HnRNPL inhibits the osteogenic differentiation of PDLCs stimulated by SrCl2 through repressing Setd2.

Osteoporosis has been shown to intensify bone loss caused by periodontitis and both share common risk factors. One strategy utilized to manage the disease has been via the release of Sr ions by Strontium Ranelate having a direct effect on preventing osteoclast activation and promoting osteoblast differentiation. Previously we have developed and characterized porous Sr-mesoporous bioactive glass (Sr-MBG) scaffolds and demonstrated their ability to promote periodontal regeneration when compared to MBG alone. Our group further discovered a splicing factor, heterogeneous nuclear ribonucleoprotein L (hnRNPL), was drastically down-regulated in periodontal ligament stem cells (PDLCs) stimulated by Sr through the activation of AKT pathway. Furthermore, hnRNPL restrained the osteogenic differentiation of PDLCs through down-regulating H3K36me3-specific methyltransferase Setd2. The goal of the present study was to investigate the mechanism of periodontal regeneration stimulated by Sr It was first found that the epigenetic mechanism of splicing factor hnRNPL participated in the osteogenesis processing of PDLCs stimulated by SrCl2 . Meanwhile, the different role of hnRNPL and SET domain containing 2 (Setd2) may provide some implication of the treatment of periodontitis patients simultaneously suffering from osteoporosis.

Adsorption of Pb2+ and Cu2+ in wastewater by lignosulfonate adsorbent prepared from corn straw.

The heavy metal ions contained in industrial wastewater are a great threat to human health. Exploring a adsorbent which have low-cost, green environmental friendly, high adsorption capacity, good recycle is key to solve heavy metal ions pollution. Lignin sulfonate was obtained by treating corn stover, and then modified lignin sulfonate was obtained by hydrothermal method. The porous structure makes heavy metal ions occupy more internal adsorption sites. Modified lignosulfonate adsorbent efficiency removes heavy metals in wastewater especially Cu2+ and Pb2+. The adsorption capacity of Cu2+ on modified lignosulfonate is 450.3 mg g-1, Pb2+ is 475.4 mg g-1. In addition, for 40 mg L-1 Cu2+ and Pb2+ using 0.4 g L-1, the adsorption equilibrium is only reached within 60 min. Meanwhile, the removal ratio of Pb is 83 %, Cd is 72 %, Cu is 87 %, Zn is 36 %, Mn is 25 %, Cr is 95 %, and Fe is 99 % in wastewater using 0.4 g L-1 adsorbent in 2 h. This research develops a practical adsorbent to remove heavy metals from actual wastewater.

Construction of poly(amino acid)s nano-delivery system and sustained release with redox-responsive.

A series of novel poly(amino acid)s materials were designed to prepare drug-loaded nanoparticles by physical encapsulation and chemical bonding. The side chain of the polymer contains a large number of amino groups, which effectively increases the loading rate of doxorubicin (DOX). The structure contains disulfide bonds that showing a strong response to the redox environment, which can achieve targeted drug release in the tumor microenvironment. Nanoparticles mainly present spherical morphology with the suitable size for participating in systemic circulation. cell experiments demonstrate the non-toxicity and good cellular uptake behavior of polymers. In vivo anti-tumor experiments shows nanoparticles could inhibit tumor growth and effectively reduce the side effects of DOX.

Construction of nano-drug delivery and antitumor system of stimuli-responsive polypeptides.

The size of the nanoparticles is moderate and the dispersion is well, which will not be recognized nonspecifically and clearance by the endothelial reticular system. In this study, stimuli-responsive polypeptides nano-delivery system has been constructed, which can realize the response to various stimuli in the tumor microenvironment. Tertiary amine groups are grafted to the side chain of polypeptides as the point of charge reversal and particle expansion. In addition, a new kind of liquid crystal monomer was prepared by substituting cholesterol-cysteamine, which can promote polymers to realize the transformation of spatial conformation by adjusting the ordered arrangement of macromolecules. The introduction of hydrophobic elements greatly enhanced the self-assembly performance of polypeptides, which could effectively improve the drug loading and encapsulation rate of nanoparticles. Nanoparticles could achieve targeted aggregation in tumor tissues, and there were no toxicity and side effects on normal bodies during treatment, with good safety in vivo.

