This document discusses mucosal delivery of vaccines. It begins by introducing mucosal surfaces as the major portal of entry for many pathogens and that immunization through mucosal routes can induce protective immunity at sites of entry. It then discusses various terms related to mucosal tissues and lymphoid structures. The remainder of the document outlines different polymer systems, formulations, design strategies and advantages/limitations for mucosal vaccine delivery, including emulsions, liposomes, polymeric nanoparticles, virosomes and melt-in-mouth strips. It also discusses single shot vaccines that provide protection from multiple diseases with one administration through use of vaccine adjuvants and antigen microencapsulation for delayed release.

1. Mucosal delivery of vaccines
• Presented by:
Alisha Bansal
M.Pharm(pharmaceutics)

2. INTRODUCTION
• Vaccination against infectious diseases has proven
to be an asset in preventing diseases and has
contributed significantly to an increase in life
expectancy.
• It is believed that the first productive interaction
among the most infectious agents and that host is
with mucosal surfaces, especially the agents and
the host is with mucosal surfaces, especially the
nasal, oropharyngeal, respiratory, genitourinary and
gastrointestinal mucosa.

4. Mucosal delivery of vaccines
• Mucosal surfaces area is major portal of entry for
many human pathogens that are the cause of
infectious diseases worldwide.
• Immunization by mucosal routes may be more
effective at inducing protective immunity against
mucosal pathogens at their sites of entry.
• Efforts have focused on efficient delivery of
vaccines antigens to mucosal sites that facilitate
uptake by local antigen-presenting cells to
generate protective mucosal immune responses.

9. TERMS
 Gut-associated lymphoid tissue (GALT)
 mucosa-associated lymphoid tissue (MALT)
 Nasopharynx-associated lymphoid tissue (NALT)
 Bronchi-associated lymphoid tissue (BALT)

10. • The adult human mucosa lines the surfaces of the
digestive, respiratory and genitourinary tracts,
covering an immune surface area that is nearly 200
times greater than that of the skin. It is estimated that
70% of the infectious agents enter the host by
mucosal routes.
• Mucosal surfaces are typically categorized as type-I
and type-II mucosa.
• Type-I mucosa includes surface area of lungs and gut.
• Type-II mucosa include surface area of mouth,
esophagus and cornea.
• The female genital tract has both type-I and type-II
mucosa.

11. • Most mucosal sites have organized lymphoid
follicles, such as NALT, and GALT, which have
assembly of scattered antigen-reactive cells of
immune system, such as B cells, T cells, and
professional antigen presenting cells such as
dendritic cells(APCs).
• These cells are responsible for the induction and
maintenance of immune responses against
mucosally delivered antigen.
• It is widely accepted that mucosal vaccination can
induce immune responses at both systemic and
mucosal sites and, prevent the invasion and
colonization of pathogens at mucosal surfaces.

12. WHY? Mucosal delivery of vaccines.
 Because injectable vaccines pose several
problems such as,
• High production cost
• Low/poor compliance
• Fear of needle borne infection
• Lack of mucosal immune response
• Injection site pain
• Local side effects

13. ADVANTAGES
• Low cost as compared to injectable vaccines.
• Easily adaptable for the purpose of mass
vaccination (especially desirable in pandemic
situation)

14. LIMITATIONS
• Hostile nature of gastrointestinal tract in case
of oral vaccine, impermeability of
biomacromolecule through the mucosal
epithelial barrier, presence of degrading
enzyme and fear of the inductiion of
tolerance.

15. POLYMERS USED FOR MUCOSAL
VACCINES
• The concept of polymeric carrier system(s)
offers advantage of delivering drugs/antigens
to a specific target site, where it has to be
released from the carrier.
• Polymeric nanoparticles/microparticles can
enhance the immune response to mucosally
administered antigens by several means.

16. Polymers used
• Polymeric materials used for the formulation of
microparticles / nanoparticles , include
POLYMERS
SYNTHETIC
PLA PLGA PCL
METHY
ETHACRYLATE
S
NATURAL
ALBUMIN CHITOSAN GALATIN ALGINATE

17. 1. CHITOSAN
• Chitosan is a cationic polysachharide
consisting of repeating units of N-acetyl-D-
glucosamine and D-glucosamine.
• Chitosan seems to augment immune
responses by enhancing the uptake of antigen
across the nasal mucosa.

18. 2. ALGINATE
• Alginate are safe, non-immunogenic and
inexpensive natural polymers with high
mucoadhesive properties.
• They are particularly used as thickeners or
emulsion stabilizers in manufacturing of
pharmaceutical formulations.
• Alginate microspheres have been used as
delivery system for antigens to mucosal
surfaces.

19. 3. GELATIN
• It is a natural, biodegradable protein obtained
by acid or base catalyzed hydrolysis of
collagen.
• Antibody-modified gelatin nanoparticles have
been used for targeted uptake by
lymphocytes.

20. 4. CARBOPOL
• Carbopol is a cross-linked poly of high
molecular weight, which is used
experimentally as an agent to enhance
adhesion to mucosal surfaces in combination
with other delivery systems and may facilitate
enhanced protection of peptides and proteins
against enzymatic degradation in the
gastrointestinal tract.

21. DESIGN AND STRATEGIES FOR
MUCOSAL DELIVERY

22. EMULSION TYPE DELIVERY
• Emulsions are heterogeneous liquid systems may be
w/o or o/w.
• Antigens are dissolved in a water phase and
emulsified in the oil in the presence of an
appropriate emulsifier.
• The controlled release characteristics of an
emulsion are determined by factors such as
– Viscosity of oil phase
– Oil to water phase ratio
– Emulsion droplet size

23. ADVANTAGES AND DISADVANTAGES
• ADVANATGES
• Slow release of antigen
• DISADVANTAGES
• Fever
• Sore arm at injection site
• Access immunogenic response

24. LIPOSOME BASED DELIVERY
• Liposomes are spherical shape vesicles containing
an aqueous core which is enclosed by a lipid bilayer.
• They are most often composed of phospholipids,
especially phosphatidylcholine, but may also
include other lipids, like Ethanolamine.

