Behavior of aqueous solutions of poly(ethylene oxide-b-propylene oxide) copolymers containing a hydrotropic agent

The effect of the hydrotropic agent, sodium p-toluenesulfonate (NaPTS), was evaluated on the micelle formation process and on phase behavior of aqueous solutions containing poly(ethylene oxide-b-propylene oxide) (PEO–PPO) copolymers. We have studied monofunctional diblock copolymers coupled with hydrocarbons groups (R—PEO—PPO—OH and R—PPO—PEO—OH, where R length is linear C₄ and C_12–14). The critical micelle concentration (CMC) and critical micelle temperature (CMT) values of the aqueous copolymers solutions were obtained from both surface tension versus concentration plots and the dye solubilization method. The influence of the hydrocarbons groups length and PPO segment position in the structure of the copolymers were also analyzed. The same measures were obtained for the aqueous solutions of hydrotropic agent which, in turn, also presented molecular aggregation. The presence of the hydrotropic agent in the aqueous copolymers solutions altered the surface tension of these solutions and the occupied molecular area per copolymer molecule at air–water interface and CMC and CMT values of the copolymers. On the other hand, the aggregation points and the surface tension of the NaPTS solutions were dependent on the copolymer structure and composition. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 2459–2468, 1998     

Synthesis and characterization of copolymers with the same proportions of polystyrene and poly(ethylene oxide) compositions but different connection sequence by the efficient Williamson reaction

The AB type diblock PS‐b‐PEO and ABA type triblock PS‐b‐PEO‐b‐PS copolymers containing the same proportions of polystyrene (PS) and poly(ethylene oxide) (PEO) but different connection sequence were synthesized and investigated. Using the sequential living anionic polymerization and ring‐opening polymerization mechanisms, diblock PS‐b‐PEO copolymers with one hydroxyl group at the PEO end were obtained. Then, using the classic and efficient Williamson reaction (realized in a ‘click’ style), triblock PS‐b‐PEO‐b‐PS copolymers were achieved by a coupling reaction between hydroxyl groups at the PEO end of PS‐b‐PEO. The PS‐b‐PEO and PS‐b‐PEO‐b‐PS copolymers were well characterized by ¹H NMR spectra and SEC measurements. The critical micelle concentration (CMC) and thermal behaviors were also investigated by steady‐state fluorescence spectra and DSC, respectively. The results showed that, because the PEO segment in triblock PS‐b‐PEO‐b‐PS was more restricted than that in diblock PS‐b‐PEO copolymer, the former PS‐b‐PEO‐b‐PS copolymer always gave higher CMC values and lower crystallization temperature (T_c), melting temperature (T_m) and degree of crystallinity (X_c) parameters. © 2015 Society of Chemical Industry     

Synthesis,aggregation and adsorption behaviour of a thermoresponsive pentablock copolymer

Poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) triblock copolymer (Pluronic F127) was modified by introducing poly(N‐isopropylacrylamide) (PNIPAM) at both the PEO ends, and the pentablock copolymer (PNIPAM₄₁–F127–PNIPAM₄₁, PN41) so prepared was characterized using gel permeation chromatography and ¹H NMR spectroscopy. The degree of polymerization of NIPAM blocks at the two ends was 41. The solution behaviour and microstructure of PN41 aggregates in water were examined using UV–visible spectroscopy, micro‐differential scanning calorimetry and small‐angle neutron scattering (SANS) and compared with F127. Two lower critical solution temperatures (LCSTs) were observed for the pentablock copolymer, corresponding to PPO and PNIPAM blocks, respectively. The adsorption of PN41 on thiol‐grafted hydrophobic gold surfaces at various temperatures was investigated using a quartz crystal microbalance. It was found that the adsorption behaviour and mechanism of PN41 were mainly determined by the interactions of the pentablock copolymers with different chain conformations in dilute aqueous solutions at various temperatures. SANS measurements were used to determine the temperature‐dependent structural evolution of polymer micelles in aqueous solution. A NOESY study revealed that above the LSCT of PNIPAM, the interaction of PPO and PNIPAM protons increases and the distance between PPO and PNIPAM decreases. © 2019 Society of Chemical Industry     

