MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Yu Pang,Wenxuan Jia,Liuyang Wang,Yang Zhang,Kaihua Gong,Liang Fang
This study aims to develop a sustained release patch for bisoprolol (BSP) to address the issue of blood pressure fluctuations caused by traditional dosing methods, ensuring continuous drug release and efficient utilization. Long-chain saturated fatty acids (C6–C12) were chosen as counterions to precisely control BSP’s permeation rate in the patch formulation, and the ion-pairing strategy’s mechanism in drug delivery was thoroughly investigated. Molecular docking results revealed significant differences in the adsorption capacities of different ion pairs in the stratum corneum (SC) and epidermis, directly influencing their residence times and thereby regulating BSP’s passive diffusion rate. Particularly, the BSP-C10 ion pair successfully reduced BSP’s permeation rate to one-third of its baseline. To enhance drug delivery efficiency and reduce costs, chemical permeation enhancers (CPEs) are typically added to sustained release patches. In contrast to traditional static analyses based on cumulative permeation, this study utilized ATR-FTIR dynamic detection of isopropyl myristate (IPM) as a preferred enhancer, studying its disruptive effects on the skin barrier during drug delivery. The study observed that during drug delivery, the interaction between IPM and skin lipids follows a U-shaped trend: initially increasing, then decreasing, with the peak occurring at 10 h. Similarly, the drug delivery rate displays a comparable pattern. The addition of IPM as CPE increased the patch utilization rate from 39.8 ± 4.31 to 79.8 ± 7.27%. This strategy aims to rapidly reduce blood pressure in the initial phase with subsequent weakening of IPM disruption, allowing the ion-pairing strategy to dominate drug delivery control and maintain stable long-term therapeutic effects. Pharmacokinetic studies demonstrated that the newly developed BSP sustained release patch maintains stable blood drug concentrations, reduces burst release effects, increases bioavailability to 84.679%, doubles MRT0–t, halves Cmax, and significantly reduces the occurrence of blood pressure fluctuations.
研究领域:
药剂学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Hanqing Zhao,Chao Liu,Degong Yang,Xiaocao Wan,Rui Shang,Peng Quan,Liang Fang
Though ion-pair strategy has been employed as an effective and promising method for controlling transdermal delivery of drugs, investigations into the underlying mechanisms involved in the controlled release process of ion-pairs are still limited. In the present study, a brand-new controlled release system combining acrylic pressure sensitive adhesive containing carboxyl group (carboxylic PSA) with ion-pair strategy was developed, and the molecular mechanism of ion-pair releasing from carboxylic PSA was systemically elucidated. Bisoprolol (BSP) and bisoprolol-lauric acid ion-pair (BSP-C 12 ) were chosen as model drugs. Carboxylic PSA was designed and synthesized. Effect of ion-pair on controlling BSP release from carboxylic PSA was evaluated by in vitro drug release study, in vitro skin permeation study and pharmacokinetic study. Molecular mobility of PSA, along with the strength of drug-PSA interaction was evaluated by thermal analysis and dielectric spectroscopy . Molecular details of drug-PSA interaction were identified by FTIR , XPS and Raman. Roles of drug-PSA interaction in the controlled release process were clarified by molecular modeling. Results showed that BSP-C 12 patch demonstrated a controlled release drug plasma profile, with lower C max (193 ± 63 ng/mL) and longer MRT (19.9 ± 3.4 h) compared to BSP patch ( C max,BSP = 450 ± 28 ng/mL, MRT BSP = 7.9 ± 0.9 h). Besides, there was no significant difference between the AUC of BSP-C 12 and BSP patch. It turned out that instead of PSA molecular mobility, molecular interaction between ion-pair and PSA played a dominant role in the controlled release process of BSP: as illustrated by FTIR , Raman and molecular docking, the ionic interaction between BSP-C 12 and PSA determined the amount of BSP released, namely the thermodynamic process; while the doubly ionic hydrogen bond between BSP-C 12 and PSA-COO – controlled the release rate, which was the kinetic process. In conclusion, it was found that the doubly ionic hydrogen bond formed between carboxylic PSA and ion-pair controlled the release profile of BSP, which broadened our understanding about the molecular mechanisms involved in ion-pair controlled release transdermal patches and contributed to the design of controlled release TDDS .
