Effect of "phase change" complex on postoperative adhesion prevention.

BACKGROUND: Postsurgical peritoneal adhesion is a major clinical problem. Numerous anti-adhesion products have been studied, but none could be easily used to provide a physical barrier. In this study, we developed a "phase change" anti-adhesion barrier for reducing peritoneal adhesion by cross-linked copolymerization of O-carboxymethyl chitosan (CMC) and CaCl2 and addition of cyclosporin A (CsA). MATERIALS AND METHODS: The CMC-CaCl2-CsA compound was characterized by equilibrium swelling rate, weight loss, releasing effect, and coagulation test, and its biosafety was characterized by acute oral toxicity, hemolysis, and cytotoxicity. Intestinal adhesion model was applied on 64 Sprague-Dawley rats, which received CMC, CMC-CaCl2, or CMC-CaCl2-CsA treatment. At postoperative days 7 and 14, the rats were euthanized, and adhesions were graded by an investigator blinded to the treatment groups, using a predetermined adhesion scoring system. The cecum and adhesion tissue were stained with hematoxylin and eosin and antibodies for matrix metalloproteinase-9 and TIMP-1 for further histopathologic examination. RESULTS: The phase change anti-adhesive material exhibited effective blood clotting and were nontoxic in clotting experiments and acute toxicity test. The degradation rate could be adjusted using phosphate-buffered solution with varying pH. Adhesions were significantly reduced in the CMC-CaCl2-CsA treatment group compared with the control group (P < 0.001). Expression of matrix metalloproteinase-9 was stronger in CMC-CaCl2-CsA treatment group at 7 days after surgery. CONCLUSIONS: "Phase-change" adhesive can undergo changes after application, and it inhibits the formation of abdominal adhesions after surgery. The material is convenient for using by surgeons and provides an effective tool for intestinal adhesion prevention.

Fabrication of Waterproof, Breathable Composite Liquid Dressing and Its Application in Diabetic Skin Ulcer Repair.

OBJECTIVES: Diabetic patients are at increased risk of severe skin infections. Covering the wound as early as possible can prevent infection and shorten the course of treatment. In this study, the authors fabricated a waterproof and breathable composite liquid dressing (CLD) that formed a barrier to bacteria and shortened healing time of diabetic rat skin ulcers. METHODS: The CLD was prepared in a formulation that, on evaporation of the liquid carrier, acts as a waterproof, breathable coating on injured skin. The coating was analyzed for water resistance, moisture vapor transmission rate (MVTR), bacterial barrier properties, sustained-release function, and biosafety. A chemically induced rat model of diabetic foot ulcers was used to examine the wound healing effect of CLD and CLD that contained Dermlin (Yensen Biotech Co, Jiangyin, Jiangsu, China). The wound healing rate, histologic changes, and epidermal growth factor expression were also evaluated. RESULTS: The CLD functioned as an effective barrier against infection, was waterproof, had a suitable MVTR, and had effective biosafety. The synergistic effects of CLD and Dermlin had a rapid wound closure rate. Histologic analysis and measurement of epidermal growth factor expression through an in vivo test revealed that the possible mechanism of the CLD effects included the reduction of inflammation and promotion of cell proliferation. CONCLUSIONS: Early treatment with the CLD can prevent infection. In combination with Dermlin, the CLD may promote better wound closure in diabetic skin ulcers. The authors' study suggests a novel strategy for ulcer healing.

[Biological characteristics and osteogenic differentiation of magnesium-doped nanoporous titanium coating].

