Xueying Huang

Eco-friendly nano-hybrid superabsorbent composite from hydroxyethyl cellulose and diatomite

The simultaneous introduction of green polysaccharides and low-cost inorganic clay into superabsorbent (SAP) polymeric networks has witnessed growing interest for developing eco-friendly and low-cost SAPs since the last decade. In this study, a high performance nano-hybrid SAP composite (HEC-g-PAA/diatomite) was prepared through the graft polymerization of acrylic acid into hydroxyethyl cellulose backbone chains under aqueous conditions in the presence of diatomite clay as an inorganic nano-filler, N,Nʹ-methylenebisacrylamide as the cross-linker and ammonium persulfate as the initiator. FTIR, XRD, and SEM investigations confirmed the successful synthesis of this HEC-g-PAA/diatomite nano-hybrid SAP composite with high porosity on the surface. The composite prepared under optimized conditions presented a significantly enhanced thermal stability according to the TGA and DSC analysis and remarkably improved water-retention properties at various temperatures compared with the clay-free counterpart. Our SAP showed the eminent maximum swelling ratio of 1174.85 g g−1 in distilled H2O and 99.55 g g−1 in 0.9 wt% NaCl salt solutions. In addition, factors influencing various amounts of water absorbency of the prepared SAP were extensively determined and discussed. Therefore, this SAP, with a high content of biodegradable and low-cost material, could be a good candidate for hygienic products, waste-water treatment, agriculture, and horticulture uses.

Intracellular Delivery of Mitomycin C with Targeted Polysaccharide Conjugates Against Multidrug Resistance

Intracellular targeted conjugates of xyloglucan and mitomycin C (MMC) were synthesized with a lysosomally degradable peptide spacer and galactosamine, a terminal moiety that can be used to target polymeric conjugates to hepatoma. The content of the MMC was about 3.5% (mol) in this conjugate. In an in vitro cytotoxicity experiment, the targeted prodrugs have higher cytotoxicity than free MMC against the drug resistant HepG2 cells. In a human tumor xenograft nude mouse model, the targeted prodrugs generated higher therapeutic effect than non-targeted prodrugs or free MMC. Together, these results suggest that targeted prodrugs, which have improved transfer efficiency and hepatocyte specificity, may be useful for the reversion of drug resistant HepG2 cells.

Synthesis and properties of a novel ecofriendly superabsorbent hydrogel nanocomposite based on xyloglucan-graft-poly(acrylic acid)/diatomite

Recently, there has been growing interest in the use of natural available materials to prepare superabsorbents due to their low-cost and environmental friendliness. In this study, a biodegradable organic–inorganic superabsorbent was prepared through graft copolymerization of acrylic acid (AA) onto xyloglucan (XG) polysaccharide chains, in the presence of diatomite as an inorganic material, N,N′-methylene-bis-acrylamide (MBA) as a cross-linker and ammonium persulfate (APS) as an initiator, in an aqueous solution (XG-g-PAA/diatomite). The synthesized hydrogel nanocomposite was characterized with FTIR, SEM, TGA and XRD. In this contribution, the properties such as swelling and water retention behavior of the XG-g-PAA/diatomite were investigated. Moreover, the influence of each starting material content on the water absorbency property of the XG-g-PAA/diatomite composite was systematically studied. The results showed that the composite water absorbency capacity was 1057.06 ± 69.53 g g−1 in deionized water and 65.67 ± 5.43 g g−1 in a 0.9 wt% NaCl saline solution under the optimized conditions. The excellent properties of the prepared SAP composite suggested that it could find a diverse range of applications such as in hygienic products, agriculture and waste-water treatment. Furthermore, being biodegradable and low-cost could be added advantages for the XG-g-PAA/diatomite superabsorbent composite.

Precise Ratiometric Control of Dual Drugs through a Single Macromolecule for Combination Therapy.

A major challenge of combinatorial therapy is the unification of the pharmacokinetics and cellular uptake of various drug molecules with precise control of the dosage thereby maximizing the combined effects. To realize ratiometric delivery and synchronized release of different drugs from a single carrier, a novel approach was designed in this study to load dual drugs onto the macromolecular carrier with different molar ratio by covalently preconjugating dual drugs through peptide linkers to form drug conjugates. In contrast to loading individual types of drugs separately, these drug conjugates enable the loading of dual drugs onto the same carrier in a precisely controllable manner to reverse multidrug resistance (MDR) of human hepatoma (HepG2) cells. As a proof of concept, the synthesis and characterization of xyloglucan-mitomycin C/doxorubicin (XG-MMC/DOX) conjugates were demonstrated. This approach enabled MMC and DOX to be conjugated to the same polymeric carrier with precise control of drug dosage. The cytotoxicity and combinatorial effects were significantly improved compared to the cocktail mixtures of XG-MMC and XG-DOX as well as the individual conjugate of the mixture. Moreover, the results also showed that there was an optimum ratio of dual drugs showing the best cytotoxicity effect and greatest synergy among other tested polymeric conjugate formulations.

