A brief overview of oral vaccine development based on nano particle drug delivery system.

1. Nanoparticle Based
Oral Delivery of
Vaccines
Presented by: Ashok Patidar
M.S.(Pharm) Natural Products
Registration no. NK19NPM332
NIPER Kolkata
NATIONAL INSTITITE OF PHARMACEUTICAL EDUCATION AND RESEARCH
Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India

2. Introduction
• Nanoparticles are sub-nanosized colloidal structures composed of
synthetic or semi-synthetic polymers that exist on a nanometre scale.
• Size range : 10–1000 nm
• They can possess physical properties such as uniformity, conductance
or special optical properties that make them desirable in materials
science and biology.
• Vaccines are composed of antigens, which may be live-attenuated,
inactivated, killed organisms or minimal fractions of pathogenic
organisms including proteins or peptides responsible for producing
the desired immune response against infections
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3. • Oral delivery of vaccines represents the most attractive mode of
administration over other routes of delivery due to the fact that the
oral vaccination is
• Noninvasive and safe
• Simple to execute
• Showing good patient compliance
• Clinical practicality
• Several formulations based on nanoparticle strategies are currently
being explored to prepare stable oral vaccine formulations.
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4. Properties of an ideal oral vaccine
• Low cost
• Easy administration without medical professionals and special devices
• Capacity for large-scale production
• Stability under lyophilization and avoidance of cold-chain storage
• Sufficient protection of antigens against gastrointestinal fluids
• High antigen loading/encapsulating capacity of particles
• Strong mucosal adjuvanticity
• Prolonged exposure of antigens to antigen-presenting cells
• Optimum size for effective transportation of particles across intestinal lumen
• Sufficient targeting ability to intestinal cells (microfold-cells)
• Produce long-term mucosal and systemic immunity
• Adequate safety profile
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5. Oral mucosal vaccines (licensed and under clinical
trial)
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6. Nanoparticle based oral vaccine delivery
system
• NPs can be engineered to encapsulate vaccine components inside or
attached to their surfaces for efficient presentation to APCs.
• NPs based carriers can be decorated with functional molecules to
target the immune cells, enhance stability and modify the release
property of antigens.
• NP-based vaccine delivery has been gaining popularity due to its
ability to co-deliver antigens and adjuvants in a single particulate
carrier
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7. Various barriers in the gastrointestinal system encountered by oral vaccines and nanoparticulate vaccine
delivery
strategies to overcome these problems
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8. Nano particulate vaccines transport across
luminal region of the intestine
(A) Phagocytosis by indwelling macrophages in the M-cell. (B) DC-mediated luminal sampling from the M-cells. (C)
Transepithelial DC extension into the luminal region of the intestine. (D) Goblet cell-mediated transport of low molecular
weight soluble antigens to CD103+ DCs. (E) Enterocytic receptor-mediated transport (FcRn receptor). (F) Transcellular
transport across the enterocytes. (G) Paracellular transport between the walls of enterocytes. DCs: Dendritic cells; M-cell:
Microfold-cell.
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9. Intestinal immune system and immune
responses after administration of particulate
vaccine
(A) After particulate antigens are taken up
at the inductive sites, they are
presented to DCs.
(B) Antigen-presenting DCs actively migrate
to the mesenteric lymph nodes for
further CD4+ T-cell activation and
subsequent IgA+ B-cell production.
(C) The dimeric or polymeric IgA binds to Ig
receptors expressed on the basolateral
surface of epithelial cells to form SIgA.
(D) The complex is further transcytosed
toward the luminal surface of the
intestine (effector sites).
DCs: Dendritic cells; LP: Lamina propria; PPs:
Peyer’s patches; SIgA: Secretory IgA
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10. Nanoparticle interaction with antigen
• Vaccine formulations comprising nanoparticles and antigens can be
classified by nanoparticle action into those based on delivery system
and immune potentiator approaches.
• A delivery system, nanoparticles can deliver antigen to the cells of
the immune system, i.e. the antigen and nanoparticle are co-ingested
by the immune cell, or act as a transient delivery system, i.e. protect
the antigen and then release it at the target location.
