Controlled release in hard to access places by poly(methyl methacrylate) microcapsules triggered by gamma irradiation

Gamma irradiation was investigated as a triggering stimulus for the activation of poly(methyl methacrylate) (PMMA) microcapsules. PMMA was exposed to varying doses of irradiation and analyzed by differential scanning calorimetry, size‐exclusion chromatography, and nuclear magnetic resonance. It was found that the glass transition temperature (T_g) of the polymer decreases at low irradiation doses. Additionally, T_g can be physically adjusted by adding a plasticizer, and both kinds of microcapsules were successfully prepared with non‐plasticized and plasticized PMMA shell. Finally, impermeable microcapsules were shown to become permeable after irradiation and release an encapsulated cross‐linker, which enables the remotely controlled formation of polydimethylsiloxanes in traditionally unavailable places. Therefore, the activation method has significant implications for industrial application. Copyright © 2015 John Wiley & Sons, Ltd.     

壳聚糖纳米微球对牛血清蛋白的包封和缓释效果研究

壳聚糖(chitosan,CS)是甲壳素脱乙酰化的产物,是由葡萄糖结构单元组成的直链多糖。CS作为一种带正电荷的天然多糖,本身具有无毒、无刺激性、无致敏性、无致突变的性质,降解产物为低分子壳寡糖和葡萄糖胺,具有良好的生物相容性和生物降解性[1-2]。CS本身具有的特性,引起了人们的     

Complex micelles formed from two diblock copolymers for applications in controlled drug release

Double‐responsive core‐shell‐corona complex micelles for applications in drug release were formed from self‐assembly of two diblock copolymers PtBA‐b‐ PNIPAM and PtBA‐b‐P4VP. The two diblock copolymers coaggregated into core‐shell complex micelles in acidic water with the hydrophobic PtBA blocks as the common core and soluble PNIPAM/P4VP blocks as the mixed shell. Increasing temperature or pH value, the micelles converted into core‐shell‐corona micelles because of the collapse of PNIPAM or P4VP blocks as the inner shell and soluble P4VP or PNIPAM chains stretching outside as the outer corona. The anti‐inflammation drug naproxen (NAP) was loaded as the model drug in micelles in acidic water and released because of the ionization of NAP in alkaline solutions. Compared with pure core‐shell micelles, release of NAP from core‐shell‐corona complex micelles avoided the burst diffusion and the release rate is more easily controlled by tuning the composition of the mixtures or by adjusting the pH of the medium. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1804–1810, 2009     

Layered microcapsules for daunorubicin loading and release as well as in vitro and in vivo studies

Anti‐cancer drug daunorubicin (DNR) was encapsulated in preformed multilayer microcapsules and was applied in tumor treatment by in vitro cell culture and in vivo animal experiments. The microcapsules were fabricated by an alternate deposition of oppositely charged polysaccharides, i.e. chitosan and alginate onto carboxymethyl cellulose (CMC) doped CaCO₃ colloidal particles in a sequential assembly procedure, followed by crosslinking of the capsule shells with glutaraldehyde (GA) and removal of the templates by disodium ethylenediaminetetraacetic acid (EDTA). The as‐prepared microcapsules showed strong ability to induce the positively charged DNR to deposit into the microcapsule interiors. Confocal microscopy and transmission electron microscopy observed homogeneous distribution of the drug within microcapsules. The loaded DNR could be released again, following a diffusion‐controlled model at the initial stage. In vitro experiments demonstrated that the encapsulated DNR can effectively induce the apoptosis of BEL‐7402 tumor cells, as evidenced by various microscopy techniques after acridine orange (AO), Hoechst 33342, and osmium tetraoxide staining. By seeding the BEL‐7402 hepatoma cells into BALB/c/nu mice, tumors were created for the animal experiments. The results showed that the encapsulated DNR had better efficacy than that of the free drug in terms of tumor inhibition in a 4 week in vivo culture period. Copyright © 2007 John Wiley & Sons, Ltd.     

Magnetic‐targeted pH‐responsive drug delivery system via layer‐by‐layer self‐assembly of polyelectrolytes onto drug‐containing emulsion droplets and its controlled release

Novel magnetic‐targeted pH‐responsive drug delivery system have been designed by the layer‐by‐layer self‐ assembly of the polyelectrolytes (oligochitosan as the polycation and sodium alginate as the polyanion) via the electrostatic interaction with the oil‐in‐water type hybrid emulsion droplets containing the superparamagnetic ferroferric oxide nanoparticles and drug molecules [dipyridamole (DIP)] as cores. Here the drug molecules were directly encapsulated into the interior of droplets without etching the templates and refilling with the desired guest molecules. The drug‐delivery system showed high encapsulation efficiency of drugs and drug‐loading capacity. The cumulative release ratio of dipyridamole from the oligochitosan/sodium alginate multilayer‐encapsulated magnetic hybrid emulsion droplets (DIP/Fe₃O₄‐OA/OA)@(OCS/SAL)₄ was up to almost 100% after 31 h at pH 1.8. However, the cumulative release ratio was only 3.3% at pH 7.4 even after 48 h. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Biodegradable hyaluronic acid/n-carboxyethyl chitosan/protein ternary complexes as implantable carriers for controlled protein release

