Combined construction of injectable tissue-engineered bone with CPC and BMMSCs and its study of repair effect on rabbit bone defect model.

OBJECTIVE: to investigate the combined construction of injectable tissue-engineered bone with calcium phosphate bone cement composite (CPC) and bone marrow mesenchymal stem cells (BMMSCs). METHODS: The proliferation activity of BMMSCs encapsulated was detected by CCK8 method on the 7th day after its self-coagulation by CPC. qRT-PCR was used to detect the expressions of mRNA. The microcapsules of BMMSCs combined with CPC were completely filled in the defect site in the experimental group, and the control group not filled. The two groups were sutured and routinely reared, double upper limb X-ray examination performed after operation. RESULTS: Those of two groups were on the rise over time, which were higher at the 1st, 3rd, 5th and 7th days than those at the previous time points (all P<0.05). The relative expressions of ALP and CALCR at the 7th day were higher than those at the day in BMMSCs combined with the CPC group and BMMSCs group (all P<0.05). The relative expression of CALCR was significantly higher in BMMSCs combined with the CPC group than that in the BMMSCs group on the 7th day (P<0.05). CONCLUSION: With good cell activity and biological activity, the combined construction of the tissue-engineered bone with BMMSCs and CPC can be used as an ideal treatment material for bone tissue repair and connection.

jaw-1D: a gain-of-function mutation responsive to paramutation-like induction of epigenetic silencing.

The Arabidopsis thaliana gain-of-function T-DNA insertion mutant jaw-1D produces miR319A, a microRNA that represses genes encoding CIN-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTORs (TCPs), a family of transcription factors that play key roles in leaf morphogenesis. In this study, we show that jaw-1D is responsive to paramutation-like epigenetic silencing. A genetic cross of jaw-1D with the polycomb gene mutant curly leaf-29 (clf-29) leads to attenuation of the jaw-1D mutant plant phenotype. This induced mutation, jaw-1D*, was associated with down-regulation of miR319A, was heritable independently from clf-29, and displayed paramutation-like non-Mendelian inheritance. Down-regulation of miR319A in jaw-1D* was linked to elevated levels of histone H3 lysine 9 dimethylation and DNA methylation at the CaMV35S enhancer located within the activation-tagging T-DNA of the jaw-1D locus. Examination of 21 independent T-DNA insertion mutant lines revealed that 11 could attenuate the jaw-1D mutant phenotype in a similar way to the paramutation induced by clf-29. These paramutagenic mutant lines shared the common feature that their T-DNA insertion was present as multi-copy tandem repeats and contained high levels of CG and CHG methylation. Our results provide important insights into paramutation-like epigenetic silencing, and caution against the use of jaw-1D in genetic interaction studies.

Quantitative Analysis of Diffusion-Weighted Imaging for Diagnosis of Puerperal Breast Abscess After Polyacrylamide Hydrogel Augmentation Mammoplasty: Compared with Other Conventional Modalities.

PURPOSE: Puerperal breast abscess after polyacrylamide hydrogel (PAAG) augmentation mammoplasty can induce breast auto-inflation resulting in serious consequences. Mammography, ultrasound, and conventional MRI are poor at detecting related PAAG abnormality histologically. We evaluated the value of diffusion-weighted imaging (DWI) in the quantitative analysis of puerperal PAAG abscess after augmentation mammoplasty. MATERIALS AND METHODS: This was a retrospective study, and a waiver for informed consent was granted. Sixteen puerperal women with breast discomfort underwent conventional breast non-enhanced MRI and axial DWI using a 3T MR scanner. Qualitative analysis of the signal intensity on DWI and conventional sequences was performed. The apparent diffusion coefficient (ADC) values of the affected and contralateral normal PAAG cysts were measured quantitatively. Paired t test was used to evaluate whether there was significant difference. RESULTS: Both affected and normal PAAG cysts showed equal signal intensity on conventional T1WI and fat saturation T2WI, which were not helpful in detecting puerperal PAAG abscess. However, the affected PAAG cysts had a significantly decreased ADC value of 1.477 ± 0.332 × 10(-3)mm(2)/s and showed obvious hypo-intensity on the ADC map and increased signal intensity on DWI compared with the ADC value of 2.775 ± 0.233 × 10(-3)mm(2)/s of the contralateral normal PAAG cysts. CONCLUSION: DWI and quantitative measurement of ADC values are of great value for the diagnosis of puerperal PAAG abscess. Standardized MRI should be suggested to these puerperal women with breast discomfort or just for the purpose of check up. DWI should be selected as the essential MRI sequence.

