PDF(Pubmed)
Abstract：
A well-made chitosan-PVP block copolymer platform was equipped with highly ordered and uniform nano-channels. This highly adhesive block copolymer platform was designed to ensure the efficient co-delivery of two synergistic-acting hypoglycemic drugs. Linagliptin oral bioavailability is 30% due to poor permeability and intestinal degradation. Its pharmacokinetics shows a non-linear profile. Empagliflozin exhibited decreased permeability and decreased solubility in aqueous media between pH 1 and 7.5. Cubosomes were functionalized as a good microdomain to guest and improve the physicochemical characteristics of drug molecules with decreased permeability and solubility. Cubosomes loaded with linagliptin (linagliptin cubosomes (LCs)) and empagliflozin (empagliflozin cubosomes ECs) were separately prepared using the top-down method and optimized by applying 23 factorial design. Optimized cubosomal systems LCs (F3) and ECs (F4) were incorporated into a chitosan-PVP gel to obtain dual cubosome-loaded platforms (LECF) optimized through 22 factorial design. The permeation study from the optimized LECF (C1) ensured enhanced empagliflozin permeation alongside continued efflux for linagliptin, resolving potential risks due to its non-linear plasma profile. The in-vivo study revealed that AUC(0-∞) of linagliptin and empagliflozin was enhanced by 2- and threefold, respectively. Therefore, the chitosan-PVP block copolymer platform buccal application for the co-delivery of linagliptin and empagliflozin could contribute to enhanced clinical effectiveness in treating diabetes.
摘要：
制作良好的壳聚糖-PVP嵌段共聚物平台配备了高度有序和均匀的纳米通道。这种高度粘附的嵌段共聚物平台被设计为确保两种协同作用的降血糖药物的有效共递送。由于渗透性差和肠道降解,利格列汀口服生物利用度为30%。其药代动力学表现出非线性特征。Empagliflozin在pH1和7.5之间的水性介质中显示出渗透性降低和溶解度降低。立方体被功能化为良好的客体微域，并改善了药物分子的物理化学特性，降低了渗透性和溶解度。使用自上而下的方法分别制备加载了利格列汀（利格列汀立方体（LC））和empagliflozin（empagliflozin立方体EC）的立方体，并通过应用23个因子设计进行了优化。将优化的立方体系统LC（F3）和EC（F4）掺入壳聚糖-PVP凝胶中，以获得通过22阶乘设计优化的双立方体负载平台（LECF）。优化LECF(C1)的渗透研究确保了利格列汀在持续外排的同时，empagliflozin的渗透增强，解决由于其非线性等离子体轮廓的潜在风险。体内研究显示，利格列汀和依帕列净的AUC(0-∞)增加了2倍和3倍，分别。因此,壳聚糖-PVP嵌段共聚物平台含服联合给药利格列汀和依帕列净可能有助于提高糖尿病治疗的临床疗效.图形摘要显示使用兔子模型在体内测试的双长方体加载平台。
