Unsaturated cyclic ureas as new non-toxic biodegradable transdermal penetration enhancers. II. Evaluation study

Wong, Osborne S.; Tsuzuki, Noriko; Nghiem, Ba Thu; Kuehnhoff, J.; Itoh, T.; Masaki, Keiji; Huntington, J.; Konishi, Ryoji; Rytting, J. Howard; Higuchi, Takeru

doi:10.1016/0378-5173(89)90220-2

Cited by 35 publications

(9 citation statements)

References 6 publications

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“…The first biodegradable enhancers, 1-alkyl-2,3-dihydro-3-hydroxyalkylimidazol-2-one esters with fatty acids, were prepared by Wong in 1988 [151,152,153]. Three derivatives showed enhancement activity at least equal to or better than Azone in both snake and mouse skin ( Table 19).…”

Section: Chiral Enhancersmentioning

confidence: 99%

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Amphiphilic Transdermal Permeation Enhancers: Structure-Activity Relationships

Vávrová

Zbytovská²,

Hrabálek³

2005

CMC

112

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Transdermal drug delivery offers numerous advantages over conventional routes of administration; however, poor permeation of most drugs across the skin barrier constitutes a serious limitation of this methodology. One of the approaches used to enlarge the number of transdermally-applicable drugs uses permeation enhancers. These compounds promote drug permeation through the skin by a reversible decrease of the barrier resistance. Enhancers can act on the stratum corneum intracellular keratin, influence desmosomes, modify the intercellular lipid domains or alter the solvent nature of the stratum corneum. Even though, hundreds of substances have been identified as permeation enhancers to date, yet our understanding of the structure-activity relationships is limited. In general, enhancers can be divided into two large groups: small polar solvents, e.g. ethanol, propylene glycol, dimethylsulfoxide and amphiphilic compounds containing a polar head and a hydrophobic chain, e.g. fatty acids and alcohols, 1-dodecylazepan-2-one (Azone), 2-nonyl-1,3-dioxolane (SEPA 009), and dodecyl-2-dimethylaminopropanoate (DDAIP). In this review we have focused on structure-activity relationships of amphiphilic permeation enhancers, including the properties of the hydrophobic chains, e.g. length, unsaturation, and branching, as well as the polar heads characteristics, e.g. hydrogen bonding ability, lipophilicity, and size. We present over 180 examples of enhancers with different polar head to illustrate the structural requirements and the possible role of the polar head. We have given an overview of the methods used for investigation of the mechanisms of permeation enhancement, namely differential scanning calorimetry (DSC), infrared (IR) and Raman spectroscopy, X-ray diffraction and future perspectives in this field. Furthermore, biodegradability and chirality of the enhancers are discussed.

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Section: Chiral Enhancersmentioning

confidence: 99%

“…These biodegradable cyclic urea analogs are composed of the 2,3-dihydroimidazol-2-one ring substituted by a hydroxyalkyl group [151][152][153]. The hydroxyl is connected to the hydrophobic chain via ester or carbonate bond.…”

Section: 3-dihydroimidazol-2-ones -Unsaturated Cyclic Ureasmentioning

confidence: 99%

Amphiphilic Transdermal Permeation Enhancers: Structure-Activity Relationships

Vávrová

Zbytovská²,

Hrabálek³

2005

CMC

112

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“…[44] Urea has, however, had a considerable impact on transdermal enhancement as the search for analogs of urea has led to the discovery of 1-alkyl-4-imidazolin-2-one, which has comparable enhancement activity to that of Azone. [45] Terpenes…”

Section: Ureamentioning

confidence: 99%

Percutaneous penetration enhancement in transdermal drug delivery

Singh¹,

Sri²

2010

Asian J Pharm

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T he transdermal route has numerous advantages over the more traditional drug delivery routes. These include high bioavailability, absence of first pass hepatic metabolism, steady drug plasma concentrations, and the fact that therapy is non-invasive. The main obstacle to permeating drug molecules is the outermost layer of the skin, the stratum corneum. Consequently, research into enhancing transdermal drug delivery (TDD) by overcoming this layer, is an area of prime interest. This review article is written to provide a coverage commentary of the recent advancements in TDD enhancement techniques.

