Preparation of Highly Loaded PAA/PAH Layer-by-layer Films by Combining Acid Transformation and Templating Methods

Enhancing the molecular loading capability of layer-by-layer(LbL)method holds high importance in environmental and biomedical application.Here,we reported a strategy to prepare highly loaded poly(acrylic acid)(PAA)/poly(allylamine hydrochloride)(PAH)LbL films by combining the particulate templating strategy and acid treatment film transformation and realized tlae efficient loading of hydrophilic small molecules.The loaded molecules can be released in a pH-controlled manner.A slow release speed was observed in the acidic solutions with pH value of 3.Abrupt releases were observed at higher pH values(5 or 7).     

Degradable dual pH- and temperature-responsive photoluminescent dendrimers

Poly(β-aminoester) dendrimers have been prepared. These systems represent the first degradable dual pH- and temperature-responsive dendrimers displaying photoluminescence. The pH/temperature sensitivities are interrelated; the lower critical solution temperature of the dendrimer decreases as the pH of the solution is increased. The sensitivities are mainly due to phase changes of the surface groups with changes in pH or temperature. These dual-responsive dendrimers are very useful in drug delivery. They may be loaded with a hydrophobic drug at low temperature without using organic solvents. The loaded drug is released very slowly and steadily at 37 °C and physiological pH, but can be quickly released at acidic pH, for example the lysosomal pH (pH 4-5), for intracellular drug release. These dendrimers also display strong photoluminescence, which can be exploited for monitoring drug loading and release. Thus, poly(β-aminoester) dendrimers constitute ideal drug carriers since their thermal sensitivity allows the loading of drugs without using organic solvents, their pH sensitivity permits fast intracellular drug release, and their photoluminescence provides a means of monitoring drug loading and release.     

Controlled loading and release of methylene blue from LbL polyurethane/poly(acrylic acid) film

The layer‐by‐layer (LbL) assembled multilayer films are widely used in the biomedical field for the controlled drug delivery. Here, multilayer films were assembled by LbL technique through alternating deposition of cationic polyurethane (PU) and poly(acrylic acid) (PAA) on glass slides. Methylene blue (MB) was used as a model drug to investigate the loading and release ability of the prepared multilayer film. The results showed that the loading rate and loading amount of MB were greatly influenced by pH value of the dye solution, and the release rate of MB was controlled both by ionic strength and pH value of immersing solution. The result also indicated that the film had a good reversibility of drug loading and release. It suggested that the PU/PAA multilayer film had potential applications in drug delivery and controlled release. Copyright © 2011 John Wiley & Sons, Ltd.     

Self‐Assembled Supramolecular Nanocarrier Hosting Two Kinds of Guests in the Site‐Isolation State

Hyperbranched polyethylenimine (HPEI) was simply mixed with a solution of amphiphilic calix[4]arene (AC4), which possesses four phenol groups and four aliphatic chains, in chloroform. This resulted in the novel supramolecular complex HPEI–AC4 through the noncovalent interaction of the amino groups of HPEI with the phenol groups of AC4. The formed HPEI–AC4 supramolecular complexes were characterized by ¹H NMR spectroscopy and dynamic light scattering. The cationic water‐soluble dye methyl blue (MB) and the anionic water‐soluble dye methyl orange (MO) were used as the model guests to test the performance of HPEI–AC4 as a supramolecular nanocarrier. It was found that HPEI–AC4 could accommodate the anionic water‐soluble MO guests into the HPEI core. The MO encapsulation capacity of HPEI–AC4 was pH sensitive, which reached maximum loading under weakly acidic conditions. The loaded MO molecules could be totally released when the pH value was reduced to be around 4.5 or raised to be around 9.5, and this process was reversible. HPEI–AC4 could not only accommodate the anionic MO with the HPEI core but could also simultaneously load the cationic MB molecules using the formed AC4 shell, thereby realizing the site isolation of the two kinds of functional units. The amount of MO and MB encapsulated by HPEI–AC4 could be controlled by varying the ratio of hydroxyl groups of AC4 to amino groups of HPEI.     

