article · Pharmaceuticals
Rising antimicrobial resistance in Klebsiella pneumoniae demands alternative therapeutic compounds. Lycopene, isolated from tomatoes, demonstrates promising computational binding affinity to vital bacterial proteins, but practical application is limited by poor solubility and low oral bioavailability. To address these delivery challenges, bilosomes were formulated as oral nanocarriers. The optimised bilosomes achieved high entrapment efficiency, a stable sub-micron size, and controlled drug liberation following Higuchi kinetics. Laboratory assessments against multidrug-resistant Klebsiella pneumoniae isolates showed that bilosome encapsulation significantly reduced the minimum inhibitory concentration, while electron microscopy confirmed direct bacterial cell deformation and lysis. In a mouse model of lung infection, orally administered bilosomes reduced inflammation, congestion, and pulmonary fibrosis, preserving normal alveolar and bronchiolar architecture. These findings show that bilosomes can serve as an effective delivery system to enhance the in vivo antimicrobial efficacy of lycopene.
Multidrug-resistant bacterial infections, including those caused by Klebsiella pneumoniae, present severe challenges to conventional antibiotic therapies. Natural plant-derived molecules offer an alternative treatment strategy, but their clinical use is often hindered by poor absorption. Demonstrating that lipid nanocarriers can successfully deliver such compounds orally provides a pathway to develop alternative therapies for severe and drug-resistant bacterial lung infections.
This technology represents an early-stage formulation approach of potential interest to pharmaceutical developers working on antimicrobial delivery systems. It could enable the oral administration of hydrophobic therapeutic compounds against multidrug-resistant respiratory pathogens. Because the findings are currently limited to laboratory testing and a mouse infection model, substantial further testing, including comprehensive toxicity studies, pharmacokinetic evaluations, and clinical trials, is required before real-world commercial application.
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Owing to the disseminating resistance among pathogenic bacteria, especially <i>Klebsiella pneumoniae</i>, there is a high need for alternate compounds with antibacterial activity. Herein, lycopene was isolated from <i>Lycopersicon esculentum</i> L. Molecular docking approach was employed to explore lycopene binding affinity to selected vital proteins of <i>K. pneumoniae</i> with the binding mechanisms being investigated. This proposed a promising antibacterial activity of lycopene. However, the pharmacological use of lycopene is hampered by its poor solubility and limited oral bioavailability. Accordingly, bilosomes were fabricated for oral lycopene delivery. The computed entrapment efficiency, mean vesicular size, and zeta potential values for the optimized formulation were 93.2 ± 0.6%, 485.8 ± 35.3 nm, and -38.3 ± 4, respectively. In vitro drug release studies revealed controlled lycopene release from constructed bilosomes, with the drug liberation being based on the Higuchi kinetics model. Transmission electron microscopic evaluation of bilosomes revealed spherical nanovesicles free from aggregates. Moreover, the in vitro and in vivo antibacterial activity of lycopene and its constructed formulations against multidrug-resistant <i>K. pneumoniae</i> isolates were explored. The optimized bilosomes exhibited the lowest minimum inhibitory concentrations ranging from 8 to 32 µg/mL. In addition, scanning electron microscopy revealed remarkable deformation and lysis of the bilosomes-treated bacterial cells. Regarding in vivo investigation, a lung infection model in mice was employed. The tested bilosomes reduced the inflammation and congestion in the treated mice's lung tissues, resulting in normal-sized bronchioles and alveoli with very few congested vessels. In addition, it resulted in a significant reduction in pulmonary fibrosis. In conclusion, this study investigated the potential activity of the naturally isolated lycopene in controlling infections triggered by multidrug-resistant <i>K. pneumoniae</i> isolates. Furthermore, it introduced bilosomes as a promising biocompatible nanocarrier for modulation of oral lycopene delivery and in vivo antimicrobial activity.
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DOI: 10.3390/ph15091043
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