Association of oral health knowledge, self-efficacy and behaviours with oral health-related quality of life in Chinese primary school children: a cross-sectional study.

OBJECTIVE: Achieving good oral health-related quality of life (OHRQOL) is of particular concern in children. The inter-relations among oral health knowledge, self-efficacy, behaviours and OHRQOL in children groups remain unclear. This study aimed to explore the inter-relations between these oral health behaviour-related factors and OHRQOL in primary school children. METHODS: In this cross-sectional study, 651 children in grades 2 and 3 were recruited in October 2020 from two primary schools in Minhang District, Shanghai, China. Data were collected through self-reported questionnaires, consisting of demographic characteristics, oral health knowledge, self-efficacy, oral health behaviours and OHRQOL. Pearson's correlation analyses were used to analyse the relationship between study variables. Structural equation models were used to test the inter-relations between OHRQOL and oral health behaviour-related factors. RESULTS: Four hypothetical structural equation models were tested and one of them was selected as the most appropriate model, which explained 15.0% of the variance in OHRQOL. This selected model showed that oral health behaviours were directly related to OHRQOL. Oral health knowledge was indirectly associated with OHRQOL through both self-efficacy and oral health behaviours. Self-efficacy was directly associated with OHRQOL or was indirectly associated with OHRQOL through oral health behaviours. CONCLUSION: This study revealed a pathway of association between children's oral health knowledge and their OHRQOL, in which children's oral health self-efficacy and behaviours had indirect effects. This provides a basis for understanding the mechanism of oral health promotion interventions to improve children's OHRQOL and helps to identify direct or indirect intervention targets.

Lapatinib-loaded acidity-triggered charge switchable polycarbonate-doxorubicin conjugate micelles for synergistic breast cancer chemotherapy.

Stimulus-responsive nanosystem is a powerful method to improve the bioavailability and reduce the side effects of anticancer agents. In the present study, a customized dual pH-responsive micellar nanoplatform (DOX+LAP-M) based on polycarbonate-doxorubicin conjugate micelles was prepared to co-deliver the chemotherapeutic agent lapatinib for inhibiting tumor growth and metastasis. DOX+LAP-M micelles with spherical morphology had a size of ~112 nm and had an initial negative surface charge, which are favorable characteristics for long-term circulation in the blood. Once the micelles accumulated in tumor tissues, the intrinsic tumor extracellular acidity triggered the charge switch of DOX+LAP-M micelles from -1 to 9 mV, thereby facilitating cell internalization and tumor penetration. Subsequently, the pH-sensitive micellar core accelerated the release of doxorubicin and lapatinib in the acidic intracellular environment. DOX+LAP-M micelles effectively inhibited the proliferation, migration, and invasion of 4T1 cells in vitro; furthermore, the administration of DOX+LAP-M micelles in 4T1 xenograft-bearing mice suppressed solid tumor growth with an inhibitory rate of 90.2% and significantly decreased pulmonary metastatic nodules, without significant systemic toxicity. This multifunctional micellar system has high potential for clinical cancer therapy.

Cationic polybutyl cyanoacrylate nanoparticles for DNA delivery.

To enhance the intracellular delivery potential of plasmid DNA using nonviral vectors, we used polybutyl cyanoacrylate (PBCA) and chitosan to prepare PBCA nanoparticles (NPs) by emulsion polymerization and prepared NP/DNA complexes through the complex coacervation of nanoparticles with the DNA. The object of our work is to evaluate the characterization and transfection efficiency of PBCA-NPs. The NPs have a zeta potential of 25.53 mV at pH 7.4 and size about 200 nm. Electrophoretic analysis suggested that the NPs with positive charges could protect the DNA from nuclease degradation and cell viability assay showed that the NPs exhibit a low cytotoxicity to human hepatocellular carcinoma (HepG2) cells. Qualitative and quantitative analysis of transfection in HepG2 cells by the nanoparticles carrying plasmid DNA encoding for enhanced green fluorescent protein (EGFP-N1) was done by digital fluorescence imaging microscopy system and fluorescence-activated cell sorting (FACS). Qualitative results showed highly efficient expression of GFP that remained stable for up to 96 hours. Quantitative results from FACS showed that PBCA-NPs were significantly more effective in transfecting HepG2 cells after 72 hours postincubation. The results of this study suggested that PBCA-NPs have favorable properties for nonviral delivery.

