Abstract
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 µg/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 µm). The BSA α-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.
Highlights
Vaccination via the lungs is an attractive proposition, as it mimics the natural infection route of pulmonary pathogens and can lead to local and systemic immune protection [1,2].Administration via inhalation offers the additional advantage of eliminating syringes and needles, and their storage and disposal, resulting in the exclusion of blood-borne infections
We investigated the influence of chitosan hydrochloride (CHL) concentration and determine the adsorption mechanism onto the surface of PGA-co-PDL NPs with encapsulated model protein bovine serum albumin (BSA) to form hybrid cationic CHL NPs
Adsorption of CHL onto the surface of PGA-co-PDL NPs can be exploited as an effective strategy to create positively charged NPs, which have potential for immunostimulation in vaccine applications
Summary
Vaccination via the lungs is an attractive proposition, as it mimics the natural infection route of pulmonary pathogens and can lead to local and systemic immune protection [1,2].Administration via inhalation offers the additional advantage of eliminating syringes and needles, and their storage and disposal, resulting in the exclusion of blood-borne infections. The lung offers many advantages from a delivery perspective, such as antigen presenting cells, including DCs, within the lungs, the large surface area for drug. Pharmaceuticals 2021, 14, 164 absorption, thin epithelium in the alveolar lung tissue, lower enzymatic activity than the gastrointestinal system, and large vascularization that can enable the efficient systemic delivery of drugs [2]. The hydrophobic nature of the polymer, compared to PLGA, is postulated to improve uptake by antigen presenting cells to improve resulting immune responses. The size and surface charge of NPs have a significant effect on cellular uptake, with cationic particles postulated to interact with cell membranes which are negatively charged more effectively through ionic interactions [3]
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