5-Fluorouracil Encapsulated Chitosan-Cellulose Fiber Bionanocomposites: Synthesis, Characterization and In Vitro Analysis towards Colorectal Cancer Cells

Abstract

Cellulose and chitosan with remarkable biocompatibility and sophisticated physiochemical characteristics can be a new dawn to the advanced drug nano-carriers in cancer treatment. This study aims to synthesize layer-by-layer bionanocomposites from chitosan and rice straw cellulose encapsulated 5-Fluorouracil (CS-CF/5FU BNCs) using the ionic gelation method and the sodium tripolyphosphate (TPP) cross-linker. Data from X-ray and Fourier-transform infrared spectroscopy showed successful preparation of CS-CF/5FU BNCs. Based on images of scanning electron microscopy, 48.73 ± 1.52 nm was estimated for an average size of the bionanocomposites as spherical chitosan nanoparticles mostly coated rod-shaped cellulose reinforcement. 5-Fluorouracil indicated an increase in thermal stability after its encapsulation in the bionanocomposites. The drug encapsulation efficiency was found to be 86 ± 2.75%. CS-CF/5FU BNCs triggered higher drug release in a media simulating the colorectal fluid with pH 7.4 (76.82 ± 1.29%) than the gastric fluid with pH 1.2 (42.37 ± 0.43%). In in vitro cytotoxicity assays, cellulose fibers, chitosan nanoparticles and the bionanocomposites indicated biocompatibility towards CCD112 normal cells. Most promisingly, CS-CF/5FU BNCs at 250 µg/mL concentration eliminated 56.42 ± 0.41% of HCT116 cancer cells and only 8.16 ± 2.11% of CCD112 normal cells. Therefore, this study demonstrates that CS-CF/5FU BNCs can be considered as an eco-friendly and innovative nanodrug candidate for potential colorectal cancer treatment.

Synthesis and Properties of Chitosan Nanoparticles CrossLinked with Tripolyphosphate

“…With adjusting the crosslinking degree of TPP and LMWC to synthesize ChNPs, improved properties of the NPs can be obtained for various applications. The optimized ratio between the LMWC to TPP cross-linker was 1:2 (v/v) as stated in our previous study [9]. Also, a separate study [8] used this ratio between TPP and chitosan, along with 1.0% acetic acid, and 2% (v/v) Tween-80 in the chitosan solution to synthesize ChNPs with suitable physiochemical characteristics.…”

“…It is the most important derivative of chitin obtained from the shells of insects and crustacean such as prawns or crabs, as well as the cell walls of fungi [8]. Many studies have used chitosan and various cross-linker to fabricate chitosan-based NPs with high biocompatibility, nontoxicity, biodegradability, and colloidal stability [8,9]. Ionic gelation, reverse micellar method, emulsification solvent diffusion are the popular method for fabrication of ChNPs [10].…”

“…Ionic gelation, reverse micellar method, emulsification solvent diffusion are the popular method for fabrication of ChNPs [10]. Among them, ionic gelation is the simplest method free from using organic solvents [9]. This technique is based on electrostatic interaction between positively charged amino groups of chitosan and the negatively charged groups of sodium tripolyphosphate (TPP) as a cross-linking agent [11].…”

“…The size of ChNPs must be concerned, which is related to the factors of the synthesis process, including stirring rate, temperature, and chitosan and TPP concentration [12]. Although, many researchers have fabricated ChNPs with TPP cross-linking following the pioneering work of Calvo et al and to evaluate the possible pharmaceutical applications, optimization of the synthesis parameters and the required characteristics of the resultant ChNPs is still an ongoing vital matter in this area [9,13]. These conditions not only affect the colloidal stability, drug loading, and release manner but also it can domain the level biocompatibility and toxicity of the particles in the biological tissues and environment.…”

Development of a Polysaccharide-Based Hydrogel Drug Delivery System (DDS): An Update

“…This suggested that NPs in different geometries could interact with cell membranes differently and might exert different biological activities. With the advent of nanotechnology, modifications can be made on native cellulose fibers to manufacture nano-celluloses including cellulose nanowhiskers (CNWs), nanocrystals and nanofibers [105][106][107][108][109]. The rod-like CNWs are believed to be a promising DDS owing to their nano-dimensions, large surface area, hydrophilic properties, and high biocompatibility and biodegradability [110].…”