Pulmonary disposition of vancomycin nebulized as lipid vesicles in rats

Abstract

Formulation of antibiotics as inhalable products is proposed to improve their therapeutic index when intended for the treatment of pulmonary infections; as vancomycin shows reduced values of lung partition coefficient, pulmonary administration might be an interesting alternative to conventional administration routes. An experimental study has been performed to compare the pulmonary disposition of vancomycin after inhalation of the drug formulated as a solution and as lipid vesicles (conventional liposomes or liposomes modified with chitosan). Vancomycin concentrations were determined in bronchoalveolar fluid, pulmonary tissue and blood samples from 27 Wistar rats distributed in three groups subjected to nebulisation of the drug formulated as a solution, conventional liposomes or chitosomes. Statistically significant differences between the mean drug concentrations in bronchoalveolar lavage (BALF) and lung tissue were found upon comparing the solution to lipid vesicles (116.95 μg ml(-1)±62.13 versus 68.34 μg ml(-1)±28.90 for liposomes and 65.36±22.11 μg g(-1) for chitosomes in BALF; 222.74±37.15 μg g(-1) versus 357.17±65.37 μg g(-1) for liposomes and 378.83±85.87 μg g(-1) for chitosomes in pulmonary tissue). The amount of available drug estimated by mass balance reached the highest values for chitosomes followed by liposomes (24289.66±4795.48 μg and 20207.91±5318.29 μg, respectively) and the lowest for the solution (18971.64±4765.38 μg). The drug transport and tissue uptake processes showed to be dependent on the nebulized formulation, being facilitated by the lipid vesicles that improved drug passage from the airway space to the pulmonary tissue and systemic circulation.

Development of Dried Emulsion/Mannitol Composite Microparticles through a Unique Spray Nozzle for Efficient Delivery of Hydrophilic Anti-tuberculosis Drug against Alveolar Macrophages

“…We consider that that the optimized SDC/MAN microparticles (1-3 µm) reached the alveoli present in the deeper lung tissue more efficiently and that MAN was then dissolved in the alveoli because it is believed that alveolar air is believed to be 100% saturated with water vapor (100% relative humidity). 30) Consequently, the SDC nanoparticles released from the MAN were probably recognized by the alveolar macrophages; therefore, relatively high concentrations of calcein-SDC nanoparticles could be ingested by the alveolar macrophages, whereas the calcein-MAN microparticles became a simple calcein solution. An advantage of the use of nanocarriers, involves the expectation that the drugs in nanoparticles have longer retention times in lung tissue.…”

Cytotoxic and Bactericidal Effects of Inhalable Ciprofloxacin-Loaded Poly(2-ethyl-2-oxazoline) Nanoparticles with Traces of Zinc Oxide

“…The digestibility of a formulated polymer as a drug carrier is very important in order to determine the longevity of performance within biological systems. Due to this feature, the range of polymers that are effective as carriers in lung delivery is limited to only a few natural and synthetic polymers, including chitosan [24,25], alginate [26,27], poly(lactic-coglycolic acid) (PLGA) [28,29], poly(lactic acid) (PLA) [30], poly(vinyl alcohol) [31,32], and polyethyleneimine [33]. Although these polymers are considered biodegradable because of their biodegradable by-products, the NPs of these polymers are yet to be determined as completely biodegradable or biocompatible [34].…”

Sildenafil Citrate Liposomes for Pulmonary Delivery by Ultrasonic Nebulization

“…Studies with isolated rat lung proved that vancomycin nebulization produced much higher drug levels in respiratory tissue and bronchoalveolar fluids than those achieved in systemic fluid [13]. Also, nebulization of liposomes facilitated the drug uptake in the lungs, compared to the drug solution [14]. Among colloidal carriers, liposomes have been shown to be safe for pulmonary administration in animals and humans.…”