MOFs的制备及其载药性能初步评价

目的：制备MOFs材料，并评价其载药性能、释药行为和生物相容性。方法：采用溶剂热合成法制备MOFs载体材料，同时通过负载青蒿琥酯(Artesunate, AS)制得AS@MOFs载药体系。从AS与MOFs质量比、反应温度、搅拌时间这三方面对MOFs载药性能的影响进行探讨，接着通过体外释放和溶血实验初步评价MOFs的释药行为和安全性。结果：当m(AS)∶m(MOFs)为2∶4、反应温度在55℃下、搅拌时间为6 h时MOFs会呈现最优的载药性能，同时体外释放显示MOFs具有pH响应性释放行为，溶血实验结果也表明AS@MOFs具有良好的生物相容性。结论：本研究成功制备了MOFs材料，且该材料具有良好的载药性能和高生物相容性。     

RGD肽修饰的pH响应型中空介孔二氧化硅纳米粒子的制备与评价

以聚多巴胺(PDA)为反应平台,对中空介孔二氧化硅纳米粒子(HMSN)进行RGD肽和聚(2-乙基-2-噁唑啉)(PEOz)双重修饰,构建了RGD肽和PEOz共同修饰的中空介孔二氧化硅纳米载体(HMSN-PEOz-RGD),以盐酸阿霉素(DOX)为模型药物构建载药体系DOX@HMSN-PEOz-RGD,用红外光谱法(FTIR)对载体进行结构表征,考察载药体系的载药量、包封率及载体的形态、粒径及Zeta电位,通过体外释药实验研究载药体系在不同pH值下的响应性释放,以人乳腺癌细胞MCF-7为模型,考察载体的生物相容性及载药体系的细胞毒性及细胞摄取过程。结果表明,HMSN-PEOz-RGD的平均粒径为(256.1±26.5) nm,粒径分布较均匀;DOX@HMSN-PEOz组和DOX@HMSN-PEOz-RGD组的体外释药都表现出明显的pH依赖性,即酸性(pH值5.0)条件下药物快速释放,而在生理pH值(pH值7.4)条件下药物释放缓慢;生物相容性实验结果显示,各载体在2.5～80μg·mL~(-1)的浓度范围内,与MCF-7细胞共培养24 h后,细胞存活率均在89%以上,表明载体具有良好的生物相容性;体外抗肿瘤活性实验结果表明,相比于其余载药制剂组,DOX@HMSN-PEOz-RGD组细胞的生长明显得到抑制,RGD修饰显著促进了DOX的细胞摄取。本研究所构建的纳米载体能够特异性靶向递送DOX,具有一定的应用前景。     

pH敏感性硼酸酯键及其递药系统的研究进展

由于肿瘤细胞的高代谢率导致供氧不足,肿瘤细胞在低灌注区的细胞外间隙与周围正常组织细胞相比具有高酸性,因此具有pH敏感性的纳米载药系统被广泛应用于癌症治疗中。硼酸酯键是一种可逆的pH敏感性的化学键,在酸性环境中此键可以断裂,将其制备成具有pH响应性硼酸酯键的纳米载药系统,可以达到pH敏感性控制释放药物的目的。     

pH敏感性生物基纳米载药粒子的研究进展

生物基来源的聚合物具有生物相容性高、无毒易降解等优势,近些年来作为药物载体在生物医药领域受到了广泛的关注。人体内的生理环境存在pH差异,利用pH作为刺激响应的信号,可以赋予聚合物纳米载药系统理想的靶向释药性能。本综述着眼于pH敏感性的生物基聚合物纳米粒子,揭示了纳米载药粒子中化学键断裂与质子化作用两种pH响应的控释机制,并针对两者的控释特点进行了分析总结。在此基础上,介绍了几种生物基药物载体的pH控释研究及其在生物医药领域的应用进展,并提出了目前利用各种生物基材料作为药物载体存在的问题。最后,针对目前存在的载药量低、敏感性不强等问题,提出了可采用多种方式联合载药、多重刺激响应结合等方式进行深入研究的展望。     

