Thermosensitive polylactide‐glycolide delivery systems for treatment of narcotic addictions

Environmental switches may be fabricated for the controlled release of pharmaceutical drug using a thermally responsive polymer with the intrinsic chemical and physical nature of stimuli‐sensitive smart materials. Particularly, much attention has been paid to the biomedical applications of poly(N‐isopropyl acrylamide) (PNIPAAm) because of its unique reversible transition at a specific lower critical solution temperature (LCST).Thermally sensitive block copolymers, poly(N‐isopropyl acrylamide‐b‐poly(L ‐lactide‐co‐glycolide) (PNIPAAm‐b‐PLGA), and polyethylene glycol‐poly (lactide‐co‐glycolide) (PEG‐PLGA) triblock copolymers with different compositions and length of PLGA block were synthesized via ring‐opening polymerization of lactide and glycolide in the presence of OH‐terminated PNIPAAm or PEG. The composition and structure of the polymer were determined by NMR and FTIR. The effect of important factors, such as ionic strength, pH, and polymer concentration on the phase transition behavior of temperature‐sensitive polymers, were investigated by cloud point measurements. The resulting thermosensitive polymers were used for the entrapment of a narcotic antagonist drug, naltrexone, as the model drug. The loading efficiency and drug release behavior of naltrexone‐loaded hydrogels were investigated. The naltrexone loaded thermosensitive polymers were able to sustain the release of naltrexone for different periods of time, depending on the polymer composition, and concentration. In vitro release studies showed that these thermosensitive polymers are able to deliver naltrexone in biologically active forms at a controlled rate for 3–8 weeks. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis and characterization of novel nano size electroactive poly 4,4′‐diaminodiphenyl sulphone

The modification of electrodeposited polyaniline film by subsequent electrodeposition of 4,4′‐diaminodiphenyl sulfone (DDS) leads to a new material having nanostructure. The coated polymer films were treated with various pH solutions. The film adherent characteristics and surface morphology were studied using SEM. The electrochemically synthesized polyDDS revealed good redox behavior. The DDS was also polymerized by the chemical oxidation method using potassium persulphate. The polymer was characterized by UV‐Vis and FTIR spectral studies. The formation of polymer through the N? H group was understood from the single N? H stretching vibrational frequency at 3459 cm^?1. The X‐ray diffraction studies revealed the formation of nano sized (28 nm) crystalline polymer. The conductivity of the polymer was determined to be 1.07 × 10^?4 S.cm^?1. The solubility of the chemically polymerized powder was ascertained, and polyDDS showed good solubility in DMF and DMSO. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1702–1707, 2005     

由聚合物门控的介孔二氧化硅基刺激响应性药物递送系统

本文主要介绍了以聚合物体系作为门控构筑的基于介孔二氧化硅纳米粒子的刺激响应性药物控释体系, 并根据聚合物类别将门控体系分为聚合物刷、 聚合物交联网络和聚合物包裹层三类. 根据聚合物“阀门”与无机纳米粒子的共价或非共价连接方式, 综述了这些杂化材料在不同外界刺激作用下的药物控制释放行为, 并给出该领域所面临的机遇和挑战.     

Formation of the porous structure during the polymerization of meta-divinylbenzene and para-divinylbenzene with toluene and 2-ethylhexanoic acid (2-EHA) as porogens

Macroporous polymers of pure meta-divinylbenzene (meta-DVB) and pure para-divinylbenzene (para-DVB) have been prepared in the presence of toluene and 2-EHA as pore forming agents. The formation of the pore structure has been studied during the polymerization by pore-size distribution measurements, together with determination of the specific surface area from nitrogen sorption isotherms using the BET treatment. In addition, the morphology and texture have been characterized by SEM during the polymerization process. Large differences in the pore-size distribution among all the polymer samples are found. The polymers prepared in toluene as porogen have a pore-size distribution, which mainly consists of small pores, while large pores appear with 2-EHA as porogen. In the presence of 2-EHA, a major change in the pore-size distribution is also observed when the monomer is shifted from para-DVB to meta-DVB, leading to a bimodal distribution. The texture characterization by SEM shows details and discriminates the samples in consistency with what may be expected from pore-size distribution measurements. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3973–3990, 1999     

