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  Inhalation System for Pulmonary Aerosol Drug Delivery in Rodents Using Large Porous Particles
 
 
Titel: Inhalation System for Pulmonary Aerosol Drug Delivery in Rodents Using Large Porous Particles
Auteur: Ben-Jebria, Abdellaziz
Eskew, Mary Lou
Edwards, David A.
Verschenen in: Aerosol science and technology
Paginering: Jaargang 32 (2000) nr. 5 pagina's 421-433
Jaar: 2000-05-01
Inhoud: The pulmonary system is an attractive noninvasive route for effective delivery of drugs for both local and systemic therapies. In this study, an inhalation system was developed to effectively aerosolize and deliver small amounts (typically 1-5 mg) of dry powder polymeric and nonpolymeric particles to the lungs of anesthetized rodents over a very short period of time using a ventilator while the animals breathed spontaneously. The new aerosols were designed for size, porosity, and lightness and were characterized by particles of low mass density (rho less than or equal to 0.1 g/cm3) and large size (d approximately 10 mum). The inhalation system was tested in vivo to determine 1) whether the relatively efficient in vitro aerosolization of these large porous particles translated into a substantial respirable fraction in vivo; 2) whether the bioavailability of an encapsulated drug for systemic therapy could be increased and the drug release in the systemic circulation could be sustained; and 3) whether an encapsulated drug for local asthma therapy could sustain bronchodilation over a prolonged time period. Unlike the conventional (small non-porous) particles which deposit primarily in the tubing and trachea (80% of all particle mass delivered), 55% of the large porous particle mass deposited in the deep lung. The total systemic bioavailabilities of inhaled porous estradiol, insulin, and testosterone relative to subcutaneous injections were 86%, 88%, and 177%, respectively. The inhaled dry powder albuterol sulfate aerosol was capable of preventing sustained bronchoconstriction (in response to carbachol challenge) for approximately one day. Our data indicate that the experimental inhalation system we developed will be an excellent device for further testing of new therapeutics available in particulate form.
Uitgever: Taylor & Francis
Bronbestand: Elektronische Wetenschappelijke Tijdschriften
 
 

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