Nasal Vaccine Delivery
M. Ramvikas, ... K.S. Jaganathan, in Micro and Nanotechnology in Vaccine Development, 2017
15.5 Different Dosage Forms of Vaccine Through the Nasal Route
Intranasal immunizations are simple, easy, convenient, and safer than other routes of administration. The delivery system selection depends upon the antigen being used for the proposed indication, patient type, and marketing preferences. There are different options available to deliver nasal vaccine such as drops,106 powder, aerosol sprays, and the application of nasal gel.
15.5.1 Nasal drops
Nasal drops are convenient and the most simple method for delivery of nasal vaccines. The nasal drops are administered using a nasal dropper or syringes. The major disadvantage of this system is the lack of dose precision107 and difficulty for the pediatric population. Some studies reported that nasal drops deposit human serum albumin in the nostrils more efficiently than nasal sprays.108
15.5.2 Nasal powder
Nasal powder formulations are highly stable compared to liquid formulations. Nasal powders can extend the residence time for powder formulations on the nasal mucosa, potentially increasing the local and systemic immune response.109 However, the production of nasal dry powders is quite complicated with required particle size, particle distribution, and performance characteristics when compared with other dosage forms.
15.5.3 Aerosol
The aerosol route of delivery of vaccines is one of the most preferred for nasal administration compared with other nasal dosage forms and also less reactogenic than the subcutaneous route of administration.110 Aerosol vaccination via the lungs targets an epithelium critical to host defense against inhaled pathogens and provides an exciting opportunity in the development of newer and more effective tuberculosis (TB), measles, and influenza vaccines. An aerosol vaccination usually depends on the target pathogen and the sites of the inductive immunity. The aerosols are available in liquid (solution, suspension, and emulsion) and solid forms. In addition to vaccine antigens, carrier/solvent, emulsifier/surfactants, corrosion inhibitors, and propellant selection and compatability play a critical role in achieving required immunogenicity in infants. Aerosol vaccine immunogenecity achievement is based on antigen particle size for prevention of upper respiratory (eg, Boredetella pertussis, Chlamydia pneumonia) and lower respiratory (eg, Streptococcus pneumoniae, Bacillus anthracis) bacteria and virus disease. Larger particles (∼5 μm) are needed for the aerosol vaccination to prevent upper respiratory tract infection and smaller particles (≤ 3 μm) for lower respiratory tract infection.111 The dried forms of vaccines with optimum particle size are traditionally prepared by freeze drying or spray drying. The aerosol form of vaccines was administered to many human subjects for a longer period and found to provide excellent protection for diseases such as influenza A and measles.112,113 Therefore aerosol immunization may be a promising method of vaccination.
15.5.4 Nasal gel
Nasal gels are generally used for colds, allergies, low humidity, or overuse of decongestant. Nasal vaccine gels are a high-viscosity solution or suspension in which antigenic molecules are dispersed. The advantages of a nasal gel include the reduction of nasal clearance and anterior leakage due to highly viscous formulation, reduction of irritation by using soothing/emollient excipients, and target delivery to mucosa for better absorption.114 In addition, it may potentially enhance the immune response, reduce the antigen and/or adjuvant dose, sustain antigen release, and improve antigen uptake with enhanced antigen stability. Special application techniques are required for the administration of nasal gel vaccines because of their highly viscous formulation and poor spreading abilities. A wide variety of gelling polymers are available for formulation such as pullulan, deaceylated gellan gum, xantham gum, chitosan, and polyethylene glycol, used to encapsulate vaccine/adjuvant formulation as gel particles. Viscosity, sol-gel transition temperature and gelling time, and gel strength and its texture are critical parameters in the development of nasal gel vaccines. Recently, pneumococcal surface protein-A nasal gel vaccine,115 Clostridium botulinum type-A neurotoxin BoHc/A, and tetanus toxoid116 were studied in animal models and enhanced both humoral and cellular immunity. Nasal gel is an alternative and promising novel dosage delivery system to achieve the immune response.