Mechanical properties and immunotherapeutic effects of dissolving microneedles with different drug loadings based on hyaluronic acid

Abstract Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague-Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings

Effects and Mechanism of Irbesartan on Tubulointerstitial fibrosis in 5/6 Nephrectomized Rats / 华中科技大学学报（医学）（英德文版）

Tubulointerstitial fibrosis(TIF)is a common pathological feature of end-stage kidney disease.Previous studies showed that upregulation of TGFβ1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction.This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFβ1 in the rodent model of chronic renal failure involving 5/6 nephrectomy.The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model.Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group,but the lesion was attenuated mostly in irbesartan-treated group.Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFβ1 which was up-regulated in operation groups.Western blot showed that irbesartan treatment down-regulated the expression of TGFβ1,phosphorylated smad2(p-smad2),AT1R and phosphorylated p38(p-p38)MAPK,but significantly up-regulated the protein expression of smad6 as compared with operation group.These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6,TGF-β1,p-smad2,AT1 and p-p38 MAPK.