聚乳酸载药微球的制备研究

聚合物微球的粒径较小,可以很好地越过阻碍物到达患病部位;并且通过控制药物的释放速率,能够实现准确给药,提高药物的利用率。聚乳酸具有良好的生物可降解性,在药物载体领域得到了广泛的应用。通过实验研究影响药物载体性能的各项因素,以硝苯地平为模型药物,采用乳化蒸发法制备载药微球,研究范德华力、药物的形态对微球和药物相容性的影响。结果表明,随着聚乳酸用量的不断加大,微球粒径逐渐增大;药物含量减少时,微球的表面光滑,且分散性较好;基于相容性规则可用于选择和设计适宜的药物载体的聚合物材料。     

PLA嵌段PEG聚合物胶束载药系统的研究进展

介绍了PLA嵌段PEG聚合物的合成、性质和质量评价方法,对其所形成的载药胶束的性能评价指标进行了总结,并综述了其作为胶束在药物载药系统中的应用,尤其是应用在抗肿瘤药物上的研究进展。结论:PLA嵌段PEG聚合物有良好的生物可降解性和相容性,为目前胶束载药系统中聚合物的研究热点,具有广泛应用前景。     

基于纤维素模板的聚合物空心微球作为药物载体的性能研究及分析

以羟丙基纤维素为模板材料,分别采用不同的聚合方法制备了2种不同形态和结构的聚合物空心微球--聚N-异丙基丙烯酰胺-co-聚丙烯酸(PNIPAm-co-PAA)微凝胶和聚N-异丙基丙烯酰胺-聚丙烯酸(PNIPAm-PAA)水凝胶微囊。以盐酸阿霉素(Dox)作为模型药物,考察了聚合物空心微球作为药物载体的载药能力和体外释放性能。研究表明,PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊和Dox分子能够通过正负电荷的相互吸引实现有效结合;载药微球具有良好的缓释性能,并对Dox的释放表现出明显的pH值敏感性和温度敏感性。体外细胞毒性实验表明,载药PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊具有很高的抗肿瘤活性,细胞相对存活率均可达20%左右。PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊在作为水溶性药物或蛋白类药物载体方面,具有潜在的应用价值,同时有望应用于木材胶黏剂防腐等。     

透明质酸自组装聚合物胶束的制备及表征

为了增强抗肿瘤药物的靶向性与抗肿瘤活性,本文制备了透明质酸-十八烷聚合物,用其对阿霉素进行包载,考察其理化性质及体外细胞毒性。合成两亲性透明质酸-十八烷聚合物,利用核磁对其结构进行确证。选择超声法制备载阿霉素的聚合物胶束,考察胶束的粒径、电位、包封率、载药量以及体外释放行为。选择乳腺癌细胞MCF-7为肿瘤细胞模型,考察载药胶束的体外抗肿瘤活性。成功合成了透明质酸-十八烷聚合物。制备的空白胶束和载药的胶束的粒径分别为（180.7±1.25）nm和（178.3±2.24）nm,Zeta电位分别为（-21.3±0.25）mV和（-18.1±0.31）mV。载阿霉素聚合物胶束的包封率为（96.1%±0.72%）,载药量为16.1%±1.18%,体外释放行为表明在72h的累计药物释放率仅为40%左右,具有明显的缓释行为。体外细胞毒性结果表明,空白聚合物胶束对肿瘤细胞几乎没有毒性,而载阿霉素的聚合物胶束具有较好的抗肿瘤活性。结论：透明质酸-十八烷聚合物胶束可以有效地包载抗肿瘤药物阿霉素,具有良好的缓释特性和抗肿瘤活性。     

甜菜碱类两性离子共聚物涂层的构建及释药行为研究

以具有生物相容性的甲基丙烯酸羧酸甜菜碱酯(CBMA)和具有疏水作用的甲基丙烯酸十八烷基酯(SMA)为单体,采用传统自由基聚合的方法制备基于甜菜碱的两性离子二元共聚物CBMA-SMA,并对其进行核磁氢谱与红外光谱表征,谱图结果显示聚合物具有预期结构。进一步以疏水性荧光染料罗丹明B为药物模型,分别构建有CBMA-SMA共聚物覆盖的载药涂层和无CBMA-SMA共聚物覆盖的载药涂层,并对不同结构载药涂层的药物释放行为进行初步探索。结果表明,药物释放开始呈线性增长,然后释放速率逐渐趋于稳定,且载药涂层表面的CBMASMA共聚物覆盖层起到了较好的扩散屏障作用,释放速率要小于无CBMA-SMA共聚物覆盖的载药涂层。     

