提高卡维地洛控制糖尿病相关性心力衰竭的疗效和生物利用度:体外和体内表征

IF 3.9 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Tamer Mohamed Mahmoud, Mohammed Ayad Alboreadi, Amr Gamal Fouad, Nada H Mohammed, Amany Belal, Fahad H Baali, Nisreen Khalid Aref Albezrah, Mohammed S Alharthi, Sherif Faysal Abdelfattah Khalil, Fatma I Abo El-Ela
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引用次数: 0

摘要

卡维地洛(CRD)是一种口服β -肾上腺素能拮抗剂,被批准用于治疗心力衰竭(HF)。然而,由于其半衰期短,溶解度差,CRD的生物利用度和有效性有限。本研究旨在开发一种CRD-novasome (CLN)鼻腔喷雾剂,以提高CRD作为糖尿病相关性心衰(DMHF)治疗的可持续性、靶向性、生物利用度和有效性。采用Box-Behnken设计制备了几种CLN配方,并对其进行了体外表征,以确定最佳配方,随后使用DMHF大鼠实验模型对其进行了体内评价。优选出的最佳CLN配方为油酸30.079 mg、Span 60 56.897 mg、胆固醇60 mg。优化后的CLN较自由CRD有显著改善,可持续性和渗透率分别提高71.39%和6.08倍。与口服游离CRD相比,经鼻给药可使CRD的生物利用度和靶效率分别提高5.74倍和4.24倍。与DMHF阳性对照相比,鼻用CLN可显著降低葡萄糖、LDH和CK-MB水平,分别降低93.68%、94.29%和96.50%,显示其疗效。组织病理学和毒性研究进一步验证了优化后的CLN的活性和安全性。这些发现表明,CLN鼻喷雾剂具有治疗DMHF的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Improving the Therapeutic Efficacy and Bioavailability of Carvedilol for Control of Diabetes-Associated Heart Failure: In Vitro and In Vivo Characterization.

Carvedilol (CRD) is an oral beta-adrenergic antagonist approved for treating heart failure (HF). However, due to its short half-life and poor solubility, CRD has limited bioavailability and effectiveness. This study aimed to develop a nasal spray of CRD-novasomes (CLN) to enhance CRD's sustainability, targeting, bioavailability, and efficacy as a therapy for diabetes mellitus-associated HF (DMHF). Several CLN formulations were created using Box-Behnken design and characterized in vitro to identify the optimized formulation, which was later evaluated in vivo using an experimental DMHF rat model. The selected optimized CLN formulation consists of 30.079 mg of oleic acid, 56.897 mg of Span 60, and 60 mg of cholesterol. The optimized CLN demonstrated significant improvements over free CRD, enhancing CRD's sustainability and permeability by 71.39% and 6.08-fold, respectively. When compared to oral free CRD, the nasal CLN increased the bioavailability and target efficiency of CRD by 5.74-fold and 4.24-fold, respectively. In relation to DMHF positive control, the nasal CLN significantly lowered glucose, LDH, and CK-MB levels by 93.68%, 94.29%, and 96.50%, respectively, showcasing its efficacy. Histopathological and toxicity studies further validated the activity and safety of the optimized CLN. These findings indicate that the nasal CLN spray shows potential as a therapy for DMHF.

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来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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