Traditional drug delivery methods are prone to large fluctuations in drug concentration and require multiple frequent doses.As a green material with excellent properties,cellulose has been widely used as a drug carrie...Traditional drug delivery methods are prone to large fluctuations in drug concentration and require multiple frequent doses.As a green material with excellent properties,cellulose has been widely used as a drug carrier for the development and preparation of drug controlled-release system.Based on the mechanisms of slow drug release,such as dissolution-diffusion release,degradation release,and nanochannel-controlled release,the preparation methods of cellulose-based drug carriers are introduced in this paper.The applications of cellulose-based drug carriers in the fields of antitumor therapy,antibacterial therapy,chronic disease treatment,and viral disease treatment are summarized with the aim of providing a useful reference for research on cellulose-based drug carriers.展开更多
The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier(NLC) drug delivery platform. An ophthalmic antiinflammatory drug, baicalin(BN) was cho...The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier(NLC) drug delivery platform. An ophthalmic antiinflammatory drug, baicalin(BN) was chosen as the model drug. BN –NLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH-and thermo-sensitive hydrogel composed of carboxymethyl chitosan(CMCS) and poloxamer 407(F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin(GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH-and thermo-sensitive. The results of in vitro release suggested BN –NLC gel can prolong the release of baicalin comparing with BN eye drops and BN –NLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient(Papp) of BN –NLC gel was much higher(4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BN –NLC gel was confirmed that had no significant irritation to cornea. Ex vivo precorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLCbased hydrogel has a promising potential for application in ocular drug delivery.展开更多
Potential of nanoscale triazine based dendritic macromolecules G1,G2 and G3 as solubility enhancers of drug was investigated.Effect of pH,concentration and generation of synthesized dendritic macromolecules on solubil...Potential of nanoscale triazine based dendritic macromolecules G1,G2 and G3 as solubility enhancers of drug was investigated.Effect of pH,concentration and generation of synthesized dendritic macromolecules on solubility of ketoprofen was studied.G3 dendrimer was further exploited as carrier for sustained release.Ketoprofen was encapsulated by inclusion complex method and also characterized by Flourier Transform Infrared spectroscopy.Sustained release study of ketoprofen from ketoprofen loaded dendrimer was carried out and compared with free ketoprofen.Hemolytic potential and Cytotoxicity assay using A-549 lung cancer cell lines revealed that synthesized triazine based dendritic macromolecules having more potential that commercially available PAMAM dendrimer.展开更多
Molecular imprinted nanoparticles(MINPs) can memorize the shape and functional group positions complementary to template, which account for the large drug loading capacity and slow drug release behavior as drug carrie...Molecular imprinted nanoparticles(MINPs) can memorize the shape and functional group positions complementary to template, which account for the large drug loading capacity and slow drug release behavior as drug carriers. We synthesized MINPs via precipitation polymerization with vinblastine(VBL) as a model drug, and investigated the drug loading,releasing property in vitro and bio-distribution in vivo. The obtained MINPs, from 300 to 450 nm,had smooth surface and favorable dispersibility. The entrapment efficacy and drug loading capacity of VBL loaded MINPs(MINPs-VBL) were 83.25% and 8.72% respectively. In PBS(pH 7.4),MINPs-VBL showed sustained release behavior. The cumulative release percentage reached about 70% during 216 h and no burst release was observed. The releasing behavior of MINPsVBL in vitro conformed to the first-order kinetics model. MINPs-VBL and commercially available vinblastine sulfate injection(VBL injection) were injected via tail vein of SD rats respectively to investigate the bio-distribution. MINPs-VBL group showed higher concentration of VBL in tissues and serum than VBL injection group after 60 min, and the drug level in liver was the highest. MINPs-VBL exhibited liver targeting trend to some extent, which was based on the evaluation of drug targeting index(DTI) and drug selecting index(DSI).展开更多
