背景:依帕司他(EPL)是一种水溶性差的羧酸衍生物,其药代动力学特征尚未完全定义。
目的:目前的研究旨在制造EPL与SBE7β-CD(IC)和EPL/SBE7β-CDCSNP(NP)的包合物。
方法:使用共沉淀方法将EPL与SBE7β-CD络合,并利用离子凝胶法将制备的复合物制成纳米颗粒。对制备的制剂进行了表征,用于粒度分析,表面形态,和体外溶出度研究。还进行了EPL对α-葡萄糖苷酶的%抑制以检查药物的抗糖尿病活性。最后,进行体内药代动力学研究以确定制备的制剂在兔血浆中的EPL浓度。通过给予单剂量的纯EPL进行体内药代动力学研究,IC,和NP。
结果:发现NP的大小为241.5nm,PDI为0.363,ζ电位为+31.8mV。制备的NP的表面是无孔的,与纯EPL相比,光滑和球形,SBE7β-CD和IC。IC和NP的累积药物释放(%)分别为73%和88%,分别,与纯药物相比(25%)。据报道,体外α-葡糖苷酶的抑制%结果为74.1%,并且计算出用于计算机分子对接的预测结合能为-6.6kcal/mol。计算出的EPL的Cmax值,IC和NP分别为4.75±3.64、66.91±7.58和84.27±6.91μg/mL,分别。对于IC和NP,EPL的消除半衰期为4小时,降低至2小时。EPL的AUC0-α,IC和NP分别为191.5±164.63、1054.23±161.77和1072.5±159.54μg/mL*h,分别。
结论:考虑到这些参数,可以得出结论,IC和NP在大大改善水溶性差的药物的递送和调节释放方面具有前瞻性应用,可能导致提高治疗效果和减少副作用。
BACKGROUND: Epalrestat (EPL) is a carboxylic acid derivative with poor aqueous solubility and its pharmacokinetic features are not fully defined.
OBJECTIVE: Current research aimed to fabricate inclusion complexation of EPL with SBE7 β-CD (IC) and EPL/SBE7 β-CD CS NPs (NP).
METHODS: EPL was complexed with SBE7 β-CD using the co-precipitation method, and the prepared complex was fabricated into nanoparticles using the ionic gelation method. The prepared formulations were characterized for particle size analysis, surface morphology, and in vitro dissolution study. The % inhibition of EPL against α-glucosidase enzyme was also conducted to check the drug\'s antidiabetic activity. Finally, an in vivo pharmacokinetic investigation was carried out to determine the concentration of EPL in rabbit plasma of the prepared formulation. In vivo pharmacokinetic studies were conducted by giving a single dose of pure EPL, IC, and NP.
RESULTS: The size of NP was found to be 241.5 nm with PDI 0.363 and zeta potential of +31.8 mV. The surface of the prepared NP was non-porous, smooth and spherical when compared with pure EPL, SBE7 β-CD and IC. The cumulative drug release (%) from IC and NP was 73% and 88%, respectively, as compared to pure drug (25%). The % inhibition results for in vitro α-glucosidase was reported to be 74.1% and the predicted binding energy for in silico molecular docking was calculated to be -6.6 kcal/mol. The calculated Cmax values for EPL, IC and NP were 4.75±3.64, 66.91±7.58 and 84.27±6.91 μg/mL, respectively. The elimination half-life of EPL was 4 h and reduced to 2 h for IC and NP. The AUC0-α for EPL, IC and NP were 191.5±164.63, 1054.23±161.77 and 1072.5±159.54 μg/mL*h, respectively.
CONCLUSIONS: Taking these parameters into consideration it can be concluded that IC and NP have prospective applications for greatly improved delivery and regulatedt release of poorly water soluble drugs, potentially leading to increase therapeutic efficacy and fewer side effects.