Magnetic carbon nanotubes with particle-free surfaces and high drug loading capacity

Open-ended, multi-wall carbon nanotubes (CNTs) with magnetic nanoparticles encapsulated within their graphitic walls (magCNTs) were fabricated by a combined action of templated growth and a ferrofluid catalyst/carbon precursor, and tested as drug hosts. The hybrid nanotubes are stable under extreme pH conditions due to particle protection provided by the graphitic shell. The magCNTs are promising for high capacity drug loading given that the magnetic functionalization did not block any of the active sites available for drug attachment, either from the CNT internal void or on the internal and external surfaces. This is in contrast to typical approaches of loading CNTs with particles that proceed through surface attachment or capillary filling of the tube interior. Additionally, the CNTs exhibit enhanced hydrophilic character, as shown by water adsorption measurements, which make them suitable for biological applications. The morphological and structural characteristics of the hybrid CNTs are evaluated in conjunction to their magnetic properties and ability for drug loading (diaminophenothiazine). The fact that the magnetic functionality is provided from 'inside the walls' can allow for multimode functionalization of the graphitic surfaces and makes the magCNTs promising for targeted therapeutic applications.     

Rapid preparation of pH-sensitive polymeric nanoparticle with high loading capacity using electrospray for oral drug delivery

Drug loading capacity is an important property for an ideal drug delivery system. However, the drug loading capacity of prepared pH-sensitive polymeric nanoparticles is usually low. To overcome this drawback, the electrospray method was used to prepare Eudragit L 100-55 nanoparticles with high drug loading capacity in one step. Omeprazole was selected as the model drug. The maximum loading capacity of nanoparticles was 43.21% by changing the mass ratio of drug to polymer, and the entrapment efficiency was nearly 100%. The prepared nanoparticle showed spherical or ellipsoidal morphology and the average diameter was about 300 nm. The pH-sensitive nanoparticle displayed pH-dependent release in vitro. In addition, a slight cytotoxicity was detected in the cytotoxicity study. The results indicated that electrospray is an easy, rapid and efficient technique for the preparation of high-loading pH-sensitive polymeric nanoparticles, and the pH-sensitive nanoparticle is a promising carrier for oral drug delivery.     

纳米羟基磷灰石及其复合材料作为药物载体的研究进展

纳米羟基磷灰石(HAp)具有良好的生物活性和药物吸附性,是一种理想的无机药物载体。本文从生物安全性、抗肿瘤活性和药物吸附性三个方面阐述了纳米HAp的载药特性,探讨了其微观形貌对载药性能的影响,对载药纳米HAp复合材料的分类、制备及载药和释药性能进行了系统综述,旨在为纳米HAp及其复合材料在药物载体领域的应用提供理论基础。      

Recent advances in the development of functionalized carbon nanotubes: a versatile vector for drug delivery

Carbon nanotubes (CNTs) possess unique physical and chemical properties and can serve as a platform for transporting a variety of bioactive molecules, such as drugs, proteins, and genes, given appropriate surface modifications. Here, we present an overview of the progress in applying CNTs as therapeutic agent carriers. Drugs can be attached to CNTs either through supramolecular chemistry to form noncovalent assembly or via covalent linkage to the functional groups preinstalled on CNTs. In addition to surface loading, packing of molecules inside the internal cavity of CNTs to protect less stable entities has also been achieved. Besides drugs, the high specific surface area of CNTs can also allow the installation of multiple molecules with different functions, e.g. target recognition and optical imaging, simultaneously to achieve synergistic effects. The drug release process tends to be gradual and sustained after being attached to CNTs, and could be tuned by various factors, such as pH, diameter of CNTs, and target recognition. The content throughout this review is mainly focused on the different protocols of loading drugs onto or into CNTs as well as how to control the drug release.     

Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent

Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol–solvent–water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48?h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.     