Construction of Aneurysmal Models on a Curved Vascular Segment of a Carotid Siphon Model for Testing Endovascular Devices.

OBJECTIVE: To investigate construction of an aneurysm on a curved vascular segment of a carotid siphon model for testing endovascular devices. METHODS: Preshaped carotid siphon models of polytetrafluoroethylene were constructed from a human cadaver for confining canine common carotid artery (CCA). The canine right external jugular vein was isolated and harvested to make a venous pouch by suturing 1 end. The right CCA was isolated, and the venous pouch was sutured onto the right CCA to make an aneurysm. The right CCA segment containing the aneurysm was excised and guided through the preshaped polytetrafluoroethylene carotid siphon model using a guidewire with the aneurysm adjusted to protrude out of the round window of the siphon model. The siphon model together with the aneurysm was sutured end-to-end onto the left CCA to form a carotid siphon model in vivo. RESULTS: Five canine models were successfully constructed; the average construction time was 120 minutes. All aneurysms and siphon models remained patent 7 days and 2 weeks later. Five covered stents for intracranial use were tested for flexibility and apposition to the vascular wall in the curved segment of the carotid siphon model in vivo. All the covered stents passed the tortuous siphon model without much difficulty and were deployed successfully to cover the aneurysm orifice without endoleak. CONCLUSIONS: The carotid siphon model in vivo can simulate well the geometry of the human carotid siphon segment and can be used to test endovascular devices for interventions.

The association of tooth loss, toothbrushing, and quality of life among cancer survivors.

BACKGROUND: Tooth loss contributes physically and psychologically to health, and quality of life has been a key indicator of the cancer survivors. However, it is less clear whether tooth loss has impact on cancer survivors' quality of life. Our study aimed to investigate the association between tooth loss, toothbrushing, and quality of life in cancer survivors. METHODS: A cross-sectional study was conducted among 9125 cancer survivors in Shanghai, China. Sociodemographic characteristics, frequency of tooth brushing, number of tooth loss were collected using a self-reported questionnaire. Quality of life was measured using the EORTC QLQ-C30. Chi-square test was used to compare the distribution of tooth loss and toothbrushing frequency among various cancer sites, sociodemographic factors, socioeconomic status, health conditions. Multiple linear regression models were performed to estimate the effects of tooth loss and toothbrushing on quality of life. RESULTS: Participants diagnosed with cancer of oral cavity, pharynx, and nasopharynx reported higher percentage of 11+ tooth loss. Cancer survivors with toothbrushing ≥2 times/d reported higher scores in physical, cognitive, and social function and had milder nausea and vomiting, compared with ones with toothbrushing <2 times/d. Tooth loss was associated with milder physical, role and emotional function scores, and severer fatigue, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, and diarrhea. CONCLUSIONS: This is the first study to investigate the impact of toothbrushing and tooth loss on quality of life among cancer survivors. Tooth loss was associated with milder physical, role and emotional function scores, and severer fatigue, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation and diarrhea. Toothbrushing had significant positive effect on cancer survivors' quality of life. The present study also provided several public health strategies to improve oral health among cancer survivors.

Preparation, characterization and transfection efficiency of cationic PEGylated PLA nanoparticles as gene delivery systems.

