VACCINE DRUG DELIVERY SYSTEM.pptx

vaccine drug delivery system m pharmacy

1. VACCINE DRUG DELIVERY SYSTEM SUBMITTED TO : SUBMITTED BY: DR. GURPREET KAUR NAVANEETH S SUNIL M PHARM 1 ST SEM

2. CONTENTS INTRODUCTION TYPES OF VACCINES UPTAKE OF ANTIGENS SINGLE SHOT VACCINES TRANSDERMAL VACCINE DELIVERY SYSTEM MUCOSAL VACCINE DELIVERY SYSTEM

3. INTRODUCTION A vaccine is a biological preparation that provides active acquired immunity to particular infectious disease. A vaccine typically contains an agent that resembles a disease causing by microorganism and is often made from weakened or killed forms of the microbe . The agent stimulates the body’s immune system to recognize the agent as a threat. The same agent further recognize in future and destroy it. The administration of vaccine is called vaccination.

4. The goal of vaccination is to stimulate a strong protective and long lasting immune response to the administered antigen.

5. PROPERTIES OF AN IDEAL VACCINE Give lifelong immunity. Prevent disease transmission. Rapidly induce immunity. Need to be Stable, cheap and safe. Effective in all subjects( the old and very young). Transmit maternal protection to the fetus .

6. ROUTES OF ADMINISTRATION Deep subcutaneous or intra muscular route (most vaccines). Oral route ( oral BCG vaccine). Intradermal route (BCG vaccine). Intranasal route ( live attenuated influenza vaccine). Scarification ( small pox vaccine).

7. COMPOSITION OF VACCINE Vaccines consist of: BULK ANTIGEN + OTHER FLUIDS(water or saline) + PRESERVATIVES + ADJUVANTS. These ensure the quality and potency of the vaccine over its shelf life. Vaccines are always formulated as to be safe and immunogenic when injected to humans. It is formulated as liquids, but may be as freeze-dried for reconstitution immediately prior to time of injection.

8. How do vaccines work? A Vaccine is a tiny weakened non-dangerous fragment of the organism and includes part of the antigen So, after get vaccinated its enough that our body can learn to build the specific antibody Then if the body encounters by the real antigen later as a part of real organism , body already knows how to defeat.

9. Herd immunity People with underlying health conditions that weaken their immune systems (such as cancer or HIV) or who have severe allergies to some vaccine components may not be able to get vaccinated with certain vaccines. These people can still be protected if they live in and amongst others who are vaccinated. When a lot of people in a community are vaccinated the pathogen has a hard time circulating because most of the people it encounters are immune. So the more that others are vaccinated, the less likely people who are unable to be protected by vaccines are at risk of even being exposed to the harmful pathogens. This is called herd immunity.

10. CLASSIFICATION OF VACCINES 1 . TRADITIONAL VACCINE : Killed vaccine Live attenuated vaccine Toxoid Subunit vaccine 2 . INNOVATIVE VACCINE : Conjugate vaccine Recombinant vector vaccine T- cell receptor peptide vaccine Valence Heterotypic

11. TRADITIONAL VACCINES Killed – The killed but previously virulent, microorganism that have been destroyed with chemicals, heat, radioactivity or antibiotics. Eg : influenza, cholera, polio. Live, attenuated – some vaccine contain live, attenuated microorganism. Some of the active viruses that have been cultivated under condition that disable their virulent properties to produce a broad immune response. Eg : yellow fever, measles.

12. Toxoid- made from inactivated toxic compound that cause illness rather than the microorganism. The toxins are inactivated by treating them with formalin. Such detoxified toxins are called toxoids. Eg : T etanus and Diphtheria. Subunit – It is a protein subunit, a fragment of it can create an immune response. Instead of the entire microbe, subunit vaccines include only the antigens that stimulate the immune system. Eg : Plague immunization

13. INNOVATIVE VACCINE Conjugate vaccine- certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking the outer coats to the stronger protein, the immune system able to recognise the antigen. Eg : Haemophilus influenza type B vaccine. Recombinant vector vaccine- by combing the physiology of the microorganism and the DNA of the other, immunity can be created against the disease . Eg : DPT

14. Valence- Monovalent : use to immunize against single antigen. Multivalent : use to immunize against two or more microorganism. Heterotypic- Vaccines,that are pathogens of other animals that do not cause disease or cause mild disease in the organism being treated. Eg : BCG vaccine made from Mycobacterium bovis to protect against tuberculosis.