Phospholipid coated poly(lactic acid) microspheres for the delivery of LHRH analogues

The aim of this work was to develop alternative peptide‐loaded microspheres using liposphere formulation—a lipid based microdispersion system. This formulation represents a new type of lipid or polymer‐based encapsulation system developed for parenteral and topical drug delivery of bioactive compounds. Our strategy was to utilize the liposphere formulation to improve the entrapment efficiency and release profile of triptorelin and leuprolide [luteinizing hormone–releasing hormone (LHRH) analogues] in vitro. Peptides (2% w/w) were loaded into lipospheres contained of polylactic acid (PLA) or poly(lactic‐co‐glycolic acid) (PLGA) with several types of phospholipids. The effects of polymer and phospholipid type and concentration, method of preparation and solvents on the liposphere characteristics, particle size, surface and bulk structure, drug diffusion rate, and erosion rate of the polymeric matrix were studied. The use of L ‐PLA (M_w = 2000) and hydrogenated soybean phosphatidylcholine (HSPC) with phospholipid–polymer ratio of 1 : 6 w/w, was the most efficient composition that formed lipospheres of particle size in the range of 10 µm with most of the phospholipid embedded on the particles surface. In a typical procedure, peptides were dissolved in N‐methyl‐2‐pyrrolidone (NMP), and dispersed in a solution of polymer and phospholipids in a mixture of NMP and chloroform with the use of 0.1% poly(vinyl alcohol) (PVA) as the emulsified aqueous medium. Uniform microspheres were prepared after solution was mixed at 2000 rpm at room temperature for 30 min. Using this formulation, the entrapment efficiency of LHRH analogues in lipospheres was up to 80%, and the peptides were released for more than 30 days. Copyright © 2002 John Wiley & Sons, Ltd.     

Dispersion polymerization of vinyl monomers in supercritical carbon dioxide in the presence of drug molecules: A one‐pot route for the preparation of controlled delivery systems

The polymerization of 1‐vinyl‐2‐pyrrolidone in supercritical carbon dioxide in the presence of ibuprofen as a model drug was investigated as a new one‐pot process for the preparation of polymer‐based drug delivery systems (DDSs). The composites were prepared at 65 °C and P = 31–42 MPa by changing the initial concentration of the drug and the concentration of a crosslinking agent and that of a hydrophobic comonomer. The effects of these parameters on the performances of the polymerization and on the in vitro release kinetics of ibuprofen were studied. In all the experiments, part of the drug was entrapped inside the polymer particles and dissolved more slowly with respect to the pure compound. Copolymerization with methyl methacrylate was the most effective route to obtain a DDS with sustained temporal release of the drug molecule. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7429–7446, 2008     

Magnolol entrapped ultra-fine fibrous mats electrospun from poly(ethylene glycol)-<Emphasis Type="Italic">b</Emphasis>-poly(L-lactide) and <Emphasis Type="Italic">in vitro</Emphasis> release

Ultra-fine fibrous mats with magnolol entrapped have been prepared by electrospinning biodegradable copolymer poly(ethylene glycol) blocked poly(L-lactide). Drug entrapment was perfect which was confirmed by scanning electron microscopy and differential scanning calorimetry. According to in vitro drug release investigation by high performance liquid chromatography, it was found that fibers with 10%, 20% and 30% drug entrapped respect to polymer (mass ratio) presented dramatically different drug release behavior and degradation behavior under the effect of proteinase K. The reason may be that fibers with 10% drug entrapped was more easily affected by enzyme while, to some degree, magnolol in fibers with 20% and 30% entrapped prevented polymer from being degraded by enzyme.     