The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time.For most drugs,sufficient in vivo circulation time is the basis of high bioavail...The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time.For most drugs,sufficient in vivo circulation time is the basis of high bioavailability.Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system,to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect.The physical and chemical properties of drug carriers,such as size,shape,surface charge and surface modification,would affect their in vivo circulation time,metabolic behavior and biodistribution.The final circulation time of carriers is determined by the balance between macrophage recognitions,blood vessel penetration and urine excretion.Therefore,when designing the drug delivery system,we should pay much attention to the properties of drug carriers to get enough in vivo circulation time to arrive at target site eventually.This article mainly reviews the effect of carrier size,size,surface charge and surface properties on its circulation time in vivo,and discusses the mechanism of these properties affecting circulation time.This review has reference significance for the research of long-circulation drug delivery system.展开更多
AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.METHODS: Recombinant complex of HDL and aclacinomycin(rHDL-ACM) was p...AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.METHODS: Recombinant complex of HDL and aclacinomycin(rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine.Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles,morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method.RESULTS: The density range of rHDL-ACM was 1.063-1.210g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%.Encapsulated efficiencies of rHDL-ACM were more than90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110rHDL-ACM particles in the range of diameter of lipoproteins.rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL(P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 μg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM(1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes,a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL. Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5 μg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells.CONCLUSION: rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721hepatoma to normal L02 hepatocytes. HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.展开更多
To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane ...To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic■ F-127, which binds folic acid(FA), Pluronic■ F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, and could improve the antitumor effects of TPL;hence, they are ideal carriers for low-dose antineoplastic drugs.展开更多
Fe3O4/carbon nanotubes(Fe3O4/CNTs) nanocomposites were prepared by polylol hightemperature decomposition of the precursor ferric chloride and CNTs in liquid triethylene glycol.After surface modification with hexaned...Fe3O4/carbon nanotubes(Fe3O4/CNTs) nanocomposites were prepared by polylol hightemperature decomposition of the precursor ferric chloride and CNTs in liquid triethylene glycol.After surface modification with hexanediamine,folate was covalently linked to the amine group of magnetic Fe3O4/CNTs nanocomposites.The products were characterized by Fourier-transform infrared spectroscopy,transmission electron microscopy,and vibrating sample magnetometry.Then Fe3O4/CNTs were used as a dual-drug carrier to co-delivery of the hydrophilic drug epirubicin hydrochloride and hydrophobic drug paclitaxel.The results indicated that the Fe3O4/CNTs had a favorable release property for epirubicin and paclitaxel,and thus had potential application in tumor-targeted combination chemotherapy.展开更多
Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment p...Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment protocol for bone tumour.However,drugs used in the treatment of bone tumour induce high toxicity to normal tissues including anaemia,neutropenia,thrombocytopenia,and heart damage which further reduce the survival rate of patients.Therefore,there is an urgent need to develop a new therapeutic approach for the treatment such that it induce maximum cell killing effect in tumor cells while sparing the healthy bone cells.In this article,some new perspectives were provided on the development of bone-targeted nano-drug carriers for bone cancer treatment.We hope such discussions wouldencourage more detailed and careful studies to support product development of bone-targeted drug carriers for bone cancer treatment.展开更多
β-TCP ceramics drug carrier was first prepared and characterized. SEM showed that β-TCP carrier was in porous amorphous structure with diameters around 10 μm. The physical properties including apparent porosity, vo...β-TCP ceramics drug carrier was first prepared and characterized. SEM showed that β-TCP carrier was in porous amorphous structure with diameters around 10 μm. The physical properties including apparent porosity, volume-weight, tensile strength and the permeability were measured and the results indicated those properties fit the clinical usage of β-TCP drug carrier. Furthermore, drug release experiment in vitro showed that the carrier could prolong drug release in simulated body fluid which provides basis for the clinical use of β-TCP ceramics as drug carrier.展开更多
The objective of this review is to outline the application of bicelles(or called bilayer micelles)and bilayer nanodisks in pharmaceutics,pharmaceutical analysis and biochemistry.The application of open disk-like struc...The objective of this review is to outline the application of bicelles(or called bilayer micelles)and bilayer nanodisks in pharmaceutics,pharmaceutical analysis and biochemistry.The application of open disk-like structures as model membrane and drug carrier has been described.The exploration of many reports in different fields suggested that these open disk-like structures have great potential in studying interactions between drug-membrane and structure/function studies of membrane-bound proteins.Furthermore,they could be applied as promising carriers for in vivo delivery of drugs,protein and peptide.展开更多
Berberine(BBR)is an isoquinoline alkaloid that can be extracted from the traditional Chinese medicine Huang Lian.It has anti-inflammatory,anti-cancer,protection of nerves,hypoglycemic,blood lipid,anti-oxidation,antiba...Berberine(BBR)is an isoquinoline alkaloid that can be extracted from the traditional Chinese medicine Huang Lian.It has anti-inflammatory,anti-cancer,protection of nerves,hypoglycemic,blood lipid,anti-oxidation,antibacterial and other effects.It can be used clinically to treat chronic colitis,bacterial vaginitis,rheumatoid arthritis,breast cancer,liver cancer,Alzheimer's disease,diabetes,obesity and other common diseases.This paper reviews the pharmacological effects of berberine and the research progress of effective drug carriers in order to provide new ideas for the clinical application of berberine.展开更多
Diblock copolymer poly(ethylene glycol) methyl ether–polylactide (MePEG–PLA) micelles were prepared by dialysis against water. Indomethacin (IMC) as a model drug was entrapped into the micelles by dialysis method. T...Diblock copolymer poly(ethylene glycol) methyl ether–polylactide (MePEG–PLA) micelles were prepared by dialysis against water. Indomethacin (IMC) as a model drug was entrapped into the micelles by dialysis method. The critical micelle concentration (CMC) of the prepared micelles in distilled water investigated by fluorescence spectroscopy was 0.0051 mg/mL which is lower than that of common low molecular weight surfactants. The diameters of MePEGPLA micelles and IMC loaded MePEGPLA micelles in a number-averaged scale measured by dynamic light scattering were 52.4 and 53.7 nm respectively. The observation with transmission electron microscope and scanning electron microscope showed that the appearance of MePEGPLA micelles was in a spherical shape. The content of IMC incorporated in the core portion of the micelles was 18% (ω). The effects of the synthesis method of the copolymer on the polydispersity of the micelles and the yield of the micelles formation were discussed.展开更多
