Dry powders based on mucus-penetrating nanoparticles entrapped microparticles for pulmonary delivery of Tobramycin

Pulmonary drug delivery system is increasingly recommended as maintenance therapy to prolong the interval between pulmonary exacerbations and to slow the progression of lung disease in cystic fibrosis (CF) patients with chronic P. aeruginosa infection due to its capability to achieve high drug concentrations at the site of infection and to minimize the risk of systemic toxicity. The most common used inhaled Tobramycin formation so far is nebulization such as Tobi^® and Bramitob^® which are regarded as inconvenient due to the long administration time and limited portability for chronic drug therapy in daily life of patients. The only dry powder formulation of Tobramycin is based on PulmoSphere^TM technology, which has many advantages over nebulizers including faster delivery, easy use, portability, reduced need for cleaning and room temperature storage. Yet a lack of proof exists to indicate their efficient mucus penetration, which is the major obstacle for pulmonary drug delivery. To overcome the shortcomings of established pulmonary antibiotic delivery, we proposed the use of mucus-penetrating nanoparticles entrapped microparticles (so-called nanocomposite microparticles) combining the advantages of both nanoparticles and microparticles. The nanoparticles were comprised of the anti-biotic tobramycin encapsulated in the polymer acetalated dextran (Ac-Dex) and PVA coating, which enables the system to penetrate the mucus and to release drug in controlled rate. The nanoparticles were then entrapped in microparticles using advanced organic spray drying techniques which can improve the targeted delivery of the drug. This system will enlighten the dry powder based antibiotic delivery providing a desirable alternative way for inhalation therapy.