MUCOSAL AND TRANSDERMAL DELIVERY OF VACCINE.pptx

MUCOSAL AND TRANSDERMAL DELIVERY OF VACCINE

1. MUCOSAL AND TRANSDERMAL DELIVERY OF VACCINE Presented By Suryawanshi Kranti Ashok First Semester, M. Pharmacy Department of Pharmaceutics Guided By Dr. A. B. Gangurde Head of Department Department of Pharmaceutics KBHSS Trust Institute Of Pharmacy, Bhaygaon Road, Malegaon

2. CONTENT Introduction Mucosal Vaccine Delivery System Design and strategy for Mucosal Delivery Transdermal Vaccine Delivery system Design and strategy for Transdermal Vaccine Delivery Reference

3. INTRODUCTION A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. A vaccine contain agent that resemble a disease.

4. The agent stimulate the body's immune system to recognize foreign agent, destroy it, and keep a record of it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters. Vaccines can be prophylactic (to prevent or ameliorate the effects of a future infection by any natural or wild pathogen), or therapeutic (vaccines against cancer).

5. First vaccine was developed in 1878 for small pox by Edward Jenner, His innovations begun with successful use of cowpox material to create immunity against smallpox. The second generation of vaccines was introduced in 1880s by Louis Pasteur who developed vaccines for chicken cholera and anthrax

6. MUCOSAL VACCINE DELIVERY SYSTEM Mucosal surfaces 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 sites of entry. Efforts have focused on efficient delivery of vaccine antigens to mucosal sites that facilitate uptake by local antigen-presenting cells to generate protective mucosal immune responses.

7. The adult human mucosa lines the surfaces of the Digestive, Respiratory and genitourinary tracts, covering an immense surface area (400 M2) that is~200 times greater than that of the skin. Mucosal surfaces are typically categorized as Type-1 and Type-2 mucosa. Type-1 mucosa include surface of the lung and gut, where as Type-2 mucosa include surfaces of the mouth, esophagus and cornea

8. PRINCIPLE OF WORKING Mucosal route allows to interact antigen with defensive mucosal layers, so induced mucosal immunity then kills pathogen before reaching the systemic circulation(next time)

9. Vaccine Mechanism

10. MUCOSAL TYPE Sublingual Intranasal Oral Vaginal Rectal

11. DESIGN AND STRATERGIES FOR MUCOSAL DELIVERY Emulsion type delivery Melt in mouth strips Liposome based delivery Polymeric nano-particles Virosomes

12. 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. The controlled release characteristics of an emulsion are determined by factors such as viscosity of oil phase, oil-to-water phase ratio and emulsion droplet size.

13. E.g. high oil content can cause unnecessary injection site irritation and too large a droplet size can result in a physically unstable product there by reducing its shelf life. Huang et developed a novel emulsion-type vaccine delivery systems of the amphiphilic bioresorbable polymer polyethylene glycol)- block-poly (lactide-co-epsilon-caprolactone) (peg-b- placl ) using ovalbumin as model antigen.

14. Results from physicochemical characterization studies and in- vitro release studies showed that they are composed of homogenous fine particles. Advantages Slow release of antigen Disadvantages Access immunogenic response Fever Sore arm at injection site

15. LIPOSOME BASED DELIVERY Liposomes are spherical shape vesicles containing an aqueous core which is enclosed by a lipid bi-layer. They are most often composed of phospholipids, especially phosphatidylcholine, but may also include other lipids, such as eggphosphatidyl-ethanolamine.

16. Preparation of Liposome Vaccine Delivery System Depending on the chemical properties, water- soluble antigens (proteins, peptides, 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.

17. Schematic representation of a small unilamellar liposome showing the versatility of incorporation of various compounds either by encapsulation in the aqueous inner space or by integration in the bilayer or surface attachment on the lipid bilayer membrane. CpG, cytosine–phosphonothioate–guanine oligodeoxynucleotide; PEG, poly(ethylene glycol).

18. POLYMERIC NANO PARTICLES Polymeric Nanoparticles (PNPS) 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.

19. 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. Biodegradable poly (alkyl cyano-acrylate) (PACA) nanoparticles have been shown to enhance the secretory immune response after their oral administration in association with ovalbumin in rats. Biodegradable poly(methyl metha acrylate) (PMMA) nanoparticles being very slowly degradable (30%-40% per year) appear to be particularly suitable for vaccine purposes because prolonged contact between antigen and immunocompetent cells favors persistent immunity.

20. VIROSOMES A virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid membrane~150mm (either a mono - or bi-layer) 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.

21. Once they have delivered the antigens, the virosomes are completely degraded within the cells.

22. MELT IN MOUTH STRIP Quick dissolving films containing Immunogens Melts into liquid that children and infants will swallow easily First designed by undergraduate students at Johns Hopkins University on Biomedical Engineering design day for Protection against Rota virus infection.

