Dai Hai Nguyen

Tetronic-grafted chitosan hydrogel as an injectable and biocompatible scaffold for biomedical applications

In recent years, injectable chitosan-based hydrogels have been widely studied towards biomedical applications because of their potential performance in drug/cell delivery and tissue regeneration. In this study, we introduce a simple and organic solvent-free method to prepare tyramine–tetronic–grafted chitosan (TTeC) via activation of four terminal hydroxyl groups of tetronic, partial tyramine conjugate into the activated product and grafting the remaining activated moiety of tetronic-tyramine onto chitosan. The grafted copolymer was well characterized by UV–Visible, 1H NMR, and Thermogravimetric analysis. The aqueous TTeC copolymer solution rapidly formed hydrogel in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) at physiological conditions. The gelation time of the hydrogel was performed within a time period of 4–60 s, when the concentrations of HRP, H2O2, and polymers varied. The hydrogel exhibited highly porous structure which could be controlled by using H2O2. In vitro cytotoxicity study with Human Foreskin Fibroblast cell using live/dead assay indicated that the hydrogel had high cytocompatibility and could play a role as a scaffold for cell adhesion. The injectable hydrogels did not cause any inflammation after two weeks and one day of the in vivo injection. The obtained results demonstrated a great potential of the TTeC hydrogel in biomedical applications.

Hierarchical self-assembly of heparin-PEG end-capped porous silica as a redox sensitive nanocarrier for doxorubicin delivery

Porous nanosilica (PNS) has been attracting a great attention in fabrication carriers for drug delivery system (DDS). However, unmodified PNS-based carriers exhibited the initial burst release of loaded bioactive molecules, which may limit their potential clinical application. In this study, the surface of PNS was conjugated with adamantylamine (A) via disulfide bonds (PNS-SS-A) which was functionalized with cyclodextrin-heparin-polyethylene glycol (CD-HPEG) for redox triggered doxorubicin (DOX) delivery. The modified PNS was successfully formed with spherical shape and diameter around 50nm determined by transmission electron microscopy (TEM). DOX was efficiently trapped in the PNS-SS-A@CD-HPEG and slowly released in phosphate buffered saline (PBS) without any initial burst effect. Importantly, the release of DOX was triggered due to the cleavage of the disulfide bonds in the presence of dithiothreitol (DTT). In addition, the MTT assay data showed that PNS-SS-A@CD-HPEG was a biocompatible nanocarrier and reduced the toxicity of DOX. These results demonstrated that PNS-SS-A@CD-HPEG has great potential as a novel nanocarrier for anticancer drug in cancer therapy.

Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release

In this report, poly(amide amine) (PAMAM) dendrimer and Heparin-grafted-monomethoxy polyethylene glycol (HEP-mPEG) were synthesized and characterized. In aqueous solution, the generation 4 PAMAM dendrimers (G4.0-PAMAM) existed as nanoparticles with particle size of 5.63nm. However, after electrostatic complexation with HEP-mPEG to form a core@shell structure G4.0-PAMAM@HEP-mPEG, the size of nanoparticles was significantly increased (73.82nm). The G4.0-PAMAM@HEP-mPEG nanoparticles showed their ability to effectively encapsulate doxorubicin (DOX) for prolonged and controlled release. The cytocompatibility of G4.0-PAMAM@HEP-mPEG nanocarriers was significantly increased compared with its parentally G4.0-PAMAM dendrimer in both mouse fibroblast NIH3T3 and the human tumor HeLa cell lines. DOX was effectively encapsulated into G4.0-PAMAM@HEP-mPEG nanoparticles to form DOX-loaded nanocarriers (DOX/G4.0-PAMAM@HEP-mPEG) with high loading efficiency (73.2%). The release of DOX from DOX/G4.0-PAMAM@HEP-mPEG nanocarriers was controlled and prolonged up to 96h compared with less than 24h from their parentally G4.0-PAMAM nanocarriers. Importantly, the released DOX retained its bioactivity by inhibiting the proliferation of monolayer-cultured cancer HeLa cells with the same degree of fresh DOX. This prepared G4.0-PAMAM@HEP-mPEG nanocarrier can be a potential candidate for drug delivery systems with high loading capacity and low systemic toxicity in cancer therapy.

