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设计和评估无机/有机杂化生物复合材料用于达非那新的定位口腔给药。

Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin.

机构信息

Faculty of Pharmacy, University of Lahore, Lahore, 56400, Pakistan.

Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC), Department of Science, South East Technological University (SETU), Waterford, X91 K0EK, Ireland.

出版信息

AAPS PharmSciTech. 2024 Sep 5;25(7):204. doi: 10.1208/s12249-024-02916-5.


DOI:10.1208/s12249-024-02916-5
PMID:39237789
Abstract

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic-organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.

摘要

良性前列腺增生(BHP)是一种常见的疾病,影响 60 岁以上的男性。经尿道前列腺切除术(TURP)是手术治疗的金标准,但也有一系列药物可用于改善生活质量,并减少 BHP 相关的尿路感染和并发症。达非那新是一种抗毒蕈碱药物,已被发现可有效缓解与 BHP 相关的膀胱过度活动症的症状,但该药物的溶解度和生物利用度较差,这是产品开发的主要挑战。本研究合成了一种具有胃 pH 抗性的无机/有机生物复合材料,用于达非那新在下消化道(GIT)的靶向口服递送。这一发展是通过在榅桲种子胶中共同沉淀碳酸钙来实现的。FTIR、XRD、DSC 和 TGA 结果表明药物与聚合物具有良好的相容性,SEM 图像显示在榅桲水凝胶系统中形成了方解石。在 72 小时后,分别在酸性(0.1N HCl)和 6.8 pH 磷酸盐缓冲液中观察到 34%和 75%的药物释放。与通过肠膜的渗透(65%)相比,通过胃膜的渗透(21.8%)限制了/减少了药物的渗透。与未治疗的患病动物组相比,所开发的复合材料显著减少了睾酮诱导的前列腺增生(2.39±0.12***)。对所有开发的复合材料均未观察到器官毒性的迹象。在这项研究中,我们开发了一种高度生物相容的无机-有机复合材料系统,该系统可有效靶向下 GIT,从而避免达非那新的首过代谢。

相似文献

[1]
Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin.

AAPS PharmSciTech. 2024-9-5

[2]
Synthesis of calcium carbonate-quince bio-composite for programmed and on-demand drug release of paracetamol at target site: a green chemistry approach.

Polym Bull (Berl). 2023

[3]
The clinical pharmacokinetics of darifenacin.

Clin Pharmacokinet. 2006

[4]
Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin.

Int J Clin Pract. 2008-11

[5]
Comparative evaluation of central muscarinic receptor binding activity by oxybutynin, tolterodine and darifenacin used to treat overactive bladder.

J Urol. 2007-2

[6]
Hansen solubility parameters and quality-by-design oriented optimized cationic nanoemulsion for transdermal drug delivery of tolterodine tartrate.

Int J Pharm. 2024-10-25

[7]
Intestinal-specific oral delivery of lactoferrin with alginate-based composite and hybrid CaCO-hydrogel beads.

Food Chem. 2024-9-1

[8]
The effects of the selective muscarinic M3 receptor antagonist darifenacin, and of hyoscine (scopolamine), on motion sickness, skin conductance & cognitive function.

Br J Clin Pharmacol. 2018-4-19

[9]
Noninvasive evaluation of brain muscarinic receptor occupancy of oxybutynin, darifenacin and imidafenacin in rats by positron emission tomography.

Life Sci. 2010-6-18

[10]
In vivo demonstration of M3 muscarinic receptor subtype selectivity of darifenacin in mice.

Life Sci. 2006-12-14

本文引用的文献

[1]
Overview of the Potential Beneficial Effects of Carotenoids on Consumer Health and Well-Being.

Antioxidants (Basel). 2023-5-10

[2]
Darifenacin Self-assembled Liquid Crystal Cubic Nanoparticles: a Sustained Release Approach for an Overnight Control of Overactive Bladder.

AAPS PharmSciTech. 2023-5-12

[3]
A Comprehensive Review on Plant-Derived Mucilage: Characterization, Functional Properties, Applications, and Its Utilization for Nanocarrier Fabrication.

Polymers (Basel). 2021-3-28

[4]
Curcuma oil ameliorates benign prostatic hyperplasia through suppression of the nuclear factor-kappa B signaling pathway in rats.

J Ethnopharmacol. 2021-10-28

[5]
The rising worldwide impact of benign prostatic hyperplasia.

BJU Int. 2021-6

[6]
Modern best practice in the management of benign prostatic hyperplasia in the elderly.

Ther Adv Urol. 2020-5-27

[7]
Natural Compounds as Sustainable Additives for Biopolymers.

Polymers (Basel). 2020-3-25

[8]
Mathematical Modeling of Release Kinetics from Supramolecular Drug Delivery Systems.

Pharmaceutics. 2019-3-21

[9]
Porous Inorganic Carriers Based on Silica, Calcium Carbonate and Calcium Phosphate for Controlled/Modulated Drug Delivery: Fresh Outlook and Future Perspectives.

Pharmaceutics. 2018-9-25

[10]
Dissolution Rate Enhancement, Design and Development of Buccal Drug Delivery of Darifenacin Hydroxypropyl β-Cyclodextrin Inclusion Complexes.

J Pharm (Cairo). 2013

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