The cationic polylactic acid (PLA) nanoparticle has emerged as a promising non-viral vector for gene delivery because of its biocompatibility and biodegradability. However, they are not capable of prolonging gene transfer and high transfection efficiency. In order to achieve prolonged delivery of cationic PLA/DNA complexes and higher transfection efficiency, in this study, we used copolymer methoxypolyethyleneglycol-PLA (MePEG-PLA), PLA and chitosan (CS) to prepare MePEG-PLA-CS NPs and PLA-CS NPs by a diafiltration method and prepared NPs/DNA complexes through the complex coacervation of nanoparticles with the pDNA. The object of our work is to evaluate the characterization and transfection efficiency of MePEG-PLA-CS versus PLA-CS NPs. The MePEG-PLA-CS NPs have a zeta potential of 15.7 mV at pH 7.4 and size under 100 nm, while the zeta potential of PLA-CS NPs was only 4.5 mV at pH 7.4. Electrophoretic analysis suggested that both MePEG-PLA-CS NPs and PLA-CS NPs with positive charges could protect the DNA from nuclease degradation and cell viability assay showed MePEG-PLA-CS NPs exhibit a low cytotoxicity to normal human liver cells. The potential of PLA-CS NPs and MePEG-PLA-CS NPs as a non-viral gene delivery vector to transfer exogenous gene in vitro and in vivo were examined. The pDNA being carried by MePEG-PLA-CS NPs, PLA-CS NPs and lipofectamine could enter and express in COS7 cells. However, the transfection efficiency of MePEG-PLA-CS/DNA complexes was better than PLA-CS/DNA and lipofectamine/DNA complexes by inversion fluorescence microscope and flow cytometry. It was distinctively to find that the transfection activity of PEGylation of complexes was improved. The nanoparticles were also tested for their ability to transport across the gastrointestinal mucosa in vivo in mice. In vivo experiments showed obviously that MePEG-PLA-CS/DNA complexes mediated higher gene expression in stomach and intestine of BALB/C mice compared to PLA-CS/DNA and lipofectamine/DNA complexes. These results suggested that MePEG-PLA-CS NPs have favorable properties for non-viral gene delivery.

Effect of poly(ethylene glycol)-block-polylactide nanoparticles on hepatic cells of mouse: low cytotoxicity, but efflux of the nanoparticles by ATP-binding cassette transporters.

The objective of this paper is to study the effects of poly(ethylene glycol)-block-polylactide (PLA-PEG) nanoparticles on hepatic cells of mouse. Blank PLA-PEG nanoparticles have been successfully prepared and MTT assay suggested that the nanoparticles with HepG2 cell co-culture model did not cause significant changes in membrane integrity in controlled concentration range (0.001-0.1 mg/ml). Immunohistochemical analysis demonstrated that large dose of PLA-PEG nanoparticles injection (42.04 mg/kg, i.v.) did not induce hepatic cell apoptosis. From biochemical assay experiments, although the levels of SOD decreased and those of MDA, NOS increased after treatment with large dose of PLA-PEG nanoparticles injection (42.04 mg/kg, i.v.), they were all not significant (p>0.05). Then Kunming mice were treated with large dose of PLA-PEG nanoparticles (42.04 mg/kg, i.v.) and after 4 days total RNA was isolated to elucidate patterns of gene expression using a mouse cDNA-microarray (SuperArray). Treatment with nanoparticles resulted in over-expression of a lot of ATP-binding cassette (ABC) transporters, especially two ABC transporters (ABCA8 and ABCC5/MRP5), and down-regulation of GSTP1, in comparison with the control. ABCA8 could extrude low molecular weight polymers after PLA-PEG nanoparticles hydrolysis outside the cells. We also discovered that ABCC5 expressed multidrug resistance protein 5 (MRP5) to pump out conjugate (GS-X) of PLA-PEG nanoparticles with GSH. The results were confirmed by RT-PCR. Results of in vitro accumulation and efflux experiments indicated that about 51-52% (51.5% and 52.0%) intracellular PLA-PEG nanoparticles was expulsed after mouse primary hepatocytes reached a saturation uptake of nanoparticles during the concentration range of 750-1000 microg/ml. The results suggested that ABC transporters (especially ABCA8) pump out the polymers after hydrolysis from mouse hepatic cells and large dose of PLA-PEG nanoparticles make mouse hepatic cells gain drug resistance to PLA-PEG nanoparticles.

