Boosting the anti-inflammatory effect of self-assembled hybrid lecithin-chitosan nanoparticles via hybridization with gold nanoparticles for the treatment of psoriasis: elemental mapping and in vivo modeling.

Gold nanoparticles are a promising drug delivery system for treatment of inflammatory skin conditions, including psoriasis, due to their small size and anti-inflammatory properties. The aim of this study was to conjugate gold nanoparticles with anti-psoriatic formulations that previously showed successful results in the treatment of psoriasis (tacrolimus-loaded chitosan nanoparticles and lecithin-chitosan nanoparticles) by virtue of their surface charges, then examine whether the hybridization with gold nanoparticles would enhance the anti-psoriatic efficacy in vivo. Successful formation of gold nanoparticles was examined by elemental mapping and selected area electron diffraction (SAED). Hybrid conjugates were examined in terms of particle size and zeta potential by dynamic light scattering (DLS). Morphological features were captured by transmission electron microscope (TEM) and X-ray diffraction (XRD) analysis was conducted, as well. All characterization was conducted for the conjugated nanoparticles and compared with their bare counterparts. The in vivo results on imiquimod (IMQ)-induced mouse model showed promising anti-psoriatic effects upon application of gold conjugated tacrolimus-loaded lecithin-chitosan hybrid nanoparticles with a significant difference from the bare hybrid nanoparticles in some of the inflammatory markers. The anti-inflammatory effect of the gold conjugate was also evident by a lower spleen to body weight ratio and a better histopathological skin condition compared to other tested formulations.

Self-assembled tacrolimus-loaded lecithin-chitosan hybrid nanoparticles for in vivo management of psoriasis.

Lecithin-chitosan hybrid nanoparticles are emerging as a promising nanocarrier for topical drug delivery. They could achieve a maximized encapsulation of hydrophobic drugs due to the lipophilic nature of lecithin that comprises the core while enhancing retention in the upper skin layers using the positively charged polymeric coat of chitosan. The aim of this study is to incorporate tacrolimus; a hydrophobic anti-proliferative agent into lecithin chitosan hybrid nanoparticles by ethanolic injection technique using a suitable co-solvent to enhance encapsulation of the drug and allow a satisfactory release profile in the upper skin layers. Tacrolimus was successfully incorporated into the synthesized particles using olive oil and Tween 80 as co-solvents, with particle size (160.9 nm ± 15.9 and 118.7 nm ± 13.3, respectively) and EE (88.27% ± 4.3 and 66.72% ± 1.8, respectively). The in vitro drug release profile showed a faster release pattern for the Tween 80-containing particles over a 48-hour period (79.98% vs. 35.57%), hence, were selected for further investigation. The hybrid nanoparticles achieved significantly higher skin deposition than the marketed product (63.51% vs. 34.07%) through a 24-hour time interval, particularly, to the stratum corneum and epidermis skin layers. The in vivo results on IMQ-mouse models revealed superior anti-psoriatic efficacy of the synthesized nanoparticles in comparison to the marketed product in terms of visual observation of the skin condition, PASI score and histopathological examination of autopsy skin samples. Additionally, the in vivo drug deposition showed superior skin deposition of the nanoparticles compared to the marketed product (74.9% vs. 13.4%).

Tacrolimus-loaded chitosan nanoparticles for enhanced skin deposition and management of plaque psoriasis.

Tacrolimus is a natural macrolide that exhibits an anti-proliferative action by T-lymphocytic cells inhibition. Hence, it was tested as a potential topical treatment to improve and control psoriatic plaques. In this study, for the first time the lipophilic tacrolimus in chitosan nanoparticles was used to achieve the desired response and dermal retention of the drug using a modified ionic gelation technique. The hydrophobic drug, tacrolimus, was successfully encapsulated into the synthesized positively-charged particles (140.8 nm ± 50.0) and EE of (65.5% ± 1.3). Local skin deposition of the drug was significantly enhanced with 82.0% ± 0.6 of the drug retained in the skin compared to 34.0% ± 0.9 from tarolimus® ointment. An outstanding response to the prepared formula was the enhanced hair growth rate in the treated animals, which can be considered an excellent sign of the skin recovery from the induced psoriatic plaques after only three days of treatment.

Tackling the various classes of nano-therapeutics employed in topical therapy of psoriasis.

Psoriasis is a dermatological chronic skin condition with underlying autoimmune etiology. It deeply affects patients' quality of life. Therefore, it was an interesting target for researchers throughout the past years. Conventionally, the treatment options include anti-inflammatory agents, immune suppressants, biologic treatment, and phototherapy. Nanotechnology offers promising characteristics that allow for tailoring a drug carrier to achieve dermal targeting, improved efficacy and minimize undesirable effects. Being the safest route, the first line of treatment and a targeted approach, we solely discussed the use of the topical route, combined with advanced drug delivery systems for the management of psoriasis in this article. Advanced systems include polymeric, metallic, lipidic and hybrid nanocarriers incorporating different active agents. All formerly mentioned types of drug delivery systems were investigated through the past decades for the purpose of topical application on psoriatic plaques. Scientists' efforts are promising to reach an optimized formula with a convenient dosage form to improve efficacy, safety, and compliance for the treatment of psoriasis. Accordingly, it will offer a better quality of life for patients.