Antimycobacterial Activity of Solid Lipid Microparticles Loaded with Ursolic Acid and Oleanolic Acid: In Vitro, In Vivo, and Toxicity Assessments

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA a...

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Veröffentlicht in:Microorganisms (Basel) Jg. 12; H. 11; S. 2140
Hauptverfasser: Saini, Vinay, Mata Espinosa, Dulce, Pandey, Alok, Dighe, Vikas, Barrios Payán, Jorge, Prasad Myneedu, Vithal, Valdez Zarate, Ivan, Rajani, Dhanji P., Anande, Lalit D., Hernandez Pando, Rogelio, Srivastava, Rohit
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 01.11.2024
MDPI
Schlagworte:
Acids
Acquired immune deficiency syndrome
Acute toxicity
AIDS
Alveoli
Animal models
anti-tuberculosis activity
Antibiotics
Bacteria
Bioavailability
Biocompatibility
Diabetes
Drug resistance
Herbal medicine
HIV
Homogenization
Human immunodeficiency virus
Hydrophobicity
in vivo acute toxicity
In vivo methods and tests
Inhalers
Isomers
Lipids
Lungs
Macrophages
Microparticles
Minimum inhibitory concentration
Multidrug resistance
Natural products
Oleanolic acid
Polyvinyl alcohol
solid lipid microparticles
Terpenes
Toxicity
Tuberculosis
Ursolic acid
United Kingdom
Bolivia
United States
New Jersey
Missouri
India
St Louis Missouri
United States > US
anti-tuberculosis activity
solid lipid microparticles
oleanolic acid
in vivo acute toxicity
tuberculosis
ursolic acid
ISSN:2076-2607, 2076-2607
Online-Zugang:Volltext
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Zusammenfassung:Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile.
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These authors contributed equally to this work.
ISSN:2076-2607
2076-2607
DOI:10.3390/microorganisms12112140