Mark M. Bailey

Nanoparticle formulations in pulmonary drug delivery

The advent of nanotechnology has reignited interest in the lungs as a major route of drug delivery for both systemic and local treatments. The large surface area of the lungs and the minimal barriers impeding access to the lung periphery make this organ a suitable portal for a variety of therapeutic interventions. Nanoparticles provide new formulation options for both dispersed liquid droplet dosage forms such as metered dose inhalers and nebulizers, and dry powder formulations. Nanoparticle formulations have many advantages over traditional dosage forms, such as enhanced dissolution properties and the potential for intracellular drug delivery. Specifically, pure drug nanoparticles, polymeric nanoparticles, polyelectrolyte complexes, and drug‐loaded liposomes offer some encouraging results for delivering drugs to and through the lungs. Methods are also being investigated to produce nanoparticles with properties suitable for improving access to the peripheral lung. Traditional techniques such as spray drying and grinding, and more recent advances in supercritical fluid extraction, precipitation, and solvent extraction have been employed to produce nanoparticle formulations for pulmonary delivery. Here, the benefits of nanoparticle formulations and current progress are compared in light of the practical encumbrances of producing formulations, and possible toxicological effects of these materials.

Pure Insulin Nanoparticle Agglomerates for Pulmonary Delivery

Diabetes is a set of diseases characterized by defects in insulin utilization, either through autoimmune destruction of insulin-producing cells (Type I) or insulin resistance (Type II). Treatment options can include regular injections of insulin, which can be painful and inconvenient, often leading to low patient compliance. To overcome this problem, novel formulations of insulin are being investigated, such as inhaled aerosols. Sufficient deposition of powder in the peripheral lung to maximize systemic absorption requires precise control over particle size and density, with particles between 1 and 5 microm in aerodynamic diameter being within the respirable range. Insulin nanoparticles were produced by titrating insulin dissolved at low pH up to the pI of the native protein, and were then further processed into microparticles using solvent displacement. Particle size, crystallinity, dissolution properties, structural stability, and bulk powder density were characterized. We have demonstrated that pure drug insulin microparticles can be produced from nanosuspensions with minimal processing steps without excipients, and with suitable properties for deposition in the peripheral lung.

Pulmonary Delivery of Ceftazidime for the Treatment of Melioidosis in a Murine Model

Burkholderia pseudomallei, the etiological agent responsible for melioidosis, exhibits a great public health toll in its endemic regions. The elevation of B. pseudomallei to a Tier I select agent underscores the urgent need for effective therapeutics and preventatives. The current treatment regimen for melioidosis is suboptimal, requiring an intensive phase of intravenous antibiotic followed by months of oral antibiotics. Inhaled antibiotics are a promising avenue to pursue for pulmonary diseases, including melioidosis, since this mode of delivery mimics the likely exposure route and can provide high drug doses directly to the infected tissue. Ceftazidime was delivered via a nose-only system to BALB/c mice challenged with B. pseudomallei. Mice treated with nebulized ceftazidime became symptomatic but survived until study end, which was comparable to those treated intraperitoneally. Upon necropsy, bacteria remained within the spleens of the majority of the experimental animals. The effectiveness of nebulized ceftazidime warrants additional studies to improve the treatment regimen and to test as a prophylactic therapy against B. pseudomallei.