Self-organized nanoparticle drug delivery systems from a folate-targeted dextran–doxorubicin conjugate loaded with doxorubicin against multidrug resistance

A folate-targeted dextran–doxorubicin conjugate (folate–dextran–DOX) for drug delivery systems (DDSs) was synthesized by grafting DOX onto dextran through cleavable hydrazone bonds and a pH-sensitive spacer for controlling the drug release. Folate was coupled onto dextran as an ideal ligand for targeting hepatocytes. The conjugate was formulated into nanoparticles with excessive deprotonated DOX (DOX nano-DDSs) under aqueous conditions, which exhibited nanoparticles with larger size of 147.9 nm in diameter and improved drug entrapment to the level of 25.2%. DOX nano-DDSs delivered higher cytotoxicity and a greater extent of intracellular uptake in vitro against drug resistant HepG2 (HepG2/DOX) cells; moreover, they displayed equivalent effects with folate–dextran–DOX micelles in terms of inhibiting tumor volume and decreasing toxicity. In addition, DOX nano-DDSs achieved significantly greater effects than free DOX. The results indicated that these targeted self-organized DOX nano-DDSs have superior reversal efficacy to free DOX and serve as a highly promising nano-platform for future cancer therapy.

Targeted nanoparticles from xyloglucan–doxorubicin conjugate loaded with doxorubicin against drug resistance

An active-targeting and smart pH-sensitive nanoparticle drug delivery system with high drug loading was developed by conjugating doxorubicin (DOX) to xyloglucan (XG) through acid-cleavable hydrazone bonds, and then encapsulating DOX by the self-assembly of xyloglucan–doxorubicin conjugates (XG–DOX) to ensure a sufficient amount of drug delivered in the tumor region. The galactose moiety of XG, as an ideal targeting moiety, could be recognized and internalized by asialoglycoprotein receptor (ASGP-R), which is especially ample in hepatocytes. And then the abundant DOX of xyloglucan–doxorubicin nanoparticle drug delivery systems (DOX nano-DDSs) could be highly accumulated and released in drug resistant tumor cells to exert maximum therapeutic effects. Compared with free DOX, the novel DOX nano-DDSs apparently showed longer circulation time, larger intracellular uptake, more drug release, higher cytotoxicity against drug resistant HepG2 (HepG2/DOX) cells and greater effects for inhibiting the growth of the tumor volume and decreasing systemic toxicity. Even though there was no significant enhancement in intracellular uptake and cytotoxicity between the DOX nano-DDSs and XG–DOX, the loading content of DOX of DOX nano-DDSs reached 23%, which is higher than that of XG–DOX conjugates. Moreover, the DOX nano-DDSs obviously presented better anti-tumor effects in in vivo assays. In conclusion, these novel DOX nano-DDSs exhibited remarkable anti-tumor effects and few side effects, which is significantly promising for the clinical therapy of cancer.

In vivo immunological activity of carboxymethylated-sulfated (1→3)-β-D-glucan from sclerotium of Poria cocos.

β-Glucans are one of the polysaccharides known as biological response modifiers extracted from the sclerotium of Poria cocos which has been used for several decades as Traditional Chinese Medicine. Due to its ability to activate immune system, it can be applied in chemotherapy after being chemically modified. In this study, sulfated (1→3)-β-D-glucan (S-P), carboxymethyl (1→3)-β-D-glucan (CMP), and carboxymethylated-sulfated (1→3)-β-D-glucan (S-CMP), which are (1→3)-β-D-glucan derivatives were synthesized. The current study was aimed to investigate in vivo potential immunological activity of S-CMP in mice. In addition, mice were separately treated with S-P, CMP and S-CMP to evaluate the relationship between single and multiple functional groups. Interestingly, S-CMP exhibited the best in vivo immunological activities and the highest inhibition rate against the implanted HepG2 tumor in BALB/c mice, with significant increase in serum hemolysin antibody titer, spleen antibody production as well as delayed type hypersensitivity compared with S-P and CMP. Furthermore, it was assumed that simultaneous introduction of carboxymethyl and sulfate groups also had great potential effect on antioxidant activity, as substantial decrease in malondialdehyde (MDA) content was remarked. Therefore, it may suggest that S-CMP has better immunological and anti-tumor effects on mice in vivo.