Biocompatible nanomaterials based on dendrimers, hydrogels and hydrogel nanocomposites for use in biomedicine

Over the past decades, biopolymer-based nanomaterials have been developed to overcome the limitations of other macro- and micro- synthetic materials as well as the ever increasing demand for the new materials in nanotechnology, biotechnology, biomedicine and others. Owning to their high stability, biodegradability, low toxicity, and biocompatibility, biopolymer-based nanomaterials hold great promise for various biomedical applications. The pursuit of this review is to briefly describe our recent studies regarding biocompatible biopolymer-based nanomaterials, particularly in the form of dendrimers, hydrogels, and hydrogel composites along with the synthetic and modification approaches for the utilization in drug delivery, tissue engineering, and biomedical implants. Moreover, in vitro and in vivo studies for the toxicity evaluation are also discussed.

Green processing of thermosensitive nanocurcumin-encapsulated chitosan hydrogel towards biomedical application

Abstract In this study, in order to enhance the aqueous solubility and to overcome the limitation of curcumin (Cur) in free form, as well as to develop a carrier for transdermal delivery of hydrophobic pharmaceutical agents such as Cur, a sonicated synthetic process of nanocurcumin (nCur) in thermally responsive Chitosan-g-Pluronic (CP) copolymer is disclosed herein. The use of CP copolymer solution as a dispersant medium is a very attractive method to avoid the use of toxic organic solvent and non-biocompatible surfactant. The obtained Cur nanoparticles had a fairly narrow distribution of 8–23 nm. nCur-dispersed CP solution showed good stability with no change in color characteristic and no phase separation after 1 month of storage. Rheological characterization of CP hydrogels had indicated sol-gel transition at the same temperature (35°C). Interestingly, the rate of Cur release for this system can be conveniently modulated as transdermal drug delivery.

Redox and pH Responsive Poly (Amidoamine) Dendrimer-Heparin Conjugates via Disulfide Linkages for Letrozole Delivery

Heparin (Hep) conjugated to poly (amidoamine) dendrimer G3.5 (P) via redox-sensitive disulfide bond (P-SS-Hep) was studied. The redox and pH dual-responsive nanocarriers were prepared by a simple method that minimized many complex steps as previous studies. The functional characterization of G3.5 coated Hep was investigated by the proton nuclear magnetic resonance spectroscopy. The size and formation were characterized by the dynamic light scattering, zeta potential, and transmission electron microscopy. P-SS-Hep was spherical in shape with average diameter about 11 nm loaded with more than 20% letrozole. This drug carrier could not only eliminate toxicity to cells and improve the drugs solubility but also increase biocompatibility of the system under reductive environment of glutathione. In particular, P-SS-Hep could enhance the effectiveness of cancer therapy after removing Hep from the surface. These results demonstrated that the P-SS-Hep conjugates could be a promising candidate as redox and pH responsive nanocarriers for cancer chemotherapy.

Functionalization of Fe3O4 nanoparticles with biodegradable chitosan-grafted-mPEG for paclitaxel delivery

Abstract In this report, magnetic Fe3O4 nanoparticles were functionalized with chitosan-grafted-poly(ethylene glycol) methyl ether (CTS-mPEG) for paclitaxel (PTX) delivery. The Fe3O4 nanoparticles were prepared via the chemical coprecipitation method and then coated with CTS-mPEG (Fe3O4@CTS-mPEG) by a simple method. The formation of Fe3O4@CTS-mPEG was characterized by several methods including proton nuclear magnetic resonance spectroscopy, Fourier transform infrared, and X-ray diffraction. Furthermore, the superparamagnetic properties of Fe3O4@CTS-mPEG were demonstrated by a vibrating sample magnetometer; the saturation magnetization reached 23 emu g–1. The sizes and morphologies of Fe3O4 and Fe3O4@CTS-mPEG nanoparticles were determined by transmission electron microscopy. The result indicated that Fe3O4@CTS-mPEGs were nearly spherical in shape with an average diameter of 20 nm, compared with the 12-nm Fe3O4 particles. Especially, PTX was effectively loaded into the coated nanoparticles, 86.9±3.4% for drug loading efficiency, and slowly released up to 120 h. These results suggest the potential applications of Fe3O4@CTS-mPEG in the development of stable drug delivery systems for cancer treatment.

