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Pharmaceutical design of a delivery system for the bacteriocin lacticin 3147
Aoibhín Ryan1, Pratikkumar Patel1, Paula M O'Connor2,3
1Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland.
Abstract:
Lacticin 3147 is a dual-acting two-peptide bacteriocin which is generally active against Gram-positive bacteria, including Listeria monocytogenes and antimicrobial-resistant bacteria such as Closteroides difficile in the colon. L. monocytogenes infections can cause life-long effects in the elderly and vulnerable and can cause severe complications in pregnant women. C. difficile causes one of the most common healthcare-associated infections and can be fatal in vulnerable groups such as the elderly. Although lacticin 3147 is degraded by intestinal proteases and has poor aqueous solubility, encapsulation of the bacteriocin could enable its use as an antimicrobial for treating these bacterial infections locally in the gastrointestinal tract. Lacticin 3147 displayed activity in aqueous solutions at a range of pH values and in gastric and intestinal fluids. Exposure to trypsin and α-chymotrypsin resulted in complete inactivation, implying that lacticin 3147 should be protected from these enzymes to achieve successful local delivery to the gastrointestinal tract. The amount of lacticin 3147 dissolved, i.e. its solution concentration, in water or buffered solutions at pH 1.6 and 7.4 was low and varied with time but increased and was stabilized in gastrointestinal fluids by the phospholipid and bile salt components present. Thus, the feasibility of a solid lipid nanoparticle (SLN) delivery system for local administration of lacticin 3147 was investigated. Bacteriocin activity was observed after encapsulation and release from a lipid matrix. Moreover, activity was seen after exposure to degrading enzymes. Further optimization of SLN delivery systems could enable the successful pharmaceutical development of active lacticin 3147 as an alternative to traditional antibiotics.
Insights
Lacticin 3147, a bacteriocin, shows potential against dangerous bacteria like Listeria and C. difficile. Encapsulation in solid lipid nanoparticles (SLN) may overcome degradation and solubility issues for effective gastrointestinal delivery.
Area of Science:
- Microbiology
- Biotechnology
- Pharmaceutical Sciences
Background:
- Lacticin 3147 is a dual-acting bacteriocin effective against Gram-positive pathogens, including Listeria monocytogenes and Clostridioides difficile.
- L. monocytogenes and C. difficile infections pose significant risks, particularly to vulnerable populations like the elderly, pregnant women, and healthcare patients.
- Lacticin 3147 faces challenges in gastrointestinal delivery due to protease degradation and poor aqueous solubility.
Purpose of the Study:
- To investigate the feasibility of using solid lipid nanoparticles (SLN) for the local delivery of lacticin 3147 in the gastrointestinal tract.
- To assess the stability and activity of lacticin 3147 when encapsulated within SLNs, particularly in the presence of gastrointestinal fluids and enzymes.
- To explore the potential of lacticin 3147, delivered via SLNs, as an alternative antimicrobial agent.
Main Methods:
- Encapsulation of lacticin 3147 within solid lipid nanoparticles (SLN).
- Assessment of lacticin 3147 activity in aqueous solutions, gastric, and intestinal fluids.
- Evaluation of lacticin 3147 stability and activity after exposure to intestinal proteases (trypsin and α-chymotrypsin).
- Testing the antimicrobial activity of encapsulated lacticin 3147 after release from the lipid matrix and exposure to degrading enzymes.
Main Results:
- Lacticin 3147 demonstrated activity across a range of pH values and in simulated gastric and intestinal fluids.
- Enzymatic degradation by trypsin and α-chymotrypsin completely inactivated lacticin 3147 in solution.
- Phospholipid and bile salt components in gastrointestinal fluids enhanced and stabilized lacticin 3147 solubility.
- Encapsulated lacticin 3147 retained antimicrobial activity after release from the SLN and even after exposure to degrading enzymes.
Conclusions:
- Solid lipid nanoparticles (SLN) show promise as a delivery system for lacticin 3147, protecting it from enzymatic degradation.
- Encapsulation can overcome the poor aqueous solubility of lacticin 3147, enabling its potential use for local gastrointestinal treatment.
- Further optimization of SLN formulations could lead to the pharmaceutical development of lacticin 3147 as a novel antimicrobial agent against resistant pathogens.
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