Reduction-responsive drug delivery based on mesoporous silica nanoparticle core with crosslinked poly(acrylic acid) shell

A novel reduction-responsive drug delivery system was successfully constructed with mesoporous silica nanoparticle (MSN) core as a drug carrier and poly(acrylic acid) (PAA) shell crosslinked by disulfide linkages as a drug release switcher. To keep the pore structure of MSN intact, PAA was covalently attached to the exterior surface of MSN before removing structure-template via radical polymerization. After removing structure-template and loading doxorubicin (DOX), the PAA shell was crosslinked by cystamine dihydrochloride through amidation reaction. The loading content and the entrapment efficiency of DOX could reach up to 40.2% and 80.4%, respectively. Because that the dissociation of disulfide linkage is reduction-responsive, the release behavior of DOX could be controlled by varying the concentration of reductant, and the release rate was 49.4% after 24 h with the existence of 2 mM glutathione (simulated environment of cancer cells), about three times higher than that of without glutathione (corresponding to normal human cells), which was only 16.9%. The in vitro cell assays demonstrated that the disulfide linkages crosslinked MSN–PAA (MSN–PAA-crosslinked) was highly biocompatible and suitable to use as drug carrier, and the DOX loaded MSN–PAA-crosslinked showed remarkable cytotoxicity to HeLa cells (human cancer cells), and relatively lower cytotoxicity to 293 cells (human normal cells). These results imply that the MSN–PAA-crosslinked is a promising platform to construct reduction-responsive controlled drug delivery system for cancer therapy.     

Porous Electrospun Fibers with Self‐Sealing Functionality: An Enabling Strategy for Trapping Biomacromolecules

Stimuli‐responsive porous polymer materials have promising biomedical application due to their ability to trap and release biomacromolecules. In this work, a class of highly porous electrospun fibers is designed using polylactide as the polymer matrix and poly(ethylene oxide) as a porogen. Carbon nanotubes (CNTs) with different concentrations are further impregnated onto the fibers to achieve self‐sealing functionality induced by photothermal conversion upon light irradiation. The fibers with 0.4 mg mL^?1 of CNTs exhibit the optimum encapsulation efficiency of model biomacromolecules such as dextran, bovine serum albumin, and nucleic acids, although their photothermal conversion ability is slightly lower than the fibers with 0.8 mg mL^?1 of CNTs. Interestingly, reversible reopening of the surface pores is accomplished with the degradation of PLA, affording a further possibility for sustained release of biomacromolecules after encapsulation. Effects of CNT loading on fiber morphology, structure, thermal/mechanical properties, degradation, and cell viability are also investigated. This novel class of porous electrospun fibers with self‐sealing capability has great potential to serve as an enabling strategy for trapping/release of biomacromolecules with promising applications in, for example, preventing inflammatory diseases by scavenging cytokines from interstitial body fluids.     

Ibuprofen loaded porous calcium phosphate nanospheres for skeletal drug delivery system

Porous calcium phosphate nanospheres were successfully fabricated by a simple sonochemical method, and used as a drug carrier of ibuprofen. Morphology, structure, ibuprofen storage capacity, and release rate of the calcium phosphate nanospheres were characterized using FE-SEM, TEM, Nitrogen adsorption, XRD, FTIR, and UV–vis adsorption spectroscopies. Results showed the obtained calcium phosphate nanospheres held a porous structure with an average diameter of 48.9 ± 17.42 nm. Moreover, the porous nanospheres possessed an adjustable load amount and release rate for ibuprofen by changing drug concentrations during the drug loading process. In addition, the effects of size and dispersancy of porous spheres on drug release rate were discussed, which was found that larger or agglomerate porous spheres could delay drug release process. This study indicated that porous calcium phosphate nanospheres were a perfect drug carrier for ibuprofen, which has potential application for the therapy of skeletal disease.     

纳米金属有机骨架ZIF-90的制备及载药性能研究

金属有机骨架材料是由金属离子与有机配体通过自组装过程杂化生成的一类具有周期性多维网状结构的多孔材料,在催化、传感、气体储存和载药等方面均表现出了优异的性能.采用一种新的实验方法(超声-搅拌法)并通过优化反应条件制备了粒径在300 nm以下的ZIF-90纳米材料,利用傅里叶红外光谱(FTIR)、粉末X射线衍射(XRD)确定了金属有机骨架的结构,利用扫描电子显微镜(SEM)确定了材料的形貌和粒径.ZIF-90纳米药物载体装载和释放抗癌药物5-氟尿嘧啶的实验结果表明,该材料装载药物的能力最高可达1.245 g/g,药物缓释时长达15h,释放率达到95％以上.该药物载体在不同pH值下的稳定性实验结果表明,该药物载体可在接近肿瘤细胞的酸性条件下通过骨架坍塌的方式快速释放药物,具有肿瘤靶向传递药物的能力.     

