Yihua Yin

Encapsulation and controlled release of hydrophilic pesticide in shell cross-linked nanocapsules containing aqueous core.

In this study, amphiphilic biocopolymers, synthesized by mixing azidobenzaldehyde (Az) and an aqueous solution of carboxymethyl chitosan (CMCS), which self-assemble into nanocapsules with a aqueous core (ACN) in aqueous media followed by photo-cross-linking to obtain shell cross-linked nanocapsules, were used to develop a controlled release pesticide system. The system was characterized by TEM and DLS. Its encapsulation efficiency was determined. The obtained result showed that it is efficient to encapsulate methomyl reaching encapsulation efficiency as high as 90% in an aqueous medium at pH 4.0, which is mainly attributed to the hydrogen bonding adsorption between methomyl molecules and the inner surface of nanocapsules. Release profiles of methomyl from methomyl-loaded nanocapsules in an aqueous solution at pH 6.0 were shown to be diffusion controlled with a half-release time (t(½)) of 36.3-69.5h from different samples. The shell cross-linking and its degree of cross-linking are assumed to be responsible for this diffusion behavior. The insecticidal activity test in laboratory showed that the control efficacy of methomyl-loaded nanocapsules against the armyworm larvae was significantly superior to the original. The relative control efficacy still maintained 100% over 7 days.

pH/redox responsive core cross-linked nanoparticles from thiolated carboxymethyl chitosan for in vitro release study of methotrexate.

A novel amphiphilic thiolated carboxymethyl chitosan was synthesized. It self-assembled into disulfide bond cross-linked nanoparticles in deionized water. The TEM showed that these nanoparticles had a core-shell structure with an average diameter of 160 nm. Dynamic light scattering showed that the nanoparticles were stable in water solution. The particle size changed with pH values and GSH concentrations, and reached a maximum diameter at pH 7.0 and 20mM GSH respectively, exhibiting an obvious pH/redox responsibility. Methotrexate was encapsulated in nanoparticles reaching encapsulation efficiency as much as 43.4%. Release profiles of methotrexate showed a release rate of 19 wt% in pH 7.4 buffer containing 10 μM GSH, whereas as high as 93 wt% in pH 5.0 buffer containing 20mM GSH, indicating that the nanoparticles may be used for tumor-specific drug release. The anticancer activity test in vitro showed that the inhibition rate of methotrexate-loaded nanoparticles against HeLa cells reached 90%.

Photo-responsive shell cross-linked micelles based on carboxymethyl chitosan and their application in controlled release of pesticide

An amphiphilic carboxymethyl chitosan conjugate with photolabile 2-nitrobenzyl side groups (NBS-CMCS) was synthesized, which could self-assemble into polymeric micelles in aqueous condition following by adding dropwise dialdehyde to form a cross-linking structure. TEM and (1)H NMR confirmed that the cross-linked micelles had a core-shell configuration with an average diameter of 140 ± 5.5 nm. DLS and TEM observations showed that the cross-linked micelles were stable in aqueous solution at pH 7.0 without light irradiation, while they could transfer into nanocapsules upon exposure to 365 nm UV light. Diuron, a photosynthetic inhibitor, was encapsulated in the cross-linked micelles reaching encapsulation efficiency as much as 91.9%. No release of the encapsulated diuron was detected without light, whereas a release rate as high as 96.8% over 8h at pH 7.0 buffer was observed under solar stimulated irradiation, indicating that the cross-linked micelles may be used as a photo-controlled sustained release carrier for the delivery of photosynthetic inhibitor.

Preparation, characterization and in vitro release study of a glutathione-dependent polymeric prodrug Cis-3-(9H-purin-6-ylthio)-acrylic acid-graft-carboxymethyl chitosan.

