Silica nanocapsules for redox-responsive delivery

Redox-responsive silica nanocapsules with a hydrophobic liquid core were synthesized by reactive templating of miniemulsion droplets with functional alkoxysilanes. Tetrasulfide bridges were successfully introduced into the inorganic shell and were found to be accessible for chemical reactions as shown by ³¹P-NMR spectroscopy. Indeed, the tetrasulfide groups could be reduced to yield thiol groups. A subsequent increase of permeability of the silica shell was observed upon reduction of the tetrasulfide groups.     

Design of polymeric nanoparticles for biomedical delivery applications

Polymeric nanoparticles-based therapeutics show great promise in the treatment of a wide range of diseases, due to the flexibility in which their structures can be modified, with intricate definition over their compositions, structures and properties. Advances in polymerization chemistries and the application of reactive, efficient and orthogonal chemical modification reactions have enabled the engineering of multifunctional polymeric nanoparticles with precise control over the architectures of the individual polymer components, to direct their assembly and subsequent transformations into nanoparticles of selective overall shapes, sizes, internal morphologies, external surface charges and functionalizations. In addition, incorporation of certain functionalities can modulate the responsiveness of these nanostructures to specific stimuli through the use of remote activation. Furthermore, they can be equipped with smart components to allow their delivery beyond certain biological barriers, such as skin, mucus, blood, extracellular matrix, cellular and subcellular organelles. This tutorial review highlights the importance of well-defined chemistries, with detailed ties to specific biological hurdles and opportunities, in the design of nanostructures for various biomedical delivery applications.     

One-step fabrication of polymeric Janus nanoparticles for drug delivery

With its unique structure of two compartments, Janus particles can be used for many applications for which monomorphic particles are inadequate, including to be used as a drug delivery system to deliver multiple payloads with widely different solubility. Here we report on a fluidic nanoprecipitation system (FNPS), capable of fabricating biocompatible Janus polymeric nanoparticles comprised of the FDA-approved polymer poly(lactic-co-glycolic acid) (PLGA). The FNPS contains dual inlets, one for each half of the particle, that insert into the precipitation stream. The system provides a one-step approach for production of Janus polymeric particles with submicrometer diameters and is likely amenable to substantial scale-up. To the best of our knowledge, this is the first demonstration of biocompatible Janus nanoparticles that encapsulate a hydrophobic drug (paclitaxel) on one side and a hydrophilic drug (doxorubicin hydrochloride) on the other.     

Curcumin-loaded biocompatible thermoresponsive polymeric nanoparticles for cancer drug delivery

This study aims at the formulation of curcumin with biodegradable thermoresponsive chitosan-g-poly (N-vinylcaprolactam) nanoparticles (TRC-NPs) for cancer drug delivery. The spherical curcumin-loaded nanoparticles of size 220 nm were characterized, and the biological properties were studied using flow cytometry and cytotoxicity by MTT assay. The in vitro drug release was higher at above LCST compared to that at below LCST. TRC-NPs in the concentration range of 100-1000 μg/mL were non-toxic to an array of cell lines. The cellular localization of the curcumin-loaded TRC-NPs was confirmed from green fluorescence inside the cells. The time-dependent curcumin uptake by the cells was quantified by UV spectrophotometer. Curcumin-loaded TRC-NPs showed specific toxicity to cancer cells at above their LCST. Flow cytometric analysis showed increased apoptosis on PC3 compared to L929 by curcumin-loaded TRC-NPs. These results indicate that novel curcumin-loaded TRC-NPs could be a promising candidate for cancer drug delivery.     

Methoxy poly(ethylene glycol)-conjugated linoleic acid polymeric micelles for paclitaxel delivery

A methoxy poly(ethylene glycol) (MePEG)-conjugated linoleic acid (CLA) polymeric conjugate is synthesized with the use of dicyclohexycarbodiimide and 4-dimethylaminopyridine as the coupling agent and the catalyst, respectively. Self-assembled MePEG-CLA conjugate micelles are prepared by dialysis in water. Fluorescence spectroscopy indicates that the MePEG-CLA conjugate exhibits a typical core-shell micellar structure, and the estimated critical micelle concentration is 1.2 × 10⁻⁵ mol L⁻¹. Dynamic light scattering and transmission electron microscopy demonstrate that the prepared MePEG-CLA micelles have spherical shape and an average diameter of approximately 100 nm. Paclitaxel is entrapped into MePEG-CLA lyophilized powder. The release of paclitaxel from the loaded micelles is investigated in vitro. A biphasic release pattern with a fast release rate followed by a slow release is observed. The text was submitted by the authors in English.     

