PREPARATION AND CHARACTERIZATION OF GEMCITABINE LOADED MPEG-PCL POLYMERIC NANOPARTICLES FOR IMPROVED TRANSPORTATION ACROSS BLOOD BRAIN BARRIER
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2016, Vol 8, Issue 1
Abstract
Objective: To prepare Gemcitabine (GCB) loaded Methoxy Polyethylene Glycol-Poly (Caprolactone), (MPEG-PCL) nanoformulations and to carry out the physicochemical characterisation with a primary objective to enhance the transport and penetration of drug across the blood-brain barrier (BBB).Methods: Gemcitabine loaded MPEG-PCL nanoparticles were formulated by using modified nanoprecipitation method. Nanoformulations were prepared by varying drug: polymer ratio. The prepared nanoparticles (NP) were evaluated for particle size, zeta potential, entrapment efficiency, drug content and in-vitro drug release studies. The in vitro cytotoxicity of drug-loaded NPs was evaluated in U-87 MG cells. Results: The prepared nanoformulations indicated a significant increase in particle size with increase in the polymeric concentration. GCB loaded MPEG-PCL nanoformulation (GCBNP 3) exhibited a particle size of 223±1.4 nm. DSC thermo grams indicated that GCB was dispersed as an amorphous state in MPEG NPs. SEM, TEM, and AFM studies indicated that the NPs were spherical, smooth surface without any cracks or pinholes. In vitro studies showed the GCBNP 3 shows an initial burst release followed by a more gradual and sustained-release phase (maximum drug release). The cytotoxicity of GCB loaded MPEG-PCL nanoformulations showed reduction in the IC50 value (4.1 µg). Apoptosis detection assay with Hoechst 33342 dye was carried out and observed an increase in fluorescence in the apoptotic cells. By invasive studies, the GCB loaded MPEG-PCL nanoformulation inhibits the cell migration significantly when compared with the pure drug.Conclusion: The GCB loaded MPEG-PCL nano particles indicated improved cytotoxic activity with minimal concentrations compared with the pure drug in U-87 MG glial cells. Hence, it can be concluded that GCB loaded MPEG-PCL nanoformulation can serve as a potential drug delivery tool for the treatment of brain tumours.Â
Authors and Affiliations
B. V. Nagarjuna Yadav, V. Ravichandiran, S. Sathesh Kumar
Keywords
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