Pressure responsive nanogel base on Alginate‐Cyclodextrin with enhanced apoptosis mechanism for colon cancer delivery

• Published in: Journal of biomedical materials research. Part A 2018-02, Vol.106 (2), p.349-359
• Main Authors: Hosseinifar, Tolou, Sheybani, Simin, Abdouss, Majid, Hassani Najafabadi, Sayed Alireza, Shafiee Ardestani, Mehdi
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; 5‐fluorouracil (5‐FU); Alginates - chemistry; Alginic acid; Apoptosis; Calorimetry, Differential Scanning; Cancer; Cell death; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Colorectal cancer; Cross-Linking Reagents - chemistry; crosslinked alginate hydrogel; Crosslinking; cyclodextrin; Cyclodextrins; Cyclodextrins - chemistry; Diffusion; Drug Delivery Systems; Drug Liberation; Emulsification; Fluorouracil - therapeutic use; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; HT29 Cells; Humans; Hydrogels; Hydrogels - chemistry; Kinetics; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Particle Size; Polyethylene Glycols - chemistry; Polyethyleneimine - chemistry; Polymers - chemical synthesis; Polymers - chemistry; Pressure; Proton Magnetic Resonance Spectroscopy; Spectroscopy, Fourier Transform Infrared; β-Cyclodextrin
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.36242

5‐Fluorouracil (5‐Fu) commonly use in the treatment of different kinds of cancer, but limited cellular uptake and death is still a problem. Herein, we report a simple process for the synthesis of pressure‐sensitive nanogels that indicate to be appropriate in the delivery of 5‐Fu. The hydrogels (Al‐CD) prepare by crosslinking of alginate (Al) with modified beta Cyclodextrin (β‐CD) as Crosslinker. Next, nanoparticles obtaine by an emulsification method. 5‐Fu as model drug loades into the Al‐CD nanogels easily by mixing it in aqueous solution with the nanoparticles. The results revealed that the Al‐CD nanogels are cytocompatible. They have also a noticeable drug encapsulation (82.1 ±5.7%) while they can release (in vitro controlled) 5‐Fu in conditions that imitate the intravascular pressure conditions. These nanogels can rapidly be taken up by HT‐29 cells (a colon cell line). In addition, a higher 5‐Fu intracellular accumulation and a significant cell death extension by apoptosis mechanism is notice when compare with free 5‐Fu. Accordingly, the developed nanogels can be employe as an excellent candidate to overcome the inefficiency of 5‐Fu in anticancer treatments and possibly can employe for further evaluation as a chemotherapical agent in applications beyond cancer. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 349–359, 2018.