Methoxy poly(ethylene glycol)-poly(D,L-lactide) block copolymers (PEG-PLA) were prepared through ring-opening polymerization.The oil in water suspension method was used to prepare block copolymer micelles. The critica...Methoxy poly(ethylene glycol)-poly(D,L-lactide) block copolymers (PEG-PLA) were prepared through ring-opening polymerization.The oil in water suspension method was used to prepare block copolymer micelles. The critical micelle concentration (CMC) by fluorescence spectroscopy was 0.0056 mg·ml -1 . The physical state of the inner core region of micelles was characterized with 1HNMR. The size of indomethacin (IMC) loaded micelles measured by dynamic light scattering (DLS) showed narrow monodisperse size distribution and the average diameters were less than 50 nm. In addition, the nanoparticles with relatively high drug loading content (DLC) were obtained.展开更多
Drug carrier biocompatible and biodegradable nanoparticles of about 15 nm were prepared by solvent evaporation technique from star-shaped poly(D,L-lactide) synthesized using dipentaerythritol as core and Tin (II) ethy...Drug carrier biocompatible and biodegradable nanoparticles of about 15 nm were prepared by solvent evaporation technique from star-shaped poly(D,L-lactide) synthesized using dipentaerythritol as core and Tin (II) ethylhexanoate as catalyst.展开更多
背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶...背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶机制作用的剖析,整合医用水凝胶与中医药在研究中联合应用的文章,进而更好地为科研工作者提供思路,对中医药与医用水凝胶联合应用具有重要意义。目的:基于组织工程研究探讨中医药联合医用水凝胶治疗疾病的策略及意义。方法:利用PubMed和中国知网数据库,检索有关中医药联合医用水凝胶在组织工程中应用的文献,检索时间为2010年1月至2022年11月,英文检索词为“hydrogel,traditional Chinese medicine,drug carrier,tissue engineering”,中文检索词为“医用水凝胶、中医药、药物载体、组织工程”。根据纳入与排除标准对所有文章进行初筛后,最终纳入61篇文章进行综述。结果与结论:①中医药联合医用水凝胶的应用虽然在关节内、组织器官内、软组织伤口和组织工程等方面有所涉及,但除了中医药结合水凝胶敷料在临床应用治疗软组织损伤外,其他方面尚处于基础实验阶段。②中医药联合医用水凝胶的发展有着巨大潜力和发展前景,但对于性能要求较高的凝胶在制造方面存在一定难度,理化性质精确掌握难度较大。③目前综合来看可注射水凝胶凭借着简便易用的特点,其在与中医药联合使用可延伸范围较广,可用于关节、器官和组织工程相关疾病的治疗;智能水凝胶有较高的灵敏度和可逆转化性也可满足特殊环境下的使用;将两者结合的中医药使用过程中还需要明确中药成分的作用机制。④中医药联合医用水凝胶治疗疾病的策略应着手于中医药对器官、组织、细胞的治疗作用联合适当种类的医用水凝胶进行匹配,可弥补传统中医给药方式和频繁给药的不足,在组织工程方面可以用水凝胶负载中药干预后的干细胞,或者同时负载中药和干细胞用于相关疾病的治疗。⑤在中医药联合医用水凝胶应用的未来研究中,还需要考虑:应当确保医用水凝胶生物性能可以量化,以不同材料不同制造工艺把握水凝胶特性,制造出所需要的符合应用条件的医用水凝胶;在中医药方面需要对已知中药单体、中药复方提取物的治疗效果和应用机制全面了解剖析,在更明了的机制下实现中医药与医用水凝胶更多更完美的结合;借助医学科技创新能力的不断提高,医用水凝胶可以创新性地结合中医药其他传统治疗方法比如针灸、推拿和拔罐等方式进行多角度运用。展开更多
背景:静电纺丝多孔纳米纤维是一种具有优良性能和可设计性的材料,将传统中药与其联合构建新型中药控释系统是实现中药的控制释放和提高生物利用度的有效途径,具有广阔应用前景。目的:综述静电纺丝中药控释系统的构建方法及其在医学领域...背景:静电纺丝多孔纳米纤维是一种具有优良性能和可设计性的材料,将传统中药与其联合构建新型中药控释系统是实现中药的控制释放和提高生物利用度的有效途径,具有广阔应用前景。目的:综述静电纺丝中药控释系统的构建方法及其在医学领域相关研究进展。方法:以“静电纺丝,中药,药物载体,释药系统,组织工程,敷料”为中文检索词,以“electrospinning,traditional Chinese medicine,drug carrier,drug delivery system,tissue engineering,dressing”为英文检索词,检索中国知网、PubMed和Web of Science数据库的关于静电纺丝中药控释系统的研究应用文献,检索时间范围为2013-2023年,最终纳入62篇文献进行综述分析。结果与结论:①构建电纺多孔纤维中药控释系统的关键要素为基质材料、中药成分和载药方式。②电纺多孔纤维中药控释系统的构建可依据应用场景和治疗目的进行,首先选定中药成分种类,然后依据药物特性选择与其适配的聚合物基体及溶液,最后依据释药需求设计纤维结构并采用适宜的载药方式。③目前在电纺纤维中药控释系统中所应用的药剂以易制备纺丝溶液的植物中药提取物为主,缺少动物中药和矿物中药的系统研究。④共混载药是研究应用最多的载药方式,且通过对溶液理化性质的优化和负载物质多样性的选择不断扩展其释药特性和适应场景;同轴、多轴及顺序纺丝等载药方式可以制备具有多层成分性质不同的复合纤维,具有广阔发展前景。⑤电纺纤维中药控释系统早期应用集中于医用敷料方面,利用中药活性成分的抗菌止血功能,近年来发现中药某些成分能促进细胞黏附增殖分化,开启了组织工程领域的探索研究。⑥目前对电纺多孔纤维中药控释系统的研究主要集中在对负载材料、工艺、理化性能、生物性能的表征和优化上,而对机制的研究较少,其在临床中的应用尚未普及,在体内的不良反应尚不明了,对其降解行为与释药行为的相互影响也缺乏研究。⑦未来研究中需要考虑:通过改善中药与纺丝溶剂的理化性能和加大中药活性成分的提纯以扩大非植物中药的应用范围,对中药成分的治疗效果和作用机制进行全面研究,并阐明控释系统的降解行为与释药行为的相互影响规律,在更准确的机制下实现中药与电纺纳米纤维更完美的联合和应用。展开更多
基金Shaanxi Province College Student Innovation and Entrepreneurship Training Program Project(Project Number:S202310708098).
文摘Traditional drug delivery methods are prone to large fluctuations in drug concentration and require multiple frequent doses.As a green material with excellent properties,cellulose has been widely used as a drug carrier for the development and preparation of drug controlled-release system.Based on the mechanisms of slow drug release,such as dissolution-diffusion release,degradation release,and nanochannel-controlled release,the preparation methods of cellulose-based drug carriers are introduced in this paper.The applications of cellulose-based drug carriers in the fields of antitumor therapy,antibacterial therapy,chronic disease treatment,and viral disease treatment are summarized with the aim of providing a useful reference for research on cellulose-based drug carriers.