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“…The solutions were kept in a water bath at 37°C. After filtration, samples were analysed immediately by HPLC (Johansen et al 1986;Wong et al 1989). The water solubility of LA-PEG and LA was tested by HPLC analysis after filtering the saturated water solution at 25°C.…”

Section: Measurement Of Enzymatic Hydrolysis and Solubilitymentioning

confidence: 99%

Synthesis and anti-melanogenic effects of lipoic acid-polyethylene glycol ester

Kim

Sim

Bae

et al. 2008

Journal of Pharmacy and Pharmacology

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To develop a new potent anti-melanogenic agent, we have conjugated lipoic acid (LA) to poly (ethylene) glycol (PEG) of molecular weight 2000 and examined the effects on inhibition of tyrosinase activity and melanin synthesis in B16F10 melanoma cells. The water-soluble LA-PEG 2000 was synthesized from LA and methylated PEG by an esterification reaction in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. Synthetic LA-PEG 2000 was confirmed by IR and 1 H-NMR spectroscopy. The new conjugate is a highly water-soluble molecule, which has lower cell cytotoxicity than LA. Treatment with LA-PEG 2000 significantly suppressed the biosynthesis of melanin by up to 63% at 0.25 mM and reduced tyrosinase activity by up to 80% at 0.50 mM in B16F10 melanoma cells. Furthermore, Western blot and RT-PCR studies indicated that treatment with LA-PEG 2000 decreased the level of tyrosinase, which is a melanogenic enzyme. Taken together, these results suggest that LA-PEG 2000 may inhibit melanin biosynthesis by down-regulating levels and expression of tyrosinase activity. Therefore, LA-PEG 2000 can be used effectively as a new agent to inhibit melanogenesis, with lower cytotoxicity than LA (parent molecule) in B16F10 melanoma cells.Primarily synthesized within melanocytes, melanin contributes to the pigmentation of the skin, hair, brain and eyes. The complex regulatory control of the biosynthetic machinery involved in melanogenesis includes receptor-mediated pathways activated by hormones, neurotransmitters, cytokines and growth factors, as well as receptor-independent mechanisms activated or modified by nutrients, micromolecules, microelements, pH, cation and anion concentrations, and the oxidoreductive potential (Slominski et al 2004). Melanin production plays an important role in prevention of sun-induced skin injury (Hill et al 1997). However, abnormal hyperpigmentation such as freckles, chloasma, lentigines and other forms of melanin hyperpigmentation can be serious aesthetic problems (Gilchrest 1996). Melanin synthesis is mainly regulated by tyrosinase, which catalyses the rate-limiting reactions (tyrosine hydroxylation to L-3, 4-dihydroxyphenylalanine [L-DOPA], and oxidation of L-DOPA to DOPA-quinone) that are common to both eu-and pheomelanogenesis. The subsequent steps after the formation of DOPA-quinone are responsible for switching between these two types of melanin. The progression of these steps, including spontaneous chemical reactions, depends on the ratio of sulfhydryl compounds such as cysteine and/or glutathione (GSH) within melanocytes. In the absence of cysteine and/or GSH, DOPAquinone is oxidized to form DOPA-chrome as the intermediate product of eumelanin, which results in the advance of eumelanogenesis. In the presence of these compounds, DOPA-quinone is coupled with their SH groups to form cysteinyl DOPA as a precursor of sulfur-containing pigment known as pheomelanin, which corresponds to the progress of pheomelanogenesis.

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Unsaturated cyclic ureas as new non-toxic biodegradable transdermal penetration enhancers. II. Evaluation study

Cited by 35 publications

References 6 publications

Amphiphilic Transdermal Permeation Enhancers: Structure-Activity Relationships

Amphiphilic Transdermal Permeation Enhancers: Structure-Activity Relationships

Percutaneous penetration enhancement in transdermal drug delivery

Synthesis and anti-melanogenic effects of lipoic acid-polyethylene glycol ester

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