PH-responsive Astragalus polysaccharides-loaded poly(lactic-co-glycolic acid) nanoparticles and their in vitro immunogenicity

Abstract

Astragalus polysaccharides (APS) have long been well known as immune boosters, but have not been fully exploited in clinical settings. Here, poly(lactic-co-glycolic acid) (PLGA) was used to form a nanocarrier for APS to enhance its bioavailability. The aim was to improve the immunoadjuvanticity of conventional APS-loaded PLGA-based nanoparticles (NPs), referred to as APSPs, and to optimize the synthesis parameters to maximize the encapsulation efficiency (EE). As slow drug release can cause insufficient immune responses, ammonium bicarbonate was used to produce pH-responsive APSPs. The optimum parameters for maximizing EE (mean maximum experimental EE: 65.23 ± 0.51%) were an oil phase (O)/internal aqueous phase (W1) ratio of 7:1, an external aqueous phase (W2)/preliminary emulsion (PE) ratio of 5:1, and a Pluronic F-68 concentration of 1.1%. Moreover, the pH-responsive APSPs had low cytotoxicity and significantly enhanced mice splenic lymphocyte proliferation. The increased T-cell CD4+/CD8+ ratio after pH-responsive APSP treatment of mice splenic lymphocytes compared with free APS, blank PLGA NP, and conventional APSP treatment demonstrated its excellent immunoadjuvanticity. This study provides abundant evidence that these novel PLGA-based pH-responsive NPs enhanced the immunoadjuvanticity of APS. Furthermore, pH-responsive APSPs synthesized using the optimum parameters exhibited long-term stability in normal storage conditions, suggesting suitability for clinical application.