Cited by 318Inhalation and Respiratory Drug DeliveryTuberculosis Research and EpidemiologyAdvanced Drug Delivery Systems

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Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis

Pandey, Rajesh, Khuller, G.K.·2005·Tuberculosis

DOI 10.1016/j.tube.2004.11.003

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Abstract

The present study was planned to evaluate the chemotherapeutic potential of nebulized solid lipid particles (SLPs) incorporating rifampicin, isoniazid and pyrazinamide against experimental tuberculosis. The SLPs prepared by the "emulsion solvent diffusion" technique possessed a favourable mass median aerodynamic diameter suitable for bronchoalveolar drug delivery. Following a single nebulization to guinea pigs, therapeutic drug concentrations were maintained in the plasma for 5 days and in the organs (lungs, liver and spleen) for 7 days whereas free drugs were cleared by 1-2 days. The mean residence time and drug bioavailability were improved several-fold in the case of drug-loaded SLPs. A similar pharmacokinetic profile was observed in Mycobacterium tuberculosis-infected guinea pigs. On nebulization of drug-loaded SLPs to infected guinea pigs at every 7th day, no tubercle bacilli could be detected in the lungs/spleen after 7 doses of treatment whereas 46 daily doses of orally administered drugs were required to obtain an equivalent therapeutic benefit. Further, there was no evidence of any biochemical hepatotoxicity. Thus, nebulization of SLP-based antitubercular drugs forms a sound basis for improving drug bioavailability and reducing the dosing frequency for better management of pulmonary tuberculosis.

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Authors: Pandey, R., & Khuller, G. K.
Affiliations: Post Graduate Institute of Medical Education and Research (IN)
Corresponding author: Khuller, G.K.
ORCID: Pandey, Rajesh
Venue: Tuberculosis
Publisher: Elsevier BV
Published: 2005-07
Volume: 85
Issue: 4
Pages: 227-234
ISSN: 1472-9792 (ISSN-L)
DOI: 10.1016/j.tube.2004.11.003
OpenAlex: W2137397041
Cited by: 318
References: 24
Citations by year: 2026: 5 · 2025: 12 · 2024: 9 · 2023: 13 · 2022: 17 · 2021: 21 · 2020: 18 · 2019: 19 · 2018: 24 · 2017: 18 · 2016: 24 · 2015: 13 · 2014: 26 · 2013: 20 · 2012: 14
FWCI: 7.42
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Tuberculosis (publishedVersion)
PubMed (publishedVersion)
Funders: Department of Science and Technology, Ministry of Science and Technology, India
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords: solid lipid particles, pulmonary tuberculosis, nebulized drug delivery, rifampicin, isoniazid, pyrazinamide, antitubercular agents, emulsion solvent diffusion, aerosol drug delivery, pharmacokinetics, drug bioavailability, Mycobacterium tuberculosis, guinea pig model, hepatotoxicity
MeSH terms: Administration, Inhalation, Animals, Antitubercular Agents, Biological Availability, Drug Carriers, Guinea Pigs, Isoniazid, Lipids, Pyrazinamide, Rifampin, Tuberculosis, Drug Delivery Systems, Area Under Curve, Nanostructures

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Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis

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