Abstract
Nano- and microencapsulation has proven to be a useful technique for the construction of drug delivery vehicles for use in vascular medicine. However, the possibility of using these techniques within the lung as an inhalation delivery mechanism has not been previously considered. A critical element of particle delivery to the lung is the degree of penetrance that can be achieved with respect to the airway tree. In this study we examined the effectiveness of near infrared (NIR) dye (Cy7) labeled calcium carbonate (vaterite) particles of 3.15, 1.35, and 0.65 μm diameter in reaching the respiratory portion of the lung. First of all, it was shown that, interaction vaterite particles and the components of the pulmonary surfactant occurs a very strong retardation of the recrystallization and dissolution of the particles, which can subsequently be used to create systems with a prolonging release of bioactive substances after the particles penetrate the distal sections of the lungs. Submicro- and microparticles, coated with Cy7 labeled albumin as a model compound, were delivered to mouse lungs via tracheostomy with subsequent imaging performed 24, 48, and 72 h after delivery by in vivo fluorescence. 20 min post administration particles of all three sizes were visible in the lung, with the deepest penetrance observed with 0.65 μm particles. In vivo biodistribution was confirmed by fluorescence tomography imaging of excised organs post 72 h. Laser scanning confocal microscopy shows 0.65 μm particles reaching the alveolar space. The delivery of fluorophore to the blood was assessed using Cy7 labeled 0.65 μm particles. Cy7 labeled 0.65 μm particles efficiently delivered fluorescent material to the blood with a peak 3 h after particle administration. The pharmacokinetics of NIR fluorescence dye will be shown. These studies establish that by using 0.65 μm particles loaded with Cy7 we can efficiently access the respiratory portion of the lung, which represents a potentially efficient delivery mechanism for both the lung and the vasculature.
Highlights
The delivery of drugs to the lower respiratory portion of the lung is a long standing and desirable goal
To examine how well our particles retain materials we examined loading them with bovine serum albumin (BSA) conjugated to the fluorescent dye Cyanine 7 NHS ester (Cy7)
It should be noted that in this study, absorption was performed in one cycle, since it was not our aim to obtain the maximum amount of the conjugate (Cy7-BSA) absorbed on vaterite particle
Summary
The delivery of drugs to the lower respiratory portion of the lung is a long standing and desirable goal. The distal portion of the lung is a desirable target for systemic delivery as it has a large surface area (∼70–140 m2); the narrow barrier for diffusion, and relative lack of degradative enzymes (Groneberg et al, 2003). The delivery of compounds to the respiratory portion is an important goal for many pulmonary diseases. According to the Global Burden of Disease Study project, four of the fifteen most prevalent causes of death occur in the respiratory portion of the lung. For the treatment of these diseases, the design of delivery systems aimed at the distal lungs is potentially of great value
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