Cytocompatible chitosan-graft-mPEG-based 5-fluorouracil-loaded polymeric nanoparticles for tumor-targeted drug delivery

Abstract

Biodegradable materials like chitosan (CH) and methoxy polyethylene glycol (mPEG) are widely being used as drug delivery carriers for various therapeutic applications. In this study, copolymer (CH-g-mPEG) of CH and carboxylic acid terminated mPEG was synthesized by carbodiimide-mediated acid amine reaction. The resultant hydrophilic copolymer was characterized by Fourier transform infrared spectroscopy and H NMR studies, revealing its relevant functional bands and proton peaks, respectively. Blank polymeric nanoparticles (B-PNPs) and 5-fluorouracil loaded polymeric nanoparticles (5-FU-PNPs) were formulated by ionic gelation method. Furthermore, folic acid functionalized FA-PNPs and FA-5-FU-PNPs were prepared for folate receptor-targeted drug delivery. FA-5-FU-PNPs were characterized by particle size, zeta potential, and in vitro drug release studies, resulting in 197.7 nm, +29.9 mv, and sustained drug release of 88% in 24 h, respectively. Cytotoxicity studies were performed for FA-PNPs and FA-5-FU-PNPs in MCF-7 cell line, which exhibited a cell viability of 80 and 41%, respectively. In vitro internalization studies were carried out for 5-FU-PNPs and FA-5-FU-PNPs which demonstrated increased cellular uptake of FA-5-FU-PNPs by receptor-mediated transport. Significant (p< .01) reduction (1.5-fold) of reactive oxygen species (ROS) accumulation was observed in lipopolysaccharides-stimulated RAW264.7 macrophages, revealing its potent antioxidant property. From the obtained results, it is concluded that folic acid functionalization of 5-FU-PNPs is an ideal approach for sustained and targeted drug delivery, thereby influencing better therapeutic effect.

Interaction of Mitoxantrone-Loaded Cholesterol Modified Pullulan Nanoparticles with Human Serum Albumin and Effect on Drug Release

“…CHP polymer NPs are nontoxic and have good biocompatibility; they can be degraded by amylase in the body. So, they are often used as a nanomaterial to load drugs in biological applications; examples are polytoluene and 5-fluorouracil [19][20][21]. In recent years, many studies have investigated the use of CHP and its derivatives as nanotargeted antitumor drug carriers, but few studies have examined the interaction between drug-loaded CHP and protein and its biological effects.…”

Injectable, Shear-Thinning, Self-Healing, and Self-Cross-Linkable Benzaldehyde-Conjugated Chitosan Hydrogels as a Tissue Adhesive

“…This disrupts the regular, ordered arrangement of the polymer chains, resulting in a more amorphous and less crystalline material. 23,24 This study presents the groundbreaking synthesis of benzaldehyde-conjugated chitosan (CH−CBA). The effects of the pH and reagent stoichiometry on the degree of substitution (DS) are systematically studied, and the effect of the DS on the turbidity of the hydrogel is assessed.…”

“…Furthermore, the self-cross-linking system can enhance the aqueous solubility of chitosan at neutral pH by reducing its crystallinity through the creation of additional chemical bonds between the chitosan polymer chains. This disrupts the regular, ordered arrangement of the polymer chains, resulting in a more amorphous and less crystalline material. , …”

Targeted Delivery of Doxorubicin in HeLa Cells Using Self‐Assembled Polymeric Nanocarriers Guided by Deep Eutectic Solvents

“…CS, a naturally occurring natural polymer derived from fungi and yeasts, [20] has been extensively investigated for biomedical applications due to its biocompatibility and non-toxic nature; it also acts as a drug carrier and enhances the permeability of cancer cells. [21] Unmodified chitosan is soluble under slightly acidic conditions and readily affects the normal cell line. However, this problem can be overcome using CS functionalized with a DES.…”

“…Lactic acid has been widely used for tissue engineering, and drug delivery, mainly since it can be readily disposed of in the human body in metabolic processes. CS, a naturally occurring natural polymer derived from fungi and yeasts, [20] has been extensively investigated for biomedical applications due to its biocompatibility and non‐toxic nature; it also acts as a drug carrier and enhances the permeability of cancer cells [21] . Unmodified chitosan is soluble under slightly acidic conditions and readily affects the normal cell line.…”