Nanoparticles based on phenylalanine ethyl ester-alginate conjugate as vitamin B2 delivery system.

Phenylalanine ethyl ester (PAE)-alginate (Alg) conjugate (PAE-Alg, PEA) was synthesized and formation of an amide bond between PAE and Alg was confirmed by Fourier transformed-infrared and (1)H nuclear magnetic resonance spectroscopy. The degree of PAE substitution was 3.5-4.7 (PAE group per hundred sugar residues of Alg) which was determined by elemental analysis. The critical aggregation concentration values determined for PEA conjugates PEA1, PEA2, and PEA3 were 0.20, 0.12, and 0.10 mg/ml, respectively. The particle size of PEA nanoparticles (PEA-NPs) decreased from 425 nm to 226 nm with the increasing degree of PAE substitution. Vitamin B2 (VB2), as a model nutrient, was encapsulated into the nanoparticles. The drug-loading content increased with increasing degree of PAE substitution. The maximum VB2 loading capacity and loading efficiency of PEA3 nanoparticles were 3.53 ± 0.03% and 91.48 ± 0.80%, respectively. The in vitro release behavior of VB2 from the PEA-NPs showed a biphasic release profile with an initial burst release of about 40-50% of VB2 in the first 10 h followed by a steady and continuous release phase for the following 50 h in PBS, pH 7.4. The human colorectal carcinoma cell line was used to investigate the cytotoxicity of PEA-NPs. Our results showed that various concentrations of nanoparticles did not cause significant cytotoxicity against cell lines at normal concentrations.

Preparation and characteristics of chitosan microspheres in different acetylation as drug carrier system.

Chitosan microspheres (CM) and reacetylated chitosan microspheres (ACM) were successfully made by the methods of oil/water emulsification and acetic anhydride. The characteristics of the microspheres as a drug carrier system were investigated. Two microsphere samples had spherical shape with the mean diameter of 80.79 microm for CM and 81.25 microm for ACM. The in vitro degradation (pH 7.4) in the presence of lysozyme showed a slow mass loss and ACM was higher degradation compared to CM. The microspheres, especially ACM, had a high drug loading capacity of Adriamycin hydrochloride (ADM) (12.4%) and had sustained release. The cytotoxicity was evaluated in vitro via MTT assay, ACM with steadily continual adhesion to cells had no fibroblast cytotoxicity. The inhibitory rates of ADM-loading CM, ACM suspension to Tca 8113 cells were significantly outperformed that of ADM solution.

[Low-grade fibromyxoid sarcoma: a clinicopathological analysis of 9 cases].

OBJECTIVE: To study the clinicopathological features, immnophenotype and differential diagnosis of low-grade fibromyxoid sarcoma (LGFMS). METHODS: The clinical, radiological and pathological features of 9 cases of LGFMS were reviewed. RESULTS: The patients consisted of six males and three females with ages ranging from 11 to 65 years (mean 31.4 years). Clinically, most cases presented as slowly growing painless masses located in the extremities, trunk and neck. Two cases had a history of a rapid recent enlargement. Three cases presented with recurrent diseases after incomplete resection. Ultrasound showed heterogeneous signal. Precontrast CT and T1-weighted MRI showed a nodular mass of low to isodensity, while contrast-enhanced CT and T2-weighted MRI demonstrated contrasting zonal areas of hypo/hyperintensity. The tumors measured 3 to 16 cm (mean 7.7 cm), with a fibrous to myxoid appearance on cut surface. Histologically, they were composed of alternating collagenous and myxoid areas. A transition between the two areas could be identified. Giant rosette-like structures were observed in 3 cases. The center of the giant rosettes was composed of eosinophilic collagen, which showed centrifugal in arrangement. There was also gradual transition between the giant rosettes and the fibromyxoid component. On high magnification, the tumor was composed of ovoid to spindle-shaped cells with hyperchromatic nuclei. Nuclear atypia was inconspicuous. The tumor cells were arranged mostly in interlacing fascicles or whorls. Vessels were not prominent and necrosis was absent. Immunohistochemically, the tumor cells showed unique staining for vimentin, consistent with a fibroblastic differentiation. CONCLUSIONS: LGFMS is a distinctive low grade fibroblastic sarcoma of young adults. Recognizing the characteristics of the rare entity may help to avoid misdiagnosis. Wide local excision is recommended to avoid local recurrences.

Biological evaluation of a novel chitosan-PVA-based local delivery system for treatment of periodontitis.

