# Tailored Nanoparticles as Vaccine Components
## 3 Types and Uses of Nanoparticles in Vaccines
### Polymeric Nanoparticles  
Polymeric NPs are made from synthetic polymers, with poly(lactide-_co_-glycolide) (PLGA) and poly(lactide-_co_-glycolic acid) (PLGA) studied the most because of their good biocompatibility and biodegradability [4; 32; 35; 50]. They are isotropic, i.e., without a shell and with the antigen distributed evenly throughout the particle. One advantage of polymeric NPs is that they afford control over the release kinetics of the loaded materials by altering the polymer such as changing its functional chemical groups, monomer ratio, or molecular weight [32; 35; 51]. Polymeric NPs are often synthesized by the double emulsion solvent evaporation technique: the polymer is dissolved in an organic solvent such as ethyl acetate, and a protein antigen is added together with an emulsifying agent such as polyvinyl alcohol. Then, by vortexing, a water-in-oil-in-water emulsion is formed, and the polymer precipitates around the antigen. The product is dried by solvent evaporation to prevent polymer degradation caused by ester hydrolysis [32]. Another synthesis method uses amphiphilic copolymers that self-assemble through hydrophobic interactions [32; 51], enclosing the antigen. Polymeric NPs enable antigen delivery to immune cells and sustained antigen release through their slow biodegradation [32; 35]. In recent years, PLGA has been utilized to carry antigens derived from diverse pathogens such as _Plasmodium vivax_ (using the monophosphoryl lipid A as the adjuvant), hepatitis B virus (HBV), and experimental model antigens such as chicken ovalbumin and tetanus toxoid [4; 32; 35; 50]. Co-encapsulation of a lipid that stimulates invariant natural killer T cells (iNKT cells) further enhanced T and B cell responses to PLGA nanoparticles [52]. The amphiphilic poly(\(\gamma\)-glutamic acid) (\(\gamma\)-PGA) also self-assembles into nano-micelles with a hydrophilic outer shell and a hydrophobic core [53; 54]. The \(\gamma\)-PGA NPs are mostly used to encapsulate hydrophobic antigens [32]. Polymeric NPs that are made of naturally polymeric polysaccharides (such as chitosan, pullulan, inulin, or alginate) can incorporate antigens and can also themselves act as adjuvants [4; 8; 26; 32; 35]. Such polysaccharide-based NPs are produced by covalent crosslinking, ionic crosslinking, polyelectrolyte complexes, or by self-assembly of hydrophobically modified polysaccharides [8; 32]. Chitosan-based NPs were especially well investigated due to their biocompatibility, biodegradability, their ability to be easily adapted according to preferred variable size (20-600 nm), and their nontoxic nature [4; 5; 26; 32; 35]. They were used in the development of several vaccines against HBV [7; 32; 35]. In vaccines against both HBV and influenza, Advax, an NP adjuvant made from inulin (an activator of complement through the alternative pathway), was used [5]. Polyelectrolytes, i.e., polymers with repeating units that carry either positive (polycations) or negative (polyanions) charges, are another important subclass of polymeric NPs in practical use [55; 56]. While they are mainly used as carriers in the delivery of bioactive sub stances, they have recently been studied as components of peptide-based subunit vaccines against group A streptococcus [55; 56]. They can be made water-soluble, biocompatible, and slowly biodegradable [56]. Polyelectrolyte complex nanoparticles (PECNs) are produced using techniques such as ionic gelation (crosslinking) and coacervation (phase separation) [56]. Some approaches use hyaluronic acid and chondro sulfate, but the most commonly used natural polymer is chitosan, as it is mucoadhesive, has enhanced tissue permeation, and enables the production of NPs under mild conditions [56]. Chitosan, a hydrolysate of fungal or insect chitin, bears 0.5 positive charges per saccharide unit at physiological pH and can be complexed with hyaluronic acid to form PECNs [56].