基金National Natural Science Foundation of China (projects 81473163 and 81773670) for supporting the research
文摘The objective of this study was to develop a novel hybrid genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier(NLC) drug delivery platform. An ophthalmic antiinflammatory drug, baicalin(BN) was chosen as the model drug. BN –NLC was prepared using melt-emulsification combined with ultra-sonication technique. Additionally, a dual pH-and thermo-sensitive hydrogel composed of carboxymethyl chitosan(CMCS) and poloxamer 407(F127) was fabricated by a cross-linking reaction with a nontoxic crosslinker genipin(GP). GP-CMCS/F127 hydrogel was characterized by FTIR, NMR, XRD and SEM. The swelling studies showed GP-CMCS/F127 hydrogel was both pH-and thermo-sensitive. The results of in vitro release suggested BN –NLC gel can prolong the release of baicalin comparing with BN eye drops and BN –NLC. Ex vivo cornea permeation study was evaluated using Franz diffusion cells. The apparent permeability coefficient(Papp) of BN –NLC gel was much higher(4.46-fold) than that of BN eye drops. Through the determination of corneal hydration levels, BN –NLC gel was confirmed that had no significant irritation to cornea. Ex vivo precorneal retention experiments were carried out by a flow-through approach. The results indicated that the NLC-based hydrogel can prolong precorneal residence time. In conclusion, the hybrid NLCbased hydrogel has a promising potential for application in ocular drug delivery.
文摘Potential of nanoscale triazine based dendritic macromolecules G1,G2 and G3 as solubility enhancers of drug was investigated.Effect of pH,concentration and generation of synthesized dendritic macromolecules on solubility of ketoprofen was studied.G3 dendrimer was further exploited as carrier for sustained release.Ketoprofen was encapsulated by inclusion complex method and also characterized by Flourier Transform Infrared spectroscopy.Sustained release study of ketoprofen from ketoprofen loaded dendrimer was carried out and compared with free ketoprofen.Hemolytic potential and Cytotoxicity assay using A-549 lung cancer cell lines revealed that synthesized triazine based dendritic macromolecules having more potential that commercially available PAMAM dendrimer.
基金supported by the National Natural Science Foundation of China (grant number: 81173566)
文摘Molecular imprinted nanoparticles(MINPs) can memorize the shape and functional group positions complementary to template, which account for the large drug loading capacity and slow drug release behavior as drug carriers. We synthesized MINPs via precipitation polymerization with vinblastine(VBL) as a model drug, and investigated the drug loading,releasing property in vitro and bio-distribution in vivo. The obtained MINPs, from 300 to 450 nm,had smooth surface and favorable dispersibility. The entrapment efficacy and drug loading capacity of VBL loaded MINPs(MINPs-VBL) were 83.25% and 8.72% respectively. In PBS(pH 7.4),MINPs-VBL showed sustained release behavior. The cumulative release percentage reached about 70% during 216 h and no burst release was observed. The releasing behavior of MINPsVBL in vitro conformed to the first-order kinetics model. MINPs-VBL and commercially available vinblastine sulfate injection(VBL injection) were injected via tail vein of SD rats respectively to investigate the bio-distribution. MINPs-VBL group showed higher concentration of VBL in tissues and serum than VBL injection group after 60 min, and the drug level in liver was the highest. MINPs-VBL exhibited liver targeting trend to some extent, which was based on the evaluation of drug targeting index(DTI) and drug selecting index(DSI).
基金supported by Military Medical Innovation Project(16CXZ032)National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(No.2018ZX09J18107-03,2018ZX09721003-005-009)。
文摘The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their circulation time.For most drugs,sufficient in vivo circulation time is the basis of high bioavailability.Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system,to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect.The physical and chemical properties of drug carriers,such as size,shape,surface charge and surface modification,would affect their in vivo circulation time,metabolic behavior and biodistribution.The final circulation time of carriers is determined by the balance between macrophage recognitions,blood vessel penetration and urine excretion.Therefore,when designing the drug delivery system,we should pay much attention to the properties of drug carriers to get enough in vivo circulation time to arrive at target site eventually.This article mainly reviews the effect of carrier size,size,surface charge and surface properties on its circulation time in vivo,and discusses the mechanism of these properties affecting circulation time.This review has reference significance for the research of long-circulation drug delivery system.
