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

Solubility of chrysin in various oils, surfactants, and co-solvents

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, Capryol^® 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.

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

or continue reading here: Nagaraja, S.; Basavarajappa, G.M.; Attimarad, M.; Pund, S. Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology. Pharmaceutics 2021, 13, 902. https://doi.org/10.3390/pharmaceutics13060902

Materials and Methods

Chrysin was purchased from Sigma-Aldrich, Inc., India. Acrysol^® K-140 and Acrysol^® K-150 (propylene glycol–polyoxyl 40–hydrogenated castor oil) were gifted by Coral Pharma Chem (Ahmedabad, India). Capmul^® MCM (glyceryl caprylate/caprate) and Captex^® 355 were gift samples from Abitech Corporation, OH, USA. Caproyl^® 90 (propylene glycol monocaprylate), Labrafac^® CC (caprylic capric triglyceride), and Labrasol^® (caprylocaproyl macrogol-8 glycerides) were gifted by Gattefosse India Pvt., Ltd. (Mumbai, India). Tween^® (polysorbate) 20 and Tween^®(polysorbate) 80 were purchased from Molychem (Mumbai, India). Cremophor^® EL, Cremophor^® RH 40, and Pluronic^®F127 were received as gift samples from BASF (Mumbai, India). Polyethylene glycol 400 and propylene glycol were purchased from Loba Chemie, Ltd. (Mumbai, India). Ethanol (96% v/v) was purchased from Research Lab Fine Chem Industries (Mumbai, India). All these chemicals were of analytical grade and used without any further purification. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Dulbecco’s modified Eagle’s medium (DMEM), Eagle’s minimum essential medium (EMEM), fetal bovine serum, antibiotic solution (100X), trypsin-EDTA solution, and Hank’s balanced salt solution (HBSS) were purchased from Himedia, India.

excipients formulation