PURPOSE: Bioactive magnesium ions were successfully incorporated into the nanoporous titanium base coating by micro-arc oxidation(MAO), and its physical properties and osteogenic effects were explored. METHODS: Non-magnesium-containing and magnesium-containing titanium porous titanium coatings(MAO, MAO-mg) were prepared by changing the composition of MAO electrolyte and controlling the doping of magnesium in porous titanium coatings. The samples were characterized by scanning electron microscope (SEM), roughness, contact angle and energy dispersive X-ray spectrometer (EDS). Mg2+ release ability of magnesium-doped nanoporous titanium coatings was determined by inductively coupled plasma/optical emission spectrometer(ICP-OES). The structure of the cytoskeleton was determined by live/dead double staining, CCK-8 detection of material proliferation-toxicity, and staining of ß-actin using FITC-phalloidin. The effects of the coating on osteogenic differentiation in vitro were determined by alizarin red (ARS), alkaline phosphatase (ALP) staining and real-time polymerase chain reaction (qRT-PCR). SPSS 25.0 software package was used for statistical analysis. RESULTS: The MAO electrolyte with magnesium ions did not change the surface characteristics of the porous titanium coating. Each group prepared by MAO had similar microporous structure(P＞0.05). There was no significant difference in surface roughness and contact angle between MAO treatment group (MAO, MAO-mg)(P＞0.05), but significantly higher than that of Ti group (P＜0.05). With the passage of cell culture time, MAO-mg group promoted cell proliferation (P＜0.05). MAO-mg group was significantly higher than other groups in ALP and ARS staining. The expression of Runx2 mRNA (P＜0.05), ALP(P＜0.05) and osteocalcin OCN(P＜0.05) in MAO-mg group was significantly higher than that in Ti and MAO groups. CONCLUSIONS: MAO successfully prepared magnesium-containing nanoporous titanium coating, and showed a significant role in promoting osteogenic differentiation.

[Study on extraction and purification technology of Hubei ophiopogon saponins].

OBJECTIVE: To explore the extraction and purification technology of total saponins from the effective parts of Liriope spicata. METHODS: Orthogonal design was used. Macroporous resin was selected to separate and purify total saponin from the effective parts of Liriope spicata. The process validation was conducted. The total saponins was determined by Ultraviolet Spectrophotometry. RESULTS: The optimal extraction conditions were as follows: 10 times the amount of ethanol (70%) for each occasion and hot reflux (3 x 2 h). Total saponins was purified by D101 macroporous resin. The concentration of eluting ethanol was 50% - 70%. Ethanol (70%) was selected as the best eluent. The result of process validation was consistent with the study. CONCLUSION: The process is simple and stable enough to significantly improve the extraction rate of the effective parts. The study can provide reference for the research and production of effective parts of traditional Chinese medicine such as Liriope spicata.

[Construction of a multiple-scale implant surface with super-hydrophilicity].

OBJECTIVE: To construct a multiple-scale organized implant surface with super-hydrophilicity. METHODS: The SiC paper polished titanium disc was sandblasted and treated with HF/HNO3 and HCl/H2SO4, then acid-etched with H2SO4/H2O2. The physicochemical properties of the surfaces were characterized by scanning electron microscope, static state contact angle and X-ray diffraction. MC3T3-E1 cells were used to evaluate the effects of the surface on the cell adhesion, proliferation and differentiation. RESULTS: The acid-etching process with a mixture of H2SO4/H2O2 superimposed the nano-scale structure on the micro-scale texture. The multiple-scale implant surface promoted its hydrophilicity and was more favorable to the responses of osteoprogenitor cells, characterized by increased DNA content, enhanced ALP activity and promoted OC production. CONCLUSION: A multiple-scale implant surface with super-hydrophilicity has been constructed in this study, which facilitates cell proliferation and adhesion.

Surgical resection of a huge cemento-ossifying fibroma in skull base by intraoral approach.

