Journal
PHARMACEUTICALS
Volume 14, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/ph14020164
Keywords
protein; hybrid nanoparticles; nanocomposite microparticles; chitosan; pulmonary delivery; inhalation; dry powder; spraydrying; vaccine
Categories
Funding
- King Saud University, Saudi Arabia through Kayyali Chair for Pharmaceutical Industry [EM-2020]
- MRC [MR/P022758/1] Funding Source: UKRI
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In this study, hybrid cationic CHL NPs encapsulating BSA were successfully prepared and incorporated into nanocomposite microcarriers. The CHL NPs/NCMPs demonstrated good stability and aerosolization properties in vitro, suggesting their potential for efficient delivery of proteins to the lungs for immunostimulatory applications.
In this study, PGA-co-PDL nanoparticles (NPs) encapsulating model antigen, bovine serum albumin (BSA), were prepared via double emulsion solvent evaporation. In addition, chitosan hydrochloride (CHL) was incorporated into the external phase of the emulsion solvent method, which resulted in surface adsorption onto the NPs to form hybrid cationic CHL NPs. The BSA encapsulated CHL NPs were encompassed into nanocomposite microcarriers (NCMPs) composed of l-leucine to produce CHL NPs/NCMPs via spray drying. The CHL NPs/NCMPs were investigated for in vitro aerosolization, release study, cell viability and uptake, and stability of protein structure. Hybrid cationic CHL NPs (CHL: 10 mg/mL) of particle size (480.2 +/- 32.2 nm), charge (+14.2 +/- 0.72 mV), and BSA loading (7.28 +/- 1.3 mu g/mg) were produced. The adsorption pattern was determined to follow the Freundlich model. Aerosolization of CHL NPs/NCMPs indicated fine particle fraction (FPF: 46.79 +/- 11.21%) and mass median aerodynamic diameter (MMAD: 1.49 +/- 0.29 mu m). The BSA alpha-helical structure was maintained, after release from the CHL NPs/NCMPs, as indicated by circular dichroism. Furthermore, dendritic cells (DCs) and A549 cells showed good viability (>= 70% at 2.5 mg/mL after 4-24 h exposure, respectively). Confocal microscopy and flow cytometry data showed hybrid cationic CHL NPs were successfully taken up by DCs within 1 h of incubation. The upregulation of CD40, CD86, and MHC-II cell surface markers indicated that the DCs were successfully activated by the hybrid cationic CHL NPs. These results suggest that the CHL NPs/NCMPs technology platform could potentially be used for the delivery of proteins to the lungs for immunostimulatory applications such as vaccines.
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