Topical Delivery of a Naproxen-Dithranol Co-drug: In Vitro Skin Penetration, Permeation, and Staining

Lau, Wing Man; White, Alex William; Heard, Charles Martin

doi:10.1007/s11095-010-0274-8

Cited by 23 publications

(11 citation statements)

References 32 publications

(33 reference statements)

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“…From this experiment, it can be hypothesised that the severe discolouration of skin and clothing due to dithranol could be significantly reduced. This hypothesis was in-line with the reduction in skin staining seen when applied to porcine skin compared to 1 [ 17 ].…”

Section: Resultssupporting

confidence: 63%

“…In many cases, linking two active species together increases the molecular weight of the co-drug beyond the topical delivery optimum of 500; similarly the logP of the co-drug may deviate from the ideal range of approximately 1–3.5. These parameters were taken into account when considering appropriate candidates for a topical co-drug [ 7 , 17 , 18 , 19 ]. To evaluate the potential of a novel small molecule approach to psoriasis, a series of co-drugs based on dithranol were synthesized and the evaluation of in vitro bioactivation of the most promising candidate molecule was also studied herein.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis and in Vitro Degradation of a Novel Co-Drug for the Treatment of Psoriasis

2013

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Psoriasis is a common, chronic and relapsing inflammatory skin disease. It affects approximately 2% of the western population and has no cure. Combination therapy for psoriasis often proves more efficacious and better tolerated than monotherapy with a single drug. Combination therapy could be administered in the form of a co-drug, where two or more therapeutic compounds active against the same condition are linked by a cleavable covalent bond. Similar to the pro-drug approach, the liberation of parent moieties post-administration, by enzymatic and/or chemical mechanisms, is a pre-requisite for effective treatment. In this study, a series of co-drugs incorporating dithranol in combination with one of several non-steroidal anti-inflammatory drugs, both useful for the treatment of psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess the optimal physicochemical properties for topical delivery. The co-drug was fully hydrolyzed in vitro by porcine liver esterase within four hours. When incubated with homogenized porcine skin, 9.5% of the parent compounds were liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co-drug would occur within the skin. The kinetics of the reaction revealed first order kinetics, Vmax = 10.3 µM·min−1 and Km = 65.1 µM. The co-drug contains a modified dithranol chromophore that was just 37% of the absorbance of dithranol at 375 nm and suggests reduced skin/clothes staining. Overall, these findings suggest that the dithranol-naproxen co-drug offers an attractive, novel approach for the treatment of psoriasis.

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Section: Resultssupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and in Vitro Degradation of a Novel Co-Drug for the Treatment of Psoriasis

2013

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“…As oil phase, mixtures of isopropyl myristate with either monocaprylin or oleic acid (1:1, w/w) were selected because of their penetration‐enhancing properties. An additional reason for employing isopropyl myristate is the previously reported increased stability of prodrugs in this solvent . The oil phase and surfactant blend were mixed at 1:9–9:1 ratios (w/w), titrated at room temperature with water under vortexing, and formulations that were fluid, clear, and did not undergo phase separation were assigned to a monophasic region in the phase diagram.…”

Section: Methodsmentioning

confidence: 99%

Stability, Cutaneous Delivery, and Antioxidant Potential of a Lipoic Acid and α-Tocopherol Codrug Incorporated in Microemulsions