An ampholytic N-carboxyethyl chitosan (CEC), with various isoelectric points (IPs), was synthesized by grafting acrylic acid on chitosan utilizing Michael's reaction. Compared to native chitosan, CEC has enhanced water solubility and dramatically accelerated enzymatic degradation; the rate of degradation is proportional to the degree of substitution (DS). The results from turbidimetric titration and fluorescence studies revealed that CEC formed complexes with either hyaluronic acid (HA) or bovine serum albumin (BSA) within a certain pH range. The HA/CEC/BSA ternary complexes could be prepared by colloid titration with quantitative yield and BSA entrapment. The rate of BSA release from the complexes was affected by pH, ionic strength, DS of CEC, and the molecular weight (MW) of HA. The endurance of BSA release from the complexes could be extended up to 20 d by formulating them with high-MW HA and CEC with low DS.BSA release profiles from HA/CEC-2/BSA complexes.     

A novel route for preparation of multifunctional polymeric nanocarriers for stimuli‐triggered drug release

Fluorescence‐incorporated, crosslinker‐free, pH‐ and thermoresponsive nanocarriers were prepared by the incorporation of drug molecules into the thermoresponsive nanocapsules, which composed of poly(N‐isopropylacrylamide) (PNIPAAm) with carboxylic acid end groups via temperature induced self‐assembling method. Well‐defined, pH‐responsive carboxylic acid group‐ended PNIPAAm homopolymer (HOOC? PNIPAAm? COOH) was synthesized by reversible addition fragmentation chain transfer polymerization with S,S′‐bis(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate (CMP) as a chain transfer agent. Rhodamine 6G (R6G), the model drug, was used for three kinds of application: First, the nanostructure fixing; second, the fluorescence‐labeling; and last, the controlled release modeling. The transmission electron microscope images showed the solution type dosing led to the encapsulation of drug molecules into the nanocarriers, while the powder‐type drug‐loading process significantly contributed to the structure preservation of nanocarriers. The controlled release behaviors with various pH values and temperatures were evaluated. These multifunctional nanocarriers have potential to be applied for the biomedical therapy by stimuli‐responsive controlled release. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 561–571     

Rose bengal-grafted biodegradable microcapsules: singlet-oxygen generation and cancer-cell incapacitation

Rose bengal-grafted chitosan (RB-CHI), synthesized through dehydration between amino and carboxyl functional groups under mild conditions, was coated onto the outer layer of preformed biodegradable microcapsules consisting of sodium alginate and chitosan. The fabricated photosensitive microcapsules were characterized by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The assembled materials maintained intact spherical morphology and thus showed good ability to form thin films. Electron spin resonance spectroscopy allowed direct observation of the generation of singlet oxygen ((1)O(2)) from photosensitive microcapsules under light excitation at about 545 nm. Furthermore, with increasing light radiation, the content of (1)O(2) increased, as detected by a chemical probe. In vitro cellular toxicity assays showed that RB-CHI-coated photosensitive microcapsules exhibit good biocompatibility in darkness and high cytotoxicity after irradiation, and could provide new photoresponsive drug-delivery vehicles.     

Development of Poly(ethylene glycol) Based Amphiphilic Copolymers for Controlled Release Delivery of Carbofuran

The formation of micelles in a solvent that is selective for one of the blocks is one of the most important and useful properties of block copolymers. We had synthesized copolymers of polyethylene glycol and various dimethyl esters, which self assemble into nano micellar aggregates in aqueous media. In the present work, we have utilized these nano micelles for the encapsulation of carbofuran, [2,3–dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate], a systemic insecticide-nematicide, for the development of controlled release formulation.     

Self-assembly strategy for the preparation of polymer-based nanoparticles for drug and gene delivery

Nanoparticulate drug-delivery systems have attained much importance because of their injectable property, the possibility to achieve passive targeting and active targeting, and unique advantages to realize stimuli tailored delivery. Molecular self-assembly is a powerful method for fabricating polymer-based nanoparticles, which involves various driving forces, such as hydrophobic interactions, electrostatic interactions, stereocomplexation, host/guest interactions and hydrogen bonding. By fine tuning one or many types of these interactions, self-assemblies with a wide range of structures and functions could be fabricated. In this article, recent developments in different self-assembly strategies for the preparation of polymer-based nanoparticulate delivery systems are discussed.     

