Fluorouracil-Loaded Gold Nanoparticles for the Treatment of Skin Cancer: Development, in Vitro Characterization, and in Vivo Evaluation in a Mouse Skin Cancer Xenograft Model

Abstract

Fluorouracil (5-FU) is an antimetabolite drug used in the treatment of various malignancies, such as colon and skin cancers. However, its systemic administration results in severe side effects. Topical 5-FU delivery for the treatment of skin cancer could circumvent these shortcomings, but it is limited by the drug poor permeability through the skin. To enhance 5-FU efficacy against skin cancer and reduce its systemic side effects, it was loaded into a gold nanoparticle (GNP)-based topical delivery system. 5-FU was loaded onto GNPs capped with CTAB through ionic interactions between 5-FU and CTAB. GNPs were prepared at different 5-FU/CTAB molar ratios and evaluated using different techniques. GNP stability and drug release were studied as a function of salt concentration and solution pH. Optimum 5-FU/CTAB-GNPs were incorporated into gel and cream bases, and their ex vivo permeability was evaluated in mice dorsal skin. The in vivo anticancer efficacy of the same preparations was evaluated in A431 tumor-bearing mice. The GNPs had spherical shape and a size of ∼16-150 nm. Maximum 5-FU entrapment was achieved at 5-FU/CTAB molar ratio of 1:1 and pH 11.5. Drug release from GNPs was sustained and pH-dependent. 5-FU GNP gel and cream had around 2-fold higher permeability through mice skin compared with free 5-FU gel and cream formulations. Further, in vivo studies in a mouse model having A431 skin cancer cells implanted in the subcutaneous space showed that the GNP gel and cream achieved 6.8- and 18.4-fold lower tumor volume compared with the untreated control, respectively. These results confirm the potential of topical 5-FU/CTAB-GNPs to enhance drug efficacy against skin cancer.

<p>Green synthesis of multifunctional PEG-carboxylate &pi; back-bonded gold nanoconjugates for breast cancer treatment</p>

“…Recently, Safwat et al reported that 5FU-loaded cetyltrimethyl ammonium bromide (CTAB)-coated AuNPs (5FU/ CTAB-AuNPs) exhibited in vitro drug release only up to 24 hours and that incorporation of 5FU/CTAB-AuNPs into Pluronic F127 gel sustained the rate of drug release. 27 Safwat et al also reported that 5FU-loaded TGA-capped AuNPs and glutathione-capped AuNPs exhibited pH-responsive in vitro drug release profiles, although drug release was completed within 12 hours. 12 In addition, Duan et al reported that 5FUloaded poly(lactic acid-4-hydroxyproline-polyethylene glycol) NPs showed an initial burst release of 5FU (~60%) up to 24 hours, followed by sustained 5FU release .90 hours.…”

“…The drug-loaded FA-polymer-AuNPs nanoconjugates (5 mg) were dispersed in 2 mL of PBS (pH 7.4), packed in a dialysis bag (MWCO=2,000) and immersed in PBS (25 mL) at 37°C under magnetic stirring. 27 The amount of drug released at different time intervals in the release medium was determined by reverse phase HPLC technique. All the experiments were carried out in triplicates and the average cumulative percentage of drug release was plotted against time.…”

Spironolactone-Loaded LeciPlexes as Potential Topical Delivery Systems for Female Acne: In Vitro Appraisal and Ex Vivo Skin Permeability Studies

“…The better SP permeability, flux, and skin deposition observed for the LeciPlex gel might be attributed to several factors. Cationic surface charge of LeciPlex facilitates their interaction with the negatively charged cell surface, which in turn leads to better drug uptake and permeation through the skin [64][65][66]. Further, the small particle size of the LeciPlexes is another important factor that contributes to their enhanced skin permeation.…”

Potential of contrast agents to enhance in vivo confocal microscopy and optical coherence tomography in dermatology: A review

“…Because gold and silver nanoparticles may also be used as vehicles for delivery of, for example, psoriasis therapy and chemotherapy , we suggest that future treatment trials would benefit from using OCT and CM imaging to track nanoparticles that have contrast agent properties in vivo.…”