23. TRANSDERMAL VACCINE DELIVERY SYSTEM The skin is the largest and most accessible organ of the body. Vaccine administration to the skin offers many advantages including ease of access, a potential for generation of both systemic and mucosal immune response. Formulation approaches such as liposomes, physical penetration enhancers such as electroporation, and technologies that create micron-sized pores in the skin, such as microneedles.

24. Skin As A Site Of Vaccine Delivery The skin has multiple barrier properties. To minimize water loss from the body. Prevent the permeation of environmental contaminants into the body. These barriers can be considered as physical, enzymatic and immunological. Physical Barriers The outermost layer, stratum corneum presents an effective physical barrier to the permeation of large molecules such as vaccines. This is the first barrier property that must be overcome to provide effective transdermal vaccine delivery

25. Enzymatic Barrier The skin possesses many enzymes that are capable of hydrolyzing peptides and proteins. Their potential to degrade topically applied vaccine antigens should be considered. Immunological Barriers When the skin is damaged, environmental contaminants can access the epidermis to initiate an immunological response.

26. Many approaches have been investigated to overcome the skins barrier properties in order to deliver antigens via the skin. All methods aim to overcome the stratum corneum barrier and target vaccine to immune- responsive cells such as Langerhans cells. Immunization by transdermal route includes some approaches like:

27. DESIGN AND STRATEGY FOR TRANSDERMAL VACCINE DELIVERY LIQUID JET INJECTORS Liquid jet injectors use a high-velocity jet (typically 100 to 200 m/s) to deliver molecules through the skin into the subcutaneous or intramuscular region. Jet injectors can be broadly classified into, Multi-use nozzle jet injectors (MUNJIS) Disposable cartridge jet injectors (DCJIS)

28. Commercially Available liquid jet injectors consists of, Power source (compressed gas or spring) Piston Drug or vaccine-loaded compartment Application nozzle, with typical orifice size in the range of 150 μm tο 300 μm Applications of jet injectors Applications of liquid-jet injectors have been focused on delivery of macromolecules that do not passively permeate the skin.

29. It has been shown to increase immune responses to both conventional and DNA-based vaccines. e.g. Hepatitis a vaccine or a influenza vaccine, were found to be increased by at least 10% when using needle-free injections compared to needle and syringe administration Commercially Available Devices Include, vision® And Choice® Which Delivers A Variable Dose Of Insulin v-go Mini- ject System For Insulin Biojector 2000 And Penjet For Smallpox Vaccination

30. Epidermal powder immunization Powder injectors were first used for DNA and RNA transfection into plants. The technique has subsequently been investigated for transdermal protein delivery, gene therapy and vaccination. The device design principles are similar to liquid injectors, with a powder compartment and compressed carrier gas, such as helium. Upon actuation, the particles are carried by the gas, to impact the skin surface at high velocity, puncturing micron-sized holes in the epidermis to facilitate skin deposition.

31. Energy based approaches Exposure of the skin to energy in the form of electrical pulses or ultrasonic waves can disrupt the stratum corneum barrier and increases its permeability. This approach has been extensively investigated for drugs and macromolecules, and to a lesser extent for vaccine delivery. Two energy based approaches Electroporation Microneedle

32. Electroporation Electroporation involves the administration of electrical pulses to create transient pores in the skin and thus increase the skin permeability to drugs and macromolecules. Inovio biomedical corporation has developed a series of hand-held, cordless electroporation devices that have been used in vaccine delivery studies. Delivery of DNA vaccines into muscle or skin tissue with electroporation systems generated robust immune responses.

33. Electroporation Devices

34. Microneedles Microneedles consist of pointed micro-sized projections, fabricated into arrays with up to a hundred needles, that penetrate through the stratum corneum to create microscopic holes, thus providing delivery pathways for vaccines and drugs. A number of different microneedle systems have been investigated including: Solid microneedles for permeabilizing skin via formation of micron-sized holes. Solid or insoluble microneedles are generally composed of metal such as titanium or silicone.

35. The microneedles permeabilize the skin by forming micron-sized holes The microneedle array is then removed and a drug/vaccine containing patch is applied. this approach is termed "poke & patch" Solid microneedles coated with dry drug or vaccine Polymeric microneedles with encapsulated drug or vaccine Coated microneedles have an insoluble core coated with drug that dissolves off within the skin The so called "coat & poke" approach

36. Microneedle Technology

37. REFERENCES Cordeiro, AS, Alonso, MJ (2015). Recent advances in vaccine delivery. Pharmaceutical Patent Analyst, in press. https://www.researchgate.net/publication/301780335_Transdermal_Delivery of Vaccines www.wiki/mucosal_delivery_of vaccines.com https://www.sciencedirect.com/science/article/pii/S0168365916300670?via%3Dihub Textbook Of Pharmaceutical Microbiology By Nk Jain. Mucosal Vaccine Design And Delivery By Kim A. Woodrow, 1 Kaila M. Bennett,2,3 And David D. Lo2. Transdermal Delivery Of Vaccines By Sarika Namjoshi And Heather A.E. Benson Curtin Health Innovation Research Institute.

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