Reversible disulfide cross-linking in layer-by-layer films: preassembly enhanced loading and pH/reductant dually controllable release

This paper describes the fabrication of polyelectrolyte multilayer film which combines preassembly of poly(allylamine hydrochloride) (PAH) and 5,10,15,20-tetraphenyl-21H,23H-porphine-p,p',p' ',p' '-tetrasulfonic acid tetrasodium hydrate (TPPS) in aqueous solution with the layer-by-layer (LbL) assembly of the PAH-TPPS complex and cross-linkable polyelectrolyte, PAASH60, which is a poly(acrylic acid) with 60% of its carboxylic acid grafted of thiol groups. During preassembly, TPPS was incorporated into PAH chains. After oxidative cross-linking to form disulfide bonds in between the layers, the multilayer with preassembly of the PAH-TPPS complex allowed for release and loading of TPPS in a reproducible way. The release of TPPS from the loaded film was a pH-controlled process. To compare with the conventional multilayer, the reloading capacity was greatly enhanced, which was related to the charge binding sites that formed by release of TPPS from the multilayer. Moreover, the release of TPPS could also be achieved by breaking off the cross-linking through reduction of disulfide bonds, and the release rates could be controlled by the reductive efficiency of the reductants in the media. In this way, the release of TPPS is pH/reductant dually controllable, thereby facilitating a new route to multistimuli controllable materials.     

布洛芬在阴离子交换树脂上的负载及其缓释

将布洛芬通过静电和疏水作用的共同作用负载于聚苯乙烯型大孔弱碱性阴离子交换树脂D301R和D301T上,最佳负载条件为:布洛芬悬浮于5~10%的乙醇水溶液中,加入树脂后在60℃下搅拌12h,负载量可达到0.49g/g树脂。研究了负载的布洛芬在模拟胃肠道的条件下(pH2下2h、pH 7.4下4h和pH 6.7下18h)的释放动力学,在前12h的释放接近于线性释放,释放率为58~60%。后12h的释放量较小,释放率为13~17%。如果每12h服药1次,第2次服药后的24h的累加释放率接近于线性释放。与聚苯乙烯骨架的大孔弱碱性阴离子交换树脂相比,聚甲基丙烯酸酯骨架的弱碱性阴离子交换树脂(甲基丙烯酸正丁酯/甲基丙烯酸N,N-二甲胺基乙酯/双甲基丙烯酸乙二醇酯共聚物)负载的布洛芬在相同释放条件下突释明显,表明布洛芬与苯乙烯型弱碱性阴离子交换树脂之间的π-π作用在布洛芬的缓释中起关键的作用。     

Biomolecular Release Stimulated by Electrochemical Signals at a Very Small Potential Applied

DNA release electrochemically stimulated by applying ?10 mV on the modified electrode was studied. The release process was based on the local (interfacial) pH change produced upon H₂O₂ reduction electrocatalyzed by the immobilized microperoxidase‐11. SiO₂ nanoparticles attached to the electrode surface and functionalized with trigonelline and boronic acid species changed their electrical charge from positive to negative upon the interfacial pH change, thus allowing electrostatic adsorption of negatively charged DNA on the positive interface and then its repulsion/release from the negative interface. The loaded/released DNA molecules were labeled with a fluorescent dye to allow easy detection of the released DNA molecules. The important feature of the developed system is the controlled DNA release upon applying very small electrical potential on the modified electrode.     

Layer-by-layer assembled microgel films with high loading capacity: reversible loading and release of dyes and nanoparticles

Multilayer films containing microgels of chemically cross-linked poly(allylamine hydrochloride) (PAH) and dextran (named PAH-D) were fabricated by layer-by-layer deposition of PAH-D and poly(styrene sulfonate) (PSS). The successful fabrication of PAH-D/PSS multilayer films was verified by quartz crystal microbalance measurements and cross-sectional scanning electron microscopy. The as-prepared PAH-D/PSS multilayer films can reversibly load and release negatively charged dyes such as methyl orange (MO) and fluorescein sodium and mercaptoacetic acid-stabilized CdTe nanoparticles. The loading capacity of the film for MO can be as large as approximately 3.0 microg/cm2 per bilayer, which corresponds to a MO density of 0.75 g/cm3 in the film. The high loading capacity of the PAH-D/PSS films originates from the cross-linked film structure with sufficient binding groups of protonated amine groups, as well as their high swelling capability by solvent. The loaded material can be released slowly when immersing the films in 0.9% normal saline. Meanwhile, the PAH-D/PSS multilayer films could deposit directly on either hydrophilic or hydrophobic substrates such as quartz, polytetrafluoroethylene, polystyrene, poly(ethylene terephthalate), and polypropylene. The microgel films of PAH-D/PSS are expected to be widely useful as matrixes for loading functional guest materials and even for controlled release.     

