Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: A comprehensive study on structure–activity relationships, molecular dynamics and dermal delivery

Teixeira, Raquel Souza; Cova, Tânia F.G.G.; Silva, Sérgio M.C.; Oliveira, Rita; Vale, M. Luísa C. do; Marques, Eduardo F.; Pais, Alberto A. C. C.; Veiga, Francisco

doi:10.1016/j.ejpb.2015.02.024

Cited by 18 publications

(12 citation statements)

References 53 publications

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“…Most of lipoaminoacids show mild antibacterial activity, serine-based lipoaminoacids were successfully tested for DNA complexation. Lysine-based and serine-based lipoaminoacids also showed capacity to enhance skin penetration of model drugs encapsulated in liposomes containing these compounds [73,74]. Despite these interesting properties, most lipoaminoacids maintain the issue of interaction with cell membranes, leading to hemolysis, frequently already at doses required for inhibition of bacterial growth.…”

Section: Structural Diversity Of Biocompatible and Ecologically Frmentioning

confidence: 99%

“…This is the case of colloidal systems aimed for ocular drug delivery, where positively charged aggregates interact with negatively charged ocular surface and hut provide longer contact time, resulting in improved ocular bioavailability of the administered drug and provide a base of long-time, prolonged release of the drug [24]. An improvement of skin penetration was reported after application of cationic amphiphiles, mainly amino-acid based [73,76,78,99]. Most importantly, cationic amphiphiles improve drug loading of many actives into pre-existing drug delivery systems (liposomes, hydrogels, and lipid particles) or improve substantially their solubility by complexing the drugs into self-assembled colloidal aggregates, micelles or vesicles.…”

Section: Quaternary Ammonium Surfactants In Pharmaceutical Applicamentioning

confidence: 99%

See 1 more Smart Citation

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications

Zakharova

Pashirova

Doktorovová

et al. 2019

IJMS

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The development of biotechnological protocols based on cationic surfactants is a modern trend focusing on the fabrication of antimicrobial and bioimaging agents, supramolecular catalysts, stabilizers of nanoparticles, and especially drug and gene nanocarriers. The main emphasis given to the design of novel ecologically friendly and biocompatible cationic surfactants makes it possible to avoid the drawbacks of nanoformulations preventing their entry to clinical trials. To solve the problem of toxicity various ways are proposed, including the use of mixed composition with nontoxic nonionic surfactants and/or hydrotropic agents, design of amphiphilic compounds bearing natural or cleavable fragments. Essential advantages of cationic surfactants are the structural diversity of their head groups allowing of chemical modification and introduction of desirable moiety to answer the green chemistry criteria. The latter can be exemplified by the design of novel families of ecological friendly cleavable surfactants, with improved biodegradability, amphiphiles with natural fragments, and geminis with low aggregation threshold. Importantly, the development of amphiphilic nanocarriers for drug delivery allows understanding the correlation between the chemical structure of surfactants, their aggregation behavior, and their functional activity. This review focuses on several aspects related to the synthesis of innovative cationic surfactants and their broad biological applications including antimicrobial activity, solubilization of hydrophobic drugs, complexation with DNA, and catalytic effect toward important biochemical reaction.

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Section: Structural Diversity Of Biocompatible and Ecologically Frmentioning

confidence: 99%

Section: Quaternary Ammonium Surfactants In Pharmaceutical Applicamentioning

confidence: 99%

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications

Zakharova

Pashirova

Doktorovová

et al. 2019

IJMS

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“…However, there are several parameters that can be considered when attempting to categorize them. Classifications based on their (a) origin, natural [ 39 , 40 , 41 , 42 , 43 ], synthetic [ 44 , 45 , 46 , 47 , 48 ], or semi-synthetic [ 44 , 49 ], and on their (b) chemical structure, alcohols [ 50 , 51 , 52 , 53 ], fatty acids [ 51 , 54 ], surfactants [ 48 , 55 ], esters [ 46 , 51 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ], amides [ 45 , 62 ], and sulfoxides [ 63 , 64 ] are the most common.…”

Section: Chemical Penetration Enhancers (Cpes)mentioning

confidence: 99%

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery

et al. 2021

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Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in poor permeation of most drugs. Several methods have been developed to overcome this limitation. One of the approaches to increase drug permeation and thus to enable TDD for a wider range of drugs consists in the use of chemical permeation enhancers (CPEs), compounds that interact with skin to ultimately increase drug flux. Amino acid derivatives show great potential as permeation enhancers, as they exhibit high biodegradability and low toxicity. Here we present an overview of amino acid derivatives investigated so far as CPEs for the delivery of hydrophilic and lipophilic drugs across the skin, focusing on the structural features which promote their enhancement capacity.

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“…14 The positive charge of a micelle aids binding with negatively charged skin cells and hair follicles. 25 Recently, positively charged surfactants 26 have been used widely to solve the problem of poor transdermal passage of MTX through animal skin. Positively charged micelles have several favorable physicochemical and biologic properties that allow targeting to specific sites in vivo: 27 nanoscale size suitable for drug delivery; structure (hydrophobic core and hydrophilic shell) that allows loading of hydrophilic drugs or protection of sensitive cargo; "tailored" architecture for sustained or controlled release.…”

Section: Introductionmentioning

confidence: 99%

<p>Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material</p>

Zhao¹,

Zheng²,

Wang³

et al. 2020

IJN

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Background: Methotrexate (MTX) is an antiproliferative drug widely used to treat inflammatory diseases and autoimmune diseases. The application of percutaneous administration is hindered due to its poor transdermal penetration. To reduce side effects and enhanced percutaneous delivery of MTX, novel methotrexate (MTX)-loaded micelles prepared with a amphiphilic cationic material, N,N-dimethyl-(N′,N′-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSAP), was designed. Materials and Methods: DMSAP was synthesized via three steps using simple chemical agents. H nuclear magnetic resonance and mass spectroscopy were used to confirm the successful synthesis of DMSAP. A safe and non-toxic phosphatidylcholine, soybean phosphatidylcholine (SPC), was added to DMSAP at different ratios to form P/D-micelles. Then, MTX-entrapped micelles (M/P/D-micelles) were prepared by electrostatic adsorption. The physicochemical properties and blood stability of micelles were examined thoroughly. In addition, the transdermal potential of the micelles was evaluated by permeation experiments. Results: In aqueous environments, DMSAP conjugates could self-assemble spontaneously into micelles with a low critical micelle concentration (CMC) of 0.056 mg/mL. Stable, spherical MTX-entrapped micelles (M/P/D-micelles) with a size of 100-120 nm and high zeta potential of +36.26 mV were prepared. In vitro permeation studies showed that M/P/ D-micelles exhibited superior skin permeability and deposition of MTX in the epidermis and dermis compared with that of free MTX. Conclusion: These special novel cationic M/P/D-micelles can enhance the permeability of MTX and are expected to be a promising percutaneous delivery system for therapy skin diseases.

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Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: A comprehensive study on structure–activity relationships, molecular dynamics and dermal delivery

Cited by 18 publications

References 53 publications

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery

<p>Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material</p>

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