Mechanism study on ion-pair complexes controlling skin permeability: Effect of ion-pair dissociation in the viable epidermis on transdermal permeation of bisoprolol

Zhao, Hanqing; Liu, Chao; Quan, Peng; Wan, Xiaocao; Shen, Meiyue; Fang, Liang

doi:10.1016/j.ijpharm.2017.08.080

Cited by 52 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The greater MW of fluorescein may imply that it would be more difficult to penetrate across the rabbit skin, which is of vital importance to reflect the transdermal process of ISDN. There have been many literature works which examined permeation characteristics of different enhancers by using fluorescein as a fluorescent probe (Chen et al., 2014; Li et al., 2017; Zhao et al., 2017). In the present research, authors examined the rabbit skin samples subsequent to the application of (a) solvent blank, (b) TER, (c)TER-C4, (d) TER-C14, and (e) NMP.…”

Section: Resultsmentioning

confidence: 99%

Permeation-enhancing effects and mechanisms of O-acylterpineol on isosorbide dinitrate: mechanistic insights based on ATR-FTIR spectroscopy, molecular modeling, and CLSM images

Wang

et al. 2019

Drug Delivery

View full text Add to dashboard Cite

The present study aimed to evaluate the penetration activity of O-acylterpineol derivatives both in vitro and in vivo, and to investigate the enhancing mechanism of O-acylterpineol derivatives which were synthesized by α-terpineol and fatty acid. The promoting activities on the isosorbide dinitrate patch were tested across full thickness rabbit skin both in vitro and in vivo. In order to elucidate the permeation mechanism, attenuated total reflection Fourier transform infrared spectroscopy, molecular modeling, and confocal laser scanning microscopy were introduced to investigate the regulation of enhancers in the skin permeability and biophysical properties. With in vitro cytotoxicity test and in vivo erythema model, the skin irritation of enhancers was also evaluated. Permeation studies showed 2-(4-methylcyclohex-3-en-l-yl) propan-2-yl tetradecanoate produced the obvious enhancement activity for ISDN both in vitro and in vivo from patches. These results were supported by ATR-FTIR, molecular modeling, and CLSM studies which revealed that O-acylterpineol could decrease the order of the alkyl chains in the skin lipids. Additionally, it was found that TER-C14 produced a relatively low skin irritation, compared with the TER which was assumed to be a safe compound. The present research suggested that some newly designed acylterpineol derivatives are shown to be suitable permeation enhancers for transdermal drug delivery, and the chain length of C14 seem to be safe and more favorable for the penetration of ISDN from DIA patches.

show abstract

Section: Resultsmentioning

confidence: 99%

Permeation-enhancing effects and mechanisms of O-acylterpineol on isosorbide dinitrate: mechanistic insights based on ATR-FTIR spectroscopy, molecular modeling, and CLSM images

Wang

et al. 2019

Drug Delivery

View full text Add to dashboard Cite

show abstract

“…The release of the drug is caused by the partition and diffusion of the ion-pair through the SC prior to dissociation in the viable epidermis. Some previous studies have reported that the delivery of the following drugs was successfully enhanced using the ion pairing method: risedronate [82], bisoprolol [83], escitalopram [84], berberine [85], zaltoprofen [86] and nicotine [87].…”

Section: Drug-vehicle Interactionmentioning

confidence: 99%

Enhancement strategies for transdermal drug delivery systems: current trends and applications

Ramadon

McCrudden

Courtenay

et al. 2021

Drug Deliv. and Transl. Res.

284

159

View full text Add to dashboard Cite

Transdermal drug delivery systems have become an intriguing research topic in pharmaceutical technology area and one of the most frequently developed pharmaceutical products in global market. The use of these systems can overcome associated drawbacks of other delivery routes, such as oral and parenteral. The authors will review current trends, and future applications of transdermal technologies, with specific focus on providing a comprehensive understanding of transdermal drug delivery systems and enhancement strategies. This article will initially discuss each transdermal enhancement method used in the development of first-generation transdermal products. These methods include drug/vehicle interactions, vesicles and particles, stratum corneum modification, energy-driven methods and stratum corneum bypassing techniques. Through suitable design and implementation of active stratum corneum bypassing methods, notably microneedle technology, transdermal delivery systems have been shown to deliver both low and high molecular weight drugs. Microneedle technology platforms have proven themselves to be more versatile than other transdermal systems with opportunities for intradermal delivery of drugs/biotherapeutics and therapeutic drug monitoring. These have shown that microneedles have been a prospective strategy for improving transdermal delivery systems. Graphical abstract

show abstract

“…However, in vitro and ex vivo functional studies suggest that a drug linked to a targeting ligand through the formation of an ion‐pair can remain associated for more than 30 min in biological fluids. [ 8 ] This is significantly longer than simple electrolyte ion‐pairs which break down in ≈1 ns. [ 9 ] Also, the physical stability of ion‐pairs could be prolonged through association with stabilizing biomolecules such as cyclodextrins (CD).…”

Section: Introductionmentioning

confidence: 99%

A Cyclodextrin‐Stabilized Spermine‐Tagged Drug Triplex that Targets Theophylline to the Lungs Selectively in Respiratory Emergency

Sofian

Benaouda

Wang

et al. 2020

Advanced Therapeutics

View full text Add to dashboard Cite

Ion‐pairing a lifesaving drug such as theophylline with a targeting moiety could have a significant impact on medical emergencies such as status asthmaticus or COVID‐19 induced pneumomediastinum. However, to achieve rapid drug targeting in vivo the ion‐pair must be protected against breakdown before the entry into the target tissue. This study aims to investigate if inserting theophylline, when ion‐paired to the polyamine transporter substrate spermine, into a cyclodextrin (CD), to form a triplex, could direct the bronchodilator to the lungs selectively after intravenous administration. NMR demonstrates that upon the formation of the triplex spermine protruded from the CD cavity and this results in energy‐dependent uptake in A549 cells (1.8‐fold enhancement), which persists for more than 20 min. In vivo, the triplex produces a 2.4‐fold and 2.2‐fold increase in theophylline in the lungs 20 min after injection in rats and mice, respectively ( p < 0.05). The lung targeting is selective with no increase in uptake into the brain or the heart where the side‐effects of theophylline are treatment‐limiting. Selectively doubling the concentration of theophylline in the lungs could improve the benefit‐risk ratio of this narrow therapeutic index medicine, which continues to be important in critical care.

show abstract

Mechanism study on ion-pair complexes controlling skin permeability: Effect of ion-pair dissociation in the viable epidermis on transdermal permeation of bisoprolol

Cited by 52 publications

References 37 publications

Permeation-enhancing effects and mechanisms of O-acylterpineol on isosorbide dinitrate: mechanistic insights based on ATR-FTIR spectroscopy, molecular modeling, and CLSM images

Permeation-enhancing effects and mechanisms of O-acylterpineol on isosorbide dinitrate: mechanistic insights based on ATR-FTIR spectroscopy, molecular modeling, and CLSM images

Enhancement strategies for transdermal drug delivery systems: current trends and applications

A Cyclodextrin‐Stabilized Spermine‐Tagged Drug Triplex that Targets Theophylline to the Lungs Selectively in Respiratory Emergency

Contact Info

Product

Resources

About