High azithromycin concentration in lungs by way of bovine serum albumin microspheres as targeted drug delivery: lung targeting efficiency in albino mice

Abstract

Background: Following administration, the antibiotic travels freely through the body and also accumulates in other parts apart from the infection site. High dosage and repeated ingestion of antibiotics in the treatment of pneumonia leads to undesirable effects and inappropriate disposition of the drug. By way of targeted lung delivery, this study was intended to eliminate inappropriate azithromycin disposition and to achieve higher azithromycin concentration to treat deeper airway infections.

Methods: The Azithromycin Albumin Microspheres (AAM) was prepared by emulsion polymerization technique. The optimized AAM was subjected to in vitro release study, release kinetics, XRD and stability studies. Further, in vivo pharmacokinetics and tissue distribution of azithromycin released from AAM and azithromycin solution in albino mice was investigated to prove suitability of moving forward the next steps in the clinic.

Results: The mean particle size of the optimized AAM was 10.02 μm, an optimal size to get deposited in the lungs by mechanical entrapment. The maximum encapsulation efficiency of 82.3 % was observed in this study. The release kinetic was significant and best fitted for Korsmeyer-Peppas model (R(2) = 0.9962, n = 0.41). The XRD and stability study showed favorable results. Azithromycin concentration in mice lungs (40.62 μg g(-1), 30 min) of AAM was appreciably higher than other tissues and plasma. In comparison with control, azithromycin concentration in lungs was 30.15 μg g(-1) after 30 min. The azithromycin AUC (929.94 μg h mL(-1)) and intake rate (re) (8.88) for lung were higher and statistically significant in AAM group. Compared with spleen and liver, the targeting efficacy (te) in mice lung increased by a factor of 40.15 and ~14.10 respectively. Subsequently by a factor of 8.94, the ratio of peak concentration (Ce) in lung was higher in AAM treated mice. The AAM lung tissue histopathology did not show any degenerative changes.

Conclusions: High azithromycin concentration in albino mice lung was adequately achieved by targeted drug delivery.

Keywords: Albumin microspheres; Azithromycin; Lung targeting; Sigma plot; Targeting efficacy.

Fig. 1

Cumulative amount of drug released () optimized AAM and () azithromycin solution (bars represent mean ± SD; n = 3)

Fig. 2

In vitro release profile of the optimized AAM-curve fitting models (bars represent mean ± SD; n = 3)

Fig. 3

XRD of (a) azithromycin; (b) BSA; (c) optimized AAM before stability study; (d) optimized AAM after refrigeration (5 ± 3 °C) for 12 months; (e) optimized AAM after acceleration (25 ± 2 °C) for 6 months

Fig. 4

(a) Semilogarithmic plot showing azithromycin distribution in mice after intravenous injection of AAM (bars represent mean ± SD; n = 3); (b) Semilogarithmic plot showing azithromycin distribution in mice after intravenous injection of azithromycin solution (bars represent mean ± SD; n = 3)

Fig. 5

(a) Cytoarchitecture of albino mice lung (azithromycin solution); (b) Cytoarchitecture of albino mice lung (AAM)