Ngoc Quyen Tran

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.

1H NMR Spectroscopy as an Effective Method for Predicting Molecular Weight of Polyaminoamine Dendrimers and Their Derivatives

We established two formulas to predict molecular weight of polyaminoamine dendrimers and their alkylated derivatives, based on the theoretical number of protons at specific positions in the dendrimers and the true value of the integral values of these protons appearing in proton nuclear magnetic resonance spectra. Calculated results indicated that molecular weight of the dendrimers is approximately equal to results from mass spectrometry. Degrees of alkylation were easily calculated for each dendrimer-alkylated derivative. According to the obtained results, we confirm that the use of the proton spectra can be an effective method to predict molecular weight of dendrimers.

Preparation of the Cationic Dendrimer-Based Hydrogels for Controlled Heparin Release

We introduce a cationic polyamidoamine (PAMAM) dendrimers and tetronic (Te) based hydrogels in which precursor copolymers were prepared with simple methods. In the synthetic process, tyramine-conjugated tetronic (TTe) was prepared via activation of its four terminal hydroxyl groups by nitrophenyl chloroformate (NPC) and then substitution of tyramine (TA) into the activated product to obtain TTe. Cationic PAMAM dendrimers G3.0 functionalized with p-hydroxyphenyl acetic acid (HPA) by use of carbodiimide coupling agent (EDC) to obtain Den-HPA. 1H-NMR confirmed the amount of HPA and TA conjugations. The aqueous TTe and Den-HPA copolymer solution rapidly formed the cationic hydrogels in the presence of horseradish peroxidase enzyme (HRP) and hydrogen peroxide (H2O2) at physiological conditions. The gelation time of the hydrogels could be modulated ranging from 7 to 73 secs, when the concentrations of HRP and H2O2 varied. The hydrogels exhibited minimal swelling degree and low degradation under physical condition. In vitro cytotoxicity study indicated that the hydrogels were highly cytocompatible as prepared at 0.15 mg/mL HRP and 0.063 wt% of H2O2 concentration. Heparin release profiles show that the cationic hydrogels can sustainably release the anionic anticoagulant drug. The obtained results demonstrated a great potential of the cationic hydrogels for coating medical devices or delivering anionic drugs.

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.

Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs

In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, 1H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15-377.14kDa and around 60-180nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4.0-P123) exhibiting a higher drug loading efficiency (up to 76.25%) in comparison with another pluronics. Live/dead fibroblast cell staining assay mentioned that all conjugated nanocarriers are highly biocompatible. The drug-loaded nanocarriers also indicated a highly anti-proliferative activity against MCF-7 breast cancer cell. The obtained results demonstrated a great potential of the highly lipophilic pluronics-conjugated nanocarriers in hydrophobic drugs delivery for biomedical applications.

Preparation of silver core-chitosan shell nanoparticles using catechol-functionalized chitosan and antibacterial studies

AbstractIn this paper, we report the preparation and stabilization of colloidal silver nanoparticle solution, with the assistance of chitosan dihydroxyphenyl acetamide (CDHPA), or oligochitosan dihydroxyphenyl acetamide (OCDHPA). The structure of the chitosan derivatives were characterized by nuclear magnetic resonance (1H NMR) spectroscopy. The morphology of the synthesized silver core-chitosan shell nanoparticles were observed by transmission electron microscopy (TEM) and X-ray diffraction (XRD) techniques, and showed a well-defined core-shell structure of polymer-coated silver nanoparticles (AgNPs). The core-shell NPs exhibited a strong antibacterial activity against E. coli and S. aureus, at a very low concentration of AgNPs (2.5 ppm). Our studies offer a new method for the preparation and protection of silver nanoparticles for antibacterial applications.

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.

Synergistic effect of citrate dispersant and capping polymers on controlling size growth of ultrafine copper nanoparticles

In this paper, we studied the synergistic effect of sodium citrate dispersant and polyvinylpyrrolidone or polyvinylalcol capping polymer on controlling the size of copper nanoparticles (CuNPs) that were prepared by the chemical reduction method. The CuNPs were characterised by using ultraviolet–visible (UV–Vis) spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. The size of the nanoparticles could be predicted via their UV–Vis absorbance. In the presence of capping polymers, the size of CuNPs was significantly changed, ranging from 2 ± 1 to 20 ± 7 nm with and without sodium citrate dispersant, respectively. Moreover, surface plasmon resonance of ultrafine CuNPs (2 nm in diameter) could be observed in the short wavelength region by using UV–Vis spectra. Our finding, could offer a new synthetic approach to the production of highly stable, small-sized CuNPs.

Aquated cisplatin and heparin-pluronic nanocomplexes exhibiting sustainable release of active platinum compound and NCI-H460 lung cancer cell antiproliferation

Abstract In recent decades, platinum compounds have been many contributions in medicine. Development of new drugs from the active platinum compounds as well as nanocarriers for targeted delivery and reducing side effects of the drugs has paid much attention. In the study, nanocomplexes were prepared from aquated species of cisplatin and pluronic-conjugated heparin which distributed in the range of 80–100 nm by Transmission Electron Microscopy and 134 nm by Dynamic light scattering (DLS). Formation of the complex was confirmed by FTIR and DLS. The nanocomplexes exhibited high drug-loading capacity (approximately 42.5% wt/wt at 37 °C and 37.5% wt/wt at 25 °C). In vitro, drug-loaded nanogels showed much slower release profiles of cisplatin CDDP in pH 7.4 (physiological pH) compared with pH 5.5 condition at 37 °C. Moreover, the cytotoxicity assay results also indicated that Hep-F127 was cytocompatible; meanwhile, CDDP-loaded nanocomplex was able to reduce the cytotoxic ability of free CDDP (IC50 = 5.68 ± 0.73 μg/ml), which still maintain a significantly antiproliferative activity on NCI-H460 lung cancer cell. The in vitro preliminarily obtained results indicate that the nanocomplex is a candidate for CDDP delivery which can be studied further in cancer therapy.