Dapsone-Loaded Invasomes as a Potential Treatment of Acne: Preparation, Characterization, and In Vivo Skin Deposition Assay

Abstract

Dapsone (DPS) is a unique sulfone with antibiotic and anti-inflammatory activity. Owing to its dual action, DPS has a great potential to treat acne. Topical DPS application is expected to be effective in treatment of mild to moderate acne conditions. Invasomes are novel vesicles composed of phosphatidylcholine, ethanol, and one or mixture of terpenes of enhanced percutaneous permeation. In this study, DPS-loaded invasomes were prepared using the thin film hydration technique. The effect of different terpenes (Limonene, Cineole, Fenchone, and Citral) in different concentrations on the properties of the prepared DPS-loaded invasomes was investigated using a full factorial experimental design, namely, the particle size, drug entrapment, and release efficiency. The optimized formulation was selected for morphological evaluation which showed spherical shaped vesicles. Further solid-state characterization using differential scanning calorimetry and X-ray diffractometry revealed that the drug was dispersed in an amorphous state within the prepared invasomes. Finally, the ability of the prepared DPS-loaded invasomes to deliver DPS through the skin was investigated in vivo using wistar rats. The maximum in vivo skin deposition amount of DPS was found to be 4.11 mcg/cm for invasomes versus 1.71 mcg/cm for the drug alcoholic solution, representing about 2.5-fold higher for the invasomes compared to the drug solution. The AUC0-10 calculated for DPS-loaded invasomes was nearly 2-fold greater than that of DPS solution (14.54 and 8.01 mcg.h/cm for the optimized invasomes and DPS solution, respectively). These results reveal that the skin retention of DPS can be enhanced using invasomes.

<p>Low-Frequency versus High-Frequency Ultrasound-Mediated Transdermal Delivery of Agomelatine-Loaded Invasomes: Development, Optimization and in-vivo Pharmacokinetic Assessment</p>

“…This could be explained with reference to the lipophilicity of each terpene; limonene (log P = 4.83), cineole (log P = 2.82), fenchone (log P = 2.13), and citral (log P = 2.02). 37 The higher the terpene's lipophilicity, the higher the AGM solubilization, and the higher the drug EE%. 38 The high drug EE% of limonene-based invasomes was revealed with El-Nabarawi et al 37 for dapsone invasomes, Prasanthi et al 38 for finasteride invasomes and Lakshmi et al 39 for curcumin invasomes.…”

“…Ethanol produces a modification of the net surface charge thereby, promoting the stabilization of the vesicular charges via electrostatic repulsion, and minimizing their subsequent de-aggregation. 13,27,37 In a parallel line, the negatively charged phosphatidyl group of PC could be positioned to the outside, while the positively charged choline group of PC would be oriented to the inside, resulting in a high magnitude of negative charges. 43…”

Invasome: A Novel Nanocarrier for Transdermal Drug Delivery

“…The strategic mechanism for terpene penetration occurs through interaction with SC intercellular lipids [57]. Terpenes are applied alone or in combination with other drug delivery systems as permeation enhancers for therapeutic applications [58][59][60][61]. But beside the potency of terpenes in comparison to different penetration enhancers, the toxicities of terpenes should be considered.…”

“…El-Nabarawi et al prepared dapsone-loaded invasomes with different terpenes (cineole, limonene, citral, and fenchone) to examine their ability to deliver dapsone through the skin. Their investigation revealed that the deposition of dapsone in the skin is significantly improved by invasomes [59].…”

<p>The Challenge of Nanovesicles for Selective Topical Delivery for Acne Treatment: Enhancing Absorption Whilst Avoiding Toxicity</p>

“…In fact, only smaller and flexible vesicles seem to penetrate intact through the stratum corneum. 74 Another study compared invasomes with two other systems (liposomes and LeciPlex, a cationic phospholipidbased vesicular system) for their ability to deliver drugs deep into the skin. Azelaic acid was encapsulated into the three proposed systems and in vitro studies were performed to investigate the antimicrobial activity against P. acne.…”