Title : Preparation and Characterization of Graphene Oxide Nanoparticle Based Suspension for Optimized Drug Delivery

Authors : Adittya Arefin, Towfica Afsana, Ar Rahman, Zaheen Salauddin, Tamnia Islam, Hiran Saha, Mohsin Kazi, Mohammad Shariare

Abstract : Purpose: Graphene Oxide (GO) nanoparticle exhibits better biocompatibility and higher loading capacity compared to other nanocarriers used in drug delivery systems. The aim of this study was to explore the possibilities of drug loading with desired particle size distribution via a pegylated graphene oxide based (GO-PEG-Drug) nanosuspension. Methods: GO was prepared by modified Hummer’s method1 and subsequently sonicated to achieve nanosize GO. The GO nanoparticles were pegylated with PEG6000 to improve the stability aspects. Then carrier (GO) based nanosuspensions for three different drugs: Acetaminophen (AMP), Diclofenac (DIC) & Methotrexate (MTX) were prepared utilizing sonication and stirring techniques. A full factorial experimental design was used using four process parameters (sonication time, pegylation time, stirring time, stirring rate) at two levels (H=High; L=Low). The suspensions were characterized using Malvern Zetasizer Nano Zs90, Scanning Electron Microscopy (SEM) and inverse phase microscopy. Ultra Violet (UV) and Fluorescence spectroscopy were used to evaluate the drug-loading on nano-graphene oxide carrier particle. Results: Microscopic and Malvern Zetasizer data showed that nanosuspension prepared in this study were in the range of 300–950nm. The average particle sizes were lowest (AMP: 340±6 nm, DIC: 356±13 nm, MTX: 935±71 nm) when the nanosuspension batches of different drugs were processed at high level of processing conditions. Longer duration of sonication exhibited lower average particle size for nanosuspensions (AMP: 340±6 nm, DIC: 356±13 nm) compared to the shorter duration of sonication (AMP: 381±12 nm, DIC: 432 ±7 nm). Similar phenomenon was observed for pegylation duration of GO nanoparticle, which suggests that nanosuspension batches processed with longer duration of pegylation resulted in lower average particle size (AMP: 340±6nm, DIC: 356±13 nm) than shorter duration of pegylation (AMP: 383±7 nm, DIC:420±17 nm). Stirring at high rate resulted in lower average particle size for nanosuspension batches (AMP: 340±6 nm, DIC: 356±13 nm) than stirring at low rate (AMP: 373±14 nm, DIC: 420±17 nm). Previous study suggests that drug loading on GO occurs via ?-? interaction2, therefore we postulate that number of ? bonds (e.g. aromatic ring) in drug molecule may facilitate drug loading on graphene oxide. In this study it was observed that drug molecule with greater number of benzene ring showed higher drug loading (MTX: 95.6%±0.1) compared to molecules with less benzene ring (DIC: 70.5%±2.5, AMP: 65.5%±0.8) [Figure 1]. Conclusion: In this study, it was observed that drugs with different structures processed using similar conditions behave differently. Drug loading efficiency was high for the nanosuspension batches processed with drugs containing greater number of aromatic rings. Processing parameters were found to have marked impact on average particle size of nanosuspension batches.

Journal : Volume : Year : 2016 Issue :
Pages : City : Denver, Colorado, USA Edition : Editors :
Publisher : AAPS annual meeting and exposition , 2016 ISBN : Book : Chapter :
Proceeding Title : American Association of Pharmaceutical scientists (AAPS) Annual Meeting and Exposition, USA. Institution : Issuer : Number :