title: pH dependent poly[2-(methacryloyloxyethyl)trimetylammonium chloride-co-methacrylic acid]hydrogels for enhanced targeted delivery of 5-fluorouracil in colon cancer cells.
abstract: Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.
authors.affiliation: Brain Science Research Laboratory, Faculty of Pharmacy, Universiti Teknologi MARA, 42300, Puncak Alam, Selangor, Malaysia, mishra_rk82@yahoo.co.in.
authors.forename: R K
authors.initials: RK
authors.lastname: Mishra
authors.forename: K
authors.initials: K
authors.lastname: Ramasamy
authors.forename: N A
authors.initials: NA
authors.lastname: Ahmad
authors.forename: Z
authors.initials: Z
authors.lastname: Eshak
authors.forename: A B A
authors.initials: AB
authors.lastname: Majeed
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: C120889:2-(trimethylammonio)ethyl methacrylate; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D020100:Hydrogels; D008689:Methacrylates; D011109:Polymethacrylic Acids; D005472:Fluorouracil