Impact of Ester Promoieties on Transdermal Delivery of Ketorolac

Liu, Kuo‐Sheng; Hsieh, Pei‐Wen; Aljuffali, Ibrahim A.; Lin, Yin-Ku; Chang, Shu‐Hao; Wang, Jhi-Joung; Fang, Jia‐You

doi:10.1002/jps.23888

Cited by 10 publications

(4 citation statements)

References 37 publications

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“…The penetrants should first partition into the SC before diffusion across the SC. The sebum spread on the SC surface contributes to a capacity-governing penetrant partitioning from the vehicle to the SC [ 21 ]. Theoretically, this partitioning is highly dependent on the lipophilicity [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption

Chuang

Lin

et al. 2017

Nutrients

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Flavonoids are bioactive phytochemicals that exhibit protective potential against cutaneous inflammation and photoaging. We selected eight flavonoid aglycones or glycosides to elucidate the chemistry behind their skin absorption capability through experimental and computational approaches. The skin delivery was conducted using nude mouse and pig skins mounted on an in vitro Franz cell assembly. The anti-inflammatory activity was examined using the O2•– and elastase inhibition in activated human neutrophils. In the equivalent dose (6 mM) application on nude mouse skin, the skin deposition of naringenin and kaempferol was 0.37 and 0.11 nM/mg, respectively, which was higher than that of the other flavonoids. Both penetrants were beneficial for targeted cutaneous therapy due to their minimal diffusion across the skin. The absorption was generally greater for topically applied aglycones than glycosides. Although naringenin could be classified as a hydrophilic flavonoid, the flexibility of the chiral center in the C ring of this flavanone could lead to better skin transport than the flavonols and flavones with a planar structure. An optimized hydrophilic and lipophilic balance of the flavonoid structure was important for governing the cutaneous delivery. The hydrogen bond acceptor and stratum corneum lipid docking estimated by molecular modeling showed some relationships with the skin deposition. The interaction with cholesteryl sulfate could be a factor for predicting the cutaneous absorption of aglycone flavonoids (correlation coefficient = 0.97). Baicalin (3 µM) showed the highest activity against oxidative burst with an O2•– inhibition percentage of 77%. Although naringenin displayed an inhibition efficiency of only 20%, this compound still demonstrated an impressive therapeutic index because of the high absorption. Our data are advantageous to providing the information on the structure–permeation relationship for topically applied flavonoids.

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Section: Discussionmentioning

confidence: 99%

Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption

Chuang

Lin

et al. 2017

Nutrients

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“…Different n -alkyl and aryl ester prodrugs of ketorolac were synthesized and their permeation across nude mouse skin evaluated in a 30% ethanol/pH 7.4 Buffer. Ketorolac tert -butyl ester 25 (Figure 7) exhibited the highest penetration of all compounds and tested with a flux of 8.21 ± 1.45 nmol/cm 2 /h, which represented an enhancement ratio of 2.5, compared to ketorolac (3.24 ± 0.25 nmol/cm 2 /h) [69].…”

Section: The Impact Of Prodrug Strategy On the Percutaneous Absorpmentioning

confidence: 99%

Prodrug Strategies for Enhancing the Percutaneous Absorption of Drugs

N’Da

2014

Molecules

113

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Abstract:The transdermal application of drugs has attracted increasing interest over the last decade or so, due to the advantages it offers, compared to other delivery methods. The development of an efficient means of transdermal delivery can increase drug concentrations, while reducing their systemic distribution, thereby avoiding certain limitations of oral administration. The efficient barrier function of the skin, however, limits the use of most drugs as transdermal agents. This limitation has led to the development of various strategies to enhance drug-skin permeation, including the use of penetration enhancers. This method unfortunately has certain proven disadvantages, such as the increased absorption of unwanted components, besides the drug, which may induce skin damage and irritancy. The prodrug approach to increase the skin's permeability to drugs represents a very promising alternative to penetration enhancers. The concept involves the chemical modification of a drug into a bioreversible entity that changes both its pharmaceutical and pharmacokinetic characteristics to enhance its delivery through the skin. In this review; we report on the in vitro attempts and successes over the last decade by using the prodrug strategy for the percutaneous delivery of pharmacological molecules.

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“…Optimization of lipophilicity can be also achieved by developing eters, acid amides, imines but the proportion of these prodrugs is very small compared to the esters [36].…”

Section: Prodrugs With Improved Lipophilicitymentioning

confidence: 99%

“…A prodrug refers to a pharmacologically inactive compound which is transformed into an active substance by either chemical or metabolic processes. Nowadays approximately 10% of drugs used in therapy are administered as prodrugs, and about half of these are hydrolyzed to the active form, in particular by hydrolysis of esters (figure 1) [1][2][3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Prodrug Strategy in Drug Development

Kelemen

Hancu

Rusu

et al. 2016

Acta Medica Marisiensis

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Prodrugs are chemically modified derivatives introduced in therapy due to their advantageous physico-chemical properties (greater stability, improved solubility, increased permeability), used in inactive form. Biological effect is exerted by the active derivatives formed in organism through chemical transformation (biotransformation). Currently, 10% of pharmaceutical products are used as prodrugs, nearly half of them being converted to active form by hydrolysis, mainly by ester hydrolysis. The use of prodrugs aims to improve the bioavailability of compounds in order to resolve some unfavorable characteristics and to reduce first-pass metabolism. Other objectives are to increase drug absorption, to extend duration of action or to achieve a better tissue/organ selective transport in case of non-oral drug delivery forms. Prodrugs can be characterized by chemical structure, activation mechanism or through the presence of certain functional groups suitable for their preparation. Currently we distinguish in therapy traditional prodrugs prepared by chemical derivatisation, bioprecursors and targeted delivery systems. The present article is a review regarding the introduction and applications of prodrug design in various areas of drug development.

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Impact of Ester Promoieties on Transdermal Delivery of Ketorolac

Cited by 10 publications

References 37 publications

Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption

Elucidating the Skin Delivery of Aglycone and Glycoside Flavonoids: How the Structures Affect Cutaneous Absorption

Prodrug Strategies for Enhancing the Percutaneous Absorption of Drugs

Prodrug Strategy in Drug Development

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