基金Supported by the National Natural Science Foundation of China,No. 39770164
文摘AIM: To investigate the possibility of recombinant highdensity lipoprotein (rHDL) being a carrier for delivering antitumoral drug to hepatoma cells.METHODS: Recombinant complex of HDL and aclacinomycin(rHDL-ACM) was prepared by cosonication of apoproteins from HDL (Apo HDL) and ACM as well as phosphatidylcholine.Characteristics of the rHDL-ACM were elucidated by electrophoretic mobility, including the size of particles,morphology and entrapment efficiency. Binding activity of rHDL-ACM to human hepatoma cells was determined by competition assay in the presence of excess native HDL. The cytotoxicity of rHDL-ACM was assessed by MTT method.RESULTS: The density range of rHDL-ACM was 1.063-1.210g/mL, and the same as that of native HDL. The purity of all rHDL-ACM preparations was more than 92%.Encapsulated efficiencies of rHDL-ACM were more than90%. rHDL-ACM particles were typical sphere model of lipoproteins and heterogeneous in particle size. The average diameter was 31.26±5.62 nm by measure of 110rHDL-ACM particles in the range of diameter of lipoproteins.rHDL-ACM could bind on SMMC-7721 cells, and such binding could be competed against in the presence of excess native HDL. rHDL-ACM had same binding capacity as native HDL. The cellular uptake of rHDL-ACM by SMMC-7721 hepatoma cells was significantly higher than that of free ACM at the concentration range of 0.5-10 μg/mL(P<0.01). Cytotoxicity of rHDL-ACM to SMMC-7721 cells was significantly higher than that of free ACM at concentration range of less than 5 μg/mL (P<0.01) and IC50 of rHDL-ACM was lower than IC50 of free ACM(1.68 nmol/L vs3 nmol/L). Compared to L02 hepatocytes,a normal liver cell line, the cellular uptake of rHDL-ACM by SMMC-7721 cells was significantly higher (P<0.01) and in a dose-dependent manner at the concentration range of 0.5-10 μg/mL. Cytotoxicity of the rHDL-ACM to SMMC-7721 cells was significantly higher than that to L02 cells at concentration range of 1-7.5 μg/mL (P<0.01). IC50 for SMMC-7721 cells (1.68 nmol/L) was lower than that for L02 cells (5.68 nmol/L), showing a preferential cytotoxicity of rHDL-ACM for SMMC-7721 cells.CONCLUSION: rHDL-ACM complex keeps the basic physical and biological binding properties of native HDL and shows a preferential cytotoxicity for SMMC-7721hepatoma to normal L02 hepatocytes. HDL is a potential carrier for delivering lipophilic antitumoral drug to hepatoma cells.
基金Funded by the National Natural Science Foundation of Hubei Province(No.2014CFB306)the National Natural Science Foundation of China(No.51772233)+1 种基金the National Key Research and Development Program of China(No.2016YFC1101605)the Science and Technology Support Program of Hubei Province(No.2015BAA085)
文摘To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic■ F-127, which binds folic acid(FA), Pluronic■ F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, and could improve the antitumor effects of TPL;hence, they are ideal carriers for low-dose antineoplastic drugs.
基金Funded by Natural Science Fund of Jiangsu Overseas Research&Training Program for University Prominent Young&Middleaged Teachers and Presidents,the Natural Science Fund of Jiangsu Province(No.BK20130094)the Enterprise-universities Cooperative Innovation Fund of Jiangsu Province(No.BY2014016)
文摘Fe3O4/carbon nanotubes(Fe3O4/CNTs) nanocomposites were prepared by polylol hightemperature decomposition of the precursor ferric chloride and CNTs in liquid triethylene glycol.After surface modification with hexanediamine,folate was covalently linked to the amine group of magnetic Fe3O4/CNTs nanocomposites.The products were characterized by Fourier-transform infrared spectroscopy,transmission electron microscopy,and vibrating sample magnetometry.Then Fe3O4/CNTs were used as a dual-drug carrier to co-delivery of the hydrophilic drug epirubicin hydrochloride and hydrophobic drug paclitaxel.The results indicated that the Fe3O4/CNTs had a favorable release property for epirubicin and paclitaxel,and thus had potential application in tumor-targeted combination chemotherapy.
基金The project supported by National Natural Science Foundation of China(81300964)the China Postdoctoral Science Foundation(2013M531611,2014T70648)
文摘Bone tumour is one of most common primary cancer which exhibits cancerous osteoblastic differentiation and malignant osteoid in patients.At present,chemotherapy(pre-and post-operative)is used as a standard treatment protocol for bone tumour.However,drugs used in the treatment of bone tumour induce high toxicity to normal tissues including anaemia,neutropenia,thrombocytopenia,and heart damage which further reduce the survival rate of patients.Therefore,there is an urgent need to develop a new therapeutic approach for the treatment such that it induce maximum cell killing effect in tumor cells while sparing the healthy bone cells.In this article,some new perspectives were provided on the development of bone-targeted nano-drug carriers for bone cancer treatment.We hope such discussions wouldencourage more detailed and careful studies to support product development of bone-targeted drug carriers for bone cancer treatment.
