Effect of polycation coating on the long-term pulsatile release of antigenic ESAT-61-20 peptide from PLGA nanoparticles

Abstract

The development of novel vaccine formulations against tuberculosis is necessary to reduce the number of new cases worldwide. Polymeric nanoparticles offer great potential as antigen delivery and immunostimulant systems for such purposes. In the study, we have encapsulated the antigenic peptide epitope of ESAT-6 protein of M. tuberculosis into PLGA nanoparticles and coated these nanoparticles with the cationic polymer of quaternized poly(4-vinylpyridine) (QPVP) to obtain a positively charged system as a potential nasal vaccine prototype. The produced spherical nanoparticles had hydrodynamic diameters between 180 and 240 nm with a narrow size distribution. The non-coated nanoparticle exhibited a 3-phase in vitro release profile that was completed in more than 4 months. In this release study, 5% of the peptide was released in the first 6 h and the nanoparticle remained silent until the 70th day. Then, an additional 5% of the peptide was released in 45 days. After coating the nanoparticle with QPVP, the release periods and peptide amounts dramatically changed. The antigenic peptideloaded nanoparticles coated with the polycation stimulated the macrophages in vitro to release more nitric oxide (NO) compared to the free peptide and non-coated nanoparticle, which reveals the immunostimulant activity of the produced nanoparticle systems. The produced non-coated nanoparticles with the prolonged pulsatile release of the antigenic peptide can be used in the development of single injection self-boosting vaccine formulations. By coating these nanoparticles, both the release profile and immunogenicity can be changed.