Polymeric Nanocapsules for Vaccine Delivery: Influence of the Polymeric Shell on the Interaction With the Immune System

Abstract

The use of biomaterials and nanosystems in antigen delivery has played a major role in the development of novel vaccine formulations in the last few decades. In an effort to gain a deeper understanding of the interactions between these systems and immunocompetent cells, we describe here a systematic in vitro and in vivo study on three types of polymeric nanocapsules (NCs). These carriers, which contained protamine (PR), polyarginine (PARG), or chitosan (CS) in the external shell, and their corresponding nanoemulsion were prepared, and their main physicochemical properties were characterized. The particles had a mean particle size in the range 250–450 nm and a positive zeta potential (~30–40 mV). The interaction of the nanosystems with different components of the immune system were investigated by measuring cellular uptake, reactive oxygen species production, activation of the complement cascade, cytokine secretion profile, and MAP kinases/nuclear factor κB activation. The results of these in vitro cell experiments showed that the NC formulations that included the arginine-rich polymers (PR and PARG) showed a superior ability to trigger different immune processes. Considering this finding, protamine and polyarginine nanocapsules (PR and PARG NCs) were selected to assess the association of the recombinant hepatitis B surface antigen (rHBsAg) as a model antigen to evaluate their ability to produce a protective immune response in mice. In this case, the results showed that PR NCs elicited higher IgG levels than PARG NCs and that this IgG response was a combination of anti-rHBsAg IgG1/IgG2a. This work highlights the potential of PR NCs for antigen delivery as an alternative to other positively charged nanocarriers.

Physicochemical Characterization of FRET-Labelled Chitosan Nanocapsules and Model Degradation Studies

“…Besides, they are muco- [ 27 ] and bioadhesive towards negatively charged biological membranes [ 28 ]. These NCs have been used as a drug delivery platform for insulin [ 29 ], flavonoids that interfere with bacterial quorum sensing [ 30 ], poorly water-soluble capsaicin [ 31 , 32 ], or vaccines [ 33 ]. Despite the fact that these NCs have consistently shown efficacy as drug delivery carriers, the precise mechanistic aspects that govern the interactions with the body and cellular fate upon being administered, are not fully understood.…”

Physicochemical Characterization of FRET-labelled Chitosan Nanocapsules and Model Degradation Studies

“…Besides, they are muco- [21] and bioadhesive towards negatively charged biological membranes [22]. These NCs have been used as a drug delivery platform for insulin [23], flavonoids that interfere with bacterial quorum sensing [24], poorly water-soluble capsaicin [25,26], or vaccines [27]. Despite the fact that these NCs have consistently shown efficacy as drug delivery carriers, the precise mechanistic aspects that govern the interactions with the body and cellular fate upon being administered, are not fully understood.…”

Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery

“…Similarly, we hope that the formulation developed here has a high interaction with the immune system and that is shows adjuvant activity when it is administered in vivo. Finally, recent studies have shown that the polymeric shell in different types of nanocapsules can influence complement activation and immune system interactions and can also influence in vivo performance [ 48 ].…”