Characterization and comparison of diblock and triblock amphiphilic copolymers of poly(δ‐valerolactone)

Three types of pegylated amphiphilic copolymers of poly(δ‐valerolactone) (PVL) were copolymerized with methoxy poly(ethylene glycol) (MePEG) and poly(ethylene glycol) (PEG₄₀₀₀ and PEG_10,000), respectively. Pegylation of PVL allowed copolymers possessing amphiphilic property and efficiently self‐assembled to form micelles with a low critical micelle concentration (CMC) in the range of 10^?7–10^?8M. The average molecular weight of copolymers was in the range of 10,000–20,000 Da, and the polydispersity of copolymers was about 1.7–1.8. Higher mobility of low molecular weight PEG (i.e., MePEG and PEG₄₀₀₀) than high molecular weight PEG_10,000 allowed valerolactone ring opening more efficient in terms of PVL/MePEG and PVL/PEG₄₀₀₀ copolymers possessing longer chain length in hydrophobic domain. Pegylated PVL with low CMC and triblock structure was preferred to encapsulate drug during micelle formation. Although all of these amphiphilic copolymers exhibited controlled release character, the micelles formed by triblock copolymer possessed a more stable core‐shell conformation than that by diblock copolymer, and resulted in the release of drug from triblock micelles slower than that from diblock micelles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1836–1841, 2006     

Effect of Hydrophobicity of PEO–PPO–PEO Block Copolymers on Micellization and Solubilization of a Model Drug Nimesulide

The present work explored the molecular implications governing the solubilization of a model drug nimesulide (NIM) in micelles of ethylene oxide-propylene oxide (EO–PO) triblock copolymers. The aggregation behavior and solubilization studies on four copolymers each with the same mol mass of central PPO block equal to 2,250 and varying % PEO was examined by means of UV–VIS. Moreover, high-sensitivity differential scanning calorimetry, and Fourier transform infrared spectrometry measurements were used to evaluate the critical micellization temperature. The solubilization at different temperatures (30, 37, 45 °C), pH (2 to 10) and in the presence of added sodium chloride (0–2 M) was monitored and the partition coefficient (P) and the free energy of solubilization (ΔG _s^o) were calculated. The site of solubilization of NIM in micelles was also probed. The NIM solubility decreased with increases in the PEO molecular weight; the drug resides in the micelle core.     

Studies on Micellar Behavior of PEO‐PBO or PEO‐PBO‐PEO Copolymers,or Surface Active Amphiphilic Ionic Liquids in Aqueous Media and Exploration of the Micellar Solutions for Solubilization of Dexamethasone and its Delayed Release

The aggregation behavior of a di‐ and tri‐block copolymers of type PEO‐PBO, PEO‐PBO‐PEO, surface‐active ionic liquid (SAIL) of type 4‐dodecyl‐4‐methylmorpholinium chloride [C₁₂mmor][Cl], and 1‐dodecyl‐1‐methylpyrrolidinium chloride [C₁₂mpyrr][Cl]) in water as well as in 10 mM of a poorly water soluble dexamethasone (dex) aqueous solution was studied by determining the critical micelle concentrations using drug solubilization, surface tension, and isothermal titration calorimetry (ITC) methods. ITC measurements were also made on solutions prepared by mixing the micellar aqueous solutions of copolymers and simple aqueous solutions of SAIL across the mole fractions at three different temperatures (298.15, 308.15, and 318.15 K). The thermodynamic parameters, namely Gibbs free energy (ΔG_m), enthalpy (ΔH_m), and entropy (ΔS_m), of micellization were calculated, and it was observed that the negative ΔG_m and positive ΔS_m for the mixture solutions increase with the increase in mole fraction of SAIL. Otherwise, the micellization is reported to be a spontaneous and highly entropy‐driven process. The dex‐solubilized micellar solutions were mixed with agar to obtain standing gels. The gel samples were dry‐cast into thin films, and the release of dex from films by simple dilution was monitored by UV measurements. The drug release data was fitted to several mechanistic models, and it was inferred that the release mechanism for dex from thin films is non‐Fickian for mixtures and Fickian in copolymer or SAIL micellar aqueous solutions. The transport of dex is diffusion‐controlled with diffusivities of 5.8–12 × 10^?11 m² s^?1 for copolymer micelles, 5–11 × 10^?11 m² s^?1 for micelles of SAIL, and 3–14 × 10^?11 m² s^?1 for the mixed micelles of copolymer and SAIL in aqueous media.     

