Bioactive injectable aggregates with nanofibrous microspheres and human dental pulp stem cells: A translational strategy in dental endodontics

Regeneration of the pulp–dentin complex with stem cells is a potential alternative to conventional root canal treatments. Human dental pulp stem cells (hDPSCs) have been extensively studied because of their ability to proliferate and differentiate into mineralized dental and non‐dental tissues. Here we combined hDPSCs with two types of injectable poly‐l ‐lactic acid (PLLA) microsphere with a nanofibrous or smooth surface to form bioactive injectable aggregates, and examined their ability to promote pulp regeneration in the root canal in an in vivo model. We investigated the biocompatibility, biosafety and odontogenic potential of fibrous (F‐BIM) and smooth bioactive injectable microspheres (S‐BIM) in vitro and in vivo. Our results demonstrated that PLLA microspheres and hDPSCs were able to form bioactive injectable aggregates that promoted dentin regeneration in both in vitro and in vivo models. Our results suggest that F‐BIM and S‐BIM may induce dentinogenesis upon in vivo grafting, and propose that the potential usefulness of the microsphere–hDPSC aggregates described here should be evaluated in clinical settings. Copyright © 2017 John Wiley & Sons, Ltd.     

克百威分子印迹固相萃取微球的制备及性能

以偶氮二异丁腈为引发剂,2~3 μm的聚苯乙烯微球为种球,克百威为模板分子,甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,采用单步溶胀法制备粒径均一的克百威分子印迹聚合物微球（MIPMs）。通过扫描电镜（SEM）、吸附平衡实验和竞争吸附实验分析了克百威MIPMs的形貌及其对克百威的结合特性及吸附选择性,并比较了克百威分子印迹固相萃取柱（MISPE）与C18固相萃取柱（C18 SPE）富集水中克百威的效果。结果表明：合成的MIPMs粒径约10 μm,表面呈蜂窝状;在90 min内可达到饱和吸附,最大吸附量为25.94 mg/g;在克百威、灭多威和三羟基克百威共存的条件下, 克百威MIPMs可实现对克百威的专一性吸附;与C18 SPE相比,克百威MISPE重复使用6次后加标回收率仍在85%以上,可用于水体中痕量克百威的检测。     

在CPS微球表面实现N-羟基邻苯二甲酰亚胺的同步合成与固载及固体催化剂催化氧化性能初探

通过分子设计的构思,仅通过两步大分子反应,便实现了N-羟基邻苯二甲酰亚胺(NHPI)在交联聚苯乙烯(CPS)微球表面的同步合成与固载,并制得了非均相催化剂微球CPS-NHPI。以氯化偏苯三酸酐(TMAC)为试剂、Lewis酸为催化剂,通过Friedel-Crafts酰基化反应,先将邻苯二甲酸酐(PA)基团键合在CPS微球表面,得到改性微球CPS-PA;再与盐酸羟胺进行酰亚胺反应,制备出固载有NHPI基团的非均相催化剂微球CPS-NHPI。重点研究了CPS微球表面发生Friedel-Crafts酰基化反应的影响因素。采用红外光谱(FT-IR)及扫描电子显微镜(SEM)等对微球CPS-NHPI进行表征,将微球CPS-NHPI分别用于分子氧氧化乙苯及环己烷两种烃类物质的氧化过程,初步考察了该微球的催化活性。研究结果表明,对于微球CPS与TMAC之间的Friedel-Crafts酰基化反应,适宜的溶剂为氯仿与N,N-二甲基乙酰胺(DMAC)混合溶剂(氯仿与DMAC的体积比为7:3),适宜的Lewis酸催化剂为SnCl₄。初步探索实验表明,催化剂微球CPS-NHPI与Co(OAc)₂ 所构成的共催化体系,在分子氧氧化乙苯及环己烷的催化氧化过程中,都表现出了良好的催化活性,温和条件下,反应35 h时乙苯氧化为苯乙酮的转化率可达37%,反应30 h时环己烷氧化为环己酮的转化率可达21%。     