Self-assembly of oligo(para-phenylenevinylene)s through arene-perfluoroarene interactions: pi gels with longitudinally controlled fiber growth and supramolecular exciplex-mediated enhanced emission

The arene-perfluoroarene (ArH-ArF) interaction, which has been extensively studied in the field of solid-state chemistry, is exploited in the hierarchical self-assembly of oligo(para-phenylenevinylene)s (OPVs) with controlled longitudinal fiber growth that leads to gelation. The size of the self-assembled fibers of a pentafluorophenyl-functionalized OPV 5 could be controlled through C-FH--C hydrogen bonding and pi stacking. The ability of fluoroaromatic compounds to form excited-state complexes with aromatic amines has been utilized to form a supramolecular exciplex, exclusively in the gel state, that exhibits enhanced emission. Thus, the commonly encountered fluorescence quenching during the self-assembly of OPVs could be considerably prevented by exciplex formation with N,N-dimethylaniline (DMA), which only occurred for the fluorinated OPV and not for the non-fluorinated analogue 4. In the former case, a threefold enhancement in the emission intensity could be observed in the gel state, whereas no change in emission occurred in solution. Thus, the major limitations of spontaneous fiber growth and fluorescence self-quenching encountered in the self-assembly of OPVs could be controlled to a great extent by using the versatile ArH-ArF interaction.     

Stimuli-responsive chitosan-graft-poly(N-vinylcaprolactam) as a promising material for controlled hydrophobic drug delivery

A novel type of pH- and thermo-responsive copolymer, chitosan-graft-poly(N-vinylcaprolactam) (chitosan-g-PNVCL), was prepared by grafting carboxyl-terminated poly(N-vinylcaprolactam) (PNVCL-COOH) chains onto a chitosan backbone as a drug-delivery carrier. The formation of chitosan-g-PNVCL was confirmed by FT-IR and 1H NMR techniques. Chitosan-g-PNVCL showed a definite phase transition at 32 degrees C as occurs in pure PNVCL. The swelling degree of the chitosan-g-PNVCL beads was found to be higher at pH 2.2 than at pH 7.4. Moreover, the swelling degree of the beads decreased with increased environmental temperature. Compared to the chitosan beads, the release profile of chitosan-g-PNVCL beads showed a slower and more controlled release of the entrapped ketoprofen. The release behavior of the chitosan-g-PNVCL beads was influenced by both the pH and temperature of the medium. The MTT assay showed no obvious cytotoxicity of chitosan-g-PNVCL against a human endothelial cell line over a concentration range of 0-400 microg x mL(-1). These results suggest that chitosan-g-PNVCL could be a potential stimuli-responsive material for controlled drug delivery, and it may improve the bioavailability, efficacy, and compliance of the encapsulated drugs. [Reaction: see text].     

Sponge-like nanostructured conducting polymers for electrically controlled drug release

An electrically controlled drug release (ECDR) system based on sponge-like nanostructured conducting polymer (CP) polypyrrole (PPy) film was developed. The nanostructured PPy film was composed of template-synthesized nanoporous PPy covered with a thin protective PPy layer. The proposed controlled release system can load drug molecules in the polymer backbones and inside the nanoholes respectively. Electrical stimulation can release drugs from both the polymer backbones and the nanoholes, which significantly improves the drug load and release efficiency. Furthermore, with one drug incorporated in the polymer backbone during electrochemical polymerization, the nanoholes inside the polymer can act as containers to store a different drug, and simultaneous electrically triggered release of different drugs can be realized with this system.     

Superparamagnetic pH‐sensitive multilayer hybrid hollow microspheres for targeted controlled release

The superparamagnetic multilayer hybrid hollow microspheres have been fabricated using the layer‐by‐layer assembly technique by the electrostatic interaction between the polyelectrolyte cation chitosan (CS) and the hybrid anion citrate modified ferroferric oxide nanoparticles (Fe₃O₄‐CA) onto the sacrificial polystyrene sulfonate microspheres templates after etching the templates by dialysis. The saturation magnetization and magnetite contents of the superparamagnetic multilayer hybrid hollow microspheres were 32.46 emu/g and 51.3%, respectively. The hybrid hollow microspheres showed pH‐sensitive characteristics. The adsorption and release of the basic dye (methylene blue) were applied to investigate the interaction between the amino groups of CS and the carboxyl groups of the Fe₃O₄‐CA nanoparticles in different pH media. The superparamagnetic pH‐sensitive multilayer hybrid hollow microspheres are expected to be used for the targeted controlled release of drugs or in diagnostics. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3135–3144, 2010     

甲壳胺药膜的控制释放研究

以阿司匹林为模型药物研究了小分子药物在甲壳腹膜中的释放行为，结果表明释放是扩散控制的，与膜厚、介质pH值，膜交联度及膜分散性密切相关。改变这些参数可达到比较恒定的延长释放和不同的给药途径。