Preparation, Characterization and Antifungal Properties of Chitosan-Silver Nanoparticles Synergize Fungicide Against Pyricularia oryzae

Rice (Oryza sativa L.) is one of the major staple food crops of nearly two-third of the worlds population. However, rice blast caused by fungus Pyricularia oryzae is generally considered the most serious disease of cultivated rice worldwide due to its extensive distribution and destructiveness under favourable climatic conditions. In this report, the combination between chitosan (CS) and silver (Ag), Ag@CS, was introduced for antifungal activity against Pyricularia oryzae extracted from blast-infected leaves. In detail, Ag@CS nanoparticles (NPs) were first synthesized and further mixed with Trihexad 700 WP (Tri), Ag@CS-Tri, against the fungus by agar diffusion method. The prepared Ag@CS-Tri NPs were characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). In aqueous condition, Ag@CS-Tri NPs were successfully prepared and existed as spherical NPs with particle size of 17.26 ± 0.89 nm, which is an ideal size for their uptake into plant cells, indicating that the size of their parentally Ag@CS NPs is small enough to combine Tri, and their diameter is large enough to effectively penetrate the cellular membrane and kill fungi. More importantly, the antifungal property of Ag@CS-Tri NPs was significantly increased with inhibition zone around 25 nm compared with only around 12 nm of Ag@CS at the same concentration of Ag (2 ppm) and CS (4000 ppm). These results demonstrated that the synergistic effect of Tri and Ag@CS NPs can be a potential candidate with high antifungal activity for the use of antibiotics in agriculture.

Development and In Vitro Evaluation of Liposomes Using Soy Lecithin to Encapsulate Paclitaxel

The formulation of a potential delivery system based on liposomes (Lips) formulated from soy lecithin (SL) for paclitaxel (PTX) was achieved (PTX-Lips). At first, PTX-Lips were prepared by thin film method using SL and cholesterol and then were characterized for their physiochemical properties (particle size, polydispersity index, zeta potential, and morphology). The results indicated that PTX-Lips were spherical in shape with a dynamic light scattering (DLS) particle size of 131 ± 30.5 nm. Besides, PTX was efficiently encapsulated in Lips, 94.5 ± 3.2% for drug loading efficiency, and slowly released up to 96 h, compared with free PTX. More importantly, cell proliferation kit I (MTT) assay data showed that Lips were biocompatible nanocarriers, and in addition the incorporation of PTX into Lips has been proven successful in reducing the toxicity of PTX. As a result, development of Lips using SL may offer a stable delivery system and promising properties for loading and sustained release of PTX in cancer therapy.

Supramolecular chemistry at interfaces: host-guest interactions for attaching PEG and 5-fluorouracil to the surface of porous nanosilica

Abstract Porous nanosilica (PNS) has been attracting much attention in fabrication of nanocarriers for a drug delivery system (DDS). However, the unmodified PNS-based carriers exhibited a significant initial burst release of drug, which may limit their potential clinical application. In this study, PNS was surface conjugated with cyclodextrin (CD) which was functionalized with adamantylamine-polyethylene glycol (APEG) for 5-fluorouracil (5-FU) delivery, in which case CD was used due to its ability to form a stable inclusion complex with 5-FU and APEG. The conjugated PNS (PNSC@APEG) was successfully prepared with spherical shape and diameter around 50 nm, determined by transmission electron microscopy (TEM). In addition, 5-FU was efficiently trapped in PNSC@APEG particles, which were around 63.4%±3.8% and was slowly released up to 3 days in phosphate buffer saline (PBS). Furthermore, the cell proliferation kit I (MTT) assay data showed that PNSC@APEG was a biocompatible nanocarrier. These results indicated that PNSC@APEG nanoparticles have a great potential as novel carriers for anticancer drug delivery.