Preparation of reactive polymeric nanoparticles (RPNPs)

A series of reactive polymeric nanoparticles (RPNPs) was prepared by free radical nonlinear copolymerization of mono (M ₁) and trivinyl acrylic (M ₂) monomers in miniemulsion. The crosslinking density was determined by the mole ratio of the trivinyl component. It was found that the unswelled latex nanoparticles showed a narrower dispersity than in the organic solution of macromolecules. In latex, the size increased with the ratio of M ₂ monomer due to its higher polarity in the aqueous medium. However, the swollen nanoparticles, dissolved or dispersed in organic solvent, showed a higher dispersity as a function of composition and the crosslinking density. The residual vinyl groups adjacent to the nanoparticles were subjected to further crosslinking reactions. The reactive vinyl groups were detected by nuclear magnetic resonance spectroscopy (NMR). The size of particles in swollen state was determined by dynamic laser light scattering (DLS) method and the dried form by scanning electron microscopy (SEM). It was found that size of RPNPs is in the range of 50 to 500 nm. These particles possess properties that may allow their application in areas as disparate as dental filling material and as a component in industrial powder-based coatings.     

Preparation and properties of thermoexpandable polymeric microspheres

In this paper,thermoexpandable polymeric microspheres were prepared by suspension polymerization with acrylonitrile(AN) and methyl methacrylate(MMA) as monomers and i-butane as a blowing agent.The micromorphology and thermal stability were researched by polarized microscopy and TGA.The diameter of the expandable microspheres increased from about 20 mm(unexpanded) to 40–80 mm(expanded) upon heating.The maximum expansion volume was higher than 22 times of the original volume and the density of the expanded microspheres was about 16.7 kg/m3.The blowing agent content in microspheres was about 20 wt% and To.e.,Tm.e.and To.s.were 80 8C,120–130 8C and 140–145 8C,respectively.     

Study on surfactant coating of polymeric nanoparticles for controlled delivery of anticancer drug

Biodegradable nanoparticles loaded with anticancer drug paclitaxel and appropriately coated with polyvinyl alcohol (PVA), polyethylene glycol (PEG) as well as d--tocopheryl polyethylene glycol 1000 succinate (TPGS) were produced and characterised by various analysis techniques such as laser light scattering (LLS) for particle size and size distribution, scanning electron microscopy (SEM) and atomic force microscopy (AFM) for particle morphology, X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared-Photoacoustic Spectroscopy (FTIR-PAS) for surface chemistry, and high performance liquid chromatography (HPLC) for drug encapsulation efficiency (EE) and in vitro release kinetics. The emphasis was given to the possible effects of surface coating on the physicochemical and pharmaceutical properties of paclitaxel loaded nanoparticles. It was found that the type and amount of the surfactant could significantly affect the drug EE in the nanoparticles, the particles characteristics and their in vitro release behaviour. The surfactants dominated on the nanoparticles surface and the coated nanoparticles displayed in spherical shape with relative smooth surface within the resolution scope of the equipment. The particle size and size distribution showed close relation to the surface coating, which may also be responsible for the drug encapsulation efficiency and the in vitro release kinetics. A favourable formulation of drug loaded nanoparticles of desired properties could be obtained by optimising the fabrication parameters.     

Preparation of amphiphilic copolymers for covalent loading of paclitaxel for drug delivery system