Cemento-ossifying fibroma, also known as ossifying fibroma, usually occurs in the mandible and less commonly in the maxilla. The huge example in the skull base is even rare. We present a case of a huge cemento-ossifying fibroma arising below the skull base of a 30-year-old woman patient. Radiologic investigations showed a giant, lobulated, heterogeneous calcified hard tissue mass, which is well circumscribed and is a mixture of radiolucent and radiopaque, situated at the rear of the right maxilla to the middle skull base. The tumor expands into the right maxillary sinus and the orbital cavity, fusing with the right maxilla at the maxillary tuberosity and blocking the bilateral choanas, which caused marked proptosis and blurred vision. The tumor was resected successfully by intraoral approach, and pathologic examination confirmed the lesion to be a cemento-ossifying fibroma. This case demonstrates that cemento-ossifying fibroma in the maxilla, not like in the mandible, may appear more aggressive because the extensive growth is unimpeded by anatomic obstacles and that the intraoral approach can be used to excise the tumor in the skull base.

Safety, tolerability, and mechanisms of antiretroviral activity of pegylated interferon Alfa-2a in HIV-1-monoinfected participants: a phase II clinical trial.

BACKGROUND: To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection. METHODS: Untreated HIV-1-infected volunteers without HCV infection received 180 microg of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferon-inducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed. RESULTS: Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/microL (90% CI, -95 to 85 cells/microL), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]). CONCLUSION: Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.

Knockdown of ectodysplasin-A receptor-associated adaptor protein exerts a tumor-suppressive effect in tongue squamous cell carcinoma cells.

Tongue squamous cell carcinoma (TSCC) is a common malignancy in oral cancer with a high mortality and morbidity. The ectodysplasin-A receptor-associated adaptor protein (EDARADD) is a death domain-containing adaptor protein that interacts with the TNF family ligand ectodysplasin A receptor. It is known that EDARADD has an effect on the development of ectodermal derivative tissues, such as hair and teeth. EDARADD expression is also associated with the development of melanoma. However, the role of EDARADD in TSCC remains unknown. The aim of the present investigation was to explore whether EDARADD plays a role in the biological function of TSCC. Immunohistochemistry was used to measure the expression of EDARADD in TSCC tissues and adjacent normal tissue. EDARADD was knocked down in a TSCC cell line in vitro using a specific lentivirus. The expression level of the EDARADD gene and the efficacy of gene knockdown were evaluated by reverse transcription-quantitative PCR, while EDARADD protein expression and the expression levels of Bcl-2, MYC and NF-κBp65 were determined by western blotting. Additionally, MTT assays, colony formation assays and apoptosis assays were carried out to examine the effect of EDARADD knockdown on the TSCC cells. A previous study showed that the majority of the TSCC tissues that were tested had high EDARADD expression. The expression of EDARADD both at mRNA and protein levels was significantly lower (P<0.01) after the gene was knocked down in the CAL27 cells compared with the level in control cells. Downregulation of EDARADD expression inhibited colony formation and proliferation and induced apoptosis of CAL27 cells when compared to control cells (P<0.01). Taken together, these results suggested that EDARADD may be actively involved in the progression of TSCC and that EDARADD may be a novel therapeutic target for the treatment of TSCC.

Evaluation of a two-stage antibacterial hydrogel dressing for healing in an infected diabetic wound.

Various types of wound dressings have been used to treat complex infections in diabetes mellitus. This study is the first to evaluate the healing effects using a two-stage dressing in infected diabetic wounds. A two-stage antibacterial hydrogel dressing (two-stage dressing) was established with two time phases, an antibacterial phase and a drug release phase. We established each phase by using a swelling and rate of drug release test. These results suggested that the antimicrobial phase is activated as soon as the two-stage dressing attaches to the skin. The drugs in the drug release layer of the dressing were released to a greater extent than expected 20-36 h after attachment to the skin, likely due to extensive water absorption. Histological analysis and measurement of vascular endothelial growth factor expression through in vivo testing suggested that the benefits of a two-stage dressing include rapid antibacterial properties, sustained drug release, and promotion of wound healing through cell proliferation as compared with the traditional composite antibacterial hydrogel dressing. Further in vivo tests confirmed that separation of the antibacterial and drug-releasing properties, along with biocompatibility and rapid wound closure rates made two-stage dressings suitable for healing of infected wounds. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1808-1817, 2017.

A novel platform designed by Au core/inorganic shell structure conjugated onto MTX/LDH for chemo-photothermal therapy.

