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Nanoparticle based oral delivery of vaccines


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

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Nanoparticle based oral delivery of vaccines

  1. 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. 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 2
  3. 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. 3
  4. 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 4
  5. 5. Oral mucosal vaccines (licensed and under clinical trial) 5
  6. 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 6
  7. 7. Various barriers in the gastrointestinal system encountered by oral vaccines and nanoparticulate vaccine delivery strategies to overcome these problems 7
  8. 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. 8
  9. 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 9
  10. 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. 10
  11. 11. Interaction of nanoparticle with antigen of interest Types of interaction: 1.Delivery system: •Conjugation •Encapsulation 2. Immune stimulator: • Adsorption • Mix. 11
  12. 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. 12
  13. 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) 13
  14. 14. Pros and cons of oral nanoparticle carriers 14
  15. 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. 15
  16. 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. 16
  17. 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. 17
  18. 18. Thank you 18