RESUMO
In the present study, iron oxide nanoparticles, in the form of maghemite core coated with lauric acid (ION), were synthesized and loaded with finasteride (FIN) or dutasteride (DUT) as a novel drug delivery system for the topical treatment of alopecia. Additionally, developed formulations (FIN-ION and DUT-ION) were completely elaborated with components involved in the follicle metabolism, i.e., lauric acid, which acts as a 5α-reductase inhibitor, and iron which deficiency has been related to hair loss aggravation. Stability assessment conducted over the course of 90 days showed they are highly stable, with pH 7.4, constant EE% (>99%), and practically unchanged particle size and zeta potential. Besides drug distribution, the actual number of iron oxide nanoparticles, through a newly developed method using ferromagnetic resonance, was determined in each skin layer following permeation experiments. Despite the same donor concentration of colloids, nanoparticle distribution in the skin varied according to the loaded molecule. While DUT did not interfere with the nanoparticle natural tendency to accumulate within the hair follicle shafts, FIN presence hampered nanosystem interaction with the skin. Still, both formulations provided a higher skin drug penetration, compared to each respective control solution. Additionally, iron nanocarriers present a desirable visual characteristic, as the dark color aspect might instantly help disguise scarce hair follicle areas. These findings suggest the nanoformulations are highly promising for alopecia therapies.
Assuntos
Alopecia , Finasterida , Inibidores de 5-alfa Redutase , Alopecia/tratamento farmacológico , Dutasterida , Compostos Férricos , HumanosRESUMO
In general, nanometer-sized drug delivery systems have a natural tendency for accommodation in the follicular cavities, which makes them advantageous in the treatment of conditions affecting these structures. Still, follicular targeting enhancement can improve therapy outcomes. Here, we compare two strategies to further promote dutasteride follicular-targeted delivery: the chemical modulation of nanosystem surface properties by coating with the natural polymer chitosan, and the application of a massage. For this, poly-(É-caprolactone)-lipid-core nanocapsules (NC) containing dutasteride were developed and had their permeation profile compared to chitosan-coated nanocapsules (NC-CS). Nanocapsules showed high drug encapsulation efficiency (>94%), and stability for up to 90 days of storage. As expected, chitosan coating increased the size and zeta potential, from 199.0 ± 0.5 nm (PdI of 0.12) and - 13.6 ± 0.6 mV to 224.9 ± 3.4 nm (PdI 0.23) and + 40.2 ± 0.8 mV, respectively. Both coated and non-coated nanoparticles targeted the hair follicles compared to a drug solution. Enhanced hair follicles targeting was observed after the massage procedure, with 5 and 2-fold increases relative to NC and NC-CS, respectively. In conclusion, this work demonstrates dutasteride nanocapsules can target the follicular casts, and a simple physical stimulation can enhance 5-times the drug amount accumulated.