In this work, an amphiphilic polymeric prodrug Cis-3-(9H-purin-6-ylthio)-acrylic acid-graft-carboxymethyl chitosan (PTA-g-CMCS) was designed and synthesized. In aqueous solution, this grafted polymer can self-assemble into spherical micelles with a size ranging from 104 to 285 nm and zeta potential ranging from -12.3 to -20.1 mV. For the release study, less than 24% of 6-Mercaptopurine (6-MP) was released from PTA-g-CMCS1 in the media containing 2 and 100 μM glutathione (GSH), whereas 37%, 54% and 75% of 6-MP was released from the media with GSH of 1, 2 and 10mM, respectively. Besides, pH and drug content of the polymeric prodrug only presented slight influence on the 6-MP release. MTT assay demonstrated that this system had higher inhibition ratio on HL-60 cells (human promyelocytic leukemia cells) in the presence of GSH and lower cytotoxicity on mouse fibroblast cell line (L929). Therefore, this nano-sized system is glutathione-dependent, and it can be employed as a potential carrier for the controlled release of 6-MP.

Preparation, characterization and properties of aminoethyl chitin hydrogels

Aminoethyl chitins (AEC) with different amino contents were synthesized from chitin and 2-chlorethylamine hydrochloride, and the AEC hydrogels were prepared by crosslinking with glutaraldehyde. The microstructures, swelling behaviors and antibacterial activities of the hydrogels were investigated. The results of Fourier transform infrared spectroscopy (FTIR), (1)H nuclear magnetic resonance ((1)H NMR) spectrum and scanning electron microscopy (SEM) showed that the hydrogels were prepared by forming the Schiff base from AEC and glutaraldehyde. The aminoethyl chitin hydrogels were sensitive to acidic environment. The swelling ratio changed with the amino content of AEC, declined with the increase of the crosslinking agent concentration and increased with the increase of the AEC concentration. In addition, the antibacterial results of the hydrogels against Staphylococcus aureus (S. aureus) indicated that the hydrogels had good antibacterial activities, and the antibacterial properties were affected by the amino content of AEC and the crosslinking agent concentration.

Preparation and antibacterial properties of O-carboxymethyl chitosan/lincomycin hydrogels.

Abstract In this study, O-carboxymethyl chitosan (O-CMCS) was synthesized from chitosan and monochloroacetic acid. Then O-CMCS hydrogel was prepared by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in which the lincomycin was packaged. The Fourier transform infrared spectrum and scanning electron microscopy were adopted to characterize the structure and morphology of the product. The influences of dosage of EDC/NHS and concentration of O-CMCS on the swelling properties of the hydrogels were investigated. The hydrogels performed good swelling capacities and obvious pH-sensitive properties. The antibacterial activities of the hydrogels were tested against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Compared with pure O-CMCS hydrogels, the antibacterial activities of O-CMCS/lincomycin hydrogels were significantly improved with the increase in the concentration of lincomycin against E. coli and S. aureus. With the increase in dosage of crosslinking agent or concentration of O-CMCS, the antibacterial activities both decreased gradually against the two bacteria. O-CMCS/lincomycin hydrogel was expected to be used for antibacterial material in view of its significant antibacterial activities.

Preparation and properties of novel hydrogel based on chitosan modified by poly(amidoamine) dendrimer.

Currently, chitosan (CTS) or chitosan derivatives hydrogels are applied in different fields, such as biological materials, medical materials and hygiene materials. In this study, novel chitosan hydrogels were successfully prepared by chitosan and poly(amidoamine) (PAMAM) dendrimer with glutaraldehyde serving as a cross-linking agent. Fourier transform infrared spectroscopy (FTIR), (1)H nuclear magnetic resonance ((1)H NMR) and gel permeation chromatography (GPC) were performed to characterize PAMAM. The structure and morphology of hydrogels were characterized by FTIR, thermo gravimetry analysis (TGA), and scanning electron microscopy (SEM). The swelling properties of the hydrogels were investigated in solutions of pH 1.0 and 7.4. The hydrogels showed good swelling capacities and pH-sensitive swelling properties. Besides, the antibacterial activities of the hydrogels against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were tested by optical density. Compared with the pure chitosan hydrogel, their antibacterial activities were significantly improved with the increase in the blending ratio of PAMAM. And with the increase in cross-linking agent and concentration of CTS, the antibacterial activities increased firstly and then slightly decreased. The hydrogel was expected to be a novel antibacterial material.

