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Single versus double occupancy solid lipid nanoparticles for delivery of the dual-acting bacteriocin, lacticin 3147
Date
2022
Abstract
The bacteriocin lacticin 3147 (lacticin) has shown activity against clinically relevant and antimicrobial-resistant bacteria such as Listeria monocytogenes and Clostridioides difficile. It is composed of two peptides, LtnĪ± and LtnĪ², which work together to form pores in the membrane of Gram-positive bacteria. Lacticin possesses poor aqueous solubility and is degraded by intestinal proteases. In a previous study, peptides encapsulated into solid lipid nanoparticles (SLNs) displayed activity in aqueous media and were protected from enzyme degradation but showed a low encapsulation efficiency (EE%) for LtnĪ±. In this study, however, lacticin was encapsulated into SLNs both individually (single occupancy, SLNĪ± + SLNĪ²) and together (double occupancy SLNĪ±Ī²) via a nano precipitation technique. This achieved SLNs of uniform size with an EE% above 87% for both peptides at loadings of 9 or 18 mg/g of lipid under single occupancy or double occupancy respectively. SLNĪ±Ī² dispersions displayed more potent activity at 3.13 and 1.56 Āµg/ml lacticin than SLNĪ± + SLNĪ² dispersions. Thus, the SLNĪ±Ī² dispersion was chosen for further analysis. SLNĪ±Ī² dispersions showed no cytotoxicity to endothelial cells. The SLN release media (fasted state simulated intestinal fluid; FaSSIF) retained activity at 1 h and 3 h indicating that lacticin may be sufficiently protected from proteases present in the duodenum. Finally, a reconstituted freeze-dried SLNĪ±Ī² dispersion was stable and achieved 99.99% bacterial killing at 3.125 Āµg/ml lacticin. Thus, an SLN based lacticin delivery system was developed, potentially enabling oral administration of the bacteriocin to the colon to treat local infections such as C. difficile.
Supervisor
Description
Publisher
Elsevier
Citation
European Journal of Pharmaceutics and Biopharmaceutics, 176 pp. 199-210
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Ryan_2022_Single.pdf
Adobe PDF, 2.62 MB
Funding code
Funding Information
Department of Chemical Sciences, University of Limerick