PLA tissue-engineered scaffolds loaded with sustained-release active substance chitosan nanoparticles: Modeling BSA-bFGF as the active substance.

The utilization of basic fibroblast growth factor (bFGF) in the development of tissue-engineered scaffolds is both challenging and imperative. In our pursuit of creating a scaffold that aligns with the natural healing process, we initially fabricated chitosan-bFGF nanoparticles (CS-bFGF NPs) through electrostatic spraying. Subsequently, polylactic acid (PLA) fiber was prepared using electrospinning technique, and the CS-bFGF NPs were uniformly embedded within the pores of porous PLA fibers. Scanning electron micrographs illustrate the smooth surface of the nanoparticles, showing a porous structure intricately attached to PLA fibers. Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) analyses provided conclusive evidence that the CS-bFGF NPs were uniformly distributed throughout the porous PLA fibers, forming a robust physical bond through electrostatic adsorption. The resultant scaffolds exhibited commendable mechanical properties and hydrophilicity, facilitating a sustained-release for 72 h. Furthermore, the biocompatibility and degradation performance of the scaffolds were substantiated by monitoring conductivity and pH changes in pure water over different time intervals, complemented by scanning electron microscopy (SEM) observations. Cell experiments confirmed the cytocompatibility of the scaffolds. In animal studies, the group treated with 16 % NPs/Scaffold demonstrated the highest epidermal reconstruction rate. In summary, our developed materials present a promising candidate for serving as a tissue engineering scaffold, showcasing exceptional biocompatibility, sustained-release characteristics, and substantial potential for promoting epidermal regeneration.

Preparation of gastrodin modified P(VDF-TrFE)-Eudragit L100-AuNPs nanofiber membranes with piezoelectric property.

In recent years, electroactive nerve conduits made from a blend of P(VDF-TrFE) (poly (vinylidene fluoride-trifluoroethylene)) with other materials have shown significant progress. However, research combining P(VDF-TrFE) conduits with drug delivery systems remains sparse. In this study, we developed a novel gastrodin-loaded P(VDF-TrFE)-Eudragit L100-gold nanoparticles (Gas@PT-EL100-AuNPs) nanofiber membrane. Fabricated through electrospinning technique, this composite membrane aimed to investigate the impacts of gastrodin and AuNPs on its properties. Experimental results indicated that the incorporation of gold nanoparticles significantly reduced the fiber diameter of the membrane and enhanced the overall performance by improving hydrophilicity and piezoelectric properties. Specifically, the addition of AuNPs substantially enhanced the piezoelectric performance of the nanofiber membrane. Furthermore, the inclusion of gastrodin not only improved the membrane's hydrophilicity but also enabled effective release of the neuroprotective drug. These findings suggest that the Gas@PT-EL100-AuNPs nanofiber membrane is a novel biomaterial with potential applications in the repair and treatment of nerve injuries.

TCP transcription factors interact with AS2 in the repression of class-I KNOX genes in Arabidopsis thaliana.