pH敏感型mPEG-Hz-PLA聚合物纳米载药胶束的制备

以合成的含有腙键的聚乙二醇大分子(mPEG-Hz-OH)为引发剂,以丙交酯为单体引发开环聚合反应,并通过调整投料比,制备出3种不同分子量的含腙键的生物可降解嵌段聚合物(mPEG-Hz-PLA).将腙键引入到聚合物的骨架中,以此构建聚合物胶束并作为pH敏感型纳米药物载体.制备的pH敏感型胶束的CMC值等于或低于5.46×10-4 mg/m L,DLS和TEM显示粒径均小于100 nm,且粒径分布均匀.非pH敏感型胶束在不同pH下的粒径变化不明显,而pH敏感型胶束在酸性环境下(pH=4.0和pH=5.0)胶束粒径出现了明显变化.以阿霉素为模型药物制备了pH敏感型载药胶束,其粒径比空白胶束大(100~200 nm),且粒径分布均匀.药物释放实验表明pH敏感型载药胶束随着释放介质pH降低累积释药量增高.MTT实验表明空白胶束对HeLa细胞和RAW264.7细胞几乎没有抑制作用,而载阿霉素的胶束对2种细胞的抑制作用都随着剂量的增大和时间的延长而增强.     

Heterostructured magnetic nanotubes

Heterostructured magnetic tubes with submicrometer dimensions were assembled by the layer-by-layer deposition of polyelectrolytes and nanoparticles in the pores of track-etched polycarbonate membranes. Multilayers composed of poly(allylamine hydrochloride) and poly(styrene sulfonate) assembled at high pH (pH > 9.0) were first assembled into the pores of track-etched polycarbonate membranes, and then multilayers of magnetite (Fe3O4) nanoparticles and PAH were deposited. Transmission electron microscopy (TEM) confirmed the formation of multilayer nanotubes with an inner shell of magnetite nanoparticles. These tubes exhibited superparamagnetic characteristics at room temperature (300 K) as determined by a SQUID magnetometer. The surface of the magnetic nanotubes could be further functionalized by adsorbing poly(ethylene oxide)-b-poly(methacrylic acid) block copolymers. The separation and release behavior of low molecular weight anionic molecules (i.e., ibuprofen, rose bengal, and acid red 8) by/from the multilayer nanotubes were studied because these tubes could potentially be used as separation or targeted delivery vehicles. The magnetic tubes could be successfully used to separate (or remove) a high concentration of dye molecules (i.e., rose bengal) from solution by activating the nanotubes in acidic solution. The release of the anionic molecules in physiologically relevant buffer solution showed that whereas bulky molecules (e.g., rose bengal) release slowly, small molecules (i.e., ibuprofen) release rapidly from the multilayers. The combination of the template method and layer-by-layer deposition of polyelectrolytes and nanoparticles provides a versatile means to create functional nanotubes with heterostructures that can be used for separation as well as targeted delivery.     

Micellization and reversible pH-sensitive phase transfer of the hyperbranched multiarm PEI-PBLG Copolymer

A novel, hyperbranched, amphiphilic multiarm biodegradable polyethylenimine-poly(gamma-benzyl-L-glutamate) (PEI-PBLG) copolymer was prepared by the ring-opening polymerization of gamma-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) with hyperbranched PEI as a macroinitiator. The copolymer could self-assemble into core-shell micelles in aqueous solution with highly hydrophobic micelle cores. As the PBLG content was increased, the size of the micelles increased and the critical micelle concentration (CMC) decreased. The surface of the micelles had a positive zeta potential. The cationic micelles were capable of complexing with plasmid DNA (pDNA), which could be released subsequently by treatment with polyanions. The PEI-PBLG copolymer formed unimolecular micelles in chloroform solution. The pH-sensitive phase-transfer behavior exhibited two critical pH points for triggering the encapsulation and release of guest molecules. Both the encapsulation and release processes were rapid and reversible. Under strong acidic or alkaline conditions, the release process became partially or completely irreversible. Thus, this copolymer system should be an attractive candidate for a gene- or drug-delivery system in aqueous media and could provide the phase-transfer carriers between water and organic media.     