静电纺载药PCL/PU高取向纳米纤维的制备及其性能研究

近年来，生物相容性纳米复合材料在药物释放等生物医学领域的应用越来越受到人们的关注。制备了PCL与聚氨酯（PU）复合的高取向载药纳米纤维，以改善高聚物纳米纤维在药物缓释、生物组织培养中的性能，扩大应用市场，为复合纤维膜在药物的控制释放方面的应用提供依据。     

Novel synthesis of ZnO nanoparticles and their enhanced anticancer activity: Role of ZnO as a drug carrier

In this work, a simple and versatile technique was developed to prepare highly crystalline ZnO nanoparticles (ZnO NPs) by organic precursor method using 5, 6 dimethyl benzimidazole and Zn(CH₃COO)₂·2H₂O followed by calcination. These synthesized ZnO NPs were used as a drug carrier to form 5-Fluorouracil (5 Fu) encapsulated ZnO NPs by varying the molar ratio (100–300:1) of ZnO NPs to 5-Fu. X-ray diffraction (XRD) results indicated that the ZnO NPs had single phase nature with the wurtzite structure. Field emission scanning electron microscopy (FESEM) and Transmission electron microscopy (TEM) results showed nanometer dimension of the NPs. FTIR analysis further reaffirmed the formation/encapsulation of ZnO NPs. UV–vis spectroscopy determined the encapsulation efficiency (EE) and loading capacity (LC) of 5-Fu drug on ZnO NPs. HPLC analysis of encapsulated NPs indicated release of 5-Fu was higher at tumor cell pH (pH 6.0) than physiological pH. Moreover, the anti-tumor activity of ZnO NPs and 5-Fu-encapsulated ZnO NPs investigated using flow cytometry demonstrated that 5-Fu encapsulated ZnO NPs have more anti-tumor activities than 5-Fu itself toward MCF-7 (Breast cancer) cell line. Also, cytotoxicity of MCF-7 increased with the increase of ZnO NPs: 5-Fu ratio. This research will introduce a new concept to synthesize 5-fluorouracil encapsulated ZnO NPs and its application towards the cancer cell line. Thus, the ZnO NPs could not only apply as the drug carrier to deliver 5-Fluorouracil into the cancer cells, but also enhances anti-tumor activity.     

Hollow mesoporous polyaniline nanoparticles with high drug payload and robust photothermal capability for cancer combination therapy

In recent years,synergistic chemo-photothermal therapy has revealed promising potential in treatments against various kinds of cancer.However,the development of superb photothermal agents with high drug loading capacity is still highly required.In this work,a hollow mesoporous polyaniline nanoparticle(HPANI NP) has been developed for encapsulating chemotherapeutic drug doxorubicin (DOX) with an remarkable drug loading content as high as 37.5％.Additional PEG modification endowed the drug-loaded HPANI NPs with improved water-dispersibility and bioavailability.Such PEG-HPANI-DOX NPs exhibited strong NIR absorbance and robust photothermal conversion capacity,exhibiting highly efficient synergistic cancer treatment.More interestingly,the responsively released DOX molecules could emit strong red fluorescence,which could be employed to monitor the cellular endocytosis and drug release profile of PEG-HPANI-DOX NPs.Finally,the as-fabricated NPs showed good biocompatibility and low tox-icity,serving as a promising nanoagent for highly efficient drug delivery and cancer combination therapy.     

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.     

Amphiphilic core-shell nanoparticles with dimer fatty acid-based aliphatic polyester core and zwitterionic poly(sulfobetaine) shell for controlled delivery of curcumin