In the study, we intend to design a suitable localized drug delivery system (LDDS) with chitosan and poly vinyl alcohol (PVA) for treating serve periodontitis. For that, a novel formulation based on the incorporation of chitosan-based microspheres into PVA film was prepared. As the core parts of the novel formulation, chitosan-based microspheres were prepared form chitosan and/or carboxymethyl-chitosan (CM-chitosan) by using water-in-oil emulsification method. Then basic in vitro and in vivo experiments focusing on biocompatibility and biodegradability of the two chitosan-based microspheres were carried out to evaluate the feasibility of the novel LDDS. In vitro tests, besides having no hemolysis, chitosan microsphere (Cs1-Ms), and CM-chitosan microsphere (Cs2-Ms) have adsorbed little proteins on their surfaces. Moreover, plasma proteins adsorbed on Cs2-Ms, most of which can easily desorbed, are much less than that adsorbed on Cs1-Ms. This indicates that Cs2-Ms perhaps has better biocompatibility than Cs1-Ms. In vivo tests, Cs1-Ms and Cs2-Ms were subcutaneously implanted in rat to investigate the host tissue inflammatory response. Implantations of Cs1-Ms and Cs2-Ms induced a little more severe inflammation when compared with the implantation of PVA film. However, the difference on in vivo biocompatibility between Cs1-Ms and Cs2-Ms could not be confirmed by the implantation model of our experiments. Both Cs1-Ms and Cs2-Ms had suffered bioerosion when they were subcutaneously implanted. The hard and compact matrixes of Cs1-Ms were degraded very slowly, and only some trifling degradation had been found until 4 weeks of implantation. In contrast, Cs2-Ms is soft and more hydrophilic, and can be quickly degraded in a form of diffluence by the physiological circumstance. All these results suggested that Cs2-Ms had better potentials used as core parts of the novel designed LDDS in the future developments.

Antibacterial mechanism of chitosan microspheres in a solid dispersing system against E. coli.

In this study, we investigated the antibacterial mechanism through the interfacial contacting inhibition behaviors of chitosan antimicrobials against Escherichia coli in solid dispersing state. Chitosan microspheres (CMs) were prepared by emulsification cross-linking reaction, and oleoyl-CMs (OCMs) were obtained by introduction of oleoyl groups to the chitosan. The CMs were with smooth surface and spherical shape of diameter of about 124 microm. The antibacterial activity was directly proportional to the concentration and the hydrophobic property of CMs. The fluorescence experiments indicated CMs had influenced the structure of membrane, especially the OCMs were speculated to interact with proteins on the cell membrane. SEM photographs showed E. coli adhered to the surface of the CMs and provided evidences for the disruption of the cells, while the bacterium conglomerated on the surface of the OCMs. The CMs changed the permeability of membrane and caused cellular leakage that correlated with the hydrophobic interaction between CMs and cytoplasmic membrane phospholipids of Gram-negative bacteria. Solid dispersing system makes the antibacterial activities of CMs counted as a sequent event-driven to study the antibacterial mechanism of chitosan originally.

Plasma protein adsorption pattern and tissue-implant reaction of poly(vinyl alcohol)/carboxymethyl-chitosan blend films.

Various poly(vinyl alcohol)/carboxymethyl-chitosan (PVA/CMCS) blend films were prepared by a mechanical blending method and characterized by SEM for their surface and cross-section morphologies. It indicated that blending high CMCS content in PVA plastic led to a rough surface and loose structure. Bovine serum albumin (BSA) and bovine fibrinogen (BFG) were chosen as representative plasma proteins to carry out adsorption tests. Equilibrium adsorption amount of proteins onto the blends decreased with the increase of CMCS content in film matrix, and BSA was more easily adsorbed onto the films than BFG in the same conditions. The blend films also exhibited different trends for BSA and BFG adsorption when pH of the media changed, but maximum adsorption approximately occurred at the isoelectric point of proteins. Moreover, increasing the ionic strength would always decrease the adsorptions of protein onto the films. In animal experiments, it was found that incorporation of CMCS and PVA gave a lower tissue reaction than pure PVA films when they were subcutaneously implanted in Wistar rats. After two weeks subcutaneous implantation, surfaces of PVA became wrinkled and cracked; however, the blend implants exhibited a alveolate porous microstructure.

Preparation and blood coagulation evaluation of chitosan microspheres.

Cross-linked chitosan microspheres (40-100 microm) with smooth surface were prepared by the methods of emulsification and ethanol coagulant. FTIR results showed that the cross-linking reaction occurred on the amino groups of chitosan molecules. The swelling characteristic of chitosan microspheres was influenced by the environment pH, being generally greater at low rather than higher pH values. The coagulation properties of chitosan microspheres were evaluated by dynamic blood clotting, platelet adhesion and activation, erythrocyte adhesion, hemolysis, and protein absorption assays. Chitosan microspheres can shorten the clotting time and induce the adhesion and activation of platelets. But the shortening of clotting time by chitosan microspheres may be related to not only platelet aggregation, but also erythrocyte aggregation. Take together, chitosan microspheres may be potential use as thrombospheres.

Cellulose acetate/chitosan multimicrospheres preparation and ranitidine hydrochloride release in vitro.

A noval cellulose acetate/chitosan multimicrospheres (CACM) was prepared by the method of w/o/w emulsion. The concentration of cellulose acetate (CA) and the ratio of CA/chitosan (CS) had influence on the CACM size, and appearance. Ranitidine hydrochloride loading, and releasing efficiency in vitro were investigated. The optimal condition for preparation of the microspheres was CA concentration at 2% and the ratio of CA/CS at 3/1. The microspheres size was 200-350 microm. The appearance of microspheres was spherical, porous, and nonaggregated. The highest loading efficiency was 21%. The ranitidine release from the CACM was 40% during 48 hr in buffers.