纳米金属有机骨架ZIF-90的制备及载药性能研究

金属有机骨架材料是由金属离子与有机配体通过自组装过程杂化生成的一类具有周期性多维网状结构的多孔材料,在催化、传感、气体储存和载药等方面均表现出了优异的性能。采用一种新的实验方法(超声-搅拌法)并通过优化反应条件制备了粒径在300nm以下的ZIF-90纳米材料,利用傅里叶红外光谱(FTIR)、粉末X射线衍射(XRD)确定了金属有机骨架的结构,利用扫描电子显微镜(SEM)确定了材料的形貌和粒径。ZIF-90纳米药物载体装载和释放抗癌药物5-氟尿嘧啶的实验结果表明,该材料装载药物的能力最高可达1.245g/g,药物缓释时长达15h,释放率达到95%以上。该药物载体在不同pH值下的稳定性实验结果表明,该药物载体可在接近肿瘤细胞的酸性条件下通过骨架坍塌的方式快速释放药物,具有肿瘤靶向传递药物的能力。     

Preparation of a cationic nanoemulsome for intratumoral drug delivery and its enhancing effect on cellular uptake in vitro

To develop an appropriate carrier for intratumoral drug delivery, cetyltrimethylammonium bromide (CTAB) modified nanoemulsome (CTAB-NES) was designed and prepared by solvent evaporation method. Coumarin-6 was chosen as the fluorescent probe and the conventional nanoemulsome (NES) without CTAB modification served as a control. The results demonstrated that CTAB-NES had a smaller particle size of 71.9 +/- 4.32 nm, considerate positive zeta potential of +48.7 +/- 0.2 mV, preferably entrapment efficiency of 97.483 +/- 0.693% and the release of coumarin-6 in 24 h was little. The in vitro cytotoxicity of CTAB-NES to the CHO cells and MCF-7 cells increased consistently with concentrations and was higher than that of NES, especially to the cancer cells. Both the fluorescence microscopy images and HPLC assay verified that the cellular uptake of CTAB-NES in MCF-7 cells was much higher than that of NES, and the uptake was time-, concentration- and temperature- dependent. The uptake mechanism results demonstrated that the internalization of CTAB-NES and NES involved clathrin- and caveolae-mediated endocytosis while macropinocytosis only influenced the uptake of CTAB-NES in MCF-7 cells for CTAB could mediate adsorptive pinocytosis. Thus, CTAB-NES with high positive charge and good intracellular uptake ability could be a promising drug carrier for intratumoral drug delivery.     

Synthesis of a biocompatible gelatin functionalized graphene nanosheets and its application for drug delivery

A simple and environmentally friendly synthetic route for the preparation of gelatin functionalized graphene nanosheets (gelatin-GNS) was reported by using exfoliated graphene oxide as a precursor, in which gelatin acted as not only a reducing reagent but also a functionalization reagent to guarantee good dispersibility and stability of the GNS in distilled water and various physiological solutions. The obtained biocompatible gelatin-GNS attaching methotrexate (MTX) via strong π-π stacking interaction, exhibited a high drug loading capacity of MTX and excellent ability for controlled drug release. The pH-dependent release behavior of MTX from MTX@gelatin-GNS showed that the release amount under acid conditions is much higher than that under neutral conditions, which experienced a gelatin-mediated sustained release process. From the cytotoxicity assay, we can see that the MTX@gelatin-GNS showed remarkable toxicity while the gelatin-GNS showed nontoxic at appropriate concentration, both of them might be taken up by A549 cells through a nonspecific endocytosis process. The prepared nanohybrids system offers a novel formulation that combines the unique properties of a biodegradable material, gelatin, and graphene for biomedical applications. Therefore, the gelatin-GNS with good stability and biocompatibility can be selected as an ideal drug carrier to be applied in biomedicine studies.     

Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an invitro study

Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ_max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.     

Inorganic materials as drug delivery systems in coronary artery stenting

Recent studies proved coronary stent implantation to be superior over conventional angioplasty in the treatment of coronary artery disease. However, restenosis remains one of the most crucial problems in interventional cardiology. Inflammatory infiltrates and foreign body reactions can be found in the tissue surrounding the struts in stenting. Thrombogenesis, proliferation of α‐actin expressing cells (smooth muscle cells) and hyperplasia of the intima occur. In order to improve the biocompatibility of the stents, new stent designs and stent coatings have been developed. One advantage of stent coating is the combination of mechanical stability of the stent with the biocompatibility of the coating. The coatings are divided into active and passive coatings. Passive coatings improve the biocompatibility of the stent, while active coatings may suppress neointima proliferation by releasing anti‐inflammatory or antiproliferative substances. Immunosuppressive drugs (tacrolimus, sirolimus) and cytostatic drugs (paclitaxel) have been tested in several studies and showed promising results. However, it could also be demonstrated that polymer‐coated stents used as a matrix for drug release reduced the hyperplasia of the intima. However, after dissipation of the immunosuppressants or cytostatics, the presence of the polymer itself lead to a delayed inflammation and proliferation causing restenosis. Thus, efforts have been made to develop inorganic coatings that are suitable for drug loading. One promising approach is a new nanoporous alumina coating. Preliminary tests with this coating revealed favourable loading characteristics and sustained drug release in vivo. The present article provides an overview on different approaches for stent coatings.     

Polymeric worm micelles as nano-carriers for drug delivery

Nanoscale carriers of active compounds, especially drugs, need not be spherical in shape. Worm micelles as blends of degradable polylactic acid (PLA) and inert block copolymer amphiphiles were prepared for controlled release and initial study of carrier transport through nano-porous media. The loading capacity of a typical hydrophobic drug, Triamterene, and the release of hydrophobic dyes were evaluated together with morphological changes of the micelles. Degradation of PLA by hydrolysis led to the self-shortening of worms and a clear transition towards spherical micelles, correlating with the release of hydrophobic dyes. Perhaps equally important for application is the flexibility of worm micelles, which we show allows them to penetrate nanoporous gels where 100?nm sized vesicles cannot enter. Such gels have served as tissue models, and so the results here collectively suggest a new class of hydrophobic drug nano-carriers that are capable of tissue permeation as well as controlled release.     

Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier

Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(γ-benzyl l-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability, size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was encapsulated in the micelles. The drug release profile, in vivo distribution and the cytotoxicity against hepatic carcinoma QGY-7703 cells of DOX-loaded micelles were studied. The results indicated that the release profile was pH-dependent with Fickian diffusion kinetics. The micelles were remarkably targeted to the liver, inducing a 4.9-fold higher DOX concentration than that for free DOX·HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX·HCl, and the cytotoxicity was time- and dosage-dependent. These results suggest that GA-functionalized micelles represent a promising carrier for drug delivery to the liver.     

Hydroxyapatite-chitosan biocomposites synthesized in the simulated body fluid and their drug loading studies

Hydroxyapatite (HAp) is a bioceramic applied in the biomedical areas, such as matrices for drug release control. Chitosan (CTS), a natural polymer, is another material has been widely investigated for its potential use in the drug delivery systems. In this study, the composites of HAp-CTS are produced in order to investigate their drug loading and release studies. First of all, HAp-CTS composites are produced in the presence of simulated body fluid (SBF). Analysis confirmed the structure of HAp-CTS composites. Secondly, composites are encapsulated with 5-Fluorouracil (5-FU). The weight ratio of CTS is varied to realize its effect on drug loading of 5-Fluorouracil, a cancer drug, for the ratios of 1:1, 1:2 and 1:4 of HAp-CTS. The weight ratio giving the greatest drug load efficiency is selected for the last step of the study. Crosslinking agent, glutaraldehyde, are changed from 0 to 5% on the selected sample, then, drug loading is examined again in various environment owing different pH. Furthermore, drug release studies are conducted. To understand the structure and morphology of the samples, XRD, FTIR, SEM and Uv-Spectrum are applied. It is observed that weight ratio of polymer and crosslinking agent can be manipulated to adjust drug loading. Release kinetics are shown the Fickian diffusion. This new produced material can be applicable for drug delivery.     

