Preparation and Properties of Graphene Oxide Derivative Based Pulmonary Drug Delivery System

GO-F127-RFP composite was prepared by none covalent bond of π-π-stacking, and the properties were investigated by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), field-emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM), drug loading content, antibacterial activity and cytotoxicity assay. The results show that GO-F127-RFP composite is successfully prepared, and the carrier GO-F127 can load more drug RFP than other carriers, GO-F127-RFP composite has the antibacterial ability and GO-F127-RFP can lower the cytotoxicity of RFP, which make it a talent lung targeted system for curing tuberculosis (TB). Introduction Partially fueled by the human immunodeficiency virus (HIV) pandemic, tuberculosis (TB) is the second deading cause of infectious diseases–associated mortality globally and the leading cause of death among those infected with HIV [1]. In2013, there were an estimated 11 million prevalent cases, and an estimated 9.0 million incident cases occurred globally [2]. After 2015, TB control will confront extant and emergent challenges, including those directly related to the disease (such as drug resistance and co-infection with HIV) and broader issues (such as the increased prominence of NCDs and instability wrought by mounting income disparities) [3]. Rifampicin (RFP) has the antibacterial activity for mycobacterium tuberculosis bacterium, gram positive bacteria and gram negative bacteria. But adverse drug reactions such as liver toxicity, digestive tract reaction, nervous system disorders and allergic reaction may deteriorate the health-related quality of life, and then may counteract a successful therapy of condition [4]. In consequence, a balance between high therapeutic efficacy and the risk of adverse drug reactions is required, and the development of novel disease-targeted drug strategies is intended for a more effective therapy and demonstrates the potential to address unmet medical needs [5]. Graphene’s large surface area, delocalized π electrons, chemical purity and the possibility of easy functionalization provide opportunities for drug delivery [6]. Herein, we present a drug carrier, graphene oxide derivatives, to load RFP by π-π-stacking between them, and the properties were investigated. Experimental Preparation of GO-F127-RFP Composites All chemicals used were of analytical grade and were used as received without any further purification. Deionized water was used in all experiments. Graphene oxide (GO) was prepared from graphite powders through the modified Hummers’ method [7]. The graphene oxide derivative (GO-F127) was prepared using graphene oxide, F-127 and DEC to avoid graphene reunion and promote dispersion in solution at room temperature for 12 h and was reduced by hydrazine hydrate at 40 °Cfor 12 h [8]. The RFP methanol solution and GO-F127 water solution were mixed and stirred for 12 h. The GO-F127-RFP composite was centrifuged, washed with deionized water for three times and gained by freeze-drying. Analytical Methods Fourier transform infrared spectra (FTIR) were recorded with the Perkin-ElmerSpectrum GXS spectrophotometer using KBr pellet. Powder X-ray diffraction (XRD) patterns were recorded by a X-ray diffractometer (MSAL-XDII) using a Cu Kα radiation microscope. The morphologies of obtained GO and GO-F127 were observed by a PHILIPS, ESEM XL 30, Holland field-emission scanning electron microscope (FE-SEM) at an accelerating voltage of 5 kV and a PHILIPS TECNAI-10 microscope, JEOL JEM-2010 (HR) transmission electron microscope (TEM). The drug load content (LC), drug load efficiency (LE) were conducted by ultraviolet and visible (UV/VIS) spectrophotometer. The antibacterial activity of GO-F127-RFPcomposite was tested by qualitative method (inhibition zone technology). Cytotoxicity of samples were tested using the MTT assay based on the cellular uptake of MTT and its subsequent reduction in the mitochondria of living cells to dark blue MTT formazan crystals. Result and Discussion FTIR Analysis The Fig. 1 showed the FTIR spectra of GO, GO-F127, RFP and GO-F127-RFP composite. That a large quantities of oxygen-containing functional groups exited in the forms of epoxy, hydroxyl and carboxyl groups on the surface of GO demonstrated the successful synthesis of GO by comparing the GO and graphite spectrogram. The broad absorption at 3200-3400 cm-1 was due to the O-H stretching vibration; the peak at 1630 cm-1 could be assigned to the C=O stretching vibration and the peak at 1059 cm-1 was correspond to C-O stretching vibration [9-11]. The new peaks at 1480 and 1102 cm-1 of GO-F127 and new peaks at 1680 cm-1, 1420 cm-1 of GO-F127-RFP composite indicated the GO-F127 and GO-F127-RFP composite were successfully prepared.