基金Funded by the "973" Chinese National Key Fundamental Research and Development Program (No.G1999064701)the Research Fund of Key Laboratory for Advanced Technology in Environmental Protection of Jiangsu Province (AE201037)
文摘β-TCP ceramics drug carrier was first prepared and characterized. SEM showed that β-TCP carrier was in porous amorphous structure with diameters around 10 μm. The physical properties including apparent porosity, volume-weight, tensile strength and the permeability were measured and the results indicated those properties fit the clinical usage of β-TCP drug carrier. Furthermore, drug release experiment in vitro showed that the carrier could prolong drug release in simulated body fluid which provides basis for the clinical use of β-TCP ceramics as drug carrier.
文摘The objective of this review is to outline the application of bicelles(or called bilayer micelles)and bilayer nanodisks in pharmaceutics,pharmaceutical analysis and biochemistry.The application of open disk-like structures as model membrane and drug carrier has been described.The exploration of many reports in different fields suggested that these open disk-like structures have great potential in studying interactions between drug-membrane and structure/function studies of membrane-bound proteins.Furthermore,they could be applied as promising carriers for in vivo delivery of drugs,protein and peptide.
基金Jilin Science and Technology Development Project(No.20190303183SF)Undergraduate Teaching Reform research Project of Jilin University(No.2019XYB318)
文摘Berberine(BBR)is an isoquinoline alkaloid that can be extracted from the traditional Chinese medicine Huang Lian.It has anti-inflammatory,anti-cancer,protection of nerves,hypoglycemic,blood lipid,anti-oxidation,antibacterial and other effects.It can be used clinically to treat chronic colitis,bacterial vaginitis,rheumatoid arthritis,breast cancer,liver cancer,Alzheimer's disease,diabetes,obesity and other common diseases.This paper reviews the pharmacological effects of berberine and the research progress of effective drug carriers in order to provide new ideas for the clinical application of berberine.
基金National Natural Science Foundation of China (No.29836130)
文摘Diblock copolymer poly(ethylene glycol) methyl ether–polylactide (MePEG–PLA) micelles were prepared by dialysis against water. Indomethacin (IMC) as a model drug was entrapped into the micelles by dialysis method. The critical micelle concentration (CMC) of the prepared micelles in distilled water investigated by fluorescence spectroscopy was 0.0051 mg/mL which is lower than that of common low molecular weight surfactants. The diameters of MePEGPLA micelles and IMC loaded MePEGPLA micelles in a number-averaged scale measured by dynamic light scattering were 52.4 and 53.7 nm respectively. The observation with transmission electron microscope and scanning electron microscope showed that the appearance of MePEGPLA micelles was in a spherical shape. The content of IMC incorporated in the core portion of the micelles was 18% (ω). The effects of the synthesis method of the copolymer on the polydispersity of the micelles and the yield of the micelles formation were discussed.
文摘Methoxy poly(ethylene glycol)-poly(D,L-lactide) block copolymers (PEG-PLA) were prepared through ring-opening polymerization.The oil in water suspension method was used to prepare block copolymer micelles. The critical micelle concentration (CMC) by fluorescence spectroscopy was 0.0056 mg·ml -1 . The physical state of the inner core region of micelles was characterized with 1HNMR. The size of indomethacin (IMC) loaded micelles measured by dynamic light scattering (DLS) showed narrow monodisperse size distribution and the average diameters were less than 50 nm. In addition, the nanoparticles with relatively high drug loading content (DLC) were obtained.
文摘Drug carrier biocompatible and biodegradable nanoparticles of about 15 nm were prepared by solvent evaporation technique from star-shaped poly(D,L-lactide) synthesized using dipentaerythritol as core and Tin (II) ethylhexanoate as catalyst.
