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Improved Lung Concentration of Levofloxacin by Targeted Gelatin Microspheres: In Vivo Pharmacokinetic Evaluation of Intake Rate, Targeting Efficacy Parameters and Peak Concentration Ratio in Albino Mice

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Abstract

Purpose

High dosage and repeated ingestion of antibiotics in the treatment of pneumonia lead to inappropriate disposition of the drug and thus increase undesirable effects. Hence, this study was intended to achieve high levofloxacin concentration in lungs by targeted levofloxacin gelatin microspheres (LGMs).

Methods

The optimized LGM prepared by emulsion method was characterized for particle size, drug encapsulation efficiency, in vitro study, X-ray diffraction (XRD), and stability studies. The in vivo lung targeting efficiency parameters such as intake rate (r e), targeting efficacy (t e), overall drug targeting efficacy (T e), percentage of drug distributed to lungs (j), and ratio of peak concentration (C e) were investigated.

Results

The mean particle size ranged from 6.28 to 19.72 μm, which can get deposited in lungs by mechanical entrapment. The curve fitting analysis showed significance for Koresmeyer–Peppas model (R-square = 0.9959). The levofloxacin area under the curve (AUC; 899.62 μg h mL−1) and r e (5.74) for lung were higher and statistically significant in LGM group. Compared with spleen and liver, the t e in mice lung increased by a factor of 33.45 and ∼12.74, respectively. The targeting ratio of LGM increased by a factor of 26.22 (compared to spleen) and ∼10.58 (compared to liver). Subsequently by a factor of 4.63, C e in lung was higher in LGM-treated mice. An overall 87.14 % of the drug was distributed to lungs when administrated as LGM formulation. The histopathology confirmed tissue tolerability.

Conclusions

The gelatin microsphere allows for surface modification, and mechanically entrapped in endothelial capillary of the lung further increases affinity leading to higher levofloxacin concentration in lungs, which helps in optimizing the therapeutic efficacy in the treatment of pneumonia.

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Acknowledgment

We are thankful to Dr. Ramesh K, Director, Karnataka College of Pharmacy, Bengaluru, Karnataka, India and Mr. Lokesh Prasad, DTL, Bengaluru Karnataka, India for valuable contribution to make this research work possible.

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Authors and Affiliations

  1. Department of Pharmaceutics, Karnataka College of Pharmacy, #33/2, Tirumenahalli, Hegde Nagar Main Road, Bengaluru, 560064, Karnataka, India

    Balakeshwa Ramaiah

  2. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, 31982, Saudi Arabia

    Sree Harsha Nagaraja

  3. Department of Pharmaceutical Technology, Karnataka College of Pharmacy, #33/2, Tirumenahalli, Hegde Nagar Main Road, Bengaluru, 560064, Karnataka, India

    Usha Ganganahalli Kapanigowda & Prakash Rao Boggarapu

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  1. Balakeshwa Ramaiah
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Correspondence to Balakeshwa Ramaiah.

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The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Ramaiah, B., Nagaraja, S.H., Kapanigowda, U.G. et al. Improved Lung Concentration of Levofloxacin by Targeted Gelatin Microspheres: In Vivo Pharmacokinetic Evaluation of Intake Rate, Targeting Efficacy Parameters and Peak Concentration Ratio in Albino Mice. J Pharm Innov 11, 289–299 (2016). https://doi.org/10.1007/s12247-016-9252-y

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