A novel platform making up of methotrexate intercalated layered double hydroxide (MTX/LDH) hybrid doped with gold nanoparticles (NPs) may have great potential both in chemo-photothermal therapy and the simultaneous drug delivery. In this paper, a promising platform of Au@PDDA-MTX/LDH was developed for anti-tumor drug delivery and synergistic therapy. Firstly, Au NPs were coated using Layer-by-Layer (LbL) technology by alternate deposition of poly (diallyldimethylammonium chloride) (PDDA) and MTX molecules, and then the resulting core-shell structures (named as Au@PDDA-MTX) were directly conjugated onto the surface of MTX/LDH hybrid by electrostatic attraction to afford Au@PDDA-MTX/LDH NPs. Here MTX was used as both the agent for surface modification and the anti-tumor drug for chemotherapy. The platform of Au@PDDA-MTX/LDH NPs not only had a high drug-loading capacity, but also showed excellent colloidal stability and interesting pH-responsive release profile. In vitro drug release studies demonstrated that MTX released from Au@PDDA-MTX/LDH was relatively slow under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. Furthermore, the combined treatment of cancer cells by using Au@PDDA-MTX/LDH for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy.

[Correlation of Persistent Free Radicals, PCDD/Fs and Metals in Waste Incineration Fly Ash].

Environmentally persistent free radicals (EPFRs) are relatively highly stable and found in the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Recent studies have concentrated on model dioxin formation reactions and there are few studies on actual waste incineration fly ash. In order to study EPFRs and the correlation with dioxins and heavy metals in waste incineration fly ash, the spins of EPFRs, concentration of PCDD/Fs and metals in samples from 6 different waste incinerators were detected. The medical waste incineration fly ash from Tianjin, municipal solid waste incineration fly ash from Jiangxi Province, black carbon and slag from municipal solid waste incinerator in Lanxi, Zhejiang Province, all contained EPFRs. Above all the signal in Tianjin sample was the strongest. Hydroxyl radicals, carbon-center radicals and semiquinone radicals were detected. Compared with other samples, Jiangxi fly ash had the highest toxic equivalent quantity (TEQ) of dioxins, up to 7.229 4 ng · g⁻¹. However, the dioxin concentration in the Tianjin sample containing the strongest EPFR signals was only 0.092 8 ng · g⁻¹. There was perhaps little direct numeric link between EPFRs and PCDD/Fs. But the spins of EPFRs in samples presented an increasing trend as the metal contents increased, especially with Al, Fe, Zn. The signal strength of radicals was purposed to be related to the metal contents. The concentration of Zn (0.813 7% ) in the Tianjin sample was the highest and this sample contained much more spins of oxygen-center radicals. We could presume the metal Zn had a greater effect on the formation of EPFRs, and was easier to induce the formation of radicals with a longer half-life period.

[Degradation of PCDD/Fs by the Mixture of V2O5-WO3/TiO2 Catalyst and Activated Carbon].

The mixture of V2O5-WO3/TiO2 catalyst and two kinds of Activated Carbons (AC) (AC-1: based on lignite; AC-2: based on coconut shell) was used to destroy gas phase PCDD/Fs with high concentration (9. 80 ng.m-3, evaluated by international toxic equivalence quantity (I-TEQ) under low thermal temperature (160°C) based on a dioxin generating system. After mixing with AC, removal efficiency (RE) and destruction efficiency (DE) of PCDD/Fs increased by 20% compared with only catalyst condition. In comparison with mixture of AC based on coconut shell, mixture of AC based on lignite had lower RE-values and higher DE-values. The adjustments of the ratio of catalyst and AC could cause the different degradation effects, and RE-values increased and DE-values decreased with increasing proportions of catalyst. When the volume fraction of oxygen was 0% in experimental atmosphere, catalyst could lose its activity and most PCDD/Fs were not oxidized but adsorbed by the mixture. RE and DE-values increased with increasing content of oxygen. The addition of ozone (concentration of 200 mg.m-3) could improve catalytic oxidation effects to a certain degree. However, ozone might react with AC, which could influence the lifetime of the mixture. Under 200°C, the mixture with proportion of AC: catalyst = 1:1 and in the present of 200 mg.m-3 ozone conditions, the highest RE and DE-value were obtained with 98. 0% and 94. 8% respectively, and the concentration of PCDD/Fs residual in off-gas was only 0. 51 ng.m-3 evaluated by I-TEQ.