Leaf organogenesis occurs within the peripheral zone of the shoot apical meristem (SAM). The initiation and subsequent development of a leaf requires the stable repression of a highly conserved class of plant genes, namely class-I KNOTTED 1-like homeobox (KNOX) genes. In Arabidopsis, this class comprises four members: SHOOT MERISTEMLESS (STM); BREVIPEDICELLUS (BP); KNAT2 and KNAT6. Two transcription factors, ASYMMETRIC LEAVES 1 (AS1) and AS2, are known to form a protein complex to repress BP, KNAT2 and KNAT6. Here, we show that AS2 physically interacts with the microRNA319 (miR319)-regulated CINCINNATA-like TEOSINTE BRANCHED 1-CYCLOIDEA-PCF (TCP) transcription factors in vitro and in vivo. By chromatin immunoprecipitation, we demonstrated that AS2 and TCPs bind to similar regions of the BP and KNAT2 promoters. In addition, DNA-binding activities of the TCP proteins rely on the presence of AS2, as the activities were dramatically reduced in the as2 mutant. The jaw-D mutant, which overexpresses MIR319a to downregulate several target TCP genes, strongly enhanced the as2 phenotypes and caused more severe ectopic expression of BP, KNAT2 and KNAT6. Our results reveal that KNOX repression requires different types of transcription factors that function together to ensure normal leaf development.

Effect of inoculation density of bone marrow mesenchymal stem cells cultured on calcium phosphate cement scaffold on osteogenic differentiation.

BACKGROUND: Calcium phosphate cements (CPCs) are biocompatible materials that have been evaluated as scaffolds in bone tissue engineering. At present, the stem cell density of inoculation on CPC scaffold varies. OBJECTIVE: The aim of this study is to analyze the effect of seeding densities on cell growth and osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) on a calcium phosphate cements (CPCs) scaffold. METHODS: BMMSCs derived from minipigs were seeded onto a CPC scaffold at three densities [1 million/mL (1M), 5 million/mL (5M) and 25 million/mL 25M)], and cultured for osteogenic induction for 1, 4 and 8 days. RESULTS: Well adhered and extended BMMSCs on the CPC scaffold showed significantly different proliferation rates within each seeding density group at different time points (P < 0.05). The number of live cells per unit area in 1M, 5M and 25M increased by 3.5, 3.9 and 2.5 folds respectively. The expression of ALP peaked at 4 days post inoculation with the fold-change being 2.6 and 2.8 times higher in 5M and 25M respectively as compared to 1M. The expression levels of OC, Coll-1 and Runx-2 peaked at 8 days post inoculation. CONCLUSIONS: An optimal seeding density may be more conducive for cell proliferation, differentiation, and extracellular matrix synthesis on scaffolds. We suggest the optimal seeding density should be 5 million/mL.

[Impact of vaginal mesh exposure on quality of life in patients undergoing transvaginal reconstructive pelvic surgery with polypropylene mesh].

OBJECTIVE: To study the impact of vaginal mesh exposure on quality of life in patients undergoing transvaginal reconstructive pelvic surgery (RPS) with polypropylene mesh. METHODS: From May 2004 to March 2011, 114 patients with severe pelvic organ prolapse (POP) undergoing transvaginal RPS with polypropylene mesh were enrolled in this study, which were divided into exposure and non-exposure group according to appearing vaginal mesh exposure at 2 months, 6 months and 1 year after operation. At the same time, pelvic floor distress inventory short form 20 (PFDI-20) and pelvic floor impact questionnaire short form 7 (PFIQ-7) were completed in those patients. RESULTS: At 2 months after operation, 96 patients were followed up, including 19 patients in exposure group and 77 patients in non-exposure group, and the rate of exposure was 19.8% (19/96); At 6 months after operation, 85 patients were followed up, including 13 patients in exposure group and 72 patients in non-exposure group, and the rate of exposure was 15.3% (13/85); At 1 year after operation, 77 patients were followed up, including 6 patients in exposure group and 71 patients in non-exposure group, and the rate of exposure was 7.8% (6/77). Mean score of PFDI-20 and PFIQ-7 in exposure group before operation was 39.6 and 57.1, which was statistically improved to 8.3 and 9.5 at 2 months after operation, 8.3 and 9.5 at 6 months after operation, 2.1 and 0 in 1 year after operation (P < 0.01). Mean score of PFDI-20 and PFIQ-7 of non-exposure group before operation was 54.2 and 66.7, which was improved to 8.3 and 4.8 at 2 months after operation, 0 at 6 months and 1 year after operation, but there was no significant difference in mean score of PFDI-20 and PFIQ-7 between the two groups (P > 0.05). CONCLUSION: Vaginal mesh exposure was common after transvaginal RPS with polypropylene mesh, however, most of them were moderate, and there was no significant impact on patients' qualifies of life.