A novel PEGylation of chitosan nanoparticles for gene delivery.

CS (chitosan) has emerged as a promising non-viral vector for gene delivery because of its ability to form complexes with pDNA (plasmid DNA) and enhance its transport across cellular membranes through endocytosis. Complexes of CS and pDNA may improve transfection efficiency; however, they are not capable of sustained DNA release and prolonging gene transfer. In order to achieve prolonged delivery of CS-DNA complexes, we prepared CS NP (nanoparticle) and CS-DNA complexes. alpha-Methoxy-omega-succinimidylpoly(ethylene glycol) was then conjugated to the surface of CS-DNA complexes using an active ester scheme; finally, the potential of PEGylation [poly(ethylene glycol)ylation] of CS NP as a non-viral gene-delivery vector to transfer exogenous genes in vitro and in vivo were examined. Electrophoretic analysis suggested that CS NPs could protect the DNA from nuclease degradation. The pDNA carried by CS NPs could enter and be expressed in HepG2 cells. However, the transfection efficiency was very low and the highest dose of DNA transferred was 1.6 microg. The transfection activities of CS-DNA-PEG were preserved and a higher dose (2.4 microg) of pDNA was transferred. This indicated that the transfection efficiency of the PEGylated complexes had been improved. In vivo experiments also showed that CS-DNA-PEG complexes mediated higher gene expression in tissues than did CS-DNA complexes, and that gene expression in tumours induced by CS-DNA-PEG complexes was the highest of all. These results suggested that PEGylation of CS-DNA complexes improves non-viral gene delivery in vitro or in vivo and has the potential to deliver therapeutic genes directly into hepatoma tissues.

Polybutylcyanoacrylate nanoparticles as novel vectors in cancer gene therapy.

To make progress toward an efficient gene vector for cancer gene therapy, a novel nonviral vector of polybutylcyanoacrylate nanoparticles (PBCA NPs) was developed. Cetyltrimethyl ammonium bromide (CTAB) was used to modify the surface of PBCA NPs, and then the plasmid DNA (pDNA) of pAFP-TK was wrapped into PBCA-CTAB NPs. Atomic force microscopy and zeta potential demonstrated that PBCA-CTAB NPs were 80-200 nm in diameter and had +15.6 mV positive surface charges. Assay using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide showed that PBCA-CTAB NPs had less cytotoxicity to 3T3 cells than HepG2 cells. The analysis of PBCA-CTAB-DNA complexes could not only protect DNA from degradation by DNase I, it could also transfer pDNA into targeted cells with high transfection efficiency. Furthermore, when PBCA-CTAB NPs combined with suicide gene pAFP-TK, alpha-fetoprotein-positive cells transfected by it were highly sensitive to ganciclovir treatment, and cell survival declined precipitously. Therefore, this target strategy using a pAFP-TK/GCV suicide gene therapy system in which PBCA-CTAB NPs serve as gene delivery vectors explores a promising area for alpha-fetoprotein-positive hepatocellular carcinoma and associated carcinoma therapy.

Application of rapid cloud point extraction method for trace cobalt analysis coupled with spectrophotometric determination.

In this work, the analytical performance of conventional spectrophotometer was improved through the coupling of effective preconcentration method with spectrophotometric determination. Rapidly synergistic cloud point extraction (RS-CPE) was used to pre-concentrate ultra trace cobalt and firstly coupled with spectrophotometric determination. The developed coupling was simple, rapid and efficient. The factors influencing RS-CPE and spectrophotometer were optimized. Under the optimal conditions, the limit of detection (LOD) was 0.6µgL(-1), with sensitivity enhancement factor of 23. The relative standard deviation (RSD) for seven replicate measurements of 50µgL(-1) of cobalt was 4.3%. The recoveries for the spiked samples were in the acceptable range of 93.8-105%.

Reversion of multidrug resistance by co-encapsulation of doxorubicin and curcumin in chitosan/poly(butyl cyanoacrylate) nanoparticles.

