Synthesis and properties of new functionalized graphene oxide drug carriers
|School||Nanjing Normal University|
|Course||Polymer Chemistry and Physics|
|Keywords||Carboxyl grapene oxide Drug delivery Chlorhexidine acetate Berberine hydrochloride Inclusion Antimicrobial capacity Blood compatibility Cytotoxicity|
Graphene, a new two-dimensional nanomaterial composed of sp2-bonded carbon atoms, is considered as a basic building block for OD fullerene, 1Dcarbon nanotubes, and 3D graphitehas. As a "rising star" material, it attracted tremendous attention from both the experimental and theoretical scientific communities due to its unique nanostr-ucture and a variety of fascinating thermal, mechanical, and electrical properties. Graphene oxide is one of graphene derivates, Its structure was much the same as graphene with only a layer of carbon atoms with carbonyl, hydroxyl, carboxyl functional groups in the two-dimensional infinite space, so the characteristics of graphene oxide are similar with graphene.In the biological environment,graphene oxide with good dispersion, high drug loading and release properties of certain characteristics and significantly improved efficacy, can be overcome easily reunion and short duration of action and efficacy issues when using of drugs alone. In the biological, graphene oxide mainly used in the field of medicine drug delivery systems, biological detection, biological imaging, cancer treatment and so on.Cyclodextrin has shown a unique effect in improving the drug bioavailability, stability, and drug solubility. Because of its ultrastructure, it can be used as an oral or injectable drug delivery agents, It provides several benefits, such as easy to absorb, and low side effects, thus was widely used in controlled release, sustained release and targeted drug formulations.Recently, P-CD and its inclusions have been increasingly extensive used in the study of new drug formulations and applications.In this paper, we selected good biocompatibility carboxyl graphene oxide as the base material. The composites of carboxyl grapene oxide(GeneO-COOH) and P-CD which are not toxic (or low toxicity) and can be degraded in vivo (GeneO-COO-β-CD) have been successfully synthesized through esterification and self-assembly technique. The samples were characterized with FTIR, TG, Raman, SEM, TEM. The analytical results indicated that carboxylic graphene oxide formed the core while a large number ofβ-cyclodextrin formed a special structure of the microspheres (β-CD:GeneO-COOH=30:1). In the microspheres, the esterification between GeneO-COOH and p-CD to form a covalent bond, while adjacentβ-CD molecules builded an outer wall equal to 100CD (about 800 nm) in layer-by-layer of fashion of self-assembly to form by hydrogen bonds. The obtained new composite GeneO-COO-β-CD possessed good dispersibility in water media and the solutions were also found to be very stable for 12 months. In addition, the cytotoxic of GeneO-COO-β-CD drug delivery was evaluated by hemolysis test and MTT, the results show thatGeneO-COO-β-CD had no cytotoxicity.Based on these studies, using the outer layer cavity ofβ-CD with "in the hydrophobic, hydrophilic outside" of GeneO-COO-β-CD microspheres drug carriers as well as the kernel of graphene nano the synergistic effects of drugs.Through the inclusion technique, include antimicrobial agents in order to achieve greater efficacy and bioavailability, enhance antibacterial effect, reduce adverse drug reactions, increase the protection of drug safety, and expand its application in biomedical purposes.Therefore, this paper selected two representative antimicrobial agents: chlorhexidine acetate Western (CA), and traditional Chinese medicine berberine hydrochloride (BH), Through the inclusion technique, two new inclusion, GeneO-COO-β-CD/CA and GeneO-COO-β-CD/BH were synthesis. The different physical and chemical properties and biological properties of inclusion were charaterized by XRD, FTIR, UV-vis. The results showed that GeneO-COO-β-CD have strong ability to include CA, when the mass ratio of GeneO-COO-P-CD and CA is 2:1 and the reaction time is 60 min. The results also showed that GeneO-COO-β-CD have strong ability to include BH,when the mass ratio of GeneO-COO-P-CD and BH is 2:1 and the reaction time is 90 min. XRD andTGA comfirmed formation of inclusion complexes and the heat resistance of CA and BH have been increased after inclusion by GeneO-COO-β-CD, respectively, the temperature of CA and BH increasing 149℃and 137℃.Solubility experiments show that the solubility of CA in inclusion GeneO-COO-β-CD/CA (17.6832μg/ml) increased 6.56 times than the original drug CA (2.6966μg/ml) while the solubility of BH in inclusion GeneO-COO-β-CD/BH (1.8301μg/ml) increased 8.02 times than the original drug BH (14.6804μg/ml).In vitro experiments to investigate the release of two types of inclusion were carried out. The inclusion of GeneO-COO-β-CD/CA showed good release in pH=1.2 HCl acid solution while the inclusion of GeneO-COO-β-CD/BH have good release in pH=7.4 PBS solution. The antibacterial activity to Escherichia coli (ATCC25922) and Staphylococcus aureus(ATCC25923) were evaluated by MIC, Zone of inhibition test, Bacterial colonies test, the inhibitory curve test and conductivity test. The results indicated that GeneO-COO-P-CD compound had no antibacterial properties, but inclsions has better antibacterial properties than pure drug, those results also show GeneO-COO-P-CD composite is a good drug delivery. The hemocompatibility of two inclusions were evaluated by hemolysis test and recalcification time test. The results showed that the hemolytic rate of two inclusions were all under the international standards, and GeneO-COO-β-CD compound and inclusions showed better anticoagulant function than pure drugs. In addition, the cell toxicity of GeneO-COO-β-CD/CA, GeneO-COO-β-CD/BH inclusions was evaluated by MTT, and the results showed that the two inclusions had no cytotoxic.Therefore, this thesis the synthesis of new drug carrier GeneO-COO-β-CD and the inclusions of GeneO-COO-β-CD/CA and GeneO-COO-β-CD/BH have good biocompatibility, and the antibiotic drugs of chlorhexidine acetate, berberine hydrochloride after GeneO-COO-(3-CD including, the antibacterial effect exhibited a strong synergistic effect,and are expected to slow as a novel, controlled-release drug formulations system applied to the biomedical field.