Cationic PGA-co-PDL nanocomposite microparticles for antigen delivery via inhalation

Authors: , , , ,

The encapsulation of antigens in nanoparticles (NPs) has been investigated extensively as an approach to enhance immunogenicity. Most particle-based forms can be modified to contain additional adjuvants to further enhance immunogenicity. Recently, chitosan hydrochloride (CHCl) has been described as a water-soluble and a positively charged polyelectrolyte, which may overcome the low water solubility of chitosan at neutral pH. The aim of this study was to prepare CHCl coated polyglycerol adipate-co-ω-pentadecalactone (PGA-co-PDL) nanoparticles encapsulating bovine serum albumin (BSA), a model antigen to produce cationic nanoparticles which further spray dried to form nanocomposite microparticles (NCMPs) suitable for antigen delivery via inhalation. Cationic BSA-NPs were prepared using a double emulsion solvent evaporation method. The NPs were collected by centrifugation, resuspended in an aqueous solution of L-leucine and spray dried to produce NCMPs. Particle size, zeta potential, drug loading, in vitro release (PBS, pH 7.4), and aerosolisation performance were characterised. Coating NPs changed zeta potential from negative (-17.44±1.2mV) to positive (+14.2±0.72mV) without changing particle size (445±46.8nm and 480.23±32.24nm). BSA loading for coated and uncoated was 33 and 7µg/mg, respectively. BSA showed a biphasic release profile from NCMPs with an initial burst release (19.6±6%) followed by a second continuous sustained release phase over 48h (81.9±12%). Aerosol characteristics revealed NCMPs with %FPF of 47.38±12% and MMAD of 1.7±0.29µm. NCMPs may be a promising carrier for delivery of antigen due to its good loading and ability to reserve BSA. Further studies are required to evaluate the effect of NCMPs on cell viability and uptakes.