title: Dual drug delivery of 5-fluorouracil (5-FU) and methotrexate (MTX) through random copolymeric nanomicelles of PLGA and polyethylenimine demonstrating enhanced cell uptake and cytotoxicity.
abstract: We now report the synthesis of a random copolymer of poly-lactic-co-glycolic acid (PLGA) grafted branched polyethylenimine (BPEI) and the use of it as a multi drug delivery system (DDS). The methotrexate (MTX) was conjugated to BPEI through DCC/NHS chemistry. The copolymer-drug conjugate (PBP-MTX) was characterised by FT-IR and (1)H NMR spectroscopy. The PBP-MTX was converted into nanomicelles with entrapped 5-fluorouracil (5-FU) through nanoprecipitation technique. The size, shape, morphology and surface charge of the nanomicelles were confirmed using different techniques. The thermal behaviour and distribution of both conjugated and entrapped drug through the polymeric matrix were assessed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). In vitro drug release pattern of the nanomicelles was examined to ascertain the release pattern of two drugs namely 5-FU and MTX. The cellular uptake studies demonstrated higher uptake of the nanomicelles in colon cancer cell line HCT 116. Further the cytotoxicity evaluation of nanomicelles illustrated promising action which confirms the use of the system as a potential DDS to colon cancer.
authors.affiliation: Chemical Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: N
authors.initials: N
authors.lastname: Ashwanikumar
authors.affiliation: Cancer Research Programme, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Nisha Asok
authors.initials: NA
authors.lastname: Kumar
authors.affiliation: Cancer Research Programme, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: S Asha
authors.initials: SA
authors.lastname: Nair
authors.affiliation: Chemical Biology, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram 695 014, Kerala, India. Electronic address: gsvinod@rgcb.res.in.
authors.forename: G S Vinod
authors.initials: GSV
authors.lastname: Kumar
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000008:administration & dosage*; D045325:HCT116 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008727:Methotrexate / Q000008:administration & dosage*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D011094:Polyethyleneimine / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D008823:Micelles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D005472:Fluorouracil; D008727:Methotrexate
keywords: 5-Fluorouracil (5-FU); Methotrexate (MTX); Nanomicelles; Uptake