Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology

Abstract

The present study is a mechanistic validation of ‘proof-of-technology’ for the effective topical delivery of chrysin nanoemulgel for localized, efficient treatment of melanoma-affected skin. Background: Currently available treatments for skin cancer are inefficient due to systemic side effects and poor transcutaneous permeation, thereby presenting a formidable challenge for the development of novel nanocarriers. Methods: We opted for a novel approach and formulated a nanocomplex system composed of hydrophobic chrysin dissolved in a lipid mix, which was further nanoemulsified in Pluronic® F-127 gel to enhance physicochemical and biopharmaceutic characteristics. Chrysin, a flavone extracted from passion flowers, exhibits potential anti-cancer activities; however, it has limited applicability due to its poor solubility. Pseudo-ternary phase diagrams were constructed to identify the best self-nanoemulsifying region by varying the compositions of oil, Caproyl® 90 surfactant, Tween® 80, and co-solvent Transcutol® HP. Chrysin-loaded nanoemulsifying compositions were characterized for various physicochemical properties. Results: This thermodynamically stable, self-emulsifying drug delivery system showed a mean droplet size of 156.9 nm, polydispersity index of 0.26, and viscosity of 9100 cps after dispersion in gel. Mechanical characterization using Texture Analyzer exhibited that the gel had a hardness of 487 g and adhesiveness of 500 g. Ex vivo permeation through rat abdominal skin revealed significant improvement in percutaneous absorption measured as flux, the apparent permeability coefficient, the steady-state diffusion coefficient, and drug deposition. In vitro cytotoxicity on A375 and SK-MEL-2 cell lines showed a significantly improved therapeutic effect, thus ensuring reduction in dose. The safety of the product was established through biocompatibility testing on the L929 cell line. Conclusion: Aqueous, gel-based, topical, nanoemulsified chrysin is a promising technology approach for effective localized transcutaneous delivery that will help reduce the frequency and overall dose usage and ultimately improve the therapeutic index.

Aerosol Delivery of Surfactant Liposomes for Management of Pulmonary Fibrosis: An Approach Supporting Pulmonary Mechanics

“…For pulmonary delivery, liposomes made from exogenous surfactants are best as they are rapidly adsorbed at the air-liquid interface in the lungs that accentuates the ability of the liposomes to open up, forming a monolayer film, and spread at the interface [36]. This facilitates in delivery of encapsulated drugs to the alveolar interface and especially to the collapsed alveoli due to the surfactant action [14]. Our study systematically explored the feasibility of aerosolized delivery of liposomal nanocarrier of naringin and provided the proof-of-concept for assist in pulmonary mechanics and improved therapeutic efficacy.…”

“…The mean particle size and polydispersity index of the resulting liposome dispersion were measured using photon cross-correlation spectroscopy (Nanophox, Sympatec, Clausthal-Zellerfeld, Lower Saxony, Germany), with detection at a scattering angle of 90 • . Three runs of 60 s were performed at 25 • C, and the mean particle size was calculated [14]. Zeta potential was evaluated using a zeta potential analyzer (DelsaNano C, Beckman Coulter, Tokyo, Japan) (DelsaNano C, Beckman Coulter, Tokyo, Japan) [15].…”

“…Capillary surfactometer (Calmia Medical, Inc., Toronto, ON, Canada) that simulates terminal human airways is used to determine airway patency [14]. A liposomal sample (0.5 µL) was introduced into the narrow section of a glass capillary of internal diameter 0.25 mm.…”

Comparison Study of Cytotoxicity of Bare and Functionalized Zinc Oxide Nanoparticles

“…Moreover, Caco-2 cells were used as model to assess the toxicity of ZnO NPs in many studies [52][53][54][55]. The application of mouse fibroblast L929 cells is most frequently undertaken to evaluate cytotoxicity and may represent a sufficient in vitro screening model for skin formulations [56][57][58]. Furthermore, the cytotoxicity assay with mouse fibroblasts L929 is in compliance with ISO 10993-5 standards, and is often used for comparative studies of different types of nanoparticles [59].…”

Ion-Triggered In Situ Gelling Nanoemulgel as a Platform for Nose-to-Brain Delivery of Small Lipophilic Molecules

“…In vitro test of cell toxicity provides a rough assessment of the ability of cells relevant to a determined application to survive in the presence of specific materials. The L929 fibroblast cells were treated with varying concentrations of the formulation diluted in a culture medium [ 48 ]. All four concentrations tested showed more than 98% viability for all the concentrations tested ( Figure 7 A).…”