90Y树脂微球治疗患者尿液中90Y放射性活度检测和分析

目的研究患者接受90Y树脂微球选择性内放射治疗(SIRT)后48 h内所排泄尿液中90Y的放射性活度, 为术后患者排泄物的管理提供建议。方法收集3名患者在术后0～24 h和24～48 h两个时间段内排泄的尿液, 并对尿液中的90Y放射性活度进行检测和分析。结果 3名患者术后0～24 h和24～48 h尿液中的90Y放射性活度排泄量分别为(1 266±258)kBq/GBq和(140±106)kBq/GBq, 90Y放射性活度浓度分别为(640±113)kBq/L和(53±12)kBq/L。结论 90Y树脂微球治疗术后肝癌患者0～24 h排泄尿液中的90Y放射性活度比24～48 h高。术后患者可通过增加排泄尿量的方式来加速排出体内游离的90Y;患者住院期间的排泄物应按照HJ 1188-2020《核医学辐射防护与安全要求》的要求处理。     

90Y树脂微球选择性内放射治疗放射防护检测与剂量评估

目的对90Y树脂微球选择性内放射治疗过程进行放射防护检测和剂量评估, 为放射防护工作提供参考。方法对90Y树脂微球介入手术治疗各操作环节和患者体表的外照射水平进行检测, 估算相关人员的受照剂量水平。结果 90Y树脂微球分装及转运过程的剂量率水平为1.12～454 μSv/h, 手术操作过程为2.06～58.2 μSv/h;3名患者术后0.5 h, 体表5 cm和1 m处的剂量率分别为22.7～64.1和0.82～2.55 μSv/h。按照每年200例患者的工作量, 90Y树脂微球药物操作对工作人员年个人有效剂量贡献为0.12～1.03 mSv/年, 术后患者对公众、家属及陪护志愿者的个人有效剂量贡献为0.02～0.24 mSv/年。结论在患者治疗、护理和出院过程中, 工作人员、陪护志愿者和公众的照射剂量均低于(GB 18871-2002《电离辐射防护与辐射源安全基本标准》)中的剂量限值和医疗机构设定的管理目标值。     

长春新碱抗肿瘤新剂型的研究进展

长春新碱作为临床一线广谱化疗药物广泛用于实体瘤的治疗,由于存在药物半衰期短、神经系统和胃肠道毒性强等缺点,使其临床应用受到限制。因此,提高长春新碱的肿瘤靶向性、延长体内滞留时间,将其制备成新型给药系统具有重要意义。近十年来国内外关于长春新碱的新剂型研究主要有纳米粒、脂质体、微泡、微球等,这些新剂型提高了长春新碱生物利用度,使其具有良好的缓控释能力或肿瘤靶向能力。针对长春新碱抗肿瘤新型给药系统的研究做一综述,为合理开发长春新碱新剂型提供理论依据。     

Characterization of the release profile of doxycycline by PLGA microspheres adjunct to non-surgical periodontal therapy

The aim of this pilot study was to assess the release of locally delivered doxycycline by poly (l-lactide-co-glycolide) (PLGA) microspheres in the periodontal pocket of patients with chronic periodontitis, treated by non-surgical periodontal therapy. Nineteen sites of non-adjacent teeth of four different patients were evaluated. Five milligram of PLGA microspheres loaded with 16 doxycycline hyclate (DOX) was administered per periodontal site. To quantify DOX released into the periodontal pocket, gingival crevicular fluid (GCF) was collected from the sites on days 2, 5, 7, 10, 15, and 20 after DOX application, and high-performance liquid chromatography was performed. Data were statistically assessed by ANOVA/Tukey test. At days 2, 5, and 7, the DOX concentration was stably sustained (23.33 ± 1.38, 23.4 ± 1.82, and 22.75 ± 1.33 μg/mL, respectively), with no significant differences over these assessment times (p > 0.05). At days 10 and 15, a tendency was observed toward a decrease in DOX concentration (21.74 ± 0.91 and 20.53 ± 4.88 μg/mL, respectively), but a significant decrease in GCF drug concentration (19.69 ± 4.70 μg/mL) was observed only on day 20. The DOX delivery system developed demonstrated a successful sustained release after local administration, as an adjunct to non-surgical periodontal therapy.     

