Synthesis, characterization and toxicological evaluation of pH-sensitive polyelectrolyte Nanogels
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Nanogels are polymeric nanoparticles that have similar characteristic to hydrogels, but have the size in nano range. The pH-sensitive nanogel have gained much interest in the field of pharmaceutical nanotechnology as they have potential to be used as nanocarriers in drug delivery system. The aim of the present study was to synthesize pH-sensitive polyelectrolyte MMA/IA nanogels using free radical polymerization containing methyl methacrylate (MMA), itaconic acid (IA), and a crosslinker ethylene glycol dimethacrylate (EGDMA). In the synthesis of nanogels four parameters i.e. ethanol/water ratios (v/v), dilution volume using ethanol/water (v/v), crosslinker EGDMA concentration, and monomers MMA/IA ratios were optimized. Their effect on particle size, PdI, zeta potential and swelling ratio were evaluated. The swelling behaviour of the nanogels was studied by measuring swelling ratio using gravimetric method. The optimized nanogels were characterized by proton nuclear magnetic resonance (1H NMR), Fourier transform infrared spectroscopy (FTIR), liquid chromatography/time-of-flight/mass spectrometry (LC-TOF-MS), X-ray powder diffraction (X-RD) and transmission electron microscopy (TEM). Polyelectrolyte characteristic was confirmed by measuring isoelectric point using aqueous electrophoresis. The in-vitro and in-vivo toxicity studies were performed by MTT assays using Caco-2 cells and Limit test using female Sprague Dawly rats, respectively. The nanogels were amorphous in nature, exhibited pH-responsive property and polyelectrolyte characteristics, which showed an isoelectric point at pH 2.78. They had an average particle size <250 nm, narrow size distribution (PdI < 0.3), and negative zeta potential. The in-vitro MTT assays indicated that the nanogels had no sign of cytotoxicity. The in vivo Limit test showed that the LD50 was greater than 2000 mg/kg body weight. The necrospy, histopathology and hematological studies also revealed no sign of toxicity. These findings suggested that the MMA/IA nanogels are pH-sensitive, non-toxic and have potential to form a polyelectrolyte complex with oppositely charged of macromolecular drugs.
KeywordsNanogels pH-sensitive Swelling Cytotoxicity Acute oral toxicity
The authors would like to thank Ministry of Education Malaysia for providing Fundamental Research Grant Scheme (203/PFarmasi/6711450) to support this work. The author (Jahanzeb Mudassir) gratefully acknowledges Universiti Sains Malaysia, Penang, Malaysia for awarding of the Fellowship.
Compliance with ethical standards
“Acute oral toxicity study on pH-sensitive nanogels for oral drug delivery” was approved by Animal Ethics Committee, Universiti Sains Malaysia (AECUSM).
“USM/Animal Ethics Approval/2012/(82) (422)”.
Conflict of interest
The authors declare that there is no conflict of interest in publishing this article.
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