A novel drug‐polymer conjugate was prepared by the copper‐catalyzed azide–alkyne cycloaddition reaction between an azide‐functional diblock copolymer and an alkyne‐functional paclitaxel (PTX). The well‐defined azide‐functional diblock copolymer, poly(ethylene glycol) (PEG)‐b‐P(OEGEEMA‐co‐AzPMA), was synthesized via the atom transfer radical polymerization of oligo(ethylene glycol) ethyl ether methacrylate (OEGEEMA) and 3‐azidopropyl methacrylate (AzPMA), using PEG‐Br as macroinitiator and CuBr/PMDETA as a catalytic system. The alkyne‐functional PTX was covalently linked to the copolymer via a click reaction, and the loading content of PTX could be easily tuned by varying the feeding ratio. Transmission electron microscopy and dynamic light scattering results indicated that the drug loaded copolymers could self‐assemble into micelles in aqueous solution. Moreover, the drug release behavior of PEG‐b‐P(OEGEEMA‐co‐AzPMA‐PTX) was pH dependent, and the cumulative release amount of PTX were 50.0% at pH 5.5, which is about two times higher than that at pH 7.4. The in vitro cytotoxicity experimental results showed that the diblock copolymer was biocompatible, with no obvious cytotoxicity, whereas the PTX‐polymer conjugate could efficiently deliver PTX into HeLa and SKOV‐3 cells, leading to excellent antitumor activity. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 366–374     

Preparation and properties of novel hydrogels from oxidized konjac glucomannan cross-linked chitosan for in vitro drug delivery

In this paper, a novel composite hydrogel was prepared by the use of dialdehyde konjac glucomannan (DAK) as macromolecular cross-linking agent for chitosan (CS). This biocompatible material cross-links and gels in minutes. The structure and morphology were characterized by various analyses. The results indicate that the hydrogels formed through the Schiff-base reaction between the amino groups of CS chains and the aldehyde groups of DAK. The cross-link density (rho(x)) increases with the enhancement of DAK content in hydrogels, while equilibrium swelling ratio (SR) and the average molecular weight between cross-links (Mc) value decrease. Drug release was evaluated by varying the pH of the release medium, reversed dependence of release rate on the equilibrium SR of hydrogel indicated that drug release may be impeded by the association of drug with the polymer. Importantly, this process offers an entirely new window of materials preparation when compared with the traditional preparation of CS-based hydrogels with small molecules cross-linking agent.     

Antiviral properties of polymeric aziridine- and biguanide-modified core-shell magnetic nanoparticles

Polycationic superparamagnetic nanoparticles (～150-250 nm) were evaluated as virucidal agents. The particles possess a core-shell structure, with cores consisting of magnetite clusters and shells of functional silica covalently bound to poly(hexamethylene biguanide) (PHMBG), polyethyleneimine (PEI), or PEI terminated with aziridine moieties. Aziridine was conjugated to the PEI shell through cationic ring-opening polymerization. The nanometric core-shell particles functionalized with biguanide or aziridine moieties are able to bind and inactivate bacteriophage MS2, herpes simplex virus HSV-1, nonenveloped infectious pancreatic necrosis virus (IPNV), and enveloped viral hemorrhagic septicaemia virus (VHSV). The virus-particle complexes can be efficiently removed from the aqueous milieu by simple magnetocollection.     

Biodegradable polymeric nanoparticles based on amphiphilic principle: construction and application in drug delivery

The use of nanotechnology in drug-delivery systems (DDS) is attractive for advanced diagnosis and treatment of cancer diseases. Biodegradable polymeric nanoparticles, for example, have promising applications as advanced drug carriers in cancer treatment. In this review, we discuss the development of drug-delivery systems based on an amphiphilic principle mainly conducted by our group for anti-cancer drug delivery. We first briefly address the synthetic chemistry for amphiphilic biodegradable polymers. In the second part, we summarize progress in the application of self-assembled polymer micelles using amphiphilic biodegradable copolymers as anti-tumor drug carriers.     

Synthesis and characterization of soft polymeric nanoparticles and composites with tunable properties

Polymeric particles comprising acrylonitrile (AN)‐based core and acrylamide derivative–based shell in the submicron range with positive and negative charges were synthesized via microemulsion polymerization. 2‐Acrylamido‐2‐methylpropane sulfonic acid (AMPS) and 3‐(acrylamidopropyl)‐trimethyl ammonium chloride (APTMACl) were used as shell‐forming charged monomers onto AN core for the synthesis of p(AN‐co‐AMPS) and p(AN‐co‐APTMACl), respectively, using an oil‐in‐water emulsion system. To tune the characteristics of the core–shell particles, AN moieties in the core were amidoximated to change the nature of the core from hydrophobic (nitrile) to hydrophilic (amidoxime) nature. Additionally, colloidal magnetite particles (Fe₃O₄) produced by chemical coprecipitation technique under alkaline and inert conditions were also included inside p(AN‐co‐AMPS) and p(AN‐co‐APTMACl) particles as dual‐responsive nanocomposites against pH and magnetic field. With the magnetic properties, AN‐based core with modifiable characteristics and acrylamide‐based polyelectrolyte shells with variable charges and sizes were further used as drug carriers. For potential targeted drug delivery application of the synthesized soft particles and their composites Naproxen and Trimethoprim were used as model drugs, and he release studies were carried in phosphate buffer saline (pH = 7.4) at ambient temperature. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Designing polymeric particles for antigen delivery