Preparation and separation of pure spherical cellulose nanocrystals from microcrystalline cellulose by complex enzymatic hydrolysis.

Spherical cellulose nanocrystals (CNCs), as a new and high value cellulose derivative, shows excellent application potential in many fields due to its special structure. The accurate and effective separation of pure spherical CNCs lays foundation for its further application. In this work, spherical CNCs were prepared by enzymatic hydrolysis of microcrystalline cellulose (MCC) with complex enzymes. In order to determine the optimal separation conditions of pure spherical CNCs, turbidity and Zeta potential were used to analyze the influence of pH on system stability, and the size and morphology of samples were characterized by DLS, AFM and SEM. The results showed that spherical CNCs with particle size of 24-76 nm can be separated from large particles with the help of alkali (pH = 9) dispersion and centrifugation speed of 3000 rpm. After three acid (pH = 4) washes, pure spherical CNCs were extracted and reducing sugars and enzyme proteins were removed. Compared with MCC, spherical CNCs had lower crystallinity but stronger reactivity and higher heat transfer. DTG results showed that the maximum weight loss temperature of spherical CNCs prepared by enzymatic hydrolysis was 309 °C.

Spherical vs rod-like cellulose nanocrystals from enzymolysis: A comparative study as reinforcing agents on polyvinyl alcohol.

In this paper, we have isolated cellulose nanocrystallines (CNCs) with different morphologies by enzymatic hydrolysis, and prepared flexible and transparent nanocomposite films with PVA matrix via solution casting. By means of SEM, UV-vis, XRD, DTG, FT-IR and mechanical methods, the effects of rod-shaped cellulose nanocrystallines (RCNCs) and spherical cellulose nanocrystallines (SCNCs) on PVA nanocomposite films were compared systematically. The results showed CNCs with different morphologies had little effect on the transparency of the composite films, and the crystallinity fluctuated with the change of CNCs additive amount. Compared with the RCNCs, SCNCs had a better improve ability to the thermal stability of the composite films by promoting pyrolysis temperature 60-80 °C. On the contrary, the maximum mechanical properties of the composite films of RCNCs were much higher than those of SCNCs, and the Young's modulus of the PVA/RCNCs composite film were increased by 120.97 % in comparison with the pure PVA.

Effects of the crystallinity on quercetin loaded the Eudragit L-100 electrospun nanofibers.

The quercetin loaded Eudragit L-100 nanofiber membrane with high ductility and a desired drug release rate was prepared in this work. The morphological characteristics of the Eudragit L-100 nanofibers with different drug loadings amount were observed by scanning electron microscope (SEM). After adding Polyethylene glycol-4000 (PEG-4000), the degree of the fiber breakage decreased and the fiber length increased. Fiber diameter analysis, X-ray diffraction (XRD), thermal analysis (TA) and differential scanning calorimetry (DSC) have demonstrated that the crystallinity of the fiber membrane was significantly reduced after adding PEG-4000. The mechanical property test also showed that the fiber membrane with PEG-4000 had a greater elongation at break. The in vitro release experiments showed that after adding PEG-4000, the drug-loaded fibers showed rapid release at a pH of 7.4. After adopting the strategy of reducing the crystallinity, the ductility of the fiber was enhanced, which could provide a fesibility to enable this nanofiber membrane to be used in sports wound healing treatment. The electrospun Eudragit L-100 nanofiber membranes loaded with quercetin have the potential to be applied in sport wound healing of skin, tissue and joints.

