Ultrasound-mediated topical delivery of econazole nitrate with potential for treating Raynaud's phenomenon

Daftardar, Saloni; Bahl, Dherya; Boddu, Sai H. S.; Altorok, Nezam; Kahaleh, Bashar

doi:10.1016/j.ijpharm.2020.119229

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…Wasan et al [62 ▪ ] reported a preclinical study investigating the formulation of a novel nifedipine cream stable to ultraviolet light. Topical PDE5 inhibitors are also being researched [63,64] and topical econazole nitrate, an antagonist of Transient Receptor Potential Melastatin 8 has been studied in vitro [61,66 ▪ ]. These are all important steps forward towards long-awaited clinical trials of topical treatments.…”

Section: Treatmentmentioning

confidence: 99%

“…Although the use of topical glyceryl trinitrate for Raynaud's phenomenon was suggested as far back as 1951 [56], progress with topical therapies has been very slow. It is hoped that recent systematic reviews on topical nitrates [57,58] herald a wave of new interest, with several publications on topical therapies over the last 3 years [59–61,62 ▪ ,63–65,66 ▪ ]. Wasan et al [62 ▪ ] reported a preclinical study investigating the formulation of a novel nifedipine cream stable to ultraviolet light.…”

Section: Treatmentmentioning

confidence: 99%

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Raynaud's phenomenon and digital ulcers: advances in evaluation and management

Herrick¹

2021

Current Opinion in Rheumatology

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Purpose of reviewThe aim of this review is to give an update on advances in evaluation and management of systemic sclerosis (SSc)-related Raynaud's phenomenon and digital ulceration, focusing on reports from the last 18 months. The increasing recognition of the huge impact of Raynaud's phenomenon and of digital ulceration on the everyday lives of patients with SSc has sparked enthusiasm internationally to develop better outcome measures and better treatments, and so a review is timely.Recent findingsThere have been recent advances in the development of patient reported outcome instruments [e.g. the Hand Disability in Systemic Sclerosis-Digital Ulcers (HDISS-DU) instrument] and also in noninvasive imaging techniques, including thermography and laser Doppler methods. Improved outcome measures will facilitate future clinical trials, both early phase proof-of-concept and later phase trials. New insights have been gained into mechanisms of action and methods of administration of ‘conventional’ therapies, for example phosphodiesterase inhibitors and intravenous prostanoids. New treatment approaches are being investigated, including topical and procedural therapies.SummaryClinicians can look forward to seeing these advances translating into clinical benefit over the next 5 years. To help ensure this, they should strive whenever possible to recruit patients with SSc-related digital vasculopathy into observational studies and clinical trials.

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Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Raynaud's phenomenon and digital ulcers: advances in evaluation and management

Herrick¹

2021

Current Opinion in Rheumatology

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“…A variety of physical methods have also been used to increase drug flux across the stratum corneum. One of these methods is sonophoresis [ 67 , 68 , 69 ]. In this technique, low-frequency ultrasound increases the vibrational energy of the lipid molecules in the stratum corneum, thereby causing fluidization and increased permeability.…”

Section: Transdermal Drug Deliverymentioning

confidence: 99%

Roles of Lipids in the Permeability Barriers of Skin and Oral Mucosa

Wertz

2021

IJMS

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PubMed searches reveal much literature regarding lipids in barrier function of skin and less literature on lipids in barrier function of the oral mucosa. In terrestrial mammals, birds, and reptiles, the skin’s permeability barrier is provided by ceramides, fatty acids, and cholesterol in the outermost layers of the epidermis, the stratum corneum. This layer consists of about 10–20 layers of cornified cells embedded in a lipid matrix. It effectively prevents loss of water and electrolytes from the underlying tissue, and it limits the penetration of potentially harmful substances from the environment. In the oral cavity, the regions of the gingiva and hard palate are covered by keratinized epithelia that much resemble the epidermis. The oral stratum corneum contains a lipid mixture similar to that in the epidermal stratum corneum but in lower amounts and is accordingly more permeable. The superficial regions of the nonkeratinized oral epithelia also provide a permeability barrier. These epithelial regions do contain ceramides, cholesterol, and free fatty acids, which may underlie barrier function. The oral epithelial permeability barriers primarily protect the underlying tissue by preventing the penetration of potentially toxic substances, including microbial products. Transdermal drug delivery, buccal absorption, and lipid-related disease are discussed.

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“…However, it has been reported that ~90% of the ECZ present in the marketed formulation (Pevaryl ® cream; (1%, w/w)) remained on the skin surface following topical application, potentially leading to irritation, redness, burning or itching [10]. In addition, ECZ nitrate cannot be completely dissolved, leading to physical phase separation of the emulsion [11]. Excipients, e.g., emulsifiers and surfactants, used to solubilize ECZ and to improve formulation stability will lower its thermodynamic activity and thus reduce drug partitioning from the topical formulation to skin-rendering it more difficult to achieve therapeutic concentrations at the site of infection [10,12].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Delivery of Econazole, Terbinafine and Amorolfine with Improved Cutaneous Bioavailability: A Novel Micelle-Based Antifungal “Tri-Therapy”

2022

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Lack of accurate diagnosis and the use of formulations designed to address the poor aqueous solubility of antifungal agents, but not optimized for delivery, contribute to unsatisfactory outcomes for topical treatment of cutaneous mycoses. The objective of this study was to develop a micelle-based antifungal formulation containing econazole (ECZ), terbinafine (TBF) and amorolfine (AMF) using D-α-tocopheryl polyethylene glycol succinate (TPGS) for simultaneous cutaneous delivery of three agents with complementary mechanisms of action. The antifungal “tri-therapy” micelle-based formulation containing 0.1% ECZ, 0.1% TBF and 0.025% AMF had a drug loading 10-fold lower than the “reference” marketed formulations (Pevaryl®, 1% ECZ; Lamisil®, 1% TBF; Loceryl®, 0.25% AMF). Finite dose application of the micelle-based formulation for 6 h resulted in a statistically equivalent deposition of ECZ (p > 0.05) and TBF (p > 0.05) from the 2 systems, and a 2-fold higher accumulation of AMF (p = 0.017). Antifungal concentrations above MIC80 against Trichophyton rubrum were achieved in each skin layer with the “tri-therapy”, which also exhibited a preferential deposition of each antifungal agent in pilosebaceous unit (PSU)-containing biopsies as compared with PSU-free biopsies (p < 0.05). A planned clinical study will test whether these promising results translate to improved therapeutic outcomes in vivo.

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Ultrasound-mediated topical delivery of econazole nitrate with potential for treating Raynaud's phenomenon

Cited by 7 publications

References 41 publications

Raynaud's phenomenon and digital ulcers: advances in evaluation and management

Raynaud's phenomenon and digital ulcers: advances in evaluation and management

Roles of Lipids in the Permeability Barriers of Skin and Oral Mucosa

Simultaneous Delivery of Econazole, Terbinafine and Amorolfine with Improved Cutaneous Bioavailability: A Novel Micelle-Based Antifungal “Tri-Therapy”

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