Engineered commensals for targeted nose-to-brain drug delivery

Area of Science:

• Neuroscience
• Microbiology
• Pharmacology

Background:

• Intranasal administration offers a direct route for brain drug delivery via the olfactory epithelium (OE).
• The OE's anatomical and absorptive limitations hinder the feasibility of this delivery pathway.
• Lactobacillus plantarum WCFS1 (Lp) is a commensal bacterium with natural OE affinity.

Purpose of the Study:

• To engineer Lactobacillus plantarum (Lp) as a vector for brain-targeted drug delivery.
• To assess the therapeutic efficacy of engineered Lp in a murine model of obesity.

Main Methods:

• Lactobacillus plantarum WCFS1 was engineered to release payload molecules in the OE.
• Engineered Lp was administered intranasally to a murine model.
• Recombinant production and secretion of appetite-regulating hormones were utilized.
• Obesity-related symptoms, including appetite, body weight, glucose metabolism, and fat mass, were evaluated.

Main Results:

• Engineered Lp successfully released payload molecules within the OE and transported them to the brain.
• Intranasal administration of engineered Lp significantly reduced appetite and body weight gain in mice.
• Improved glucose metabolism and reduced fat mass deposition were observed.
• The engineered Lp demonstrated therapeutic efficacy in obesity prevention.

Conclusions:

• Lactobacillus plantarum (Lp) can be effectively engineered as an intranasal delivery vehicle for brain-targeted therapeutics.
• This approach shows significant potential for developing novel treatments for obesity and related metabolic disorders.
• Further research into Lp-mediated brain delivery could open new avenues for neurological and metabolic disease therapies.