Role of polyester resin on the epoxy matrix system

Interpenetrating polymer network (IPN) as a polymer blend matrix was prepared using different ratios of polyester (PE) to epoxy (E) resins. It was observed that 11.33 wt % PE in the blend provides maximum mechanical properties, particularly the modulus for the casting, and such a blend is referred to as “optimum casting” (OC). The density of the blends containing up to 11.33% PE, especially of OC, was found to have increased by the presence of PE in the E network significantly more than would have been estimated from the calculation based on the rule of additivity. The thermal expansion coefficient parameter (Δα_i) of the OC was found to be 2.68 × 10^?4K^?1. The scanning electron micrograph (SEM) of the fracture surface of OC only showed a glass-like smooth surface. The change in the mechanical properties due to the varying proportions of PE in the blend was studied critically on the basis of failure mechanisms and morphological features. The differential thermogravimetric analysis (DTGA) of OC indicated only one peak in spite of the presence of two resin constituents, whereas castings with an excess of PE in the blend showed multiple peaks. Interestingly, as far as the DTGA is concerned, a domain of seemingly OC origin was found to remain, even in the blends containing PE resin above its optimum level (> 11.33 wt %). ©1995 John Wiley & Sons, Inc.     

Poly(styrene-acrylic acid) magnetic polymer microspheres

Magnetic polymer microspheres have been considered as a kind of new biopolymer materials with great advantages in bioseparation engineering and biomedicine engineering because they have not only polymer functional groups but also magnetic characteristics. Styrene-acrylic acid copolymer (p(S-AA)) magnetic microspheres were synthesized by dispersion polymerization with Fe₃O₄ as core and p(S-AA) as shell. The microspheres were characterized by SEM, size analysis, molecular weight and solid content measurement. All of them indicate that the microspheres are small in size, narrow in distribution, stable in chemistry and rich in functional groups on their surface. __________ Translated from Journal of Beijing Union University (Natural Science) 2008, 21(3): 82–84     

Molecular simulation to discover rheological properties and soil-binding ability of PHPA polymer on montmorillonite surface

Synthetic polymer fluids are increasingly being applied to support excavations in deep foundations. As these fluids are molecularly engineered, their underlying microstructure interaction with in situ soils significantly affect excavation stability and soil dispersion. However, little molecular-scale research has been done on the rheological behavior of partially hydrolyzed polyacrylamides (PHPA) polymer fluids on the clay surface. Molecular models of the clay–polymer systems are constructed using PHPA on montmorillonite (MMT) clay surface. Initial rheological properties and soil-binding ability at different shear rates, temperatures, and polymer concentrations are first studied using molecular dynamics (MD) simulations. It is found that the functional groups of PHPA can interact with the MMT surface and form a viscous film under the atomic interaction of hydrogen bonds, water bridges, and electrostatic attraction. The shear stress, σ increases with the shear rate and follows the power-law model. And the viscosity, η decreases as the shear rate increases, which is consistent with the experimental trend. However, the σ and η decrease with the increase of temperature. And the action mode of PHPA concentration has been identified from the MD perspective. This work provides insight into the molecular mechanism for PHPA's rheology on the clay surface and their interaction.     

Temperature-Triggered Modification of Polymer- Solvent Interactions: From Fluid-to-Gel Transitions to Particle Capture

Temperature-responsive polymers are of considerable interest in the literature. In this work the ability to combine temperature-responsive polymer-solvent interactions with architectural control to achieve a range of macroscopic effects is considered. The first part of the work considers poly(DEA) (N,N-dieth ylacrylamide) microgel particles. The particles exhibit temperature-triggered particle collapse at temperatures more than ca. 27 °C. As a consequence concentrated temperature-responsive microgel dispersions change from gels to fluids when heated. The opposite effect is observed when dispersions or emulsions are stabilised by temperature-responsive polymer surfactants. Recent results involving a gel-forming castor oil-in-water emulsion are considered. The gelled emulsion releases a model drug (lidocaine) according to first-order kinetics. We extend the principle of temperature-triggered control of particle-surface interactions to test a new approach for immobilising particles on surfaces. The method consists of electrodepositing Laponite particles onto a carbon surface, grafting of poly(NIPAM) (N-isopropylacrylamide) onto the deposited particles and then increasing the temperature of the modified surface to trigger capture of dispersed polystyrene particles. This new approach uses chemistry that is potentially applicable to any conductive surface.     

