Search

Liquid crystalline nanoparticles (LCNs) are an attractive drugs topical delivery system due to the great internal ordering, wide interfacial area and structural similarities with the skin. In this work, LCNs were designed to encapsulate triptolide (TP) and to complex on its surface small interfering RNAs (siRNA) targeting TNF-α and IL-6, aiming at topical co-delivery and regulating multi-targets in psoriasis. These multifunctional LCNs showed appropriate physicochemical properties for topical application, such as a mean size of 150 nm, low polydispersion, TP encapsulation greater than 90% and efficient complexation with siRNA. The internal reverse hexagonal mesostructure of LCNs was confirmed by SAXS while their morphology was assessed by cryo-TEM. In vitro permeation studies revealed an increase of more than 20-fold in the distribution of TP through the porcine epidermis/dermis was achieved after the application of LCN-TP or LCN TP in hydrogel. In cell culture, LCNs showed good compatibility and rapid internalization, which was attributed to macropinocytosis and caveolin-mediated endocytosis. Anti-inflammatory potential of multifunctional LCNs was assessed by reducing of TNF-α, IL-6, IL-1β and TGF-β1 levels in LPS-stimulated macrophages. These results support the hypothesis that the co-delivery of TP and siRNAs by LCNs may be a new strategy for psoriasis topical therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Since the late 20th century, we have witnessed a growing and substantial advance in nanomedicine, in part due to the development of multifunctional and multimodal nanoplatforms that have enabled improved efficacy, biocompatibility, and novel therapeutic applications. Non-lamellar liquid-crystalline nanoparticles, especially, reverse hexagonal and cubic bicontinuous mesophases, have gained the attention of the scientific-academic community due to their intriguing and functional characteristics, such as self-organization into two- and three-dimensional supramolecular structures, high symmetry, and ability to accommodate hydrophobic and hydrophilic small molecules, peptides, proteins, nucleic acids, and imaging agents. Furthermore, these particles can be easily modified with specific and/or bioresponsive molecules allowing targeting and improved therapeutic performance. In this contribution we provide an overview of advances in the design and architecture of LCNPs, strategies to overcome biological barriers and main findings about interactions with different types of interfaces. We highlight recent applications in topical, oral, pulmonary and intravenous drug delivery in preclinical in vivo studies. We discussed the current scenario and translational obstacles faced for clinical translation, as well as our perspectives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Short-interfering RNAs (siRNAs) are a potential strategy for the treatment of cutaneous diseases. In this context, liquid crystalline nanoparticles functionalized with specific proteins and peptide-transduction domains (PTDs), which act as penetration enhancers, are a promising carrier for siRNA delivery through the skin. Herein, hexagonal phase liquid crystal nanoparticles based on monoolein (MO) and/or oleic acid (OA) containing (or lacking) the cationic polymer polyethylenimine (PEI) and the cationic lipid oleylamine (OAM) were functionalized with the membrane transduction peptides transcriptional activator (TAT) or penetratin (PNT). These nanoparticles were complexed with siRNA and characterized by particle size, polydispersity, zeta potential, complexation efficiency and siRNA release. The formulations containing cationic agents presented positive zeta potentials, sizes on the nanometer scale, and complexed siRNAs at concentrations of 10 μM; these agents were successfully released in a heparin competition assay. Cell culture studies demonstrated that nanoparticles composed of MO:OA:PEI functionalized with TAT were the most efficient at transfecting L929 cells, and the uptake efficiency was enhanced by TAT peptide functionalization. Thereafter, the selected formulations were evaluated for in vivo skin irritation, penetration and in vivo efficacy using a chemically induced inflammatory animal model. These nanoparticles did not irritate the skin and provided higher siRNA penetration and delivery into the skin than control formulations. Additionally, efficacy studies in the animal model showed that the association of TAT with the nanodispersion provided higher suppression of tumor necrosis factor (TNF)-α. Thus, the development of liquid crystalline nanodispersions containing TAT may lead to improved topical siRNA delivery for the treatment of inflammatory skin diseases.