15. UPTAKE OF ANTIGEN ANTIGENS: The components of the disease-causing organisms or the vaccine components that trigger the immune response are known as antigen. ANTIBODIES: These antigens trigger the production of antibodies by the immune system. Antibodies bind to corresponding antigens and induce their destruction by other immune cells.

16. Steps involved The induced immune response to either a disease-causing organism or to a vaccine makes the body’s immune cells to be capable of quickly recognizing, reacting to, and control the relevant disease causing organism. When the body’s immune system is subsequently exposed to a same disease-causing organism, the immune system will target the antigen and eliminate the infection before it can cause harm to the body.

17. EXOGENOUS ANTIGENS ► Exogenous antigens are derived from proteins that enter from outside into the body. ► These includes various bacterial, viral, protozoal, fungal and parasitic antigens which are derived from outside the body

18. Stages of exogenous antigen uptake Access or uptake of exogenous antigens and pathogens to intracellular pathways of degradation Degradation of antigens to peptides by proteolysis Loading of peptides on major histocompatibility complex (MHC)and form Antigen-MHC complex Then transport and expression of peptide-MHC complex on the surface of cell for recognition by T cells

19. What is MHC? The Major Histocompatibility Complex (MHC) is a set of cell surface proteins that essential for the Acquired immune system to recognize foreign molecules The main function of MHC molecules is to bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells

20. ENDOGENOUS ANTIGEN ► Endogenous antigens are derived from proteins produced inside the cell. ► These includes altered self-protein antigens (e.g. tumor antigens) and non-self protein antigens (e.g. viral antigens).

21. Stages of endogenous antigen uptake Antigens/pathogens already present in the cell Antigens synthesized in cytoplasm undergo limited proteolytic degradation to form peptides Formation of complex of peptide -MHC Then transport and expression of peptide-MHC complex on the surface of cell for recognition by T cells

22. SINGLE SHOT VACCINE In traditional vaccines are requires booster dose and repeated dose to induced immunity. . Single shot vaccines are given for preventing four to six diseases with only one injection. These disadvantages have spurred the development of single shot vaccine that can provide protection against infection with only one injection

23. Concepts ► The single shot vaccine is a combination product of a prime component antigen with appropriate adjuvant and a microsphere component. ► Adjuvants increase the therapeutic efficiency of such vaccines. ► Microsphere component that encapsulated antigen and provides the booster immunization by delayed release of the antigen.

24. FORMULATION OF SINGLE SHORT VACCINES Antigen/protein Vaccine adjuvants gel types: aluminium hydroxide , calcium phosphate oil emulsion and emulsifier based: liposomes , bio microspheres Biodegradable polymers natural polymers: albumin, collagen, gelatin synthetic bio polymer : aliphatic polyesters

25. VACCINE ADJUVANT Adjuvant are the substances added to vaccine to help them work better .Adding an adjuvant triggers the immune system to became more sensitive to the vaccine. Need for Adjuvant ;- ► To increase the therapeutic efficiency ► They form depot of antigen at site of inoculation with slow release of antigen. ► It can improve the performance of vaccines by targeting the antigen to APC

26. TRANSDERMAL VACCINE DELIVERY SYSTEM ► INTRODUCTION: The transdermal drug delivery system is a technique that provides drug absorption via the skin. Skin is known to be the highly immunogenic site for vaccination. Transdermal delivery is one of the needle free method of vaccine delivery.

27. NEEDLE-FREE DELIVERY ► Needle-free technology (Jet injectors), were developed in the 1930s and used extensively over 50 yr in mass vaccination programs in people for smallpox, polio, and measles .

28. JET INJECTORS Jet injector uses either spring mechanism or it consist of pressurized gases in a small cartridge or large canister form to force the aerosolized drug into the solution or through the skin either directly into the muscle or into the subcutaneous or intradermal layers. A high enough pressure can be generated by a fluid in intimate contact with the skin, then the liquid will punch a hole in to the skin and be delivered in to the tissues

29. MECHANISM OF JET INJECTOR ► It consist of a power source (compressed gas or spring), piston, drug-loaded compartment and a nozzle with orifice size typically ranging between 150 and 300microns. ► Upon triggering the actuation mechanism, the power source pushes the piston. ► there by leading to a quick increase in pressure. ► This forces the drug solution through the nozzle orifice as a liquid jet with velocity ranging between 100 and 200m/s.