Recombinant human serum albumin hydrogel as a novel drug delivery vehicle

Serum albumin acts as a physiological carrier for various compounds including drugs. A hydrogel consisting of recombinant human serum albumin (rHSA) was prepared to take advantage of drug binding ability of albumin for a sustained drug release carrier. The hydrogel was prepared by mixing rHSA and dithiothreitol and casted to a polystyrene mold. Hydrogel formation was thought to occur through the intermolecular interaction of the hydrophobic groups by protein denaturation. The release of sodium benzoate and salicylic acid from the hydrogel completed in 2 h, while warfarin release continued for 24 h. The total amounts of the drugs released from 100 mg of 15 and 5% rHSA hydrogel were 2.3 and 1.4 μmol for warfarin, 1.4 and 1.1 μmol for salicylic acid and 0.9 and 0.9 μmol for sodium benzoate. These results reflected the order of the binding ability of drugs for intact albumin indicating that the drug binding ability of HSA still remained after the hydrogel formation. However, fibroblast cells attached and proliferated well on the hydrogel, indicating that denaturation of rHSA proceeded to the extent to allow the cell attachment. The present rHSA hydrogel might be suitable for a sustained release carrier of drugs having affinity for albumin.     

Non‐Magnetic Injectable Implant for Magnetic Field‐Driven Thermochemotherapy and Dual Stimuli‐Responsive Drug Delivery: Transformable Liquid Metal Hybrid Platform for Cancer Theranostics

Transformable liquid metal (LM)‐based materials have attracted considerable research interest in biomedicine. However, the potential biomedical applications of LMs have not yet been fully explored. Herein, for the first trial, the inductive heating property of gallium–indium eutectic alloy (EGaIn) under alterative magnetic field is systematically investigated. By virtue of its inherent metallic nature, LM possesses excellent magnetic heating property as compared to the conventional magnetite nanoparticles, therefore enabling its unique application as non‐magnetic agents in magnetic hyperthermia. Moreover, the extremely high surface tension of LM could be dramatically lowered by a rather facile PEGylation approach, making LM an ideal carrier for other theranostic cargos. By incorporating doxorubicin (DOX)‐loaded mesoporous silica (DOX‐MS) within PEGylated LM, a magnetic field‐driven transformable LM hybrid platform capable of pH/AFM dual stimuli‐responsive drug release and magnetic thermochemotherapy are successfully fabricated. The potential application for breast cancer treatment is demonstrated. Furthermore, the large X‐ray attenuation ability of LM endows the hybrid with the promising ability for CT imaging. This work explores a new biomedical use of LM and a promising cancer treatment protocol based on LM hybrid for magnetic hyperthermia combined with dual stimuli‐responsive chemotherapy and CT imaging.     

Synthesis and characterization of mesoporous silica/poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) functional hybrid useful for drug delivery

Recent studies indicate the use of mesoporous silica and polymeric sensitive hydrogels as suitable for drug delivery systems due to their specific characteristics. Polymeric hydrogels, such as poly(N-isopropylacrylamide) [P(N-iPAAm)], show volumetric expansion/contraction behaviour at 306 K, which that can be used to develop a thermosensitive drug delivery system. In this study, we report a facile and direct synthesis route to obtain hybrid functional nanosystems based on silica-P(N-iPAAm) by using a neutral surfactant and without any functionalization method and the assessment of its release rate of a model drug. The materials were characterized by Fourier transform infrared spectroscopy, nitrogen adsorption, scanning electron microscopy, transmission electron microscopy and thermal analysis. A release assay with atenolol monitored by UV–Vis spectroscopy was performed for pure SBA-15 and a hybrid system at different temperatures in order to evaluate the influence of the thermosensitive behaviour of the polymer on the release kinetics. The response of the hybrid system as a drug delivery device is influenced by the volumetric contraction of P(N-iPAAm) up to the lower critical solution temperature (LCST) due to phase transition. Above the LCST, drug release depends essentially on the temperature.