Polyethylene glycol derivatization of the non-active ion in active pharmaceutical ingredient ionic liquids enhances transdermal delivery

Zavgorodnya, Oleksandra; Shamshina, Julia L.; Mittenthal, Max S.; McCrary, Parker D.; Rachiero, Giovanni P.; Rogers, Robin D.

doi:10.1039/c6nj03709g

Cited by 35 publications

(12 citation statements)

References 66 publications

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“…More specifically, Vincent et al [80] and Langgartner, J. et al [81] similarly demonstrated that transport across biological membranes bearing a highly polar anionic framework can be facilitated if the APIs are paired with lipophilic ammonium ions that act as phase transfer agents. Additionally, Rogers et al [82] recently demonstrated on synthetic membrane models that API-OSILs that contain lipophilic cations, preferably with established hydrogen bonds, exhibit an increased membrane transport as compared to API-OSILs with weaker electrostatic interactions or even traditional halide or metal salts. Finally, it is important to note that both hydrophobic and hydrophilic ionic liquids have been recently studied as penetration enhancers [16,20,83,84].…”

Section: Studies On Resistant Bacteriamentioning

confidence: 99%

Synthesis and Antibacterial Activity of Ionic Liquids and Organic Salts Based on Penicillin G and Amoxicillin hydrolysate Derivatives against Resistant Bacteria

et al. 2020

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The preparation and characterization of ionic liquids and organic salts (OSILs) that contain anionic penicillin G [secoPen] and amoxicillin [seco-Amx] hydrolysate derivatives and their in vitro antibacterial activity against sensitive and resistant Escherichia coli and Staphylococcus aureus strains is reported. Eleven hydrolyzed β-lactam-OSILs were obtained after precipitation in moderate-to-high yields via the neutralization of the basic ammonia buffer of antibiotics with different cation hydroxide salts. The obtained minimum inhibitory concentration (MIC) data of the prepared compounds showed a relative decrease of the inhibitory concentrations (RDIC) in the order of 100 in the case of [C2OHMIM][seco-Pen] against sensitive S. aureus ATCC25923 and, most strikingly, higher than 1000 with [C16Pyr][seco-Amx] against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. These outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.

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Section: Studies On Resistant Bacteriamentioning

confidence: 99%

Synthesis and Antibacterial Activity of Ionic Liquids and Organic Salts Based on Penicillin G and Amoxicillin hydrolysate Derivatives against Resistant Bacteria

et al. 2020

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“…This strategy was first investigated by Megwa et al [61], who combined the salicylate anion with alkylammonium and quaternary ammonium cations to improve the skin permeation of the API. After this pioneering work, other studies attempted to improve the permeation of salicylates across membranes, being reported as new salicylate-based ILs [62] and ILs with derivatives of poly(ethylene glycol) [63]. The selection of more biocompatible cations, such as amino acids, has been also considered for this purpose [64].…”

Section: Ils As Permeation Enhancers and Microemulsion Components For Drug Deliverymentioning

confidence: 99%

Ionic Liquids in Drug Delivery

et al. 2021

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Ionic liquids (ILs) are molten salts composed of a large organic cation and an organic/inorganic anion. Due to their ionic character, most ILs present advantageous properties over conventional solvents, such as negligible volatility at atmospheric conditions and high thermal and chemical stabilities. The wide variety of IL anion–cation combinations allows these solvents to be designed to display a strong solvation ability for a myriad of active pharmaceutical ingredients (APIs) and (bio)polymers. Given these properties, ILs have been used as solvents and as formulation components in different areas of drug delivery, as well as novel liquid forms of APIs (API-ILs) applied in different stages of development of novel drug delivery systems. Furthermore, their combination with polymers and biopolymers has enabled the design of drug delivery systems for new therapeutic routes of administration.

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“…Recently, a group at McGill University described the development of ILs to improve the delivery of poorly soluble drugs through the skin. Zavgorodnya et al studied the effects of various counterions on the membrane permeability of salicylate-based APIs-ILs [43]. Specifically, they paired three counterions (choline, tributylammonium, and triethylene glycol monomethyl ether tributylammonium) with a salicylate anion to generate three different API-ILs and assessed their impact on transdermal diffusion using a silicone membrane as a skin mimic.…”

Section: Chemical Permeation Enhancer-based Systemsmentioning

confidence: 99%

A Snapshot of Transdermal and Topical Drug Delivery Research in Canada

2019

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The minimally- or non-invasive delivery of therapeutic agents through the skin has several advantages compared to other delivery routes and plays an important role in medical care routines. The development and refinement of new technologies is leading to a drastic expansion of the arsenal of drugs that can benefit from this delivery strategy and is further intensifying its impact in medicine. Within Canada, as well, a few research groups have worked on the development of state-of-the-art transdermal delivery technologies. Within this short review, we aim to provide a critical overview of the development of these technologies in the Canadian environment.

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Polyethylene glycol derivatization of the non-active ion in active pharmaceutical ingredient ionic liquids enhances transdermal delivery

Abstract: Introducing PEGylated moieties into the counterion structure of API–ILs can significantly enhance the transport through a membrane without a solvent.

Cited by 35 publications

References 66 publications

Synthesis and Antibacterial Activity of Ionic Liquids and Organic Salts Based on Penicillin G and Amoxicillin hydrolysate Derivatives against Resistant Bacteria

Synthesis and Antibacterial Activity of Ionic Liquids and Organic Salts Based on Penicillin G and Amoxicillin hydrolysate Derivatives against Resistant Bacteria

Ionic Liquids in Drug Delivery

A Snapshot of Transdermal and Topical Drug Delivery Research in Canada

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