25. Preparation of Liposome Vaccine
Delivery System
Depending on the chemical properties, water-soluble antigens
(proteins, peptide, nucleic acids, carbohydrates, haptens) are
entrapped within the aqueous inner space of liposomes
Lipophilic compounds (lipopeptides, antigens, adjuvants, linker
molecules) are intercalated into the lipid bilayer
Antigens or adjuvants can be attached to the liposome surface
either by adsorption or stable chemical linking

26. ADVANTAGES AND DISADVANTAGES
• ADVANATGES
• Easy surface modification
• Synthesized from non toxic material
• Wide range of antigen encapsulation
• plasticity
• DISADVANTAGES
• Stability problem
• Low antigen loading

27. POLYMERIC NANO PARICLES
• Polymeric nan particles are submicron-sized
colloidal particles.
• Polymeric nanoparticles because of their size are
preferentially taken up by the mucosa associated
lymphoid Tissue.
• Limited doses of antigen are sufficient to induce
effective immunization.
• Hence, the use of nanoparticles for oral delivery
of antigens is suitable because of their ability to
release proteins and to protect them from
enzymatic degradation in the GIT.

28. VIROSOMES
• A Virosome is a a drug or vacine delivery mechanism
consisting of unilamellar phospholipid membrane vesicle
incorporating virus derived proteins to allow the virosomes
to fuse with target cells.
• These proteins enable the virosome membranes to fuse
with cells of the immune system and thus deliver the
specific antigens directly to their target cells.
• They elicit a specific immune response even with weak-
immunogenic antigens.
• Once they have delivered the antigens, the virosomes are
completely degraded within the cells.

30. MELT IN MOUTH STRIPS
• Quick dissolving films containing immunogens.
• Melts into liquid that children and infants will swallow
easily.
• These strips stick and dissolves on the tongue in less than
a minute. (useful for newborns who sometimes spit out
the liquid)
• EXAMPLE: ROTAVIRUS is a common cause of severe
diarrhea and vomiting in children. ROTAVIRUS VACCINE at
present is available in a liquid or freeze-dried form that
must be chilled for transport and storage, making it very
expensive for use in impoverished areas.

34. SINGLE SHOT
VACCINES

35. SINGLE SHOT VACCINES
• To provide effective patient protection, many
traditional vaccines require multiple
injections, which results in a costly and
inconvenient regimen. These disadvantages
have spurred the development of single-shot
vaccines that can provide protection against
infection with only one injection.

36. INTRODUCTION
• The single-shot vaccine is a combination product
of a prime component—antigen with an
appropriate adjuvant—and a microsphere
component that encapsulates antigen and
provides the booster immunizations by delayed
release of the antigen.
• They are given at a single contact point for
preventing 4 to 6 disease.
• In order to increase the therapeutic efficiency of
such vaccines, adjuvants are used.

37. DEFINITION • The single shot vaccine is
a combination product of
a prime component
antigen with an
microsphere component
and appropriate adjuvant
and an encapsulated
antigen which will
provide the booster
immunizations by
delayed release of the
antigen.
Polio vaccine

38. OBJECTIVES
• To elicit a protective immune response for a
long duration from a single-contact
immunization.
• Potentiate the immune response to the
vaccine without manifesting any adverse
effects.
• Incorporate many vaccines in a single
formulation.

39. VACCINE ADJUVANTS
• Adjuvants are the substance added to vaccines
to help them work better.
• Adding an adjuvant trigger the immune
system to become more sensitive to the
vaccine.

40. Why do we need adjuvants?
• To increase the therapeutic efficiency.
• They form depot of antigen at the site of
inoculation with slow release of antigens.
• It can improve the performance of vaccines by
targeting the antigen.

41. EXAMPLES OF ADJUVANTS
 ALUM
 VIROSOMES
 CYTOKINES
ALUM
• It is the most commonly used adjuvant
• Consists of Aluminium salts that are insoluble in
water
• Recently it is used in vaccines for HEPATITIS B

42. VIROSOMES
• They resemble to viruses but non-infectious
• They are included in FLU VACCINE and HEPATITIS A
VACCINE in europe
• Virosomes that are incorporated in these vaccines
have antigens and other proteins on their surface
• They are small proteins that serves as chemical
messenger of the immune system.
CYTOKINES

43. RECENT TRENDS
• Approaches for designing a prevent HIV
vaccine.
• Vaccine against Dengue.
• Malaria is mosquito born disease caused by a
parasite. Recent studies showed that upon
encapsulating a submit malarial antigen SPF66
in PLGA-mixture microspheres resulted in high
antibody levels in mice.

44. REFERENCES
1. Garg Neeraj, Mangal Sharad, Khambete
Hemant.”Recent patents on drug delivery &
formulation”;Mucosal Delivery of Vaccines:Role of
Mucoadhesive/Biodegradable Polymers
2010;4,114-128.
2. Saroja CH, Lakshmi PK”Recent trends in vaccine
delivery systems”:A Review International J pharm
investig.2011 apr-jun;1(2):64-74
3. Slideshare on vaccine delivery system by Ms Janu
Vashi, department of pharmaceutics, AR and GHP
college of pharmacy.

45. 4. Slideshare on vaccine delivery system by Sishant
Rav Divya BBAU Lucknow.
5.https;//www.slideshare.net/ANUSHANADIKATLA/
vaccine-delivery-79561747.