Journal Article

Poly (<span class="smallCaps">dl</span>-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis

Rajesh Pandey, Anjali Sharma, A. Zahoor, Sadhna Sharma, G. K. Khuller and B. Prasad

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 52, issue 6, pages 981-986
Published in print December 2003 | ISSN: 0305-7453
Published online December 2003 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkg477
Poly (dl-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis

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Objectives: To improve the bioavailability of antitubercular drugs (ATDs) as well as to assess the feasibility of administering ATDs via the respiratory route, this study reports the formulation of three frontline ATDs, i.e. rifampicin, isoniazid and pyrazinamide encapsulated in poly (dl-lactide-co-glycolide) nanoparticles suitable for nebulization.

Methods: Drug-loaded nanoparticles were prepared by the multiple emulsion technique, vacuum-dried and nebulized to guinea pigs. The formulation was evaluated with respect to the pharmacokinetics of each drug and its chemotherapeutic potential in Mycobacterium tuberculosis infected guinea pigs.

Results: The aerosolized particles exhibited a mass median aerodynamic diameter of 1.88 ± 0.11 µm, favourable for bronchoalveolar lung delivery. A single nebulization to guinea pigs resulted in sustained therapeutic drug levels in the plasma for 6–8 days and in the lungs for up to 11 days. The elimination half-life and mean residence time of the drugs were significantly prolonged compared to when the parent drugs were administered orally, resulting in an enhanced relative bioavailability (compared to oral administration) for encapsulated drugs (12.7-, 32.8- and 14.7-fold for rifampicin, isoniazid and pyrazinamide, respectively). The absolute bioavailability [compared to intravenous (iv) administration] was also increased by 6.5-, 19.1- and 13.4-fold for rifampicin, isoniazid and pyrazinamide, respectively. On nebulization of nanoparticles containing drugs to M. tuberculosis infected guinea pigs at every 10th day, no tubercle bacilli could be detected in the lung after five doses of treatment whereas 46 daily doses of orally administered drug were required to obtain an equivalent therapeutic benefit.

Conclusions: Nebulization of nanoparticles-based ATDs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary tuberculosis.

Keywords: Keywords: poly(dl-lactide-co-glycolide), nanoparticles, antitubercular drugs, nebulization, tuberculosis

Journal Article.  3798 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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