文摘背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶机制作用的剖析,整合医用水凝胶与中医药在研究中联合应用的文章,进而更好地为科研工作者提供思路,对中医药与医用水凝胶联合应用具有重要意义。目的:基于组织工程研究探讨中医药联合医用水凝胶治疗疾病的策略及意义。方法:利用PubMed和中国知网数据库,检索有关中医药联合医用水凝胶在组织工程中应用的文献,检索时间为2010年1月至2022年11月,英文检索词为“hydrogel,traditional Chinese medicine,drug carrier,tissue engineering”,中文检索词为“医用水凝胶、中医药、药物载体、组织工程”。根据纳入与排除标准对所有文章进行初筛后,最终纳入61篇文章进行综述。结果与结论:①中医药联合医用水凝胶的应用虽然在关节内、组织器官内、软组织伤口和组织工程等方面有所涉及,但除了中医药结合水凝胶敷料在临床应用治疗软组织损伤外,其他方面尚处于基础实验阶段。②中医药联合医用水凝胶的发展有着巨大潜力和发展前景,但对于性能要求较高的凝胶在制造方面存在一定难度,理化性质精确掌握难度较大。③目前综合来看可注射水凝胶凭借着简便易用的特点,其在与中医药联合使用可延伸范围较广,可用于关节、器官和组织工程相关疾病的治疗;智能水凝胶有较高的灵敏度和可逆转化性也可满足特殊环境下的使用;将两者结合的中医药使用过程中还需要明确中药成分的作用机制。④中医药联合医用水凝胶治疗疾病的策略应着手于中医药对器官、组织、细胞的治疗作用联合适当种类的医用水凝胶进行匹配,可弥补传统中医给药方式和频繁给药的不足,在组织工程方面可以用水凝胶负载中药干预后的干细胞,或者同时负载中药和干细胞用于相关疾病的治疗。⑤在中医药联合医用水凝胶应用的未来研究中,还需要考虑:应当确保医用水凝胶生物性能可以量化,以不同材料不同制造工艺把握水凝胶特性,制造出所需要的符合应用条件的医用水凝胶;在中医药方面需要对已知中药单体、中药复方提取物的治疗效果和应用机制全面了解剖析,在更明了的机制下实现中医药与医用水凝胶更多更完美的结合;借助医学科技创新能力的不断提高,医用水凝胶可以创新性地结合中医药其他传统治疗方法比如针灸、推拿和拔罐等方式进行多角度运用。
文摘背景:静电纺丝多孔纳米纤维是一种具有优良性能和可设计性的材料,将传统中药与其联合构建新型中药控释系统是实现中药的控制释放和提高生物利用度的有效途径,具有广阔应用前景。目的:综述静电纺丝中药控释系统的构建方法及其在医学领域相关研究进展。方法:以“静电纺丝,中药,药物载体,释药系统,组织工程,敷料”为中文检索词,以“electrospinning,traditional Chinese medicine,drug carrier,drug delivery system,tissue engineering,dressing”为英文检索词,检索中国知网、PubMed和Web of Science数据库的关于静电纺丝中药控释系统的研究应用文献,检索时间范围为2013-2023年,最终纳入62篇文献进行综述分析。结果与结论:①构建电纺多孔纤维中药控释系统的关键要素为基质材料、中药成分和载药方式。②电纺多孔纤维中药控释系统的构建可依据应用场景和治疗目的进行,首先选定中药成分种类,然后依据药物特性选择与其适配的聚合物基体及溶液,最后依据释药需求设计纤维结构并采用适宜的载药方式。③目前在电纺纤维中药控释系统中所应用的药剂以易制备纺丝溶液的植物中药提取物为主,缺少动物中药和矿物中药的系统研究。④共混载药是研究应用最多的载药方式,且通过对溶液理化性质的优化和负载物质多样性的选择不断扩展其释药特性和适应场景;同轴、多轴及顺序纺丝等载药方式可以制备具有多层成分性质不同的复合纤维,具有广阔发展前景。⑤电纺纤维中药控释系统早期应用集中于医用敷料方面,利用中药活性成分的抗菌止血功能,近年来发现中药某些成分能促进细胞黏附增殖分化,开启了组织工程领域的探索研究。⑥目前对电纺多孔纤维中药控释系统的研究主要集中在对负载材料、工艺、理化性能、生物性能的表征和优化上,而对机制的研究较少,其在临床中的应用尚未普及,在体内的不良反应尚不明了,对其降解行为与释药行为的相互影响也缺乏研究。⑦未来研究中需要考虑:通过改善中药与纺丝溶剂的理化性能和加大中药活性成分的提纯以扩大非植物中药的应用范围,对中药成分的治疗效果和作用机制进行全面研究,并阐明控释系统的降解行为与释药行为的相互影响规律,在更准确的机制下实现中药与电纺纳米纤维更完美的联合和应用。