Preparation, characterization, and in vitro drug release behavior of glutathione-sensitive long-circulation micelles based on polyethylene glycol prodrug

Abstract In this paper, a kind of glutathione-sensitive polymeric micelles was prepared through assembling in aqueous solution of an amphiphilic polymeric prodrug which was synthesized by linkage of 6-mercaptopurine (6-MP) and polyethylene glycol monomethyl ether using propiolic acid as a connecting arm. The glutathione (GSH)-sensitive strategy is based on a Michael addition–elimination reaction, that is the amphiphilic polymeric prodrug which contains α, β-unsaturated carbonyl group acts as a Michael acceptor to receive the attack of nucleophile – glutathione, and undergoes elimination reaction to release the original drug. Transmission electron microscope observation showed that the polymeric micelles (PMs) had a spherical-like morphology with a mean diameter of 28 ± 3.2 nm. The dynamic light scattering investigation data exhibited that the size and distribution changes of PMs are negligible after being placed for 15 days. In vitro drug release study indicated that only less than 13% of 6-MP was released from the micelles under GSH stimulation at micromolar level, while 34.5, 53.7, and 77.8% accumulative release rates were achieved under GSH stimulation at millimolar level (1, 2 and 10 mM), respectively. The cell inhibition rate of PM solution against HL-60 cells carried out by MTT method reached 85%. The cellular uptake and the intracellular drug release of PMs in HL-60 cells were observed through determining the intracellular 6-MP content by UV–vis spectrophotometer. In vitro macrophage uptake study showed a low phagocytosis rate, indicating the long-circulation ability of the PMs.

Preparation, characterization, and in vitro efficacy of O-carboxymethyl chitosan conjugate of melphalan

A series of melphalan-O-carboxymethyl chitosan (Mel-OCM-chitosan) conjugates with different spacers were prepared and structurally characterized. All conjugates showed satisfactory water-solubility (160-217 times of Mel solubility). In vitro drug release behaviors by both chemical and enzymatic hydrolysis were investigated. The prodrugs released Mel rapidly within papain and lysosomal enzymes of about 40-75%, while released only about 4-5% in buffer and plasma, which suggested that the conjugates have good plasma stability and the hydrolysis in both papain and lysosomes occurs mostly via enzymolysis. It was found that the spacers have important effect on the drug content, water solubility, drug release properties and cytotoxicity of Mel-OCM-chitosan conjugates. Cytotoxicity studies by MTT assay demonstrated that these conjugates had 52-70% of cytotoxicity against RPMI8226 cells in vitro as compared with free Mel, indicating the conjugates did not lose anti-cancer activity of Mel. Overall these studies indicated Mel-OCM-chitosan conjugates as potential prodrugs for cancer treatment.

A novel melphalan polymeric prodrug: preparation and property study.

The clinical application of melphalan (Me), an anticancer drug for the treatment of hematologic malignancies, has been limited due to its poor water solubility, rapid elimination and lack of target specificity. To solve these problems, O,N-carboxymethyl chitosan-peptide-melphalan conjugates were synthesized and characterized. All polymeric prodrugs showed satisfactory water solubility. It was found that the molecular weight of O,N-carboxymethyl chitosan (O,N-CMCS) and the peptide spacer played a crucial role in controlling the drug content, diameter and drug release properties of O,N-carboxymethyl chitosan-peptide-melphalan conjugates. The studies of in vitro drug release and cell cytotoxicity by MTT assay revealed that, employing the polymeric conjugation strategy and using the peptides glycylglycine (Gly-Gly) as a spacer, the conjugates have good cathepsin X-sensitivity and lower toxicity and the drug release behavior improved remarkably. In conclusion, O,N-carboxymethyl chitosan-peptide-melphalan conjugates could be promising prodrugs for anticancer application.