Polymer-coated gelatin capsules as oral delivery devices and their gastrointestinal tract behaviour in humans

In oral delivery of protein and peptide drugs there is a great need for suitable devices for delivering the therapeutic agent-incorporated microspheres selectively in the intestine. It is essential that the drug-loaded multiple unit carrier system should be protected from the harsh environment of the stomach and deliver the carrier system in the large intestine where drug action or absorption is desired. Gelatin capsules were coated with various concentrations of sodium alginate and cross-linked with appropiate concentrations of calcium chloride and tested in vitro for resistance to gastric and intestinal medium. Gelatin capsules coated with 20% w/v of the polymer which gave the most promising result in vitro were evaluated in human volunteers for their in vivo gastro intestinal tract behaviour. The radiographical studies show that while the uncoated gelatin capsules disintegrated in the stomach within 15 min of ingestion, the alginate coated gelatin capsules remained intact as long as they were retained in the stomach (up to 3 h) and then migrated to the ileocecal region of the intestine and disintegrated.     

Fabrication of a Layered Microstructured Polymeric Microspheres as a Cell Carrier for Nucleus Pulposus Regeneration

Abstract

This study aimed to investigate the feasibility of nanostructured 3D poly(lactide-co-glycolide) (PLGA) constructs, which are loaded with dexamethasone (DEX) and growth factor embedded hepaiin/poly(L-lysine) nanoparticles by a layer-by-layer system, to serve as an effective scaffold for nucleus pulposus (NP) tissue engineering. Our results demonstrated that the microsphere constructs were capable of simultaneously releasing basic fibroblast growth factor and DEX with approximately zero-order kinetics. The dual bead microspheres showed no cytotoxicity, and promoted the proliferation of the rat mesenchymal stem cells (rMSCs) by lactate dehydrogenase assay and CCK-8 assay. After 4 weeks of culture in vitro, the rMSCs- scaffold hybrids contained significantly higher levels of sulfated GAG/DNA and type-II collagen than the control samples. Moreover, quantity real-time PCR analysis revealed that the expression of disc-matrix proteins, including type-II collagen, aggrecan and versican, in the rMSCs-scaffold hybrids was significantly higher than the control group, whereas the expression of osteogenic differentiation marker type-I collagen was decreased. Taken together, these data indicate that the heparin bound bFGF-coated and DEX-loaded PLGA microsphere constructs is an effective bioactive scaffold for the regeneration of NP tissue.     

Vascularization into a porous sponge by sustained release of basic fibroblast growth factor

Vascularization into a poly(vinyl alcohol) (PVA) sponge was investigated using basic fibroblast growth factor (bFGF). This growth factor was impregnated into biodegradable gelatin microspheres for its sustained release and then the bFGF-containing microspheres or free bFGF were incorporated into PVA sponges. Following subcutaneous implantation into the back of mice, the bFGF-containing gelatin microspheres induced vascularization in and around the sponge to a significantly greater extent than that of free bFGF from 3 days after implantation. Significant ingrowth of fibrous tissue into the sponge was also observed when bFGF-containing microspheres were added to the sponge in contrast to free bFGF. Tissue ingrowth occurred into the deeper portion of the sponge over time while it accompanied formation of new capillaries. Empty gelatin microspheres had no effect on vascularization and the level of fibrous tissue ingrowth into the sponge was similar to that of the control group. It was concluded that incorporation of gelatin microspheres containing bFGF into the PVA sponge was effective in prevascularization of the sponge pores.