Co-encapsulated doxorubicin (DOX) and curcumin (CUR) in poly(butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared with emulsion polymerization and interfacial polymerization. The mean particle size and mean zeta potential of CUR-DOX-PBCA-NPs were 133 ± 5.34 nm in diameter and +32.23 ± 4.56 mV, respectively. The entrapment efficiencies of doxorubicin and curcumin were 49.98 ± 3.32% and 94.52 ± 3.14%, respectively. Anticancer activities and reversal efficacy of the formulations and various combination approaches were assessed using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide assay and western blotting. The results showed that the dual-agent loaded PBCA-NPs system had the similar cytotoxicity to co-administration of two single-agent loaded PBCA-NPs (DOX-PBCA-NPs+CUR-PBCA-NPs), which was slightly higher than that of the free drug combination (DOX+CUR) and one free drug/another agent loaded PBCA-NPs combination (DOX+CUR-PBCA-NPs or CUR+DOX-PBCA-NPs). The simultaneous administration of doxorubicin and curcumin achieved the highest reversal efficacy and down-regulation of P-glycoprotein in MCF-7/ADR cell lines, an MCF-7 breast carcer cell line resistant to adriamycin. Multidrug resistance can be enhanced by combination delivery of encapsulated cytotoxic drugs and reversal agents.

Meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles were internalized by SW480 cells by a clathrin-mediated endocytosis pathway to induce high photocytotoxicity.

We studied the uptake of meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles by SW480 cells and carried out a systematic investigation of the cellular internalization mechanism of TCPP nanoparticles, also studied the photocytotoxicity of TCPP nanoparticles. At first, meso-tetra (carboxyphenyl) porphyrin (TCPP) nanoparticles were prepared by the method of mixing solvent techniques. SW480 cellular uptakes of photosensitizers (TCPP nanoparticles, TCPP-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles and free TCPP) were analyzed by the method of fluorospectrophotometry. Endocytosis mechanism investigation was carried out by preincubating SW480 cells at 4 degrees C, and preincubating SW480 cells with sucrose, K+-free buffer solution and filipin. Clathrin HC expression after incubating SW480 cells with these three photosensitizers was analyzed by methods of Western blot and RT-PCR. At last, we analyzed the photo-cytotoxicity after incubating SW480 cells with photosensitizers and receiving irradiation. SW480 cells showed rapid uptake (0.0083fmoles TCPP/cell) of TCPP nanoparticles after 1h incubation. We also demonstrated that the uptake of TCPP nanoparticles by SW480 cells was a clathrin-mediated endocytosis pathway. As a result of rapid internalization of TCPP nanoparticles by SW480 cells, this special photosensitizer showed very high photocytotoxic effect on SW480 cells in vitro. The nano-sized photosensitizer with no matrix cover: TCPP nanoparticles, can produce higher photocytotoxicity than other photosensitizers (TCPP-loaded PLGA nanoparticles and free TCPP). The in vivo tumor growth inhibition experiment indicated that TCPP nanoparticles plus PDT treatment induced the most dramatic tumor-inhibiting efficacy in all TCPP treated groups. The results of this study suggest that TCPP nanoparticles represent a potential and powerful photodynamic therapy agent.

Arg-Gly-Asp (RGD) peptide conjugated poly(lactic acid)-poly(ethylene oxide) micelle for targeted drug delivery.

