*3.6.5 Vaccine delivery*

Recently, there have been many research topics related to nanoparticles as carriers for vaccines. The main idea is to use the nanoparticle as an effective carrier to deliver an inactivated organism to the membrane to stimulate the immune system. One study found that it is possible to generate genital mucosa immunity from vaccines that are added to the nasal mucosa. The synthesized proteins passed into the mucosal membrane surface by using nanoparticles to absorb the antigen using adjuvant facilitation [53–55].

There are several mechanisms to load antigens into the nanoparticles, such as encapsulation, encapsulation with coating, encapsulation with targeting, physical adsorption, chemical conjugation, and conjugation with a targeting mechanism. Hydrophobic interactions are known to be effective ways to load antigens into nanoparticles by physical adsorption processes, which apply weak interactions to dissociate antigens and nanoparticles in the body. During protein synthesis, the encapsulated antigens are mixed with nanoparticle precursors, which is a consequence of the release of the encapsulated antigen when the nanoparticle degrades *in vivo*.

The first clinical trial application received was for the use of nanoparticles for influenza and human immunodeficiency virus (HIV) proteins. A recombinant HIV glycoprotein 120 (HIV-gp120) antigen mix in nanoparticles was studied in mice and guinea pigs by intranasal immunization and demonstrated a robust serum antigp120 immunoglobulin G (IgG) response [53]. The constituent of Prepandrix® has been approved for the use of the flu vaccine AS03 (an adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion) during the influenza pandemic. AS03 has been used as a reference for other vaccines, such as Arepanrix®, to control influenza infection caused by H1N1 and H5N1 [54].

The balance between immunogenic benefits and safety needs to be considered and is achieved by selecting the correct adjuvant, antigen, and emulsion composition. These factors are considered the main factors of concern during vaccine development, as they directly affect the benefit-risk balance. Vaccine efficiency is vital, and this factor is the major element controlling pandemics through the selection of the correct oil composition, adjuvant, surfactant, and antigen for the specific disease.

Aliphatic polyester-based nanoparticles could be delivered as adjuvants for vaccines during the coronavirus disease 2019 (COVID-19) pandemic [56, 57]. Polymers are the main material for vaccine delivery. For example, the most popular aliphatic polyesters have been used in vaccine adjuvants for lymph nodes targeting HIV, *Bacillus anthracis*, *Chlamydia trachomatis*, and malaria [58]. Moreover, the addition of a poly(ethylene glycol) (PEG) coating around PLA (PEG-PLA) nanoparticles has been found to facilitate the transport of the antigen of tetanus toxoid to the rat nasal epithelium for nasal vaccine delivery [59].