Preparation and characterization of the ribbon-like cellulose nanocrystals by the cellulase enzymolysis of cotton pulp fibers.

The enzymolytic preparation of cellulose nanocrystals (CNCs) has the unique advantages due to its green chemistry process. In this work, the cotton pulp fibers were enzymolyzed with the cellulase to prepare the ribbon-like CNC, and the samples were characterized by SEM, FTIR, XRD and DLS. The results indicated the CNC with the length 250-900 nm and width 30-45 nm could be produced from cotton pulp fibers at the lower cellulase concentration, the time 5-11 h and temperature 50 ºC. When the cellulase concentration rose up to 100 /ml, the granular CNC appeared, and at 300 µ/ml all of the formed CNC were granular. FTIR and XRD analyses proved that the ribbon-like CNC had the same crystal style and chemical structure with original cotton pulp fibers, but its crystallinity was weakened slightly. Despite the fact that there are the weakened crystallinity and aggregates, the as-prepared samples were still called as CNCs for simplicity. In addition, the article has discussed the mechanism for the forming ribbon-like CNC from the enzymolysis of cotton pulp fibers.

Methylation and PTEN activation in dental pulp mesenchymal stem cells promotes osteogenesis and reduces oncogenesis.

Lineage commitment and tumorigenesis, traits distinguishing stem cells, have not been well characterized and compared in mesenchymal stem cells derived from human dental pulp (DP-MSCs) and bone marrow (BM-MSCs). Here, we report DP-MSCs exhibit increased osteogenic potential, possess decreased adipogenic potential, form dentin pulp-like complexes, and are resistant to oncogenic transformation when compared to BM-MSCs. Genome-wide RNA-seq and differential expression analysis reveal differences in adipocyte and osteoblast differentiation pathways, bone marrow neoplasm pathway, and PTEN/PI3K/AKT pathway. Higher PTEN expression in DP-MSCs than in BM-MSCs is responsible for the lineage commitment and tumorigenesis differences in both cells. Additionally, the PTEN promoter in BM-MSCs exhibits higher DNA methylation levels and repressive mark H3K9Me2 enrichment when compared to DP-MSCs, which is mediated by increased DNMT3B and G9a expression, respectively. The study demonstrates how several epigenetic factors broadly affect lineage commitment and tumorigenesis, which should be considered when developing therapeutic uses of stem cells.

Preparation and characterization of the spherical nanosized cellulose by the enzymatic hydrolysis of pulp fibers.

In this work, the pulp fibers were enzymolyzed to prepare the nanosized cellulose (NC). The as-prepared samples were characterized by optical microscopy, electron microscopy, and Raman spectra. The experimental results indicated that enzymatic hydrolysis of pulp fibers could produce the spherical NC with a mean particle size of about 30nm, which had the excellent monodispersity and uniformity. When the concentration of complex enzymes was 20u/mL (cellulase: xylanase=9: 1), the yield of NC was 13.6%. The single cellulase was used, even if the enzyme concentration reached up to 200u/mL, only a mixture of strip and granular flocculation were obtained. The positive synergistic effect between xylanase and cellulase could be due to the enzymolysis of hemicellulose located on the cellulose microfibers to be favorable of cutting and splitting of the microfibers by the endoglucanase in cellulase.

Amino acid-based anti-fouling functionalization of silica nanoparticles using divinyl sulfone.