Tuning salicylate‐based polymers to overcome lag time and extend release via copolymers and polymer blends

This work describes how physicochemical properties of salicylate‐based poly(anhydride‐esters) (PAEs) can be tuned for drug delivery and optimized by comparing copolymerization with polymer blending. These alterations reduced the lag time of drug release, while still maintaining a long‐term drug release profile. The chemical composition of the copolymers and polymer blends was determined by proton nuclear magnetic resonance and additional properties such as molecular weight, glass transition temperature and contact angle measurements were obtained. In vitro salicylic acid release from the copolymers and blends is studied in an environment mimicking physiological conditions. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 685–689     

Characterization and release of triptolide-loaded poly (d,l-lactic acid) nanoparticles

Triptolide (TP), which has immunosuppressive effect, anti-neoplastic activity, anti-fertility function and severe toxicities on digestive, urogenital, blood circulatory system, was used as a model drug in this study. TP-loaded poly (d,l-lactic acid) (PLA) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method (modified-SESD method). Dynamic light scattering system (DLS), transmission electron microscope (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray powder diffractometry and Fourier transform infra-red spectroscopy (FT-IR) were employed to characterize the nanoparticles fabricated for size and size distribution, surface morphology, the physical state of drug in nanoparticles, and the interaction between the drug and polymer. Encapsulation efficiency (EE) and the in vitro release of TP in nanoparticles were measured by the reverse phase high-performance liquid chromatography (RP-HPLC). The produced nanoparticles exhibited a narrow size distribution with a mean size of approximately 150 nm and polydispersity index of 0.088. The morphology of the nanoparticles exhibited a fine spherical shape with smooth surfaces without aggregation or adhesion. TP-entrapped in nanoparticles was found in the form of amorphous or semicrystalline. It was found that a weak interaction existed between the drug and polymer. In all experiments, more than 65% of EE were obtained. The in vitro release profile of TP from nanoparticles exhibited a typical biphasic release phenomenon, namely initial burst release and consequently sustained release. In this case, the particle size played an important role for the drug release. The modified-SESD method was a potential and advantage method to produce an ideal polymer nanoparticles for drug delivery system (DDS).     

Supported Membranes with Well‐Defined Polymer Tethers—Incorporation of Cell Receptors

We report the design of supported lipid membranes attached to the surface by tailored lipopolymer tethers. A series of well‐defined lipopolymers were synthesized by means of living cationic polymerization of 2‐methyl‐2‐oxazolines. The polymers were equipped with a silane coupling group on the proximal, and lipid anchors on the distal chain ends. The length of the intermediate hydrophilic polymer tether was varied (n=14, 18, 33) to change the distance between the membrane and the substrate. Supported membranes have been prepared in two‐steps. First, a suitable lipopolymer/lipid mixture was deposited by Langmuir–Blodgett transfer, and annealed to establish the covalent coupling to the surface. On the dry lipopolymer/lipid monolayer, the upper leaflet was deposited by vesicle fusion. Optimization of both preparation steps resulted in the formation of stable and defect‐free membranes. Impacts of the spacer length and the lipopolymer fraction upon the lateral diffusivity of the lipids were systematically compared by fluorescence recovery after photobleaching (FRAP). First experiments on the incorporation of a large transmembrane cell receptor (integrin α_IIbβ₃) into the polymer‐tethered membrane suggested that the length of the polymer tether plays a crucial role in distribution of the proteins on the surface.     

