Squarticles as a Lipid Nanocarrier for Delivering Diphencyprone and Minoxidil to Hair Follicles and Human Dermal Papilla Cells

Abstract

Abstract. Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related cells is important in the treatment of alopecia. Here we report the development of "squarticles," nanoparticles formed from sebum-derived lipids such as squalene and fatty esters, for use in achieving targeted drug delivery to the follicles. Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions (NE), were prepared. The physicochemical properties of squarticles, including size, zeta potential, drug encapsulation efficiency, and drug release, were examined. Squarticles were compared to a free control solution with respect to skin absorption, follicular accumulation, and dermal papilla cell targeting. The particle size of the NLC type was 177 nm; that of the NE type was 194 nm. Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles. An improved drug deposition in the skin was observed in the in vitro absorption test. Compared to the free control, the squarticles reduced minoxidil penetration through the skin. This may indicate a minimized absorption into systemic circulation. Follicular uptake by squarticles was 2-and 7-fold higher for DPCP and minoxidil respectively compared to the free control. Fluorescence and confocal images of the skin confirmed a great accumulation of squarticles in the follicles and the deeper skin strata. Vascular endothelial growth factor expression in dermal papilla cells was significantly upregulated after the loading of minoxidil into the squarticles. In vitro papilla cell viability and in vivo skin irritancy tests in nude mice suggested a good tolerability of squarticles to skin. Squarticles provide a promising nanocarrier for topical delivery of DPCP and minoxidil.

Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

“…11 We had previously developed the nanoemulsions, which are termed squarticles, that contain squalene as the lipid cores and Pluronic F68/phosphatidylcholines as the emulsifiers for enhancing anti-alopecia drug uptake in hair follicles. 12 Squalene is a polyunsaturated hydrocarbon with a lipophilic character and high biocompatibility. This nonpolar compound is reported to increase the elimination of xenobiotics due to its affinity to lipophilic molecules.…”

Getting Under the skin: What is the Potential of the Transfollicular Route in Drug delivery?

“…Hence, specific means of opening HF gain importance when targeted therapeutic approaches aim at exploiting the entire infundibular volume and delivering compounds to a maximum of HF in a defined skin area. Among chemical methods, hexane, ethanol or detergents have been successfully applied to open the HF orifices [12]. Also, physical means which do not require special equipment represent interesting approaches.…”

“…Editorial drug specific accumulation in the HF infundibulum and create persistent levels of drug in the sebaceous gland [15]. Also, particle-based formulations of minoxidil have been tested for the treatment of androgenetica alopecia [12];…”

Iontophoresis on minoxidil sulphate-loaded chitosan nanoparticles accelerates drug release, decreasing their targeting effect to hair follicles

“…2 To elevate these indices, last researches have focused on developing more efficient formulations, i.e., formulations capable of targeting the active compound to hair follicles and sustaining its release. 3 For this, solid lipid nanoparticles, 4 penetration enhancer-containing vesicles 5 and squarticles nanoparticles, formed from sebum-derived lipids, 6 have been proposed. Although many studies have indeed demonstrated improved skin permeation, it is important to consider that minoxidil, a pyridine-derivative, is a potent antihypertensive agent; hence, dermal exposure and a consequent systemic effect should be avoided to minimize adverse side effects.…”