Thomas

Vieira

Hass

et al. 2014

Journal of Pharmaceutical Sciences

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The aim of this study was to assess the skin penetration, stability and antioxidant effects of a α-tocopherol-lipoic acid co-drug. To enhance penetration, we evaluated three microemulsions varying in water content and composition of the oil phase (isopropyl myristate with either monocaprylin or oleic acid). The co-drug was incorporated at 1% (w/w). Co-drug hydrolysis in the microemulsion increased with increases in time (up to 48 h) and formulation water content (10–30%, w/w). Microemulsions increased the co-drug delivery into viable layers of porcine ear skin by 2.9–7.8–fold compared to a control formulation (20% monocaprylin in isopropyl myristate) after 24 h. Penetration enhancement was influenced by the oil phase, with the formulation containing monocaprylin displaying the most pronounced effect. Antioxidant activity, assessed in skin bioequivalents using the thiobarbituric acid-reactive substances (TBARS) assay, demonstrated that TBARS levels decreased by 39% after treatment with the co-drug-containing microemulsion compared to the unloaded formulation. In addition to the co-drug, tocopherol (8.2 ± 0.6 μg/cm2) was detected in the viable bioequivalent tissues, suggesting that the co-drug was partly hydrolyzed after 12 h. Taken together, these results support the potential of nanodispersed formulations containing a tocopherol-lipoic acid co-drug to improve skin antioxidant activity.

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“…Full thickness of the skin membrane were cut and liberated from the underlying cartilage using a scalpel, with any adhering subcutaneous fat and tissues carefully removed. The skin was then cut into 1.77 cm 2 sections and stored at -80 °C prior to use [19].…”

Section: Ex Vivo Diffusion Cell Experimentsmentioning

confidence: 99%

“…The diffusion experiments were carried out using the diffusion cell system as previously described [19]. The diffusion cell system (Taiping Business Mansion, Nanjing, China) comprised of six diffusion cells, diffusion cell drive, and circulating water bath for diffusion cells temperature control.…”

Section: Diffusion Cell Experimentsmentioning

confidence: 99%

In Search of an Innovative Agent for Skin Care - Putting an Ancient Herbal Cosmetic Formula on Modern Bioactivity Testing Platforms

2019

J Clin Investig Dermatol

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Inviting Innovations in wrinkles, sagginess, pigmentation or even neoplastic changes [4]. While these undesirable effects could be minimised with avoidance of strong sunlight and harmful exposures, topical applications of various types of agents have been very common practices The usage of topical agents, also known as cosmetics for the management of skin conditions and improvement of its outlook is a common practice among different cultures. The word "cosmetics" arises from the Greek "kosmeticos" meaning "adorn". Since then, any material used for beautification or improvement of appearance is known as cosmetics [5]. This need for adorning the appearance and conditions of the face has been an urge in the human race of different regions and cultures since ancient times, leading to the invention of different remedies which were handed down for generations with unabated enthusiasm.Herbal medicines have been used as skin-whitening agents since ancient times [6,7]."Qi Bai San (QBS)" is one of such ancient herbal cosmetic classic especially used by Royal Family members and dignitaries as topical agent [7]. According to Yong Lei Qian Fang written by Zhong Nan Li, a famous Chinese medicine practitioner during the Yuen Dynasty, QBS was traditionally used for the treatment of skin pigmentations and consisted of seven different Chinese herbs [8]. This formula may vary slightly but contain herbs of which all in Chinese language carry the word "White", signifying its whitening effects. These herbs include Ampelopsis Radix (dried root tuber of Ampelopsis japonica (Thunb.) Makino), Atractylodis Macrocephalae Rhizoma (dried rhizome of Atractylodes macrocephala Koidz.),

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Topical Delivery of a Naproxen-Dithranol Co-drug: In Vitro Skin Penetration, Permeation, and Staining

Abstract: Topical delivery of Nap-DTH not only improves the delivery of naproxen and dithranol, but also reduces unwanted effects of the parent moieties, in particular the skin staining, which is a major issue concerning the use of dithranol.

Cited by 23 publications

References 32 publications

Design, Synthesis and in Vitro Degradation of a Novel Co-Drug for the Treatment of Psoriasis

Design, Synthesis and in Vitro Degradation of a Novel Co-Drug for the Treatment of Psoriasis

Stability, Cutaneous Delivery, and Antioxidant Potential of a Lipoic Acid and α-Tocopherol Codrug Incorporated in Microemulsions

In Search of an Innovative Agent for Skin Care - Putting an Ancient Herbal Cosmetic Formula on Modern Bioactivity Testing Platforms

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