A Peptide Dendron‐Based Shrinkable Metallo‐Hydrogel for Charged Species Separation and Stepwise Release of Drugs

A shrinkable supramolecular metallo‐hydrogel based on the L ‐glutamic acid dendron and magnesium showed reversible volume‐phase transition depending on pH changes. The hydrogel further showed selective shrinkage upon addition of positively charged species, while it remained in the gel state when negatively charged species were incorporated. Based on this property, the gel could be used as the matrix to efficiently separate ionic dye mixtures, in which the cationic dye was incorporated predominantly in the shrunken gel, while the negatively charged dye was released into the aqueous solution. More interestingly, the shrinkable gel can be used as a model drug‐delivery vehicle for the stepwise release of a two‐component drug system, in which the negatively charged drug is released first and then the second component is released with a pH trigger.     

Synthesis and characterization of ramose tetralactosyl-lysyl-chitosan-5-fluorouracil and its in vitro release

In order to improve drug loading and achieve a good release effect, this paper adopts the ramose method, choosing chitosan as the carrier and 5-fluorouracil (5-Fu) as a model drug. Ramose chitosan-lysyl-5-Fu(3) and ramose tetralactosyl-lysyl-chitosan-5-Fu(6) were synthesized successfully, then the in vitro release of (6) was researched. The results show that the drug loading of (3) and (6) are 9.17 and 1.63% (w/w), respectively. The in vitro release behavior of (6) in pH 7.4 phosphate buffer solution and pH 1.2 HCl?CKCl solution were studied. The zero order release time that (6) maintains in alkaline and acidic media are 64 and 24?h, and the total release by 184?h are 71.97 and 82.34%, respectively. The performance is smooth throughout the whole stage of release, and the concentration of cumulative release is lower in the alkaline environment than in the acidic environment over the same time.     

Effect of formulation variables on entrapment efficiency and release characteristics of bovine serum albumin from carboxymethyl xanthan microparticles

Xanthan gum was derivatized to sodium carboxymethyl xanthan (SCMX) gum with a view to prepare bovine serum albumin (BSA)‐loaded carboxymethyl xanthan (CMX) microparticles through interaction with metal ion in a completely aqueous environment. The effect of various formulation variables, such as a pH of SCMX gum solution, concentration of BSA and SCMX gum, and gelation time on BSA entrapment efficiency and release of the protein in different media were studied. While BSA entrapment efficiency was found to decrease with increase in gelation time and initial BSA loading, the same was found to increase with increase in concentration of SCMX gum. Although the release of BSA in acidic medium was almost equal to that in alkaline medium, as compared up to 2 hr, the release in alkaline medium was found to be prolonged to a different extent depending upon the formulation variables. Copyright © 2008 John Wiley & Sons, Ltd.     

Incorporation of block copolymer micelles into multilayer films for use as nanodelivery systems

This work demonstrates the potential application of stimulus responsive block copolymer micelles as triggerable delivery systems for use within multilayer films. Cationic, pH-responsive micelles of poly[2-(dimethylamino)ethyl methacrylate-block-poly(2-(diethylamino)ethyl methacrylate)] (PDMA-PDEA) were deposited on anionic polystyrene latex particles. The charge reversal of the surface and the amount of adsorbed polymer were monitored by zeta potential measurements and colloidal titrations, respectively. Prior to adsorption, the PDMA-PDEA micelles were loaded with a hydrophobic dye, and UV-vis spectroscopy was used to determine the amount of dye encapsulated within a monolayer of micelles. It was found that subtle chemical modification of the PDMA-PDEA diblock copolymer via permanent quaternization of the PDEA block results in micelles with tunable loading capacities. Multilayers of cationic micelles of partially quaternized PDMA-PDEA and anionic polyelectrolyte (poly(sodium 4-styrene sulfonate)) were deposited on the surface of polystyrene latex particles by sequential adsorption. UV-vis analysis of the dye present within the multilayer after the addition of each layer demonstrates that the micelles are sufficiently robust to retain encapsulated dye after multiple adsorption/washing cycles and can thus create a film that can be increasingly loaded with dye as more micelle layers are adsorbed. Multiple washing cycles were performed on micellar monolayers of PDMA-PDEA to demonstrate how such systems can be used to bring about triggerable release of actives. When performing several consecutive washing steps at pH 9.3, the micelle structure of the PDMA-PDEA micelles in the monolayer is retained, resulting in only a small reduction in the amount of encapsulated dye. In contrast, washing at pH 4, the structure of the micelle layers is severely disrupted, resulting in a fast release of the encapsulated dye into the bulk. Finally, if a sufficient number of micelle/homopolyelectrolyte layers are adsorbed, it is possible to selectively dissolve the latex template, resulting in hollow capsules.     