研究领域:
药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 3
·1-8
·
IF 6.232
Sun Xiaodong,Chen Cheng,Li Xiaoqi,Du Yingxiang,Zhao Shiyuan,Feng Zijie
A new bilayer chiral stationary phase for use in open tubular capillary electrochromatography (OT-CEC) system is described. Gold nanoparticles were modified with L-cysteine, with a tetramethylammonium lactobionate ionic liquid that acts as the chiral selector. The gold nanoparticle-coated column provides good enantioseparation and favorable reproducibility. Compared with an uncoated separation system, the column developed displays improved separation of the racemic β-blockers propranolol, esmolol, bisoprolol and sotalol (resolutions of enotiomers are 6.29, 6.11, 6.12 and 6.02, respectively). The materials and coatings were characterized by scanning electron microscopy and transmission electron microscopy. The main driving forces (CEC and electro-osmotic flow) were studied to evaluate the variation of the immobilized columns. The effects of buffer pH value, concentration of chiral selector, type of organic modifier and applied voltage were optimized. Satisfactory relative standard deviations were achieved in run-to-run, day-to-day and column-to-column experiments.
Schematic preparation of a capillary column with bilayer chiral selectors coated gold nanoparticles. This novel OT-CEC system was applied for separation of four basic racemic β-blockers.
研究领域:
分析化学
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药学
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纳米技术
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色谱学
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产品关联
DOI
PubMed
高影响因子
CHIRALITY
·
2025
·Vol. 37
·期 11
·e70060
·
IF 3
Shuling Dong,Jiayi Sun,Fan Ding,Ji Wu,Ronghua Fan,Li Zhou
In this work, a new strategy was proposed for the preparation of a chiral stationary phase based on β-cyclodextrin and calix[4]arene polymer. The chiral stationary phase was characterized by scanning electron microscopy, energy dispersive x-ray spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The introduction of calix[4]arene polymer increased chirality recognition by increasing recognition sites and interactions, including hydrogen bonding, π–π interaction and synergistic inclusion effect. Compared with the home-made β-cyclodextrin–based chiral column, the prepared β-cyclodextrin–calix[4]arene polymer-based chiral column showed superior enantioseparation performance toward 1-phenylethanol, prothioconazole, promethazine, propranolol, and bisoprolol. These chiral compounds can be separated within 10 min under reversed-phase mode with resolutions ranging from 1.62 to 1.80. These findings will provide an important reference for developing novel supramolecule-based chiral stationary phases.
研究领域:
分析化学
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超分子化学
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色谱学
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分离科学
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产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2021
·Vol. 8
·期 7
·1978-1991
·
IF 8.131
Ming Yan,Yilin Wu,Rongxin Lin,Faguang Ma,Zhongyi Jiang
Although many researchers have done several studies on improving the selective separation performance of membrane materials, the conceptions and applications of membrane-based molecular imprinting separation and recognition with both high permselectivity and rebinding capacity have still faced challenges. Herein, for the first time, the bioinspired polydopamine (PDA)-modified porous regenerated cellulose membrane (pRCMs) with Au-based imprinting structure was constructed for the synthesis of molecularly imprinted nanocomposite membranes (MINMs); propranolol was used as template molecule. Importantly, based on the as-constructed PDA-modified layers, abundant Au-modified particles have been uniformly distributed onto the surfaces of membranes, and Au/PDA-based structures can be used as the imprinted-initiated factors for the preparation of sandwich-like-imprinted sites by developing a two-step temperature propranolol-imprinting method. Moreover, superior rebinding capacity (76.87 mg g−1) and selectivity (4.27–4.56) of MINMs has been successfully achieved; the as-prepared MINMs also showed excellent regeneration and permselectivity of propranolol (16.01–18.34) by constructing large amounts of propranolol-imprinted sites on the Au/PDA-based surface. Therefore, under optimized conditions, MINMs would finally obtain reproducible, accessible, and stable membrane-based separation system of the propranolol molecule.
研究领域:
材料科学
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生物医学工程
·
环境科学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）