Fabrication of D-α-tocopheryl polyethylene glycol 1000 succinates and human serum albumin conjugated chitosan nanoparticles of bosutinib for colon targeting application; in vitro-in vivo investigation

• Published in: International journal of biological macromolecules 2023-12, Vol.253, p.127531-127531, Article 127531
• Main Authors: Manthalkar, Laxmi, Bhattacharya, Sankha, Hatware, Ketan, Sreelaya, Putrevu, Shah, Disha, Jain, Arinjay, Phatak, Niraj
• Format: Article
• Language: English
• Subjects: Bosutinib; Chitosan; Colorectal cancer; Cytotoxicity; D-α-tocopheryl polyethylene glycol 1000 (TPGS); Drug delivery; Human serum albumin; Targeted therapy
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.127531

For more effective chemotherapy and targeted treatment of colorectal cancer, this study seeks to develop chitosan (CH)-human serum albumin (HAS)-D-α-tocopheryl polyethylene glycol 1000 (TPGS) nanoparticles (BOS-CH-HSA-TPGS-NPs) coated with Bosutinib (BOS). Nuclear magnetic resonance (NMR) indicated that chitosan's structure was modified by carbodiimide coupling with HSA. We used a Box-Behnken design to find the ideal region for particle size, zeta potential, and entrapment efficiency, eventually emerging at a formulation with these values: 187.14 ± 3.2 nm, 76.2 ± 0.96 %, and 21.1 ± 2.3 mV. Differential scanning calorimetry (DSC), Transmission electron microscopy (TEM), X-ray diffraction (XRD), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), High-performance liquid chromatography (HPLC) were all used to characterize the sample in detail. At a phosphate buffer pH of 7.4, in vitro drug release tests showed both Higuchi model release (0.954) and Fickian diffusion (n = 0.5). Compared to free BOS, HCT116 cell lines showed considerably higher cytotoxicity in in vitro cytotoxicity assays. In male albino Wistar rats, the BOS-CH-HSA-TPGS-NPs also showed enhanced pharmacokinetics, targeting efficiency, and biocompatibility. When used to the treatment of colorectal cancer, the BOS-CH-HSA-TPGS NPs show promise as a sustained-release therapy with improved therapeutic effects by addressing the challenges of poor solubility, poor permeability, and toxic side effects. [Display omitted] •Synthesized TPGS-coated CH-HSA carbodiimide-conjugated NPs encapsulating Bosutinib (BOS).•Analyzed material properties and process factors using Box-Behnken design for quality enhancement.•Utilized FTIR, XRD, SEM, AFM for characterization, assessed in-vitro drug release, and HCT116 cytotoxicity.•In-vivo rat study indicated superior targeting, colon-specific uptake, and biocompatibility.•Optimized BOS-CH-HSA-TPGS NPs exhibiting sustained in-vitro anti-cancer activity on HCT116 cells.