Methotrexate intercalated layered double hydroxides with the mediation of surfactants: Mechanism exploration and bioassay study.

Methotrexatum intercalated layered double hydroxides (MTX/LDHs) hybrids were synthesized by the co-precipitation method and three kinds of nonionic surfactants with different hydrocarbon chain lengths were used. The resulting hybrids were then characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). XRD and FTIR investigations manifest the successful intercalation of MTX anions into the interlayer of LDHs. TEM graphs indicate that the morphology of the hybrids changes with the variation of the chain length of the surfactants, i.e., the particles synthesized using polyethylene glycol (PEG-7) present regular disc morphology with good monodispersity, while samples with the mediation of alkyl polyglycoside (APG-14) are heavily aggregated and samples with the addition of polyvinylpyrrolidone (PVP-10) exhibit irregular branches. Furthermore, the release and bioassay experiments show that monodisperse MTX/LDHs present good controlled-release and are more efficient in the suppression of the tumor cells.

Facile synthesis of methotrexate intercalated layered double hydroxides: particle control, structure and bioassay explore.

To study the influence of particle size on drug efficacy and other properties, a series of methotrexate intercalated layered double hydroxides (MTX/LDHs) were synthesized through the traditional coprecipitation method, using a mixture of water and polyethylene glycol (PEG-400) as the solvent. To adjust the particle size of MTX/LDHs, the dropping way, the volume ratio of water to PEG-400 and different hydrothermal treatment time changed accordingly, and the results indicate that the particle size can be controlled between 90 and 140 nm. Elemental C/H/N and inductive coupled plasma (ICP) analysis indicated that different synthesis conditions almost have no effect on the compositions of the nanohybrids. X-ray diffraction (XRD) patterns manifested the successful intercalation of MTX anions into the LDH interlayers, and it's also found out that different volume ratios of water to PEG-400 and variable dropping way can affect the crystallinity of the final samples, i.e., the volume ratio of 3:1 and pH decreasing are proved to be optimum conditions. Furthermore, both antiparallel monolayer and bilayers adopting different orientations are suggested for four samples from XRD results. Fourier transform infrared spectroscopy (FTIR) investigations proved the coexistence of CO3(2-) and MTX anions in the interlayer of the nanohybrids. MTX/LDH particles exhibited hexagonal platelet morphology with round corner and different dropping ways can affect the morphology greatly. Moreover, a DSC study indicated that longer time treatment can weaken the bond between the MTX anions and LDH layers. The kinetic release profiles told us that larger MTX/LDH particles have enhanced the ability of LDH layers to protect interlayer molecules. At last, the bioassay study indicated that the nanohybrids with larger diameters have higher tumor suppression efficiency.

[Inhibition of chlorobenzene formation via various routes during waste incineration by ammonium sulfate and urea].

Chlorobenzene (CBz) is the precursor of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) generated in the processes of waste incineration, and it is regarded as a good indicator of PCDD/Fs for realizing PCDD/Fs online monitoring, moreover, pentachlorobenzene (PeCBz) and Hexachlorobenzene (HxCBz) belong to Persistent Organic Pollutants (POPs). However, the emission control of CBz in waste incineration does not attract enough attention, so this study focused on the inhibition of the 3 CBz formation routes in waste combustion by ammonium sulfate and urea, including CB formation from fly ash, CB formation from 1,2-dichlorobenzene (1,2-DiCBz) and the combustion of model medical waste. The results showed that both ammonium sulfate and urea reduced CBz yield during these three thermal processes. For instance, the inhibition rates of tetrachlorobenzene (TeCBz), PeCBz and HxCBz were 66.8%, 57.4% and 50.4%, respectively, when 1% urea was co-combusted with medical waste. By comparing the effect of ammonium sulfate and urea on CBz formation by three routes, urea was considered as a comparatively stable inhibitor for CBz.

