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

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2014-10, Vol.122, p.520-528
• Main Authors: Ashwanikumar, N., Kumar, Nisha Asok, Nair, S. Asha, Kumar, G.S. Vinod
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil (5-FU); Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Calorimetry, Differential Scanning; Cancer; Colon; Differential scanning calorimetry; Drug Carriers; Drug delivery systems; Drug Screening Assays, Antitumor; Drugs; Fluorouracil - administration & dosage; HCT116 Cells; Humans; Lactic Acid - chemistry; Methotrexate (MTX); Methotrexate - administration & dosage; Micelles; Microscopy, Electron, Transmission; Nanomicelles; Nanostructure; Nanostructures; Polyethyleneimine - chemistry; Polyethylenimine; Polyglycolic Acid - chemistry; Proton Magnetic Resonance Spectroscopy; Spectroscopy, Fourier Transform Infrared; Uptake; Uptakes; X-Ray Diffraction
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2014.07.024

•Random copolymer synthesis of PLGA and BPEI for MTX conjugation by DCC/NHS chemistry.•Preparation of nanomicelles of 5-FU–PBP–MTX with ultimate desired properties.•Superior 5-FU entrapment in PBP–MTX nanomicelles.•High amount of cellular uptake and cytotoxicity exhibited by the nanomicelles in vitro. 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 1H 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.