UNLABELLED: Natural amino acids are zwitterionic molecules and the good biocompatibility promises them potential candidates as anti-fouling materials. Here, we developed a new method to functionalize silica nanoparticles with a natural amino acid-based anti-fouling layer. Amino acids were covalently immobilized on 3-aminopropyltriethoxysilane modified silica nanoparticles using divinyl sulfone through a two-step reaction in aqueous solution at room temperature. The progress was monitored with NMR, X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM) and zeta potential measurements. A library of amino acids was screened and the nonspecific protein adsorption of bovine serum albumin (BSA) and fetal bovine serum (FBS) were investigated using dynamic light scattering method. The results showed that cysteine, lysine and arginine functionalized silica nanoparticles can effectively resist protein adsorption due to the zwitterionic structure. Among them, lysine functionalized silica nanoparticles had the best anti-fouling performance, which showed hydrodynamic diameter increases of only 10% after incubated in BSA solution and 20% after incubated in FBS solution for 24h. The neat aqueous modification process can conveniently create a thin zwitterionic layer on silica particles, and it has a great potential in biomolecule immobilization and biofunctional surface preparation. STATEMENT OF SIGNIFICANCE: Zwitterionic polymer is an outstanding class of anti-fouling material; but the difficulty in synthesis is challenging its spread utilization. In this study, we developed a new method to create an amino acid-based zwitterionic layer on APTES functionalized silica nanoparticles through a two-step reaction in aqueous solution at room temperature. The surface chemistry was monitored with NMR, XPS, TEM and zeta potential measurements. With this method, a library of amino acid conjugated-silica nanoparticles was synthesized and their anti-fouling performance was evaluated using dynamic light scattering method. The results showed that the cysteine, lysine and arginine conjugated nanoparticles all can effectively resist nonspecific protein adsorption. Among them, lysine conjugated nanoparticles show the best anti-fouling performance, which showed hydrodynamic diameter increases of only 10% after incubated in BSA solution and 20% after incubated in FBS solution for 24 hours. These results indicates that the anti-fouling silica nanoparticles are of great potential in many biomedical applications, especially biosensing and diagnose imaging. The modification reactions in aqueous solution at room temperature are easily conducted in laboratory, indicating high potential in the functionalization of silica particles/surfaces with other biomolecules.

Risk Factors for Mesh Exposure after Transvaginal Mesh Surgery.

BACKGROUND: Mesh exposure after surgery continues to be a clinical challenge for urogynecological surgeons. The purpose of this study was to explore the risk factors for polypropylene (PP) mesh exposure after transvaginal mesh (TVM) surgery. METHODS: This study included 195 patients with advanced pelvic organ prolapse (POP), who underwent TVM from January 2004 to December 2012 at the First Affiliated Hospital of Chinese PLA General Hospital. Clinical data were evaluated including patient's demography, TVM type, concomitant procedures, operation time, blood loss, postoperative morbidity, and mesh exposure. Mesh exposure was identified through postoperative vaginal examination. Statistical analysis was performed to identify risk factors for mesh exposure. RESULTS: Two-hundred and nine transvaginal PP meshes were placed, including 194 in the anterior wall and 15 in the posterior wall. Concomitant tension-free vaginal tape was performed in 61 cases. The mean follow-up time was 35.1 ± 23.6 months. PP mesh exposure was identified in 32 cases (16.4%), with 31 in the anterior wall and 1 in the posterior wall. Significant difference was found in operating time and concomitant procedures between exposed and nonexposed groups (F = 7.443, P = 0.007; F = 4.307, P = 0.039, respectively). Binary logistic regression revealed that the number of concomitant procedures and operation time were risk factors for mesh exposure (P = 0.001, P = 0.043). CONCLUSION: Concomitant procedures and increased operating time increase the risk for postoperative mesh exposure in patients undergoing TVM surgery for POP.

The effect of oil-water partition coefficient on the distribution and cellular uptake of liposome-encapsulated gold nanoparticles.