Improved biocompatibility of novel poly(L-lactic acid)/ß-tricalcium phosphate scaffolds prepared by an organic solvent-free method.

A porous poly(L-lactic acid)/ß-tricalcium phosphate (PLLA/ß-TCP) composite scaffold was fabricated using a novel technique comprising powder mixing, compression molding, low-temperature treatment, and particulate leaching without any organic solvent. The effect of this scaffold on osteoblast proliferation and differentiation was evaluated in vitro. The fabricated scaffold had a homogeneously interconnected porous structure with a porosity of 70% and compressive strength of 1.35 MPa. The methylthiazol tetrazolium values and alkaline phosphatase (ALP) activity of osteoblasts seeded on the solvent-free scaffold were significant higher than those of the control. Using real-time PCR, gene expressions of ALP, osteocalcin, and type 1 collagen were shown to be upregulated. As the method does not use any organic solvent, it eliminates problems associated with organic solvent residue and therefore improves the cell compatibility. It has a promising potential for the preparation of porous scaffold for bone tissue engineering.

[A comparison of the clinical anesthetic efficacy of articaine infiltration and lidocaine blocking for microport extraction of impacted mandibular molar].

OBJECTIVE: To compare the clinical efficacy of the infiltration anesthesia with primacaine and the nerve blocking anesthesia with lidocaine for microport extraction of impacted lower third molar. METHODS; 104 chosen patients had both sides of impacted lower third molars extracted in this study. Patients were given local anesthesia with either primacaine or lidocaine randomly at each side, and then underwent microport extraction. Clinical factors including effective proportion (EP), effecting time point (ETP), visual analogue scale of pain (VASp), alteration of systolic pressures (ASP) and analgesia duration (AD) were evaluated statistically by means of paired t-test. RESULTS: The EP of experimental group was higher than the control group (P = 0.024). The ETP of soft tissue and alveoli-dental pulp was (1.04 +/- 0.21), (2.44 +/- 2.60) min in the experimental group, and much earlier than that of the control group (P = 0.002, P = 0.032). The VASp and ASP of experimental group were lower than the control group (P = 0.041, P = 0.018). AD was (103.6 +/- 35.5) min, and higher than the control group (P = 0.04). CONCLUSION: The infiltration anesthesia with primacaine has been proven to be a easier, reliable and quick-acting method. We suggest it an alternative method replacing the 2% lidocaine blocking during microport extraction of impacted lower third molar.

Physicochemical characterization, in vitro, and in vivo evaluation of indomethacin-loaded nanocarriers self-assembled by amphiphilic polyphosphazene.

Copolymeric nanocarriers assembled by amphiphilic polyphosphazene bearing poly(N-isopropylacrylamide) (PNIPAAm) and ethyl glycinate (EtGly) as substitutes, were investigated as drug vehicles for indomethacin (IND). The physicochemical characteristics of the novel nanocontainers were studied, including lower critical solution temperature (LCST), critical micelle concentration (CMC) and drug loading capacity. LCST measurements revealed that copolymer is more sensitive to the introduction of salts into aqueous solution compared with homopolymer. A significant decrease in CMC was observed when the temperature increased above LCST. As evidenced by transmission electron microscopy (TEM) measurement, morphological transformation from multicompartment into spherical nanoparticles was observed when nanocarriers with higher IND content were concerned. In vitro release tests suggested that IND-loaded nanocontainers exhibited pH dependent release profiles. In vivo pharmacokinetic study after subcutaneous administration provided a relatively sustained release behavior. Additionally, compared with free drug solution at the same dose, IND concentration in rat plasma showed a prolonged retention in experimental group treated with IND-loaded micelles. In vivo pharmacodynamic study based on both carrageenan-induced acute and complete Freund's adjuvant (CFA) induced adjuvant-arthritis models indicated that sustained therapeutic efficacy could be achieved through intraarticular injection of IND-loaded micelles. Most importantly, local delivery of IND can avoid the severe gastrointestinal stimulation, which is frequently associated with oral administration.

