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5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles. [ABSTRACT FROM AUTHOR]

Self-expanding metal stents (SEMSs) are currently the gold standard for the localised management of malignant gastrointestinal (GI) stenosis and/or obstructions. Despite encouraging clinical success, in-stent restenosis caused by tumour growth is a significant challenge. Incorporating chemotherapeutic drugs into GI stents is an emerging strategy to provide localised and sustained release of drugs to intestinal malignant tissues to prevent tumour growth. Therefore, the aim of this work was to develop and evaluate a local GI stent-based delivery system that provides a controlled release of 5-fluorouracil (5FU) over a course of several weeks to months, for the treatment of colorectal cancer and cancer-related stenosis/obstructions. The 5FU-loaded GI stents were fabricated via sequential dip-coating of commercial GI stents with a drug-loaded polyurethane (PU) basecoat and a drug-free poly(ethylene-co-vinyl acetate) (PEVA) topcoat. For comparison, two types of commercial stents were investigated, including bare and silicone (Si) membrane-covered stents. The physicochemical properties of the 5FU-loaded stents were evaluated using photoacoustic Fourier-transform infrared (PA-FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and thermal analysis. In vitro release studies in biological medium revealed that the 5FU-loaded stents provided a sustained release of drug over the period studied (18 d), and cell viability, cell cycle distribution and apoptosis assays showed that the released 5FU had comparable anticancer activity against human colon cancer cells (HCT-116) to pure 5FU. This study demonstrates that dip-coating is a facile and reliable approach for fabricating drug-eluting stents (DESs) that are promising candidates for the treatment of GI obstructions and/or restenosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel green chromatographic method for the simultaneous determination of 5-fluorouracil and cisplatin. • Evaluation of the greenness profile using NEMI, GAPI, Eco-scale and AGREE tools. • Application of a newly developed HPLC method to evaluate the drug release of co-loaded 5-fluorouracil and cisplatin films. The combination of 5-fluorouracil (5-FU) and cisplatin (Cis) has been used for the treatment of many cancers. The combination demonstrates synergy and improved clinical outcomes encouraging developing a formulation with both drugs. An analytical procedure is essential for formulation studies; however, no method has been reported for the concurrent determination and quantification of both 5-FU and Cis to date. A novel, simple, accurate, and precise HPLC method was developed using a C 18 column (250 mm × 4.6 mm, 5 µm) and mobile phase composed of 0.5 mM sodium dodecyl sulfate: methanol (98:2, v/v), adjusted to pH 2.5 with phosphoric acid. A flow rate of 0.5 mL/min was applied and a photodiode array was utilized for detection and the retention times were 9.89 min (265 nm) for 5-FU and 5.36 min (210 nm) for Cis. Validation procedures were performed, and the method was found to be linear at ranges of 0.9–60.0 µg/mL for 5-FU and 6.0–60.0 µg/mL for Cis. The limits of detection (LOD) and quantitation (LOQ) were 0.10 and 0.25 µg/mL for 5-FU and 2.00 and 4.00 µg/mL for Cis, respectively. Other parameters such as precision, selectivity, robustness, and stability results were within acceptable limits. The method was applied to a model co-eluting film and its release profile was studied. Additionally, the method's greenness was evaluated by four assessment tools namely the national environmental method index (NEMI), analytical eco scale assessment (ESA), green analytical procedure index (GAPI), and Analytical GREEnness Metric Approach and Software (AGREE). The results demonstrated compliance with green analytical chemistry (GAC) practices. This research acts as a step towards further investigation of drug stability under different stress conditions and quantification of the intact drugs in presence of their degradation products. [ABSTRACT FROM AUTHOR]

[Display omitted] • Drug-in-adhesive patches containing 5-fluorouracil for the treatment of skin cancer. • Pressure-sensitive adhesives using Eudragit® E and plasticizers for topical application. • Solubility parameters and thermal analysis for polymer-plasticizer miscibility evaluation. Topical patches containing 5-fluorouracil (5-FU) are a feasible alternative to overcome the shortcomings of commercial cream for the treatment of non-melanoma skin cancer (NMSC). Plasticizers are a critical component of drug-in-adhesive (DIA) patches as they can significantly affect the mechanical, adhesive and drug release characteristics of the patches. Eudragit® E (EuE) is a methacrylate-based cationic copolymer capable of producing flexible and adhesive films for topical application. In this study, the effect of plasticizers on the mechanical, adhesive and 5-FU release characteristics of EuE-based patches was comprehensively evaluated. While the elongation at break (%) and adhesion of the films were significantly increased with increasing triacetin, dibutyl sebacate (DBS) and triethyl citrate (TEC) concentrations, the tensile strength showed an inverse relationship. EuE plasticized with 40% triacetin, 30% DBS or 40% w/w TEC produced elastic and adhesive films most suitable for topical application. In vitro release studies of the 5-FU-loaded patches demonstrated an initial burst release pattern during the first 10 min followed by a slow release over 120 min. In summary, this study provides important information on effect of plasticizers for preparation of EuE-based patches with desired mechanical, adhesive and release characteristics of 5-FU towards their potential application in the treatment of NMSC. [ABSTRACT FROM AUTHOR]