Aerosol and nasal delivery of vaccines and antiviral drugs against seasonal and pandemic influenza.

Influenza is primarily a respiratory tract infection involving the exacerbation and inflammation of the respiratory tract, which can progress to life-threatening pneumonia, hypercytokinemia, edema, acute lung injury, respiratory failure and death. Viral mutations and drug resistance are the leading challenges in influenza prevention and treatment. Aerosol inhalation provides rapid availability and sustained therapeutic levels of antiviral drugs in the respiratory tract, without causing a systemic burden to unaffected tissues and organs. Furthermore, aerosol delivery enhances the bioavailability of antiviral drugs with poor oral adsorption. Nasal spray delivery of vaccines provides a safe and needle-free means of vaccination, and contains live-attenuated virus that induces mucosal immunity and provides long-lasting immunity relative to injectable inactivated vaccines. Since influenza is a disease with respiratory clinical manifestations, specific delivery of antiviral drugs or vaccines to the respiratory tract may represent a safe and effective approach to combat influenza.

Therapeutic efficacy of "nubiotics" against burn wound infection by Pseudomonas aeruginosa.

"Nubiotics" are a novel class of proprietary protonated nucleic acid-based drugs shown to have potent in vitro antibacterial activities against a number of gram-positive and gram-negative bacteria. These nubiotics are evaluated here for their in vivo therapeutic efficacy for the treatment of burn wound infection caused by Pseudomonas aeruginosa. To achieve this, a burn wound infection model was established in mice by using a highly pathogenic burn wound clinical isolate of P. aeruginosa. Lethal doses of the bacteria were determined for two routes of infection (subcutaneous and topical), representing systemic and local forms of infection, respectively. Using this infection model, treatment with nubiotics by various routes of drug administration was evaluated and optimized. A total of 12 nubiotics and their analogues were tested and of these, Nu-2, -3, -4, and -5 were found to be extremely efficacious in the postexposure treatment of burn wound infection (60 to 100% survival rates versus 0% for untreated control [P < 0.05]). These nubiotics were effective when given either systemically by intravenous and/or subcutaneous administration or given locally to the affected site in the skin by topical application. Treatment by these two routes resulted in almost 100% survival rates and complete eradication of the bacteria from infection sites in the livers, spleens, and blood. These nubiotics were found to be as effective as intravenously administered ciprofloxacin, a potent and broad-spectrum fluoroquinolone. These results suggest that nubiotics may be a promising and effective approach for the treatment of burn wound infection caused by P. aeruginosa.

Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection.

The effect of liposome delivery on the controlled release and therapeutic efficacy of ciprofloxacin against intracellular Francisella tularensis infection in vivo was evaluated in this study. Ciprofloxacin was encapsulated in small unilamellar vesicles by a remote loading procedure using an ammonium sulfate gradient. This procedure produced uniform sized liposomes (100 nm) with an entrapment rate of 90+/-3.5%. Following administration of unencapsulated or liposome-encapsulated ciprofloxacin by intravenous injection or aerosol inhalation, levels of ciprofloxacin in sera, lungs, liver and spleen were determined using 14C-ciprofloxacin as radiotracer for ciprofloxacin. Intravenous injection of liposome-encapsulated ciprofloxacin resulted in higher serum levels of drug in serum, as well as increased drug retention in lungs, liver and spleen, compared to that of free encapsulated drug. Aerosol administration of liposome-encapsulated ciprofloxacin by jet nebulization resulted in significantly higher drug levels and prolonged drug retention in the lower respiratory tract compared to the free drug. Aerosol inhalation of liposome-encapsulated ciprofloxacin, given either prophylactically or therapeutically, provided complete protection to mice against a pulmonary lethal infection model of F. tularensis. In contrast, ciprofloxacin given in its free form, was ineffective. These results suggest that liposome encapsulation of ciprofloxacin enhances drug delivery to the primary site of infection and results in increasing therapeutic efficacy against F. tularensis.