In this study, a new poly(lactic acid)-poly (ethylene oxide)-Arg-Gly-Asp (PLA-PEO-RGD) derivative was synthesized, and paclitaxel-loaded PLA-PEO-RGD micelles were prepared by this derivative. The solubility assay showed that micelles mixed with Pluronic F-68 as surfactant could increase the solubility of this hydrophobic paclitaxel in aqueous solution. The cell-binding assay showed that PLA-PEO-RGD micelle (IC(50) = 11.13 +/- 1.38 nmol/L) had about 3.6-fold higher integrin avidity than PLA-PEO-RGD conjugates (IC(50) = 40.33 +/- 3.12 nmol/L). The avidity of micelle was also higher than RGD4C peptide (IC(50) = 24.44 +/- 1.21 nmol/L). The in vitro drug release profile of drug-loaded PLA-PEO-RGD micelles exhibited initial burst release to 37% +/- 2% (w/w) during the first 12 h, and then the release rate became steady in a controlled release manner. Furthermore, treatment of the MDA-MB-435 breast cancer cell line with paclitaxel-loaded PLA-PEO-RGD micelles yielded cytotoxicities, with EC(50) values of approximately 30 mumol/L. The paclitaxel-loaded PLA-PEO-RGD micelles treated group showed the most dramatic tumor reduction in MDA-MB-435 tumor-bearing nude mice, and the final mean tumor load was 31 +/- 16 mm(3) (mean +/- SD; n = 8). (125)I-labeled micelles administration resulted in significant (p < 0.001) higher tumor uptake (2.68% +/- 0.14%, ID/g) of PLA-PEO-RGD micelles compared to PLA-PEO micelles (0.84% +/- 0.09%, ID/g) after 2.5 h postinjection. Biodistribution study showed the best blood clearance of PLA-PEO-RGD micelles after 4.5 h postinjection. The results of this study suggest that paclitaxel-loaded PLA-PEO-RGD micelles based on the specific recognition of alpha(V)beta(3) integrin represent a potential and powerful target delivery technology.

Acute oral toxicity evaluation of biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA).

In this article, a novel biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA), was prepared by UV-initiated free radical polymerization. The obtained hydrogel was characterized by (1)H NMR and FTIR. The acute toxicity tests and histopathological study were performed in BALB/c mice. In acute oral toxicity test, mice were orally administered with a total 15 g/kg body weight (b.w.) of P(CL-MAA-EG) hydrogels, and were observed continuously for 14 days. For histopathologic study, samples including heart, liver, lung, kidneys, spleen, stomach, and intestine, were histochemically prepared and stained with hematoxylin-eosin for histopathologic examination. No mortality or significant signs of acute toxicity was observed during the whole observation period, and no macroscopic alteration was found in the organs. Histopathological analysis of various organs also did not show any significant pathological changes. Thus, the maximal tolerance dose of P(CL-MAA-EG) hydrogels was calculated to be higher than 15 g/kg b.w. in BALB/c mice. It was suggested that the studied P(CL-MAA-EG) hydrogel in this article were nontoxic after acute oral administration and it might be a promising candidate as a novel oral drug carrier.

Relationship between sterol/steroid structure and participation in ordered lipid domains (lipid rafts): implications for lipid raft structure and function.

The formation and stability of ordered lipid domains (rafts) in model membrane vesicles were studied using a series of sterols and steroids structurally similar to cholesterol. In one assay, insolubility in Triton X-100 was assessed in bilayers composed of sterol/steroid mixed with dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine, or a 1:1 mixture of these phospholipids. In a second assay fluorescence quenching was used to determine the degree of ordered domain formation in bilayers containing sterol/steroid and a 1:1 mixture of DPPC and a quencher-carrying phosphatidylcholine. Both methods showed that several single modifications of the cholesterol structure weaken, but do not fully abolish, the ability of sterols and steroids to promote ordered domain formation when mixed with DPPC. Some of these modifications included a shift of the double bond from the 5-6 carbons (cholesterol) to 4-5 carbons (allocholesterol), derivatization of the 3-OH (cholesterol methyl ether, cholesteryl formate), and alteration of the 3-hydroxy to a keto group (cholestanone). An oxysterol involved in atherosclerosis, 7-ketocholesterol, formed domains with DPPC that were as thermally stable as those with cholesterol although not as tightly packed as judged by fluorescence anisotropy. It was also found that 7-ketocholesterol has fluorescence quenching properties making it a useful spectroscopic probe. Lathosterol, which has a 7-8 carbon double bond in place of the 5-6 double bond of cholesterol, formed rafts with DPPC that were at least as detergent-resistant as, and even more thermally stable than, rafts containing cholesterol. Because lathosterol is an intermediate in cholesterol biosynthesis, we conclude it is unlikely that sterol biosynthesis continues past lathosterol in order to create a raft-favoring lipid.