Objective: To determine the main components of Astragalus membranaceus (Fisch.) Bge (A. membranaceus, Huang Qi), Astragaloside IV (AIV) and Astragalus polysaccharides (AP), to characterize their properties, evaluate their in vivo efficacy, and to analyze drug diffusion using dissolving microneedle (DMN) technology in vivo. Methods: Respectively, AIV- and AP-loaded DMNs comprising chitosan (CTS) and polyvinyl alcohol (PVA) were prepared via dual-mold forming. Their morphology, mechanical properties, in vivo solubility, and skin irritation characteristics were tested. In vivo efficacy was assessed in cyclophosphamide-induced immunosuppressed mice, in vivo diffusion of AIV and AP by DMNs and conventional methods was compared, and the rheological properties of AIV-CTS-PVA and AP-CTS-PVA mixtures were measured. Results: Subcutaneous dissolution and absorption of AIV-CTS-PVA and AP-CTS-PVA microneedles (MNs) at low doses (50%–17% of intraperitoneal AIV injection and 12%–4% of intravenous AP injection) reduced the spleen index and acid phosphatase activity in immunosuppressed mouse models, increased the thymus index, and achieved equivalent or better systemic therapeutic effects. Compared with injections, AIV and AP achieved controllable solid-liquid conversion through delivery with CTS-PVA MNs, resulting in highly localized aggregation within 48 h, reducing the initial explosive effect of the drug, and achieving stable and slow drug release. Conclusion The present study enhances our understanding of the efficacy and remote effects of drug-loaded DMNs from a traditional Chinese medicine (TCM) perspective, thereby promoting the development of precise and efficient delivery of TCM and further expanding the drug-loading range and application scenarios for DMNs.

Objective:To study the virological and serological indicators before treatment and 24 weeks after treatment to predict the partial virological response (PVR) of 48-week entecavir (ETV) treatment, and formulate early clinical adjustment treatment plans for HBeAg-positive CHB patients.Methods:HBeAg-positive CHB-na?ve patients diagnosed in the Department of Infectious Diseases, Shengjing Hospital, China Medical University, who were treated with oral ETV monotherapy from January 2018 were enrolled. The groups were divided according to the test results of HBV DNA at 48 weeks. Among them, HBV DNA < 20 IU/ml was the complete viral response (CVR) group, and HBV DNA ≥ 20 IU/ml was the PVR group. The virological and serological indexes of the two groups before treatment and 24 weeks after treatment were compared. ROC curve univariate analysis and multivariate logistic regression were performed to find out the early predictors of PVR in HBeAg-positive CHB patients receiving ETV therapy for 48 weeks.Results:As of July 2020, a total of 90 cases had completed 48 weeks of treatment, including 50 cases of CVR (55.56%) and 40 cases of PVR (44.44%). Before treatment and at 24 weeks of treatment, HBsAg, HBeAg and HBV DNA in the PVR group were significantly higher than those in the CVR group ( P < 0.001). Univariate analysis showed that HBV DNA quantification (AUC = 0.961, P < 0.001, PPV = 97.06%, NPV = 87.50%) and HBeAg quantification (AUC = 0.883, P < 0.001, PPV = 90.63%, NPV = 81.03%) had higher predictive value at 24 weeks of treatment. Multivariate analysis showed that HBeAg > 1.952 log 10 S/CO ( OR = 3.177, 95% CI: 1.261 ~ 8.267, P = 0.018) and HBV DNA > 2.205 log 10 IU / ml ( OR = 43.197, 95% CI: 6.858 ~ 272.069, P < 0.001) were independent predictors of PVR at 24 weeks of treatment, and their combination had the best predictive effect. Conclusion:In HBeAg-positive CHB patients receiving ETV treatment for 48 weeks, HBV DNA combined with HBeAg quantification can be an early predictor of PVR at 24 weeks. Additionally, patients with both HBV DNA and HBeAg > 2 log 10 at 24 weeks of treatment must wait 48 weeks to obtain CVR, so it is recommended that treatment strategies should be adjusted at this time.