Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 84, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2023.104473
Keywords
Chitosan; mPEG-COOH; Cystamine dihydrochloride; Redox-responsive drug release; Targeted cancer therapy; Inflammatory mediators
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This study presents a novel synthesis method of redox-responsive copolymers using chitosan and methoxy poly-ethylene glycol (mPEG), as well as the formulation of prednisone-loaded nanoparticles (P-NPs) for glutathione (GSH)-responsive release. The specific ligand atrial natriuretic peptide (ANP) was conjugated to the P-NPs (ANP-P-NPs) for targeted drug delivery. Physiochemical characterizations showed that the nanoparticle sizes were below 200 nm, with an entrapment efficiency of 73.89 +/- 0.45% and a zeta potential of approximately -20 mV. The in vitro and in vivo studies demonstrated the potential of these redox-responsive nanoparticles as safe and efficient drug delivery vehicles.
The current study reveals a novel redox-responsive copolymer synthesis using chitosan and methoxy poly-ethylene glycol (mPEG), as well as the formulation of prednisone-loaded nanoparticles (P-NPs) for glutathione (GSH)-responsive release. A specific ligand for cancer-cell receptor, atrial natriuretic peptide (ANP), was con-jugated to P-NPs (ANP-P-NPs) for target-specific drug delivery. Analyses of physiochemical characterizations were conducted. As a result, the nanoparticle sizes were less than 200 nm, entrapment efficiency was estimated to be 73.89 +/- 0.45%, and the zeta potential was approximately-20 mV. In the presence of GSH, particle size analysis, and in-vitro release studies show an increase in the size and rapid release of the drug, whereas these results were negligible in the absence of GSH. Furthermore, nanoparticle biocompatibility was examined in L132 cells, anti-cancer effect and receptor-mediated internalization studies in A549 cells, and anti-inflammatory ac-tivity was observed in RAW264.7 macrophages. An in vivo anti-inflammatory test was conducted using a mouse model of ovalbumin-induced airway inflammation. The results indicate that the nanoparticles have better anti-inflammatory activity, suppressing pro-inflammatory mediators due to their stimuli-responsive properties. In summary, the macromolecule chitosan-based redox-responsive nanoparticles demonstrate potential as safe and efficient drug delivery vehicles.
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