Aggregation and pH responsive disassembly of a new acid-labile surfactant synthesized by thiol-acrylate Michael addition reaction

Nucleophilic thiol-acrylate Michael reaction between a hydrophobic thiol and hydrophilic acrylate derivative generated a nonionic surfactant with acid-labile β-thiopropionate linker. Micellization of the surfactant, its ability to encapsulate hydrophobic dye, acid-induced disruption of the aggregate and pH-selective dye release profile have been revealed in this report. The micellar aggregates were found to be stable under neutral conditions, but they could be disrupted in acidic pH (5.3), and thus the encapsulated hydrophobic dye molecules could be selectively released. Appropriate control experiments revealed that the sulfur atom in the β-position is essential for acidic hydrolysis of the ester functionality of the surfactant.     

Preparation of microparticles composed of cinnamoyl gelatin and cinnamoyl alginate by spray-drying method and effect of UV irradiation and pH value on their release property

Microparticles composed of cinnamoyl gelatin (CinGel) and cinnamoyl alginate (CinAlg) were prepared as a UV irradiation- and pH-responsive carrier by a spray-drying method. CinGel and CinAlg were prepared by a condensation reaction. Using a colorimetric method, the gelatin to CA mass ratio and the alginate to CA mass ratio were calculated to be 1:0.04 and 1:0.02, respectively. The complexation of CinGel and CinAlg in aqueous solution took place when the medium was acidic (e.g., pH 4.0) and the maximum complexation was obtained when the CinGel/CinAlg mass ratio was 7:3. On SEM photographs, some spray-dried CinGel/CinAlg particles were spherical and others were irregularly shaped, and the diameter was a few to tens of micrometers. The release degrees of amaranth loaded in UV-treated microparticles were lower than those of the dye loaded in UV-untreated ones, possibly because of the photo cross-linkage of CinGel and CinAlg. Regardless of whether the microparticles were UV-treated, the release degree at pH 4.0 was significantly lower than the release degree at pH 6.0 and pH 8.0, possibly because of complexation of CinGel and CinAlg under the acidic condition.     

pH-Dependent Release from Monoolein Cubic Phase Containing Hydrophobically Modified Chitosan

Monoolein (MO) cubic phase incorporating hydrophobically modified chosan (Hm chitosan) was prepared to obtain a pH-dependent release. Following calorimetric study, Hm chitosan had little effect on the crystal structure of MO cubic phase under acidic condition where Hm chitosan is readily soluble. At a higher pH (e.g., pH 9.0), however, the crystal structure of MO cubic phase was disturbed, possibly due to the insolubilization of Hm chitosan at the alkali condition. Whether the dye included in the cubic phase is anionic (amaranth) or cationic (methylene blue), the release from the cubic phase was suppressed as the pH of release medium increased. The structural change of cubic phase caused by the insolubilization of Hm chitosan, or the blockage of the water channel of the cubic phase by precipitated Hm chitosan would be responsible for the suppressed released.     

Loading and release of charged dyes using ultrathin hydrogels

The anionic dyes methyl orange (MO) and allura red (AR) were used as model drugs to assess the loading and release by layer-by-layer assembled ultrathin hydrogels prepared via the amide formation of poly(acrylic acid-co-N-isopropylacrylamide) with AAc contents of 5, 10, and 15 mol % plus poly(vinylamine hydrochloride). The amount of MO loaded was potentially controlled by changing the dye concentrations, film thickness, and AAc content of the copolymers. The release of AR was controlled by the NaCl concentration and pH. We conclude that the polymeric matrices of ultrathin hydrogels have great potential for the loading and release of charged drugs.     

Synthesis of poly(acrylic acid) (PAA) modified Pluronic P123 copolymers for pH-stimulated release of doxorubicin

Pluronic P123 was chain-extended at their terminal groups using atom transfer radical polymerization to form poly(acrylic acid) (PAA) tails and obtain the PAA-b-P123-b-PAA (P123-PAA) copolymer. The incorporation of PAA had the effect of increasing the carrier's drug loading capacity of an anti-cancer drug, Doxorubicin (DOX), and also allowed for pH-controlled release of the drug. Drug release assays showed that up to 60% of DOX cargo could be retained in the DOX/P123-PAA complex for 3 days at normal physiological pH (7.4). This was then followed by a secondary burst release of DOX when the environment became more acidic (pH 5). Therefore, it was possible that the more acidic physiological environment of tumor sites could be used to trigger an accelerated release of DOX from the drug carriers. The material was demonstrated for potential application in the delivery of cationic drugs for cancer treatment.