Synthesis and properties of hydrophilic segmented block copolymers based on poly(ethylene oxide)‐ran‐poly(propylene oxide)

The present article discusses the synthesis and various properties of segmented block copolymers with random copolymer segments of poly(ethylene oxide) and poly(propylene oxide) (PEO‐r‐PPO) together with monodisperse amide segments. The PEO‐r‐PPO contained 25 wt % PPO units and the segment presented a molecular weight of 2500 g/mol. The synthesized copolymers were analyzed by differential scanning calorimetry, Fourier transform infra‐red spectroscopy, atomic force microscopy and dynamic mechanical thermal analysis. In addition, the hydrophilicity and the contact angles (CAs) were studied. The PEO‐r‐PPO segments displayed a single low glass transition temperature, as well as a low PEO crystallinity and melting temperature, which gave enhanced low‐temperature properties of the copolymer. The water absorption values remained high. In comparison to mixtures of PEO/PPO segments, the random dispersion of PPO units in the PEO segments was more effective in reducing the PEO crystallinity and melting temperature, without affecting the hydrophilicity. Increasing the polyether segment length with terephthalic groups from 2500 to 10,000 g/mol increased the hydrophilicity and the room temperature elasticity. Furthermore, the CAs were found to be low 22–39° and changed with the crosslink density. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci 117:1394–1404, 2010     

Linear and branched polyoxide‐based copolymers: Methods to determine the CMC

Evaluation of the physical–chemical properties of aqueous solutions of nonionic surfactants based on polyoxides can be performed by different methods. Depending on the technique used, there can be a significant variation in the critical micelle concentration (CMC) found. This is related to the sensitivity of the technique regarding the unimers and micelles present in the solution as well as the structure of the surfactant evaluated. In this work, the CMC values of aqueous solutions of linear and branched poly(ethylene oxide‐polypropylene oxide) (PEO‐PPO) block copolymers were determined by tensiometry, fluorescence, and particle size analysis, using copolymers having adjacent structures (that is, hydrophilic and hydrophobic segments located adjacently in the copolymer) and alternating structures. Tensiometry was used to measure the surface tension as a function of the copolymer concentration in aqueous solution. Fluorescence was used to determine the fluorescence intensity of pyrene to plot the graphs of the I₁/I₃ and I_E/I_M relations according to the surfactant concentration. Finally, particle size analysis was used to determine the diffusion coefficient of the particles. The results showed that the fluorescence and particle size techniques provide lower (and mutually concordant) CMC values and can be considered more precise because these methods directly analyze the bulk of the solution. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Poly(allyl glycidyl ether)‐block‐poly(ethylene oxide): A novel promising polymeric intermediate for the preparation of micellar drug delivery systems

Novel diblock copolymers designed for the preparation of micellar drug delivery systems, consisting of hydrophobic poly(allyl glycidyl ether) (PAGE) and hydrophilic poly(ethylene oxide) (PEO), were prepared, and their self‐assembly into micellar structures was studied. Copolymers differing in the length of the polymer blocks were purified and characterized. These amphiphilic copolymers with narrow molecular weight distributions were prepared through the anionic polymerization of allyl glycidyl ether with PEO monomethyl ether sodium salt as the macroinitiator. The PAGE–PEO copolymer readily formed small micelles with narrow size distributions via simple dissolution in water. The addition of pendant double bonds to the hydrophobic part of the chain was intended for further covalent modifications. Catalytic hydrogenation, the radical crosslinking of the micelle core, and the addition of thiol to double bonds of the copolymer were examples of such modifications that were proved to proceed with a quantitative yield for this copolymer. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 201–211, 2005     

Solubilization,micellar transition and biocidal assay of loaded antioxidants in Tetronic® 1304 micelles

