Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects

Abstract

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid Clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeared to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient -2-drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatorybased skin/scalp diseases. Graphical Abstract AbbreviationsAA: Alopecia areata ANOVA: Analysis of variance CCT: capric/caprylic triglyceride CP: Clobetasol propionate

Hesperetin-loaded lipid-core nanocapsules in polyamide: a new textile formulation for topical drug delivery

“…In this case, the negative zeta potential value is close to zero as a consequence of the chemical composition (polyester coated by polysorbate 80), in which stabilization mechanism is based on the steric hindrance effect. 13,34 The reproducibility of size distribution batch-to-batch shows that the formulation is kinetically stable, ie, the system has a delayed aggregation phase separation. The PCL used in the nanocapsule formulation has -COOH end groups, which can present an acidbase balance forming carboxylates, rendering the surface negatively charged.…”

“…The core chemical composition allows these nanocapsules to control drug penetration in different tissues. 13 A variety of nanosystems such as nanostructured lipid carriers, nanosuspensions and nanocrystals have been studied with Hst, 15,23,24 but the current study proposes the encapsulation of Hst in LNCs.…”

“…7 To solve this limitation, a large number of studies have been published describing new delivery systems such as inclusion complexes with cyclodextrins [8][9][10][11] and nanoparticles. 7,[12][13][14][15] Nanoparticle systems have been considered promising carriers of therapeutic drugs, and the application of these particles as carriers of natural compounds has been extensively studied over the past few years. 16 One of the main challenges in relation to chronic diseases is patient adherence to prescribed treatments.…”

Tacrolimus nanoparticles based on chitosan combined with nicotinamide: enhancing percutaneous delivery and treatment efficacy for atopic dermatitis and reducing dose

“…22,[24][25][26][27][28][29][30] These nanocarriers facilitate drug delivery to structural features of the skin, such as hair follicles, or interact with skin lipids to mediate transportation and create a drug depot in the skin for sustained release. 31,32 Moreover, cationic nanoparticles have shown advantages of enhancing drug permeation over neutral or negatively charged nanoparticles as drug nanocarriers; significant progress has been made in cationic nanoparticles for drug delivery. 33,34 In the present study, chitosan nanoparticles (CS-NPs) were used as the carrier of FK506 for percutaneous delivery.…”

“…2) NPs with diameter more than 10 nm are unlikely to penetrate through the SC into viable human skin but tend to accumulate in hair follicle openings and furrows, resulting in the formation of a drug depot on the skin surface for sustained release and permeation in the skin without damaging the natural barrier of the skin. 31,[53][54][55][56] Moreover, CS works as a permeation enhancer due to its positive charges and mucoadhesive properties. Consequently, the FK506-NIC-CS-NPs system exploited both virtues of NIC and NPs to obtain synergetic effects on FK506 percutaneous delivery.…”