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 vitro drug 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 of in vivo studies using radiolabeling techniques (with 99mTc 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12645-014-0003-9) contains supplementary material, which is available to authorized users.
Highlights
The past few decades have seen a tremendous advancement in the area of drug delivery using polymeric particulate carrier systems for small and large molecules
Crosslinked polymeric systems can be prepared by chemical crosslinking of the polymeric matrices in the presence of various crosslinkers such as ethyleneglycol dimethacrylate (EGDMA), polycaprolactone (PCL) diacrylate, methyl methacrylate (MMA), divinyl benzene (DVB), pentaerythritol triacrylate (PETA), pentaerythritol tetraacrylate, etc
Crosslinked nanoparticles of polyethylene glycol were prepared by free radical polymerization and crosslinking of PEGDA chains with EGDMA and pentaerythritol tetraacrylate (PETRA) in the presence of AIBN
Summary
The past few decades have seen a tremendous advancement in the area of drug delivery using polymeric particulate carrier systems for small and large molecules. The entrapment efficiency can be further enhanced by varying the crosslink density which is determined by the number of crosslinks governed by the type of crosslinker used for the preparation of the network Drug encapsulation in these crosslinked polymeric systems such as PEG based systems could be tailored by several parameters, viz.-a-viz. This is undeniably a highly advantageous aspect while using anti-cancer drugs as their side effects may result in compromised efficacy Both biodegradable and biocompatible polymers have been investigated to prepare crosslinked networks that can carry chemotherapeutic drug payloads for therapeutic and delivery purposes. It was proposed to use PEG as the core polymer for our work in order to further exploit its favorable attributes
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