30. MICRONEEDLES It consist of pointed micro sized projections fabricated into arrays up to hundred needles to penetrate the skin surface thereby allow the vaccine delivery. It is made of titanium or silicone. There are several approaches for the delivery of vaccines by the microneedles namely: Poke and patch method Coat and poke method Poke and release method Poke and flow method

31. 1.Poke and patch method The microneedle permeabilize the skin by forming micro sized holes through the stratum corneum. Then the microneedle array is removed and then the vaccine containing patch is applied. This approach is termed as poke and patch method.

32. 2.Coat and poke method Solid microneedles are coated with dry powder in the skin. Coated microneedles have an insoluble core coated with dry powder vaccine that dissolves off within the skin. This approach is termed as “coat & poke”.

33. 3.Poke and release method Polymer microneedles contain the vaccine in a solid solution of needle that dissolves, swells or degrades on skin insertion, then releases the vaccine This approach is termed as “poke & release”.

34. 4. Poke and flow method Hollow microneedles through which the vaccine solution can be infused into the skin. Insoluble hollow microneedles create holes through which the vaccine solution can pass into the skin This approach is termed as “poke & flow”.

35. MUCOSAL VACCINE DELIVERY SYSTEM Mucosal surface area is major portal of entry for many human pathogens that are the cause of infectious disease worldwide. Immunization by mucosal routes may be more effective at inducing protective immunity against mucosal pathogens at their site of entry. Discovery of safe and effective mucosal adjuvants are also being sought to enhance the magnitude and quality of the protective immune response. It is estimated that 70% of infectious agents enter the host by mucosal routes.

36. INTRANASAL VACCINE DELIVERY Nasal administrations of vaccines have been shown to achieve a better systemic bioavailability and protection from gastric enzymes compared with parenteral and oral administration. Thus increasing the general efficacy of the vaccine Nasal immunization does not require needles and syringes ORAL VACCINE DELIVERY Oral vaccination is the preferred route for patients, it is easy to administer to all ages of patient. Oral vaccination is much easier to arrange for large-scale vaccination programs. There are examples of oral administration of oral polio.

37. ORAL CAVITY VACCINE DELIVERY Sublingual (SL) vaccines also lead to systemic uptake of antigens into the bloodstream, avoiding first-pass metabolism by the liver and facilitating a more direct stimulation of immunity. Tablets or mucoadhesive films create there most stable vaccines that dissolve under the tongue. INTRA PULMONARY VACCINE DELIVERY The lungs are a good target for vaccine administration due to their large surface area and the presence of large numbers of antigen-processing alveolar macrophages and dendritic cells. There are a variety of delivery devices for achieving drug delivery to the lungs, including inhalers and nebulizer. eg -BCG Vaccine

38. DESIGN AND STRATERGIES FOR MUCOSAL DELIVERY EMULSION TYPE DELIVERY LIPOSOME BASED DELIVERY POLYMERIC NANO PARTICLES VIROSOMES MELT IN MOUTH STRIPS

39. 1.Emulsion type delivery Emulsions are heterogeneous liquid systems may be water-in-oil emulsions(w/o) , oil in water emulsions(o/w), or more complex systems such as water in oil in water (w/o/w) multiple emulsions, micro emulsions, or nano emulsions. Antigens are dissolved in a water phase and emulsified in the oil in the presence of an appropriate emulsifier. Eg : High oil content – injection site irritation. Too large droplet size – physically unstable product.

40. 2.Liposome based delivery Liposomes are spherical shape vesicles containing an aqueous core which is enclosed by a lipid bilayer. Depending on the chemical properties, water soluble antigens (proteins, peptides, nucleic acids , carbohydrates) are entrapped within the aqueous inner space of liposomes. Antigens or adjuvants can be attached to the liposome surface either by adsorption or stable chemical linking

41. 3.Polymeric nano particles Polymeric nanoparticles 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 gut.

42. Biodegradable Poly Methyl Metha Acrylate (PMMA) nanoparticles being very slowly degradable ( 30% - 40% per year) appears to be particularly suitable for vaccine purpose because prolonged contact between antigen and immunocompetent cells favours persistent immunity.

43. 4.Virosomes A virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid membrane of 150 mm (either mono or bilayer) 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.

44. Once they have delivered the antigens, the virosomes are completely degraded within the cells. Virosomes represent vesicular systems into which antigens can be loaded into virosomes or adsorbed onto the virosomal surface through hydrophobic interactions.

45. 5.Melt in mouth strips Quick dissolving films containing immunogens/antigens. Melts into liquid that children and infants will swallow easily. The strips stick and dissolves on the tongue in less than a minute Eg : Rotavirus vaccine is available in mouth strips.

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