星点设计-效应面法优化pH值依赖型岩黄连碱口服结肠靶向纳米粒

目的 采用星点设计-效应面法（central composite design-response surface methodology,CCD-RSM）优化pH值依赖型岩黄连碱口服结肠靶向纳米粒（dehydrocavidine-chitosan/pectin-nanoparticles,DC-CS/PT-NPs）制备工艺,并对其进行质量表征及体外释放行为评价。方法 采用离子凝胶法制备DC-CS/PT-NPs,以粒径、PDI、ζ电位、包封率、载药量作为评价指标,采用单因素考察和CCD-RSM优化DC-CS/PT-NPs制备工艺。通过透射电子显微镜（transmission electron microscope,TEM）、扫描电子显微镜（scanning electron microscope,SEM）、傅里叶红外光谱（Fourier transform infrared spectroscopy,FTIR）、差示扫描量热法（differential scanning calorimetry,DSC）和X射线衍射法（X-ray diffraction,XRD）对DC-CS/PT-NPs进行表征,并进行体外释放性能评价。结果 最佳处方为壳聚糖质量浓度为1.5 mg/mL,果胶质量浓度为1.5 mg/mL,TPP质量浓度为2.0 mg/mL,壳聚糖pH值为5.0。DC-CS/PT-NPs包封率为（61.64±1.77）%,载药量为（8.05±0.18）%,粒径为（418.65±4.92）nm,ζ电位为（-14.14±0.22）mV。DC-CS/PT-NPs呈均匀的球形或类球形;制备成纳米粒后,药物的晶型发生了改变;体外释药结果表明,DC-CS/PT-NPs在人工胃液中2 h仅释放24.35%,在人工小肠液中4 h累积释放率<40%,在人工结肠液中10 h累积释放率>85%。结论 CCD-RSM所建立的模型可用于DC-CS/PT-NPs处方优化,DC-CS/PTNPs具有良好的体外结肠释药特征。     

壳聚糖的制备条件及其大鼠体内的分布

以虾壳为原料,本文报道了制备条件对壳聚糖性能的影响,利用核磁共振,质谱等方法,测定了壳聚糖的分子结构,采用氚标记法,进行了＾３Ｈ－壳聚糖在大鼠体内的组织分布试验。     

Characterization of PEG–iron oxide hydrogel nanocomposites for dual hyperthermia and paclitaxel delivery

Hyperthermia, the heating of tissue from 41 to 45?°C, has been shown to improve the efficacy of cancer therapy when used in conjunction with irradiation and/or chemotherapy. In this work, hydrogel nanocomposites have been developed that can control the delivery of both heat and a chemotherapeutic agent (e.g. paclitaxel). The nanocomposites studied involve a stealth, poly(ethylene glycol) (PEG)-based system comprised of PEG (n?=?1000) methyl ether methacrylate and PEG (n?=?400) dimethacrylate with iron oxide nanoparticles physically entrapped within the hydrogel matrices. The capability of the hydrogel nanocomposites to be heated in an alternating magnetic field was demonstrated. The heating of the hydrogel systems was dependent on the crosslinking of the hydrogel network where hydrogels with lower swelling ratios were found to heat to a greater extent than those with higher ratios. In addition, paclitaxel was shown to exhibit non-Fickian release from the hydrogel systems, with the amount of drug released dependent on the hydrogel network structure. Three cell lines: M059K (glioblastoma), MDA MB 231 (breast carcinoma), and A549 (lung adenocarcinoma) were exposed to paclitaxel only, hyperthermia only, and both paclitaxel and hyperthermia to determine if a synergistic cytotoxic effect was possible for these cell lines. The efficacy of paclitaxel was greater with hyperthermia for the A549 cells; however, the M059K and MDA MB 231 did not show the same response.     

Alginate/quaternized carboxymethyl chitosan/clay nanocomposite microspheres: preparation and drug-controlled release behavior

Drug-delivery systems, using natural drug carriers, have become increasingly important because of their nontoxicity and biodegradability. In this study, firstly, quaternized carboxymethyl chitosan (QCMC) was intercalated into the interlayer of organic montmorillonite (OMMT) to obtain the QCMC/OMMT nanocomposites, their structure, morphology, and thermal stability were investigated. Next, crosslinked alginate/QCMC/OMMT (AQCOM) microsphere was obtained by crosslinking with CaCl₂, and the drug-controlled release behavior was evaluated with bovine serum albumin (BSA) as model drug. The results suggested that, carboxyl groups in alginate and QCMC crosslinked with Ca²⁺, quaternary ammonium groups in QCMC or OMMT electrostatically interacted with carboxyl groups in alginate, and there was stable three-dimensional network in AQCOM microsphere. The swelling ratio of AQCOM microspheres decreased with the increase of OMMT content, the lowest one was only about 45% compared to the microsphere without OMMT of 197%. Besides, the in vitro release results for BSA indicated that the AQCOM microsphere displayed more excellent encapsulation and controlled release capacities than the microsphere without OMMT. The in vitro active cutaneous anaphylaxis test was carried out on Guinea pigs, which revealed that AQCOM microsphere did not cause anaphylaxis. Therefore, QCMC/OMMT nanocomposites from natural materials are considerably suitable to apply as drug-controlled release carriers.     

