Study of the percutaneous penetration of flurbiprofen by cutaneous and subcutaneous microdialysis after iontophoretic delivery in rat.

The percutaneous penetration of flurbiprofen delivered by iontophoresis was investigated in the hairless rat. Unbound concentrations of flurbiprofen in dermis and subcutaneous tissue were continuously measured by on-line microdialysis. Simultaneously, a conventional blood sampling was performed.

Local and systemic immune responses to intratracheal instillation of antigen and DNA vaccines in mice.

Purpose: The purpose of this study was to determine the immunization efficacy of antigen and DNA vaccines after delivery to the lung, to assess the integrity of the pulmonary tissue after vaccination, and to elucidate mechanisms involved in the induction of immunity.

Methods: Ovalbumin, the plasmid encoding ovalbumin, the hepatitis B surface antigen (HBsAg), or plasmid encoding HBsAg were intratracheally instilled or injected in quadriceps in mice. The immune response and its Th polarization were analyzed over time.

Alveolar macrophages are a primary barrier to pulmonary absorption of macromolecules.

We demonstrate that a primary source of elimination of inhaled macromolecules after delivery to the lungs and before absorption into the systemic circulation owes to clearance by alveolar macrophages (AM). Depletion of AM by liposome-encapsulated dichloromethylene diphosphonate is shown to cause severalfold enhancement in systemic absorption of IgG and human chorionic gonadotropin after intratracheal instillation in rats. Lowering the doses of IgG delivered to the lungs alleviates local degradation and results in a dramatic increase in systemic absorption of the protein as well.

Confocal imaging of rat lungs following intratracheal delivery of dry powders or solutions of fluorescent probes.

The overall pulmonary disposition of various fluorescent probes was viewed by confocal imaging following intratracheal delivery in the rat in vivo. The green fluorescent dyes, coumarin-6, a 350 Da lipophilic molecule; calcein, a 623 Da hydrophilic molecule; or FITC-albumin, a 65000 Da hydrophilic molecule; were insufflated as a dry powder or instilled as a solution in the lungs of rat in vivo. Immediately, 2 or 24 h following delivery, the lungs were colored with sulforhodamine and fixed by vascular perfusion.