Dexamethasone-Loaded Lipomers: Development, Characterization, and Skin Biodistribution Studies

Abstract

Follicular targeting has gained more attention in recent decades, due to the possibility of obtaining a depot effect in topical administration and its potential as a tool to treat hair follicle-related diseases. Lipid core ethyl cellulose lipomers were developed and optimized, following which characterization of their physicochemical properties was carried out. Dexamethasone was encapsulated in the lipomers (size, 115 nm; polydispersity, 0.24; zeta-potential (Z-potential), +30 mV) and their in vitro release profiles against dexamethasone in solution were investigated by vertical diffusion Franz cells. The skin biodistribution of the fluorescent-loaded lipomers was observed using confocal microscopy, demonstrating the accumulation of both lipomers and fluorochromes in the hair follicles of pig skin. To confirm this fact, immunofluorescence of the dexamethasone-loaded lipomers was carried out in pig hair follicles. The anti-inflammatory (via TNFα) efficacy of the dexamethasone-loaded lipomers was demonstrated in vitro in an HEK001 human keratinocytes cell culture and the in vitro cytotoxicity of the nanoformulation was investigated.

The Physicochemical, Biopharmaceutical, and In Vitro Efficacy Properties of Freeze-Dried Dexamethasone-Loaded Lipomers

“…The DEX-lipomer formulation was previously developed by an emulsion solvent evaporation method [ 7 ]. Briefly, EC, MCT, span 60, and DEX (2.33% w / w , 0.2% w / w , 0.16%, and 1% w / w , respectively) were dissolved in EA:ET (5:1) and emulsified with purified water with tween 80 and the preservative benzalkonium chloride (1.5% w / w and 0.2% w / w , respectively) with a UP400st ultrasonic device (Hielscher Ultrasonics, Teltow, Germany) with an amplitude of 40% for 5 min.…”

“…A previously described HPLC method [ 7 ] was employed to quantify the DEX concentration in the release and permeation experiments ( Section 2.5 and Section 2.6 , respectively). Briefly, an isocratic elution with a mobile phase composed by acetonitrile:KH 2 PO 4 0.05M (60:40) passed at 1.8 mL/min through a C18 HPLC column (250 × 4.6 mm, 3 µm) at 25 °C.…”

“…The in vitro release of DEX from non-FD DEX-lipomers, FD-DEX-lipomers, FD-DEX-lipomers hydrogel, and Free-DEX hydrogel was studied using 12 mL vertical Franz Cells (Vidrafoc, Barcelona, Spain) with a diffusional area of 1.54 cm 2 . Experimental variables were the same as previously used [ 7 ]: briefly, receptor medium (ethanol:purified water 50:50) at 32 °C, 60 mg of DEX placed in the donor compartment, and 0.3 mL of sample volume obtained at regular time intervals of up to 24 h. A 12–14 KDa dialysis membrane (Spectrum Chemical, New Brunswick, NJ, USA) was placed between the donor and receptor compartments. Model fitting to several kinetic equations ( Table 2 ) was performed with the DD-solver Excel add-in [ 19 ] using the lowest Akaike Information Criteria (AIC) as the model selection criteria.…”

“…When patients are refractory to topical treatment, corticosteroids could be administrated intralesionally or systemically [ 6 ], but these routes of administration are associated with a higher incidence of adverse effects and patient discomfort. With the aim of improving the therapeutic index of the corticoid topical treatment, a dexamethasone (DEX)-lipomers formulation was developed as a promising tool to treat alopecia areata as a result of its accumulation in the hair follicles [ 7 ]. The follicular targeting was demonstrated by confocal fluorescence microscopy and immunohistofluorescence.…”

Preclinical Evaluation of Lipid-Based Nanosystems

“…F. Fernández-Campos et al [ 1 ] developed lipomers (i.e., lipid core polymeric nanocapsules) loaded with dexamethasone and studied their potential to improve the topical treatment of alopecia areata and other hair-follicle inflammatory diseases. The occurrence of follicular targeting of lipomers suggests that it is possible to have a drug deposition effect within the pilosebaceous unit, which reduces the frequency of administrations, although the safety and efficacy profiles of these lipomers must first be confirmed in clinical trials.…”