Development of chitosan/gelatin hydrogels incorporation of biphasic calcium phosphate nanoparticles for bone tissue engineering

Abstract

The chitosan/gelatin hydrogel incorporated with biphasic calcium phosphate nanoparticles (BCP-NPs) as scaffold (CGB) for bone tissue engineering was reported in this article. Such nanocomposite hydrogels were fabricated by using cycled freeze-thawing method, of which physicochemical and biological properties were regulated by adjusting the weight ratio of chitosan/gelatin/BCP-NPs. The needle-like BCP-NPs were dispersed into composites uniformly, and physically cross-linked with chitosan and gelatin, which were identified via Scanning Electron Microscope (SEM) images and Fourier Transform Infrared Spectroscopy (FT-IR) analysis. The porosity, equilibrium swelling ratio, and compressive strength of CGB scaffolds were mainly influenced by the BCP-NPs concentration. In vitro degradation analysis in simulated body fluids (SBF) displayed that CGB scaffolds were degraded up to at least 30?wt% in one month. Also, CCK-8 analysis confirmed that the prepared scaffolds had a good cytocompatibility through in culturing with bone marrow mesenchymal stem cells (BMSCs). Finally, In vivo animal experiments revealed that new bone tissue was observed inside the scaffolds, and gradually increased with increasing months, when implanted CGB scaffolds into large necrotic lesions of rabbit femoral head. The above results suggested that prepared CGB nanocomposites had the potential to be applied in bone tissue engineering.     

Fabrication of a live cell-containing multilayered polymer hydrogel membrane with micrometer-scale thickness to evaluate pharmaceutical activity

We propose a spinning-assisted layer-by-layer method for simple fabrication of a multilayered polymer hydrogel membrane that contains living cells. Hydrogel formation occurred based on the spontaneous cross-linking reaction between two polymers in aqueous solution. A water-soluble 2-methacryloyloxyethyl phosphorylcholine polymer bearing phenylboronic acid groups (PMBV) and poly(vinyl alcohol) (PVA) were used as polymers for hydrogel membrane formation. Changing the number of hydrogel membrane layers, polymer concentration, spinning rate, and processing time for diffusion-dependent gelation of PMBV and PVA facilitated the regulation of the multilayered polymer hydrogel membrane thickness and morphology. We concluded that a multilayered polymer hydrogel membrane prepared using 5.0 wt% PMBV and 5.0 wt% PVA at a spinning rate of 2000 rpm was suitable for precise spatial control of cells in single layers. This multilayered polymer hydrogel membrane was used to prepare a single cell-laden layer to minimize barriers to the diffusion of bioactive compounds while preserving the three-dimensional (3-D) context. The pharmaceutical effects of one of the anticancer agents, paclitaxel, on a human cervical cancer line, HeLa cells, were evaluated in vitro, and the usability of this culture model was demonstrated.     

The impact of a rectal hydrogel spacer on dosimetric and toxicity outcomes among patients undergoing combination therapy with external beam radiotherapy and low-dose-rate brachytherapy

PurposeRectal hydrogel spacers have been shown to decrease rectal radiation dose and toxicity. In this study, we compared prostate and rectal dosimetry and acute toxicity outcomes in patients who had and had not received a rectal hydrogel spacer prior to combination therapy with external beam radiotherapy and low-dose-rate brachytherapy.Materials and MethodsAll patients with intermediate-risk and high-risk prostate cancer who received combination therapy at our institution were identified between 2014 and 2019. Dosimetric outcomes of brachytherapy implants and quality of life (QOL) outcomes were compared between patients who had and had not received a hydrogel spacer.ResultsA Total of 168 patients meeting our inclusion criteria were identified. Twenty-two patients had received a rectal hydrogel spacer, among whom the mean separation between the rectum and prostate was 7.5 mm, and the V100_rectum was reduced by 47% (0.09 cc vs. 0.17 cc, p = 0.04). There was no difference in the percentage of patients achieving a D90 of ≥100 Gy between those who had and had not received a spacer. The mean rate of change in I-PSS and SHIM scores did not differ between the two groups at 2 months after PID.ConclusionLDR brachytherapy appears feasible after the placement of a rectal hydrogel spacer. While there was a significantly reduced V100_rectum among patients who had received a hydrogel spacer, there was no statistically significant difference in patients achieving a D90_prostate of ≥100 Gy. Although there was no difference appreciated in QOL scores, the length of follow-up was limited in the rectal-spacer group.     

