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1.
Eur J Pharm Biopharm ; 200: 114328, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763329

ABSTRACT

Aggressive colon cancer treatment poses significant challenges. This study investigates the potential of innovative carbohydrate-based nanoparticles for targeted Capecitabine (CTB) delivery. CTB nanoparticles were synthesized by conjugating CTB with potato starch and chitosan using ultrasonication, hydrolysis, and ionotropic gelation. Characterization included drug loading, rheology, Surface-Enhanced Raman Spectroscopy (SERS), Fourier-Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Thermogravimetric Analysis (TGA). In vitro and in vivo antitumor activity was evaluated using HT-29 cells and N, N-dimethylhydrazine-induced Balb/c mice, respectively. Cellular assays assessed angiogenesis, migration, proliferation, and apoptosis. Nanoparticles exhibited a mean size of 245 nm, positive zeta potential (+30 mV), high loading efficacy (76 %), and sustained drug release (92 % over 100 h). CTB-loaded nanoparticles displayed superior colon histology, reduced tumour scores, and inhibited VEGD and CD31 expression compared to free CTB. Cellular assays confirmed significant antitumor effects, including reduced tube formation, migration, and proliferation, and increased apoptosis. This study demonstrates the promise of CTB-loaded potato starch-chitosan nanoparticles for aggressive colon cancer treatment. These findings highlight the potential of these nanoparticles for further evaluation in diverse cancer models.


Subject(s)
Capecitabine , Chitosan , Colonic Neoplasms , Mice, Inbred BALB C , Nanoparticles , Solanum tuberosum , Starch , Animals , Chitosan/chemistry , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Starch/chemistry , Solanum tuberosum/chemistry , Capecitabine/administration & dosage , Capecitabine/pharmacology , Humans , Mice , Nanoparticles/chemistry , HT29 Cells , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/chemistry , Drug Liberation , Drug Carriers/chemistry , Apoptosis/drug effects , Drug Delivery Systems/methods , Cell Proliferation/drug effects , Male
2.
Int J Biol Macromol ; 253(Pt 1): 126716, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37673158

ABSTRACT

This research seeks to optimize a chitosan-stabilized Pickering emulsion (PE) containing 5-fluorouracil (5-FU) as a potential Squamous Cell Carcinoma therapy. The 5-Fluorouracil was also thoroughly analysed using UV spectrophotometry and RP-HPLC, demonstrating exceptional linearity, sensitivity, precision, and robustness. The techniques of characterization revealed Pickering emulsion (PE) morphology, solid-like gel properties, successful encapsulation, and promising anticancer effects. FTIR was used to validate the efficacy of encapsulation, and DSC was used to confirm the post-encapsulation drug stability. The 0.6 % chitosan-stabilized PE showed exceptional stability and drug loading efficiency. Anti-EGFR-5-FU-CS-PE gel was developed for sustained drug release in the treatment of Squamous Cell Carcinoma. Anti-EGFR-5-FU-CS-PE demonstrated potent anticancer effects in vitro, with a lower IC50 than 5-FU and 5-FU-CS-PE. Anti-EGFR-5-FU-PE Pickering emulsions based on chitosan were investigated for their rheological properties, cellular interactions, and therapeutic potential. Both emulsions and gel exhibited sustained in vitro drug release after successful encapsulation. Anti-EGFR-5-FU-CS-PE induced apoptosis, decreased mitochondrial membrane potential, and inhibited the migration of cancer cells. Wistar mice were tested for safety and tumour growth inhibition. All formulations exhibited exceptional six-month stability. Anti-EGFR-5-FU-CS-PE emerges as a viable therapeutic option, necessitating additional research.


Subject(s)
Carcinoma, Squamous Cell , Chitosan , Nanoparticles , Rats , Mice , Animals , Fluorouracil/pharmacology , Rats, Wistar , Emulsions
3.
Nanomedicine (Lond) ; 18(9): 713-741, 2023 04.
Article in English | MEDLINE | ID: mdl-37309754

ABSTRACT

Aims: Panitumumab (anti-Erb)-conjugated polycaprolactone (PCL) nanoparticles loaded with bosutinib (BTNB) were used to develop a targeted drug-delivery system for colon cancer cells. Materials & methods: Using carbodiimide coupling, anti-Erb was conjugated to BTNB-loaded PCL nanoparticles. Dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction and thermogravimetric analysis were used to analyze nanoparticles. Results: According to in vitro studies, anti-Erb-BTNB-PCL nanoparticles inhibited HCT116 cells more than BTNB alone. Cell arrest at different phases was examined for apoptotic potential. An in vivo efficacy study showed that anti-Erb-BTNB-PCL nanoparticles could target tumors selectively. Conclusion: Anti-Erb-conjugated BTNB nanoparticles could specifically target colon cancer.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Nanoparticles , Humans , Panitumumab , Polyesters/chemistry , Nanoparticles/chemistry , Colorectal Neoplasms/drug therapy , ErbB Receptors
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