• Immune potentiator approaches: nanoparticles activate certain
immune pathways which might then enhance antigen processing and
improve immunogenicity.
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11. Interaction of nanoparticle with antigen of
interest
Types of interaction:
1.Delivery system:
•Conjugation
•Encapsulation
2. Immune stimulator:
• Adsorption
• Mix.
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12. Nanoparticle-biosystem clearance
• Clearance of nanoparticles could be achieved through degradation by
the immune system or by renal or biliary clearance.
• biliary clearance through liver allows excretion of nanoparticles larger
than 200 nm.
• Renal clearance through kidneys can excrete nanoparticles smaller
than 8 nm.
• Surface charge that follows the order of positively-charged < neutral
< negatively charge.
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13. Techniques to determine interaction
with Immune cells
Many different in vivo molecular imaging techniques used are
magnetic resonance imaging (MRI)
 positron emission tomography (PET),
fluorescence imaging, single photon emission computed tomography
(SPECT),
 X-ray computed tomography (CT)
 ultrasound imaging
Superparamagnetic iron oxide nanoparticles (SPION)
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14. Pros and cons of oral nanoparticle
carriers
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15. Key issues
• The main challenges associated with oral vaccine delivery are sufficient protection of the
integrity of the antigens and effective transportation across the intestinal epithelium.
• Efficacy of oral vaccines is mostly hampered by the low population of microfold-cells (M-
cells) in the intestines.
• An alternative novel targeted delivery system is sought for effective delivery of oral
vaccines to M-cells, intestinal dendritic cells and enterocytes.
• Several polymer and lipid-based nanocarriers have shown potential to enhance the
immunogenicity of oral vaccines; however, there is no clear specific mechanism
identified to show how these carriers promote enhanced mucosal and immune
responses.
• Certain modifications of existing nanoparticulate delivery systems may drastically change
stability/efficacy of vaccines. For example, bilosomes in contrast to liposomes have
shown greatly improved stability in the gastrointestinal tract and during
production/storage.
• Further developments in nanoparticle vaccines should concentrate on simple and robust
design of the formulations for easy scale-up and commercialization.
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16. Bibliography
• Mantis NJ, Rol N, Corthe´sy B. Secretory IgA’s complex roles in immunity and
mucosal homeostasis in the gut. Mucosal Immunol 2011;4(6):603-11.
• Lycke N. Recent progress in mucosal vaccine development: potential and
limitations. Nat Rev Immunol 2012;12(8):592-605.
• Mohamadzadeh M, Durmaz E, Zadeh M, et al. Targeted expression of anthrax
protective antigen by Lactobacillus gasseri as an anthrax vaccine. Future
Microbiol 2010;5(8):1289-96.
• Kobayashi A, Donaldson DS, Erridge C, et al. The functional maturation of M cells
is dramatically reduced in the Peyer’s patches of aged mice. Mucosal Immunol
2013;6(5):1027-37.
• Swartz MA. The physiology of the lymphatic system. Advanced Drug Delivery
Reviews 2001;50:3–20.
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17. Bibliography
• Mody KT, Popat A, Mahony D, Cavallaro AS, Yu C, Mitter N. Mesoporous silica
nanoparticles as antigen carriers and adjuvants for vaccine delivery. Nanoscale
2013;5:5167–79.
• Stieneker F, Kreuter J, Lower J. High antibody-titers in mice with
polymethylmethacrylate nanoparticles as adjuvant for HIV vaccines. AIDS 1991;5:
431–5.
• He Q, Mitchell AR, Johnson SL, Wagner-Bartak C, Morcol T, Bell SJD. Calcium
phosphate nanoparticle adjuvant. Clinical and Diagnostic Laboratory Immunology
2000;7:899–903.
• Seubert A, Monaci E, Pizza M, O’Hagan DT, Wack A. The adjuvants aluminum
hydroxide and MF59 induce monocyte and granulocyte chemoattractants and
enhance monocyte differentiation toward dendritic cells. Journal of Immunology
2008;180:5402–12.
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18. Thank you
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