Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: physicochemical characterization and in vivo targeted delivery to the lungs

Abstract

Current medical treatments against recurrent pulmonary infections caused by Pseudomonas aeruginosa, such as cystic fibrosis (CF) disorder, involve the administration of inhalable antibiotics.

Inhalable hybrid nanocarriers for respiratory disorders

“…Islan et al prepared spherical microparticles in the range of 3–5 μm, which is ideal for pulmonary delivery. As evidenced from the in vivo data, the microparticles reached 7.4 times the concentration of pure drug solution in the lung at a dose of 0.7 mg and at 1.4 mg, the lung levels were 2.8 times higher than pure drug [42] . Hybrid systems can be efficiently used to incorporate nuclease that helps in the breakdown of DNA chains, which are products of cell lysis and lead to mucus accumulation.…”

“…Therefore there is a size range that determines the extent to which a formulation may reach the desired site of action. Drug delivery to deep lung tissues is dependent on size [41] , [42] . Respirable particles between 1 and 5 μm are suitable for achieving significant drug concentrations.…”

Tailored Nanocarriers for the Pulmonary Delivery of Levofloxacin against Pseudomonas aeruginosa: A Comparative Study

“…25 Such sustained release is consistent with levofloxacin release from microparticles for inhaled administration. 29 In order to fine-tune the release profile, a physical mix of free and encapsulated drug can be envisioned, similar to the dual- release formulation of ciprofloxacin, Levoquin, which has recently been used in clinical trials. 53 Antimicrobial activity was assessed in broth for four P. aeruginosa strains isolated from CF patients, as well as on a control ATCC strain, by viability measurements 54 (Figure S1).…”

“…60 Further preclinical evaluation could involve more relevant in vitro models, such as a 3D lung epithelial model infected by P. aeruginosa. 73 Finally, drug deposition and retention in the lungs should be determined in vivo using healthy mice 29 before assessing the antimicrobial activity in mice with chronic P. aeruginosa infection 74 or in CF models of lung infections, such as pigs and ferrets. 23,75 ■ ASSOCIATED CONTENT * S Supporting Information…”

“…7 Therefore, improving its delivery would empower its therapeutic efficiency for CF patients. Levofloxacin has already been encapsulated into chitosan nanoparticles, 27 hybrid lipid−polymer nanoparticles, 15 niosomes, 28 solid lipid microparticles, 29 and liposomes 30 and conjugated to gold nanoparticles, 31 but it's in vitro antibacterial activity against P. aeruginosa has shown mitigated results. 30 The encapsulation of levofloxacin in liposomes has also been envisioned for the treatment of pulmonary inflammation, 32 ocular antibiotic delivery, 33,34 and antituberculosis treatment 35 but, to the best of our knowledge, it has never been optimized for pulmonary antibiotic treatment.…”