Building up polymer architectures on graphene oxide sheet surfaces through sequential atom transfer radical polymerization

The reactivity between the active species of atom transfer radical addition and the unsaturated groups of graphene oxides (GOs) has been demonstrated in this work. The reaction and the sequential surface‐initiated atom transfer radical polymerization provide a convenient approach to anchor various polymer chains and to buildup various polymer architectures, such as linear polymer, V‐shape block polymer, multibonded polymer layer, and hierarchical brush‐on‐layer polymer, on GO sheet surfaces. The chemical structures and morphology of the polymer‐modified GOs have been characterized with Fourier transform infrared spectroscopy, Raman spectroscopy, X‐ray photoelectron spectroscopy, and atomic force microscopy. After organomodification, the GOs exhibit a good dispersion ability in organic solvent over 80 days, amphiphilic characteristics, and temperature‐responsive properties. Reduction of the GOs has been performed to result in graphene‐like materials showing certain extent of electron conductivities. An effective approach to synthesize GO/polymer hybrid materials possessing various polymer architectures and attractive properties has been developed. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1588–1596     

Glass and Structural Transitions Measured at Polymer Surfaces on the Nanoscale

This paper reviews our recent progress in determining the surface glass transition temperature, T_g, of free and substrate confined amorphous polymer films. We will introduce novel instrumental approaches and discuss surface and bulk concepts of T_g. The T_g of surfaces will be compared to the bulk, and we will discuss the effect of interfacial interactions (confinements), surface energy, disentanglement, adhesion forces, viscosity and structural changes on the glass transition. Measurements have been conducted with scanning force microscopy in two different shear modes: dynamic friction force mode and locally static shear modulation mode. The applicability of these two nano-contact modes to T_g will be discussed.This revised version was published online in November 2005 with corrections to the Cover Date.     

Studies on curing kinetics of a novel combined liquid crystalline epoxy containing tetramethylbiphenyl and aromatic ester‐type mesogenic group with diaminodiphenylsulfone

The curing kinetics of a novel liquid crystalline epoxy resin with combining biphenyl and aromatic ester‐type mesogenic unit, diglycidyl ether of 4,4′‐bis(4‐hydroxybenzoyloxy)‐3,3′,5,5′‐tetramethyl biphenyl (DGE‐BHBTMBP), and the curing agent diaminodiphenylsulfone (DDS) was studied using the advanced isoconvensional method (AICM). DGE‐BHBTMBP/DDS curing system was investigated the curing behavior by means of differential scanning calorimetry (DSC) during isothermal and nonisothermal processes. Only one exothermal peak appeared in isothermal DSC curves. A variation of the effective activation energy with the extent of conversion was obtained by AICM. Three different curing stages were confirmed. In the initial curing stage, the value of E_a is dramatically decreased from ～90 to ～20 kJ/mol in the conversion region 0–0.2 for the formation of LC phase. In the middle stage, the value of E_a keeps about ～80 kJ/mol for cooperative effect of reaction mechanism and diffusion control. In the final stage, a significant increase of E_a from 84 to 136 kJ/mol could be caused by the mobility of longer polymer chains. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3922–3928, 2007     

Gold Nanorods with Phase‐Changing Polymer Corona for Remotely Near‐Infrared‐Triggered Drug Release