Local delivery of indomethacin to arthritis-bearing rats through polymeric micelles based on amphiphilic polyphosphazenes.

PURPOSE: Preparation, in vitro and in vivo evaluation of indomethacin-loaded polymeric micelles based on amphiphilic polyphosphazene. METHODS: Amphiphilic polyphosphazenes (PNIPAAm/EAB-PPPs) with poly (N-isopropylacrylamide) (PNIPAAm) and ethyl 4-aminobenzoate (EAB) as side groups were synthesized through thermal ring-opening polymerization and subsequent substitution reactions. Indomethacin (IND) loaded polymeric micelles based on PNIPAAm/EAB-PPPs were prepared by dialysis procedure. In vitro IND release kinetics was investigated in 0.1 M PBS (pH 7.4), while in vivo pharmacokinetics was performed in Sprague-Dawley rats. In vivo pharmacodynamic study was carried out based on two animal models, i.e. carrageenan-induced acute paw edema and complete Freund's adjuvant (CFA) induced ankle arthritis model. RESULTS: Drug loading capacity of micelles based on this type of amphiphilic copolymers was mainly determined by copolymer composition and the chemical structure of drug. In addition to the compatibility between drug and micellar core, hydrogen bonding interaction between drug and hydrophilic corona may significantly influence drug loading as well. In vitro drug release in PBS suggested that there was no significant difference in release rate between micelles based on copolymers with various EAB content. Compared with the rats administered with free IND aqueous solution, IND concentration in rats' plasma showed a prolonged maintenance in experimental group treated with IND-loaded polymeric micelles. In vivo pharmacodynamic study indicated that sustained therapeutic efficacy could be achieved through topical injection of the aqueous solution of IND-loaded micelles. Local delivery of IND can avoid the severe gastrointestinal stimulation, which was frequently associated with oral administration as evidenced by ulceration evaluation. CONCLUSIONS: The promising results of current preliminary study suggest that this type of amphiphilic copolymers could be used as injectable drug carriers for hydrophobic drugs.

[Histological regeneration process of "neo-esophagus"].

BACKGROUND & OBJECTIVE: During the reconstruction process of organs or tissues, different implant materials can lead to different healing results because of different extracellular matrix interfaces and tissue biocompatibilities. This study was to observe the regeneration process of "neo-esophagus"after implanting an artificial esophagus, and investigate its healing mechanism. METHODS: Histopathologic studies on neo-esophagus in 1, 3, 6, 12, and 24 months after implantation were performed using gross-giant specimen technique and special staining methods. The processes of tissue molding and reconstruction, and regeneration of high-level cell organ in "neo-esophagus"were observed. RESULTS: The artificial esophagus temporarily replaced the defective esophagus at the early stage after implantation, and dropped off about 1 month after operation. The epithelization of neo-esophagus induced by host tissue was completed about 3-6 months after operation. The submucous muscle layer, mucous glands, nerve fiber, and capillaries were reconstructed about 12 months after operation. The narrowing of "neo-esophagus" occurred about 3-6 months after operation and was relieved 12 months after operation. CONCLUSIONS: The implanted artificial esophagus made of bio-material can replace the defective esophagus at the early stage, and induce connective tissues, including collagen and fibroblasts, to deposit and cover on it to form neo-esophagus. The neo-esophagus is developed by epithelization and reconstruction of submucous muscle layer, mucous glands, nerve fiber, and capillaries 12 months after operation. The narrowing of "neo-esophagus" is caused by overgrowth and contraction of scars.