The shape, size, and surface features of nanoparticles greatly influence the structure and properties of resulting hybrid nanosystems. In this work, gold nanoparticles (GNPs) were modified via S-Au covalent bonding by glycol monomethyl ether thioctate with poly(ethylene glycol) methyl ether of different molecular weights (i.e., 350, 550, and 750Da). These modified GNPs (i.e., GNP350, GNP550, and GNP750) showed different oil-water partition coefficients (Kp), as detected using inductively coupled plasma-atomic emission spectroscopy. The different Kp values of the gold conjugates (i.e., 13.98, 2.11, and 0.036 for GNP350, GNP550, and GNP750, respectively) resulted in different conjugate localization within liposomes, as observed by transmission electron microscopy. In addition, the cellular uptake of hybrid liposomes co-encapsulating gold conjugates and Nile red was evaluated using intracellular fluorescence intensity. The results indicated that precise GNP localization in the hydrophilic or hydrophobic liposome cavity could be achieved by regulating the GNP oil-water partition coefficient via surface modification; such localization could further affect the properties and functions of hybrid liposomes, including their cellular uptake profiles. This study furthers the understanding not only of the interaction between liposomes and inorganic nanoparticles but also of adjusting liposome-gold hybrid nanostructure properties via the surface chemistry of gold materials.

G5-PEG PAMAM dendrimer incorporating nanostructured lipid carriers enhance oral bioavailability and plasma lipid-lowering effect of probucol.

This work aimed to improve the oral bioavailability and plasma lipid-lowering effect of probucol (PB) by constructing a combined drug delivery system (CDDS) composed of nanostructured lipid carrier (NLC) and PEGylated poly(amidoamine) dendrimer (PEG-PAMAM). PEG-PAMAM with dendrimer generations of 5 (G5-PEG) or 7 (G7-PEG) were incorporated in PB-NLCs to form PB-CDDSs, PB-NLCs/G5-PEG and PB-NLCs/G7-PEG. The resultant two kinds of PB-CDDSs were characterized by particle size, zeta potential, drug encapsulation efficacy, PB release rates, and physical stability. Formulation effects of NLC and CDDS on the cellular uptake of hydrophobic drug were explored in Caco-2 cells by fluorescent Cy5 dye as a hydrophobic drug model. Furthermore, in vivo pharmacokinetics of the PB-CDDS composed of G5-PEG and PB-NLCs were investigated in a low density lipoprotein receptor knockout (LDLr-/-) mouse model, including plateau plasma PB concentrations after oral administration of multiple doses, and bioavailability after oral administration of a single dose of different PB formulations. In addition, lipid-lowering effect of PB-NLCs/G5-PEG was studied. The results indicate that both G5-PEG and G7-PEG significantly improved aqueous solubility of PB. The two PB-CDDSs exhibited similar particle size (around 150nm) as PB-NLCs, but slower PB burst release rate, higher total PB release amount, and better particle morphology and storage stability than PB-NLCs. In comparison with traditional NLC, CDDS dramatically enhanced cellular uptake of Cy5 into Caco-2 cells. In vivo results demonstrate that PB-NLCs/G5-PEG had the highest plateau plasma PB concentration and oral bioavailability, and the greatest cholesterol-lowering effect in comparison with PB suspensions and PB-NLCs. Therefore, G5-PEG incorporating NLC can be exploited as a promising drug delivery system to improve oral bioavailability and lipid-lowering effect of PB.

The performance of thiol-terminated PEG-paclitaxel-conjugated gold nanoparticles.

A series of thiol-terminated polyethylene glycol (PEG)-paclitaxel (PTX) derivatives are designed and synthesized to fabricate PTX-conjugated gold nanoparticles (PTX@GNPs) and improve their overall performance. By extending the molecular weight of PEG from 400 to 1000 Da, the optimized water solubility of the conjugate reaches 184 mg/mL, equal to 4.6 × 10(5) times that of PTX alone (0.4 µg/mL). High drug loading is obtained by eliminating the steric hindrance between PTX molecules on the surface of GNPs. The gold conjugate shows double simultaneous stimulation-induced drug release behavior in the presence of both esterase and high concentrations of glutathione. The synergic release characteristics of this conjugate results in significant performance improvements, including prolonged circulation due to high stability in vivo, targeted release of PTX inside tumor cells, and increased tumor cell killing efficiency. Improving the in vitro properties of the conjugate not only significantly enhances its therapeutic efficacy in a murine liver cancer model, but also allows drug-conjugated gold nanoparticles to be used as a promising nanoprodrug system in the cancer therapeutics.