Herein, we report a new drug‐delivery system (DDS) that is comprised of a near‐infrared (NIR)‐light‐sensitive gold‐nanorod (GNR) core and a phase‐changing poly(ε‐caprolactone)‐b‐poly(ethylene glycol) polymer corona (GNR@PCL‐b‐PEG). The underlying mechanism of the drug‐loading and triggered‐release behaviors involves the entrapment of drug payloads among the PCL crystallites and a heat‐induced phase change, respectively. A low premature release of the pre‐loaded doxorubicin was observed in PBS buffer (pH 7.4) at 37 °C (<10 % of the entire payload after 48 h). However, release could be activated within 30 min by conventional heating at 50 °C, above the T_m of the crystalline PCL domain (43.5 °C), with about 60 % release over the subsequent 42 h at 37 °C. The NIR‐induced heating of an aqueous suspension of GNR@PCL‐b‐PEG under NIR irradiation (802 nm) was investigated in terms of the irradiation period, power, and concentration‐dependent heating behavior, as well as the NIR‐induced shape‐transformation of the GNR cores. Remotely NIR‐triggered release was also explored upon NIR irradiation for 30 min and about 70 % release was achieved in the following 42 h at 37 °C, with a mild warming (<4 °C) of the surroundings. The cytotoxicity of GNR@PCL‐b‐PEG against the mouse fibroblastic‐like L929 cell‐line was assessed by MTS assay and good compatibility was confirmed with a cell viability of over 90 % after incubation for 72 h. The cellular uptake of GNR@PCL‐b‐PEG by melanoma MEL‐5 cells was also confirmed, with an averaged uptake of 1250(±110) particles cell^?1 after incubation for 12 h (50 μg mL^?1). This GNR@PCL‐b‐PEG DDS is aimed at addressing the different requirements for therapeutic treatments and is envisaged to provide new insights into DDS targeting for remotely triggered release by NIR activation.     

Supramolecular structures and properties models of macrocyclic polymer complexes

Two novel supramolecular complexes of types [Ru(L)(H₂L)Cl·OH₂] and [Ru(HL_n)Cl₃] (where H₂L is a potential tetradentate ligand derived from hydrazine hydrate and diethyl malonate, and HL_n is a potential bidentate ligand derived from coupling of allyl azo‐β‐diketone) have been synthesized and characterized by elemental analysis, conductance and magnetic measurements, followed by ¹H NMR, to determine the effect of substituents on the intramolecular hydrogen bond. The electronic properties and models of the bonding of ligands and complexes were investigated by UV–Vis and IR spectroscopies. The first type of complex contains terminal hydrazinic nitrogen atoms with an unshared electron pair and may take part in nucleophilic condensations. Therefore, the reactions of allyl‐β‐diketone complexes with malonic dihydrazide have also been studied, as these cause ring closure and formation of supramolecular macrocyclic ligand complexes. The wavelengths of the principal electronic absorption peaks have been accounted for quantitatively in terms of crystal field theory, and various parameters have been evaluated. On the basis of the electronic spectra, an octahedral geometry has been established for the polymer complexes C. The macrocyclic polymer complexes D are pentacoordinate, and a trigonal‐bipyramidal environment (D_3h) is suggested for the ruthenium(III) ion. The effect of the Hammett constant on the ligand field parameters is also discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

Polymer Structure‐Guided Self‐Assisted Preparation of Poly(ester‐thioether)‐Based Hollow Porous Microspheres and Hierarchically Interconnected Microcages for Drug Release

Porous polymer microspheres (PPMs) have been widely applied in various biomedical fields. Herein, the self‐assisted preparation of poly(ester‐thioether)‐based porous microspheres and hierarchical microcages, whose pore sizes can be controlled by varying the polymer structures, is reported. Poly(ester‐thioether)s with alkyl side chains (carbon atom numbers were 2, 4, and 8) can generate hollow porous microspheres; the longer alkyl chain length, the larger pore size of microspheres. The allyl‐modified poly(ester‐thioether) (PHBDT‐g‐C₃) can form highly open, hierarchically interconnected microcages. A formation mechanism of these PPMs is proposed; the hydrophobic side chains‐mediated stabilization of oil droplets dictate the droplet aggregation and following solvent evaporation, which is the key to the formation of PPMs. The hierarchically interconnected microcages of PHBDT‐g‐C₃ are due to the partially crosslinking of polymers. Pore sizes of PPMs can be further tuned by a simple mixing strategy of poly(ester‐thioether)s with different pore‐forming abilities. The potential application of these PPMs as H₂O₂‐responsive vehicles for delivery of hydrophobic (Nile Red) and hydrophilic (doxorubicin hydrochloride) cargos is also investigated. The microspheres with larger pore sizes show faster in vitro drug release. The poly(ester‐thioether)‐based polymer microspheres can open a new avenue for the design of PPMs and provide a H₂O₂‐responsive drug delivery platform.