Multifunctional nanocarriers are gaining increasing research interest as polymeric platforms for targeted drug delivery in cancer therapy and diagnosis. In this work, preparation and characterization of surfactant-free polyester nanoparticles (NPs) from a bio-based poly(butylene sebacate-co-butylene dilinoleate)s, poly(butylene sebacate) (PBSE)/poly(butylene dilinoleate) (PBDL), using nanoprecipitation, is reported. The polymeric nanoparticles (sizes narrowly distributed in a range less than 100?nm) were loaded with curcumin (CURC) with an encapsulation efficiency of 98% and drug loading (DL) content of 5–10% wt_drug/wt_polymer. The CURC-loaded nanoparticles were efficiently coated with a novel poly(sulfobetaine)-type zwitterionic polymer synthesized by nitroxide-mediated polymerization and postpolymerization functionalization step. Free and CURC formulated into noncoated and poly(sulfobetaine)-type zwitterionic polymer-coated nanoparticles were further investigated for cytotoxicity and antioxidant activity in a panel of human cell lines and rat liver microsomes, respectively. Formulated into coated NPs, CURC has superior cytotoxic and antioxidant activity versus the free drug and CURC incorporated in noncoated NPs. In addition, cell viability experiments of nonloaded nanoparticles, both coated and noncoated, demonstrated that developed nanoparticles are nontoxic, making them potentially suitable candidates for systemic passive targeting in cancer therapy, namely for treatment of solid tumors exhibiting high tumor accumulation of NPs due to enhanced permeability and retention effect. Polyzwitterion-coated nanoparticles exhibited slower drug release compared with the noncoated ones (half as much after 24?h) presumably due to the presence of the polymer shell around nanoparticles associated with a wider diffusion layer around the particles.     

Synthesis of Triazole-Based Nonionic Surfactants for Nanostructured Drug Delivery: Investigation of Their Physicochemical and Biological Aspects

Synthesis of novel nonionic surfactants has attracted attention of synthetic chemists due to the issues of the currently used commercial surfactants. The synthesis of three biocompatible triazole-based nonionic surfactants is reported for nanovesicular drug loading. The surfactants were synthesized in a three-step reaction and characterized using ¹HNMR and mass spectroscopy techniques. They were investigated for their critical micelle concentration (CMC) using a UV–Visible spectrophotometer. Their biocompatibility was investigated against cell culture and in blood. All the synthesized nonionic surfactants were further explored for their nanovesicular drug loading using clarithromycin as a model hydrophobic drug. Nonionic surfactants revealed lower CMC in 35–45 μM and were less hemolytic and cytotoxic. They were capable of self-assembling in nanosize niosomal vesicles encapsulating increased amounts of drug. The results suggest the synthesized nonionic surfactants as biocompatible nanotechnology-based drug-delivery vehicles.     

抗肿瘤药物蒽醌-氮芥衍生物的设计与合成

运用拼合原理以芳香氮芥4-[N,N-二(2-氯乙基)氨基]苯甲酸为药效基团,不同链长的二胺或醇胺为连接剂,蒽醌为嵌入剂设计合成了六个未见报道的潜在的以DNA为靶向的抗肿瘤药物蒽醌-氮芥衍生物.所合成的化合物结构经H NMR及MS加以确证.     

Surfactant free-poly(lactic-co-glycolic acid) coated artesunate loaded citrate-functionalized hydroxyapatite nanorods as a nanocapsule for improving artesunate delivery and antitumor efficiency

The development of targeted drug delivery systems with controlled drug release and enhanced drug bioavailability has attracted increasing attention as a candidate for clinical applications. We designed biocompatible citrate-functionalized hydroxyapatite nanorods (Cit-HAp NRs) loaded with artesunate (ART) for use in colon cancer therapies. These were then encapsulated into surfactant free PLGA nanoparticles (ART@Cit-HAp NRs/SF-PLGA NPs). The synthesized Cit-HAp NRs, ART-loaded Cit-HAp NRs and ART@Cit-HAp NRs/SF-PLGA NPs were characterized using a variety of comprehensive techniques. An ART loading efficiency of ～92% was observed upon using a 1:10 mass ratio (ART: Cit-HAp NRs). We revealed that the adsorption of ART on Cit-HAp NRs proceeds via a pseudo-second-order adsorption mechanism. The in vitro ART release from the nanocomposites (ART@Cit-HAp NRs/SF-PLGA NPs) exhibits a pH dependent release and the rate of ART release from the ART@Cit-HAp NRs/SF-PLGA NPs was slower than the release from Cit-HAp NRs. The effects of ART@Cit-HAp NRs/SF-PLGA NPs were evaluated in human colon cancer (HCT 116 and Caco-2) cell lines. ART@Cit-HAp NRs/SF-PLGA NPs demonstrated higher anti-proliferation activity compared with free ART. The delivery of ART using Citrate-functionalized hydroxyapatite encapsulated, surfactant free PLGA nanoparticles as a carrier could improve their anti-cancer activities.     

Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy

Cancer is one of the primary causes of worldwide human deaths. Most cancer patients receive chemotherapy and radiotherapy, but these treatments are usually only partially efficacious and lead to a variety of serious side effects. Therefore, it is necessary to develop new therapeutic strategies. The emergence of nanotechnology has had a profound impact on general clinical treatment. The application of nanotechnology has facilitated the development of nano-drug delivery systems (NDDSs) that are highly tumor selective and allow for the slow release of active anticancer drugs. In recent years, vehicles such as liposomes, dendrimers and polymer nanomaterials have been considered promising carriers for tumor-specific drug delivery, reducing toxicity and improving biocompatibility. Among them, polymer nanoparticles (NPs) are one of the most innovative methods of non-invasive drug delivery. Here, we review the application of polymer NPs in drug delivery, gene therapy, and early diagnostics for cancer therapy.     

Novel semi-interpenetrating network hydrogels based on monosaccharide oligomers with itaconic moiety: synthesis and properties

Hydrogel-based drug delivery systems encounter great scientific attention nowadays. Semi-interpenetrating network systems with hydrogel features have been studied as potential drug carriers due to their water intake capacity, biocompatibility and biodegradability. One of the most important features of drug delivery systems is biocompatibility and as such materials derived from natural resources seem to be more appropriate to act as excipients. In this respect, two new semi-interpenetrating networks (semi-IPNs) with hydrogel features based on chitosan, two novel oligomers derived from monosaccharides and 2-hydroxyethylmethacrylate (HEMA) have been synthesized and characterized using FTIR, thermogravimetry, SEM/EDX and swelling behavior. The new sugar-derived oligomers (GI and MI) with double bonds available for further polymerization were obtained by polycondensation of 1,3-propanediol with dicarboxylic acids derived from glucose/mannose skeleton with itaconic anhydride moieties. GI and MI oligomers were characterized by FTIR, NMR spectroscopy and ESI–MS spectrometry, which showed molecular weights of about 7000 Da and linear polymerization chain structure. The new semi-IPNs show good thermal behavior and these hydrogels display a swelling tendency by loading significantly more water in an acid environment than in a neutral solution. Moreover, these superabsorbent hydrogels are able to load significant amount of hydrosoluble active principle (herein the antibiotic levofloxacin) and their releasing profile is marked by an important “burst effect”.     

Insight into the impact of zinc doping on the structural,surface, and biological properties of magnasium oxide nanoparticles stabilized by Vateria indica (L.) fruit extract

The present study is an attempt to delineate the effect of zinc doping on the green synthesized magnesium oxide (MgO) NPs. Pure (MgOVI) and zinc doped (ZnMgOVI) NPs were synthesized employing an aqueous fruit extract of V. indica as capping and reducing agents. The various analytical techniques viz. FTIR, PXRD, FESEM, and EDS spectroscopy together with elemental mapping analyses substantiated the formation of pure and doped NPs with crystallite sizes 23.74 and 25.41 nm. The study of surface properties through BET analysis unfolded the formation of mesoporous NPs with a surface area of 7.4 and 5.3 m²g^-1 for pure and doped NPs respectively. Additionally, the refinement of obtained PXRD data through Rietveld refinement corroborated the changes in cell parameters after zinc doping. The anti-inflammatory activity carried out unveiled the biocompatibility of obtained NPs by exhibiting a % HRBCS of 83.65 ± 0.002 and 85.69 ± 0.003 for MgOVI and ZnMgOVI NPs. The in-vitro antidiabetic activity of MgOVI and ZnMgOVI NPs performed revealed their excellent α-amylase inhibition activity (86.29 ± 0.001and 86.44 ± 0.002%). Furthermore, the NPs also displayed anti-microbial activities against Staphylococcus aureus, Bacillus subtulis, Pseudomonas aeroginosa, Pseudomonas syringae, and Escherichia coli. Thus the studies have evinced the superlative antidiabetic and antimicrobial potentialities of MgOVI and ZnMgOVI NPs with high biocompatibility.