The current study scrutinizes the solubilization behaviour of pharmaceutically active antioxidants, namely hydrocinnamic acid (HCA), cinnamic acid (CA) and phenyl propiolic acid (PPA), in the micelles of polyethylene oxide‐polypropylene oxide (PEO‐PPO) based star‐block copolymer: Tetronic® 1304 (T1304). A correlation between the molecular orbital energy levels of PEO‐PPO units of T1304 and the active parts of the antioxidants are well explained using a simulation study. The antioxidants modulate core–shell micelles of T1304 with enhanced solubilization dependent on their unsaturation and hydrophobicity, as depicted from UV–visible spectroscopy. Antioxidants as an additive induce micellization in 5% w/v T1304 thereby modulating the phase behaviour, as indicated by the decrease in the cloud point. The cloud point results are well complemented by steady state fluorescence spectroscopy findings, depicting a decrease in critical micelle temperature due to the solubilization of antioxidants into the T1304 micelles. A significant difference between the hydrodynamic diameter (D_h) of unloaded and loaded polymer micelles with antioxidants is observed from dynamic light scattering, ensuring the solubilization of the antioxidants in T1304 micelles. These results can apparently be attributed to the interaction and the charge induced by the antioxidants on non‐ionic T1304 micelles which increase the micellar size. Furthermore, the role of unsaturation and hydrophobicity of the employed antioxidants in 5% T1304 demonstrates the solution viscosity (η) change as a function of temperature. In addition, small‐angle neutron scattering depicts the shape transition (spherical to ellipsoidal to polymersomes) with temperature. The antioxidant loaded 5% T1304 micellar systems exhibit brilliant biocidal activity against the tested microbes, suggesting their antimicrobial application. © 2019 Society of Chemical Industry     

Synthesis of poly(fluorinated styrene)‐block‐poly(ethylene oxide) amphiphilic copolymers via atom transfer radical polymerization: potential application as paper coating materials

BACKGROUND: The surface of a substrate which comprises a fibrous material is brought into contact with a type of amphiphilic block copolymer which comprises hydrophilic/hydrophobic polymeric blocks. These amphiphilic copolymers have been synthesized by atom transfer radical polymerization (ATRP) technique. The atom transfer radical polymerization of poly(2,3,4,5,6‐pentafluorostyrene)‐block‐poly(ethylene oxide) (PFS‐b‐PEO) copolymers (di‐ and triblock structures) with various ranges of PEO molecular weights was initiated by a PEO chloro‐telechelic macroinitiator. The polymerization, carried out in bulk and catalysed by copper(I) chloride in the presence of 2,2′‐bipyridine ligand, led to A–B–A amphiphilic triblock and A–B amphiphilic diblock structures. RESULTS: With most of the macroinitiators, the living nature of the polymerizations led to block copolymers with narrow molecular weight distributions (1.09 < M_w/M_n < 1.33) and well‐controlled molecular structures. These block copolymers turned out to be water‐soluble through adjustment of the PEO block content (>90 wt%). Of all the block copolymers synthesized, PFS‐b‐PEO(10k)‐b‐PFS containing 10 wt% PFS was found to retard water absorption considerably. CONCLUSION: The printability of paper treated with the copolymers was evaluated with contact angle measurements and felt pen tests. The adsorption of such copolymers at the solid/liquid interface is relevant to the wetting and spreading of liquids on hydrophobic/hydrophilic surfaces. Copyright © 2009 Society of Chemical Industry     

Thermosensitive self‐assembly micelles from A2BA2‐type poly(N‐isopropyl acrylamide)2‐b‐Poly(lactic acid)‐b‐Poly(N‐isopropyl acrylamide)2 four‐armed star block copolymers and their applications as drug carriers

A novel A₂BA₂‐type thermosensitive four‐armed star block copolymer, poly(N‐isopropyl acrylamide)₂‐b‐poly(lactic acid)‐b‐poly(N‐isopropyl acrylamide)₂, was synthesized by atom transfer radical polymerization and characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography. The copolymers can self‐assemble into nanoscale spherical core–shell micelles. Dynamic light scattering, surface tension, and ultraviolet–visible determination revealed that the micelles had hydrodynamic diameters (D_h) below 200 nm, critical micelle concentrations from 50 to 55 mg/L, ζ potentials from ?7 to ?19 mV, and cloud points (CPs) of 34–36°C, depending on the [Monomer]/[Macroinitiator] ratios. The CPs and ζ potential absolute values were slightly decreased in simulated physiological media, whereas D_h increased somewhat. The hydrophobic camptothecin (CPT) was entrapped in polymer micelles to investigate the thermo‐induced drug release. The stability of the CPT‐loaded micelles was evaluated by changes in the CPT contents loaded in the micelles and micellar sizes. The MTT cell viability was used to validate the biocompatibility of the developed copolymer micelle aggregates. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4137–4146, 2013     

