Naringenin (NRG) is a polyphenolic phytochemical belonging to the class of flavanones and is widely distributed in citrus fruits and some other fruits such as bergamot, tomatoes, cocoa, and cherries. NRG presents several interesting pharmacological properties, such as anti-cancer, anti-oxidant, and anti-inflammatory activities. However, the therapeutic potential of NRG is hampered due to its hydrophobic nature, which leads to poor bioavailability. Here, we review a wide range of nanocarriers that have been used as delivery systems for NRG, including polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanosuspensions, and nanoemulsions. These nanomedicine formulations of NRG have been applied as a potential treatment for several diseases, using a wide range of in vitro, ex vivo, and in vivo models and different routes of administration. From this review, it can be concluded that NRG is a potential therapeutic option for the treatment of various diseases such as cancer, neurological disorders, liver diseases, ocular disorders, inflammatory diseases, skin diseases, and diabetes when formulated in the appropriate nanocarriers.

https://www.mdpi.com/1999-4923/13/2/291/pdf

Naringenin Nano-Delivery Systems and Their Therapeutic Applications

Skin drug delivery using lipid vesicles: A starting guideline for their development.

The topical and transdermal routes of drug administration are long known to the field of pharmaceutics. These routes have been explored for the delivery of a wide range of therapeutic agents over c...

Liposomes and transferosomes: A breakthrough in topical and transdermal delivery

"Nanocarrier-based dermopharmaceutical formulations for the topical management of atopic dermatitis".

Cutaneous melanoma is one of the most aggressive and metastatic forms of skin cancer. However, current therapeutic options present several limitations, and the annual death rate due to melanoma increases every year. Dermal delivery of nanomedicines can effectively eradicate primary melanoma lesions, avoid the metastatic process, and improve survival. Rose Bengal (RB) is a sono-photosensitizer drug with intrinsic cytotoxicity toward melanoma without external stimuli but the biopharmaceutical profile limits its clinical use. Here, we propose deformable lipid nanovesicles, also known as transfersomes (TF), for the targeted dermal delivery of RB to melanoma lesions to eradicate them in the absence of external stimuli. Considering RB's poor ability to cross the stratum corneum and its photosensitizer nature, transfersomal carriers were selected simultaneously to enhance RB penetration to the deepest skin layers and protect RB from undesired photodegradation. RB-loaded TF dispersion (RB-TF), prepared by a modified reverse-phase evaporation method, were nanosized with a ζ-potential value below -30 mV. The spectrophotometric and fluorimetric analysis revealed that RB efficiently interacted with the lipid phase. The morphological investigations (transmission electron microscopy and small-angle X-ray scattering) proved that RB intercalated within the phospholipid bilayer of TF originating unilamellar and deformable vesicles, in contrast to the rigid multilamellar unloaded ones. Such outcomes agree with the results of the in vitro permeation study, where the lack of a burst RB permeation peak for RB-TF, observed instead for the free drug, suggests that a significant amount of RB interacted with lipid nanovesicles. Also, RB-TF proved to protect RB from undesired photodegradation over 24 h of direct light exposure. The ex vivo epidermis permeation study proved that RB-TF significantly increased RB's amount permeating the epidermis compared to the free drug (78.31 vs 38.31%). Finally, the antiproliferative assays on melanoma cells suggested that RB-TF effectively reduced cell growth compared to free RB at the concentrations tested (25 and 50 μM). RB-TF could potentially increase selectivity toward cancer cells. Considering the outcomes of the characterization and cytotoxicity studies performed on RB-TF, we conclude that RB-TF represents a valid potential alternative tool to fight against primary melanoma lesions via dermal delivery in the absence of light.

https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.1c00468

Improving Dermal Delivery of Rose Bengal by Deformable Lipid Nanovesicles for Topical Treatment of Melanoma.

Psoriasis and atopic dermatitis are widespread pathologies with a need to improve their treatment. Topical administration of cyclosporine A (CyA) could be used if targeted to the skin, thus avoiding systemic levels. Unfortunately, CyA molecular weight and lipophilicity prevent its diffusion through human skin. Four novel lipid vesicles have been prepared by different methodologies to overcome this problem. The vesicles were characterized in terms of particle size, size polydispersity, Z-potential, morphology, drug encapsulation, phospholipid content, and vesicle flexibility. Freeze-drying in presence and absence of cryoprotective agents was also performed, to guarantee long-term stability. The ability to deliver CyA into the skin was assessed using human epidermis in Franz diffusion cells and compared with the delivery of drug solutions with enhancers. The technical characteristics of four types of vesicle make them suitable to carry drugs. Moreover, these liposomal formulations were able to effectively deliver CyA in vitro into the skin. The present work introduces a promising approach for the topical treatment of skin pathologies with an immune component.

Ultraflexible lipid vesicles allow topical absorption of cyclosporin A

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Ultraflexible lipid vesicles allow topical absorption of cyclosporin A