biomedical imaging.

Multiphoton high-resolution 3D imaging of Langerhans cells and keratinocytes in the mouse skin model adopted for epidermal powdered immunization.

Langerhans cells (LCs) can be targeted with DNA-coated gold micro-projectiles ("Gene Gun") to induce potent cellular and humoral immune responses. It is likely that the relative volumetric distribution of LCs and keratinocytes within the epidermis impacts on the efficacy of Gene Gun immunization protocols. This study quantified the three-dimensional (3D) distribution of LCs and keratinocytes in the mouse skin model with a near-infrared multiphoton laser-scanning microscope (NIR-MPLSM).

Characterization of powdered epidermal vaccine delivery with multiphoton microscopy.

Multiphoton laser scanning microscopy (MPLSM) has been adapted to non-invasively characterize hand-held powdered epidermal vaccine delivery technology. A near infrared femtosecond pulsed laser, wavelength at approximately 920 nm, was used to evoke autofluorescence of endogenous fluorophores within ex vivo porcine and human skin. Consequently, sub cellular resolution three-dimensional images of stratum corneum and viable epidermal cells were acquired and utilized to observe the morphological deformation of these cells as a result of micro-particle penetration.