title: Potential carriers of chemotherapeutic drugs: matrix based nanoparticulate polymeric systems.
abstract: In this work matrix based nanoparticulate polymer systems have been designed using the diacrylate derivative of the well-known biocompatible polymer, poly(ethylene glycol) (PEG). This has been crosslinked using bifunctional (ethyleneglycol dimethacrylate) and tetrafunctional (pentaerythritol tetraacrylate) crosslinkers in varied concentrations (10-90%) to result in a polymeric network. The crosslinked polymers thus obtained were characterized by spectroscopic techniques (NMR and FTIR) and then prepared nanoparticles by the nanoprecipitation technique. Particle size analysis showed sizes of ~150 nm (PDI < 1) (with tetrafunctional crosslinker) and ~300 nm (with bifunctional crosslinker). Both the systems however showed unimodal narrow particle size distributions with negative zeta potential values of -15.6 and -7.3 respectively. Cytotoxicity of these formulations was evaluated by MTT assay showing non-cytotoxic nature of these carrier systems.In vitrodrug loading and release studies were carried out using a model chemotherapeutic drug, methotrexate(MTX). These MTX loaded nanoformulations have also been evaluated biologically with the help ofin vivostudies using radiolabeling techniques (with99mTc radionuclide). The blood kinetics profile of the formulations was studied on New Zealand Albino rabbits while the biodistribution studies were performed on balb/c mice (with EAT tumours), which revealed a hepatobiliary mode of elimination. These preliminary studies clearly demonstrated the ability of these multifunctional crosslinkers to result in tight nanosized networks with biocompatible polymers such as PEG and their potential to carry chemotherapeutic drugs.
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization(DRDO), Brig S. K. Mazumdar Road, Timarpur, Delhi 110054 India.
authors.forename: Dipti Kakkar
authors.initials: DK
authors.lastname: Thukral
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization(DRDO), Brig S. K. Mazumdar Road, Timarpur, Delhi 110054 India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Dumoga
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization(DRDO), Brig S. K. Mazumdar Road, Timarpur, Delhi 110054 India.
authors.forename: Shelly
authors.initials: S
authors.lastname: Arora
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization(DRDO), Brig S. K. Mazumdar Road, Timarpur, Delhi 110054 India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research & Development Organization(DRDO), Brig S. K. Mazumdar Road, Timarpur, Delhi 110054 India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
keywords: Crosslinkers; Methotrexate; Polyethylene glycol; Radiolabeling; Technetium