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Emerging Technologies to Target Drug Delivery to the Skin – the Role of Crystals and Carrier-Based Systems in the Case Study of Dapsone

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Abstract

Dapsone (DAP) is a long-established molecule that remains a promising therapeutic agent for various diseases mainly because it combines antimicrobial and anti-inflammatory activities. Its oral application, however, is limited by the dose-dependent hematological side effects that may rise from systemic exposure. As an alternative to overcome this limitation, the administration of DAP to the skin has witnessed prominent interest in the past 20 years, particularly when applied to the treatment of dermatological disorders. In this review, all technological strategies proposed to the topical delivery of DAP are presented. Most of the reported studies have been devoted to the clinical use and safety of a gel formulation containing both solubilized and microcrystalline drug, however, the technological characteristics of such preparation are still missing. In parallel, the incorporation of DAP into vesicular and particulate carriers (e.g. nano- and microemulsions, niosomes, invasomes, bilosomes, cubosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocapsules and polymer-lipid-polymer hybrid nanoparticles) appears to be an alternative to provide greater drug release control, enhanced drug solubilization and follicular targeting. Indeed, the main application of DAP topical formulations reported in the literature was the treatment of acne vulgaris, a disease located in the hair follicle. Other diseases affecting different regions of the skin (e.g. cutaneous lupus erythematosus and cutaneous leishmaniasis), however, may also benefit from a topical therapeutic regimen containing DAP. Therefore, the investigation of appendageal route in comparison to passive transmembrane diffusion as a function of targeted disease, as well as pharmacokinetic studies, are perspectives highlighted herein. Such studies may drive future efforts towards the rational development of safe and effective technologies to deliver DAP to the skin.

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Abbreviations

AUC:

Area under the curve

BCS:

Biopharmaceutical classification system

CLE:

Cutaneous lupus erythematosus

DAC/NRF:

The German Drug Codex/New German Formulary

DAP:

Dapsone

EE:

Encapsulation efficiency

FDA:

U.S. Food and Drug Administration

HET-CAM:

Hen’s Egg Test – Chorioallantoic Membrane

ME:

Microemulsion

NE:

Nanoemulsion

NLC:

Nanostructured lipid carriers

SLN:

Solid lipid nanoparticles

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ACKNOWLEDGMENTS AND DISCLOSURE

Authors thank the Brazilian governmental agencies CNPq/MCTI (Universal 01/2016 - Grant number: 408229/2016-0) and CAPES/MEC for the financial support and fellowships, respectively. GSR would like to specifically thank CAPES for the fellowship PDEE PRINT-CAPES/UFSC call 06/PGFAR/2019. Declarations of Interest: None.

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  1. Postgraduate Program in Pharmacy (PGFar), Federal University of Santa Catarina, Trindade, SC, 88040-900, Florianopolis, Brazil

    Gabriela Schneider-Rauber, Debora Fretes Argenta & Thiago Caon

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  1. Gabriela Schneider-Rauber
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  2. Debora Fretes Argenta
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ǂ The patents CA 2,776,702 (98) and US 2017/0119703 A1 (99) also mention the preparation of DAP formulations other than gels, for instance suspension, cream, liquid, paste, lotion, nanoemulsion, microemulsion, reverse emulsion, liposomal cream and ointment.

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Schneider-Rauber, G., Argenta, D.F. & Caon, T. Emerging Technologies to Target Drug Delivery to the Skin – the Role of Crystals and Carrier-Based Systems in the Case Study of Dapsone. Pharm Res 37, 240 (2020). https://doi.org/10.1007/s11095-020-02951-4

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