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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Vydáno v:	Microorganisms (Basel) Ročník 12; číslo 11; s. 2140
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland MDPI AG 01.11.2024 MDPI
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work.
ISSN:	2076-2607 2076-2607
DOI:	10.3390/microorganisms12112140