By targeting dendritic cells, polymeric carriers in the nano to lower micron range constitute very interesting tools for antigen delivery. In this critical review, we review how new immunological insights can be exploited to design new carriers allowing one to tune immune responses and to further increase vaccine potency (137 references).     

Stimulus-responsive polymeric nanoparticles for biomedical applications

Polymeric nanoparticles with unique properties are regarded as the most promising materials for biomedical applications including drug delivery and in vitro/in vivo imaging.Among them,stimulus-responsive polymeric nanoparticles,usually termed as intelligent nanoparticles,could undergo structure,shape,and property changes after being exposed to external signals including pH,temperature,magnetic field,and light,which could be used to modulate the macroscopical behavior of the nanoparticles.This paper reviews ...     

半乳糖保护的Au纳米颗粒的制备及性能研究

通过一种简易的方法,利用D-半乳糖胺和氯金酸制备出了能够用于肝癌细胞靶向识别的Au纳米颗粒探针.该纳米颗粒形貌和尺寸均一并且生物相容性良好.通过改变反应体系的pH能够对Au纳米颗粒的尺寸进行调控.此外,这种新型的纳米颗粒对RCA120还具有超高的检测灵敏度,实验结果显示其检测限度可以达到2μg·L^-1.     

Preparation and characterization of metronidazole‐loaded chitosan nanoparticles for drug delivery application

This study describes the preparation of mucoadhesive chitosan nanoparticles containing metronidazole (MZ) intended for colon‐specific delivery. The chitosan nanoparticles were prepared by the ionic gelation method and their in vitro properties were studied. The release profiles of MZ from the nanoparticles were determined by UV–Vis absorption measurement at λ_max 278 nm. Scanning electron microscopy was used for morphology observation. The nanoparticles exhibited mucoadhesive properties, which diminished with increasing drug content. The nanoparticles with a particle size range between 200 and 300 nm exhibited excellent mucoadhesive properties. The results show that the formulated nanoparticles have succeeded in controlling the release of MZ over a 12‐hr period. In conclusion, the release of MZ was found to be dependent upon the composition of the nanoparticles, the ratio of the components and possible particle size, as well as bioadhesive ability. Copyright © 2008 John Wiley & Sons, Ltd.     

Cell-permeable and biocompatible polymeric nanoparticles for apoptosis imaging

Here, we report for the first time cell-permeable and biocompatible polymeric nanoparticles consisting of a polymer conjugated to a near-infrared (NIR) fluorescence (Cy5.5)-linked effector caspase-specific peptide. The close spatial proximity of the NIR fluorochromes in polymeric nanoparticles results in an autoquenched state, but polymer nanoparticles give rise to strong NIR fluorescence signal under apoptotic cells. Thus, the smart polymeric nanoparticle developed here is an attractive probe for real-time imaging of apoptosis in single cells.     

A polymeric composite carrier for oral delivery of peptide drugs: Bilaminated hydrogel film loaded with nanoparticles

A smart polymeric composite carrier consisting of carboxylated chitosan grafted nanoparticles (CCGN) and bilaminated films with one alginate-Ca²⁺ mucoadhesive layer and one hydrophobic backing layer was developed as a novel carrier for peptide. Calcein, hydrophilic and hydrolytic degradative, was entrapped into CCGN as a model peptide and its release behavior was investigated. Morphology study showed a uniform distribution of CCGN in the homogeneous and porous hydrogel. CCGN was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size measurement, and ζ potential measurement. The composite carrier was characterized by differential scanning calorimetry (DSC), scanning electron microscope (SEM) and fluorescence microscopy. The carrier exhibited high mucoadhesive force and pH-sensitivity, in that release of the nanoparticles and the model peptide calcein were both restricted in acidic environment while a fast and complete release was achieved in neutral medium. Therefore, this novel carrier would be a promising candidate for hydrophilic peptide drugs via oral administration.