Therapeutic Effect of Triptolide Polymer Mesoscale Nanoparticles on Diabetic Nephropathy Mice

Abstract

Triptolide (TP) has potential adoption value in the treatment of nephropathy, but its poor water solubility causes toxicity and side effects to various degrees in the kidney, liver, and other organs. In this research, TP-mesoscale nanoparticles (TP-MNPs) were synthesized by the amide reaction of poly(lactic-co-glycolic acid) (PLGA) and methoxy polyethylene glycol amine (mPEG-NH2) as drug carrier materials. The structure of TP-MNPs was characterized by 1H NMR, scanning electron microscopy (SEM), and zeta potential using a nanoparticle potential analyzer. Liquid chromatography–mass spectrometry (HPLC–MS) was utilized to determine the content of TP in TP-MNPs and calculate the entrapment rate (ER) and drug loading (DL) of TP-MNPs. The cytotoxicity of TP-MNPs was detected by CCK8. Eight mice were enrolled in Blank group (no treatment), and the other 24 model group animals were rolled into model group (DM), TP group (TP intervention), and TP-MNP group (TP-MNPs intervention) randomly, with eight mice in each group. The urine protein content, serum albumin (Alb), blood glucose (Glu), creatinine (Cre), total cholesterol (TCHO), and triglyceride (TG) contents of mice in various groups after intervention were compared. The results revealed that average diameter of MNPs was (379.6±26.44) nm, that of TP-MNPs was (424.3±56.29) nm, and average zeta potentials of TP, MNPs, and TP-MNPs were (−28.29±3.85) mV, (−15.51±1.79) mV, and (−13.45±1.81) mV, respectively. The curve changed with TP concentration. With increasing TP concentration, the ER of TP-MNPs decreased drastically, and the DL demonstrated a drastic upward trend. Furthermore, the cell activities of HK-2, NRK-52E, LO2, and AML-12 treated with TP-MNPs were higher versus TP group (P <0.05). Urine protein content, body weight, renal index, serum Glu, TCHO, and TG content in the DM group were markedly superior to Blank group (P <0.001), while urine protein content in TP-MNP group was considerably inferior to the DM group (P <0.01). Alb and Cre in the serum of mice in DM group were substantially lower versus Blank group (P <0.01), while those in TP group were lower than Blank group (P <0.05). Alb and Cre in TP-MNP group were superior to DM group (P <0.05). In summary, TP-MNPs prepared in this research had ideal biocompatibility, could effectively improve urinary protein, body weight, renal index, and serum biochemical indexes caused by DM, and had a certain therapeutic effect on diabetic nephropathy (DN) mice.