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LAB-Based Drug Delivery System Development

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Leveraging over a decade of experience in microbial genetics and formulation science, CD Formulation has established a versatile lactic acid bacteria (LAB) delivery system. Our engineered probiotic strains are precisely tailored for the targeted transport and release of diverse therapeutics. By fully developing customized LAB delivery vectors, we aim to enable safer and more effective treatments for cancer, IBD, vaccines and more.

How Can LAB Be Used in Drug Delivery?

Lactobacillus cell membrane coated PLGA nanoparticles for drug deliveryLactobacillus cell membrane coated PLGA nanoparticles for drug delivery (Weng L.; et al. 2022)

  • Drug Vector Development

LABs show promise as living drug delivery vehicles due to their ability to colonize the GI tract. Used in drug vectors, LAB can be engineered to produce and secrete payloads in targeted tissues, making them useful for mucosal delivery applications such as vaccines, drugs and gene therapies.

  • Biomimetic Nanoparticle Development

Membranes extracted from probiotic LAB can coat nanoparticle surfaces, mimicking bacterial membranes. These bioinspired particles can encapsulate drugs similar to LAB's metabolic functions. These bioinspired particles enable localization and dosing advantages for improved delivery outcomes.

What Types of LABs Can We Use to Develop Drug Delivery Systems?

What Types of LABs Can We Use to Develop Drug Delivery Systems

  • Lactococcus
  • Lactobacillus
  • Enterococcus
  • Bifidobacterium
  • Pediococcus
  • Leuconostoc
  • Streptococcus
  • Oenococcus

What Can We Do to Develop LAB-Based Drug Delivery System?

Strain Customization
  • Screen LAB strains for colonization/persistence at target sites such as the gut and vaginal mucosa.
  • Evaluate intrinsic production properties.
  • Engineer strains with higher expression and tighter regulation.
  • Attenuate pathogenic strains while retaining delivery attributes.
  • Test survival under various environmental stresses.
Vector Construction
  • Select appropriate plasmids and promoters based on strain type.
  • Design plasmids incorporating inducible promoters, signal sequences for secretion/surface display.
  • Develop genetic parts for tunable functions like detection of biomarkers.
DNA Vaccine Delivery
  • Modify Lactobacillus strains to deliver DNA vaccine constructs.
  • Enhance Lactobacillus adhesion to mucosal surfaces for effective vaccine delivery.
  • Develop methods to maintain DNA vaccine integrity and stability within the Lactobacillus during storage and transit.
  • Assess the immune response generated by Lactobacillus-delivered DNA vaccines in preclinical models.
LABM-Coated Nanoparticle Development
  • Choose suitable LAB strains based on desired properties.
  • Extract the cell membrane from LAB to serve as the coating material for nanoparticles.
  • Prepare nanoparticles with the desired properties.
  • Coat the nanoparticles with the LAB cell membrane (LABM) by employing techniques like sonication and extrusion.
  • Analyze the coated nanoparticles for their size, morphology, stability, zeta potential, and membrane integrity.
  • Assess the pharmacokinetics, biodistribution, cellular uptake, and therapeutic efficacy of LAB cell membrane-coated nanoparticles.

Our Technologies for LAB-Based Drug Delivery System Development

  • Comprehensive strain bank with diverse Lactobacilli isolated from the GI tract with optimized production properties.
  • Molecular toolbox including cloning vectors, strong inducible promoters, signal sequences for targeted secretion/display.
  • Genome editing expertise using CRISPR for precise modifications like gene knock-in/knock-out.
  • Surface display technologies impart targeting attributes like selective tissue adhesion. 
  • Analytical skills for robust product quantification, characterization and quality control.
  • Formulation technologies for stabilizing live biotherapeutics and targeting different routes of administration.
  • In vitro and in vivo validation platform using relevant cell and animal infection models.

Advantages of Our LAB-Based Drug Delivery System Development Services

  • LAB has a natural affinity for mucosal surfaces, making it an ideal vehicle for delivering drugs to mucosal tissues, such as the gastrointestinal tract, respiratory system, or urogenital tract.
  • LAB strains often possess inherent probiotic properties, offering potential additional health benefits to the host, such as improved gut microbiota balance and immune modulation.
  • Our team possesses advanced knowledge and expertise in genetic engineering techniques, enabling the precise modification of Lactobacillus strains for drug delivery purposes.

At CD Formulation, our LAB-based drug delivery system development services offer a cutting-edge solution for targeted and efficient nucleic acid therapeutics delivery. With our expertise in genetic engineering, we can modify Lactobacillus strains to precisely deliver drugs to specific organs, tissues, or mucosal surfaces. Contact us today to discuss your drug delivery needs and collaborate on innovative solutions!

References

  1. Blanch-Asensio M.; et al. Expanding the genetic programmability of Lactiplantibacillus plantarum. Microb Biotechnol. 2023, available online.
  2. Batista V.L.; et al. Lactic Acid Bacteria as Delivery Vehicle for Therapeutics Applications. Methods Mol Biol. 2021, 2183:447-459.
  3. Weng L.; et al. Lactobacillus cell envelope-coated nanoparticles for antibiotic delivery against cariogenic biofilm and dental caries. J Nanobiotechnology. 2022, 20(1):356.
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