Surface studies of albumin immobilized onto PE and PVC films

The aim of this study is to evaluate the thrombogenic behaviour of the low density polyethylene and poly(vinyl chloride) modified by radiation-grafting technique. After copolymerization with acrylic acid by y-rays from a ⁶⁰Co source, BSA was immobilized onto functionalized graft copolymers. The biological interaction between these materials and blood was studies by in vitro methods. The BSA immobilization effectively suppressed the adhesion and activation of platelets when it contacted whole blood.     

Comparative study of the use of poly(glycolic acid), calcium alginate and pluronics in the engineering of autologous porcine cartilage

New cartilage formation has been successfully achieved by a technology referred to as tissue engineering. Polymers and hydrogels such as poly(glycolic acid), calcium alginate, and poly(ethylene) and poly(propylene) hydrogels have been used as cell carriers to regenerate cartilage in the nude mouse model. The next step toward human applications of engineered cartilage is to demonstrate their potential in immunocompetent animal models. This study compared the suitability of three polymers for generating tissue engineered elastic cartilage using autologous cells in an immuno-competent porcine animal model. Auricular cartilage was obtained from pigs. Chondrocytes were isolated and seeded onto fiber based poly(glycolic acid) (PGA) scaffolds or suspended in calcium alginate or pluronic F127 gel at constant concentrations. Chondrocyte-polymer constructs were either implanted (PGA) or injected (calcium alginate and pluronic) as autologous implants subcutaneously into the pigs from which the cells had been isolated. Specimens were harvested and analyzed grossly and histologically after 6 weeks in vivo. All explants demonstrated cartilage formation to a variable degree. When using PGA or calcium alginate, the overall histological appearance of the tissue formed is that of fibrocartilage with thick bundles of collagen dispersed in the tissue. When using pluronics as scaffold, histologic features resemble those of native elastic cartilage, showing a more organized arrangement of the cells, which seems to correlate to functional properties as elastin presence in the tissue engineered cartilage. Elastic cartilage engineered in an immunocompetent animal model varies with the type of polymer used. The behavior of the cell-polymer constructs is not fully understood and outcome seems to be related to several factors, including inflammatory reaction. Further studies with similar models are needed to determine the feasibility of engineering tissue generated from different cell-polymer constructs prior to human application.     

Fabrication of Tapered Fluidic Microchannels Conducive to Angiogenic Sprouting within Gelatin Methacryloyl Hydrogels

IntroductionThe transplantation of stem cells/tissue constructs into root canal space is a promising strategy for regenerating lost pulp tissue. However, the root canal system, which is cone shaped with a taper from the larger coronal end to the smaller apical end, limits the vascular supply and, therefore, the regenerative capacity. The current study aimed to fabricate built-in microchannels with different tapers to explore various approaches to endothelialize these microchannels.MethodsThe fluidic microchannels with varying tapers (parallel, 0.04, and 0.06) were fabricated within gelatin methacryloyl (GelMA) hydrogel (with or without stem cell from the apical papilla [SCAP] encapsulation) of different concentrations (5%, 7.5%, and 10% [w/v]). Green fluorescent protein–expressing human umbilical vein endothelial cells (HUVECs-GFP) were seeded alone or with SCAPs in coculture into these microchannels. Angiogenic sprouting was assessed by fluorescence and a confocal microscope and ImageJ software (National Institutes of Health, Bethesda, MD). Immunostaining was conducted to illustrate monolayer formation. Data were statistically analyzed by 1-way/2-way analysis of variance.ResultsHUVEC-only inoculation formed an endothelial monolayer inside the microchannel without angiogenic sprouting. HUVECs-GFP/SCAPs cocultured at a 1:1 ratio produced the longest sprouting compared with the other 3 ratios. The average length of the sprouting in the 0.04 taper microchannel was significantly longer compared with that in the parallel and 0.06 taper microchannels. Significant differences in HUVEC-GFP sprouting were observed in 5% GelMA hydrogel. Encapsulation of SCAPs within hydrogel further stimulated the sprouting of HUVECs.ConclusionsThe coculture of SCAPs and HUVECs-GFP at a ratio of 1:1 in 0.04 taper fluidic microchannels fabricated with 5% (w/v) GelMA hydrogel with SCAPs encapsulated was found to be the optimal condition to enhance angiogenesis inside tapered microchannels.