Xyloglucan as a mitomycin C carrier to reverse multidrug resistance

Hepatocellular carcinoma (HCC) is still considered as the third highest cause of cancer death in developing countries. In our previous study, we confirmed that the galactose residues of natural polysaccharide xyloglucan (XG) turns out to be selected uptake by asialoglycoprotein receptor (ASGPR) and the xyloglucan can be used as drug carriers and achieve some enhancement in the therapeutic effect of HCC via ASGPR mediated endocytosis. In this study, we selected mitomycin C (MMC) as the anticancer model drug and a macromolecular drug delivery system (DDS) with different degrees of substitution that was synthesized by conjugating mitomycin C with xyloglucan. The degree of substitution of xyloglucan–mitomycin C conjugates (XG–MMC) was about 9.7%. Another sample obtained a higher degree of substitution (p-MMC) of approximately 31%. The content of MMC in XG–MMC and p-MMC was determined and calculated to be about 3.1% and 6.4%, respectively. In the in vitro cytotoxicity experiment, the prodrugs presented higher cytotoxicity than free MMC against the drug resistant HepG2 cells. Moreover, the IC50 of XG–MMC (0.997 μg mL−1) was much lower than that of p-MMC (2.56 μg mL−1) and XG–MMC exhibited higher drug uptake amounts (187.9 ng) than that of p-MMC (63.5 ng). The in vivo cytotoxicity was also evaluated, and the result was in good agreement with the in vitro cytotoxicity experiment.

PTX encapsulated by an XG–DOX conjugate for combination therapy against multi-drug resistance

So far, several anti-cancer drugs have shown low efficacy in the clinic because of multi-drug resistance (MDR), which always leads to the failure of chemotherapy. In addition, high doses of these chemotherapeutic drugs such as doxorubicin (DOX) and paclitaxel (PTX) result in high toxicity. Considering the above problems, a kind of dual drug loading onto a conjugate was designed, which makes good use of two drugs. In this new nano-drug delivery system, DOX works as a hydrophobic core and xyloglucan (XG) works as a hydrophilic shell to form stable nanoparticles in aqueous solution. Thereafter, PTX is encapsulated by this XG–DOX conjugate (PTX nano-DDS). Results have demonstrated that PTX nano-DDS possesses outstanding advantages over ordinary systems, including precise control over the molar ratio of the drugs and high hepatic targeting. Moreover, through the combination of two drugs, the system can maximize efficacy through synergism between PTX and DOX. It also has minimal side effects and is effective against MDR cancer cells. This kind of system is therefore practical for development as a new type of targeted dual drug delivery system in combination therapy.

Intracellular delivery of 10-hydroxycamptothecin with targeted nanostructured lipid carriers against multidrug resistance.

Abstract 10-Hydroxycamptothecin (HCPT) is a clinical therapy agent against hepatoma. The chemotherapy of HCPT is strongly obstructed by the emergence of multidrug resistance (MDR), serious systemic toxicity, malfunction of rapid phagocytic and renal clearance disorder which are undesirable for its chemotherapy. In this paper, a drug delivery system (DDS) for HCPT has been developed in order to overcome MDR. Nanostructured lipid carriers (NLC) coated with xyloglucan (XG) was prepared by soya oil and XG consisting of side chains with galactose residues, a terminal moiety that can be used to target HCPT to hepatoma. The therapeutic potential of XG-NLC/HCPT was investigated on HepG2/HCPT cells and on human tumor xenograft nude mouse model (implanted with HepG2/HCPT cells). XG-NLC/HCPT not only indicated superior cytotoxicity against the drug resistant HepG2 cells but also in vivo, generated a higher therapeutic effect. Systemic toxicity study demonstrated that the carrier reduced systemic toxicity. XG-NLC/HCPT proved a great potential to serve as DDS to overcome MDR of HepG2/HCPT cells. These results suggested that XG NLC/HCPT represent a promising carrier for drug delivery to the hepatoma and reverse the drug resistant of HepG2 cells and XG could be exploited as a potential targeting device for liver tissue.