Electrospun oral formulations for combined photo-chemotherapy of colon cancer

Abstract

In this work, we report new formulations for the combined photo-chemotherapy of colon cancer. Fibers were fabricated via coaxial-electrospinning with the intent of targeting delivery of the anti-cancer drug carmofur (CAR) and the photosensitizer rose bengal (RB) selectively to the colon site. The fibers comprised a hydroxypropyl methylcellulose (HPMC) core loaded with the active ingredients, and a pH-sensitive Eudragit L100-55 shell. The fibers were found to be homogeneous and cylindrical and have visible core-shell structures. X-ray diffraction and differential scanning calorimetry demonstrated that both CAR and RB were present in the fibers in the amorphous physical form. In vitro drug release studies showed that the fibers have the potential to selectively deliver drugs to the colon, with only 10-15 % release noted in the acidic conditions of the stomach but sustained release at pH 7.4. Cytotoxicity studies were undertaken on human dermal fibroblast (HDF) and colon cancer (Caco-2) cells, and the influence of light on cell death was also explored. The fibers loaded with CAR alone showed obvious toxicity to both cell lines, with and without the application of light. The RB-loaded fibers led to high viability (ca. 80 % for both cell types) in the absence of light, but much greater toxicity was noted (30-60 %) with light. The same trends were observed with the formulation containing both CAR and RB, but with lower viabilities. The RB and RB/CAR loaded systems show clear selectivity for cancerous over non-cancerous cells. Finally, mucoadhesion studies revealed there were strong adhesive forces between the rat colonic mucosa and the fibers after they had passed through an acidic environment. Such electrospun fibers thus could have potential in the development of oral therapies for colon 2 cancer.

pH-Responsive nanocomposite fibres allowing MRI monitoring of drug release

“…Their encapsulation in Eudragit-based fibres is expected to overcome this issue, with the polymers providing protection from acidic environments due to their lack of solubility at low pH. 31 In order to test their stability, 10 mg of S100/Carmofur/SPION or L100/Carmofur/SPION fibres were incubated in 25 mL of pH 1.5 aqueous HCl solution, similar to the pH of gastric liquids. 32 To compare their acid stability with bare nanoparticles, 2 mg of PVP-SPIONs was subjected to the same treatment.…”

Drug Delivery Applications of Coaxial Electrospun Nanofibres in Cancer Therapy

“…It was confirmed that the fibre improved selectivity for cancerous cells, obviously in the favour of RB. Moreover, targeted treatment was performed by releasing most of the drugs into the colon pH environment, which adhered to the colon wall for over 4 h [ 72 ]. Liu and co-workers built another implantable coaxial composite hydrogel fibre and combined PTT and chemotherapy to control the progression of cancer locally.…”

Versatile use of Carmofur: A comprehensive review of its chemistry and pharmacology

“…Li et al (2019b) prepared core/shell fibers by coaxial electrospinning with a hydroxypropyl methylcellulose core and Eudragit L100‐55 shell for combined photochemotherapy in colon cancer. The fiber shells were stable in acidic pH but dissolved in pH 7.4.…”

“…Moreover, the photo‐chemotherapy showed greater selectivity for the cancerous cells compared to healthy cells in vitro. In addition, these fibers had excellent adherence to the colon wall which provided substantial ground to do further investigation to treat color cancer via oral administration of carmofur by this technique (Li et al, 2019b).…”

“…Another F I G U R E 2 Inhibition of acid ceramidase by carmofur as proposed by Dementiev et al (2019) group developed water-soluble cross-linked reverse vesicles for hydrophobic drug loading and observed substantial (25.8%) drug loading with carmofur (Zhang et al, 2019). Li et al (2019b) prepared core/shell fibers by coaxial electrospinning with a hydroxypropyl methylcellulose core and Eudragit L100-55 shell for combined photochemotherapy in colon cancer. The fiber shells were stable in acidic pH but dissolved in pH 7.4.…”