A novel thermosensitive triblock copolymer from 100% renewably sourced poly(trimethylene ether) glycol

Bio‐based amphiphilic triblock copolymers with 100% renewably sourced poly(trimethylene ether) glycol (PO3G) as the hydrophobic blocks and statistical copolymer of 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO₂MA) and oligo(ethylene glycol)methacrylate (OEGMA) [P(MEO₂MA‐stat‐OEGMA)] as the hydrophilic blocks are synthesized and characterized. It is found that the molar ratio of MEO₂MA/OEGMA among the resulting copolymers is approximately 70/30. The degree of polymerization (DP) of P(MEO₂MA‐stat‐OEGMA) block ranges from 16 to 90, and the DP of PO3G block is fixed at 35. The amphiphilic copolymers could form core‐shell micelles self‐assembly in aqueous solution at low concentrations, and the micelles are in spherical shape with sizes varying from 121 to 188 nm. With the increasing length of hydrophilic blocks, the critical micelle concentration increases from 2.15 to 13.8 mg L^?1, and the lower critical solution temperature improves from 32.5 to 38.4 °C. The in vitro doxorubicin (DOX) release study shows that all DOX‐loaded micelles have a higher release rate at 37 °C than that at 25 °C. Cytotoxicity test reveals that the blank micelles are nearly nontoxic. These results indicate that the block copolymer micelles containing 100% renewably sourced PO3G can serve as a potential drug delivery carrier. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46112.     

Synthesis and self‐assembly behavior of pH‐responsive amphiphilic copolymers containing ketal functional groups

Polymeric micelles that are responsive to pH are particularly attractive for application in drug delivery systems. In this study, one type of amphiphilic block copolymers with hydrophobic building blocks bearing pH‐sensitive ketal groups was designed. In an acidic environment, the polarity transfer from amphiphile to double hydrophile for this copolymer destroyed the driving force of micelle formation, which triggered the release of encapsulated hydrophobic molecules. The amphiphilic block copolymers monomethoxy‐poly(ethylene glycol)‐block‐poly(2,2‐dimethyl‐1,3‐dioxolane‐4‐yl)methyl acrylate (MPEG‐block‐PDMDMA) was fabricated by atom transfer radical polymerization using MPEG‐Br as macroinitiator. The critical micelle concentration of various compositions of this copolymer in aqueous solution ranged from 4.0 to 10.0 mg L^?1, and the partition equilibrium constant (K_v) of pyrene in micellar solutions of the copolymers varied from 1.61 × 10⁵ to 4.86 × 10⁵. Their overall effective hydrodynamic diameters from dynamic light scattering measurements were between 80 and 400 nm, and the micellar morphology showed spherical geometry as investigated using transmission electron microscopy. At pH = 1.0, all of these polymeric micelles presented 100% payload release in 24 h of incubation, while at pH = 3.0, nearly 70 and 25% of pyrene was released for MPEG‐block‐PDMDMA (44/18) and MPEG‐block‐PDMDMA (44/25) in 260 h, respectively. The pH‐responsive MPEG‐block‐PDMDMA polymeric micelles having good encapsulation efficiency for hydrophobic drugs are potential candidates for biomedical and drug delivery applications. Copyright © 2010 Society of Chemical Industry     

Self‐assembly micelles from novel tri‐armed star C3‐(PS‐b‐PNIPAM) block copolymers for anticancer drug release

Novel tri‐armed star polystyrene‐block‐poly(N‐isopropylacrylamide) block copolymers with trimesic acid as central molecules were synthesized by successive two‐step atom transfer radical polymerization, and confirmed by Fourier‐transform infrared spectra, ¹H nuclear magnetic resonance, and laser light scattering gel chromatography system. The copolymers could self‐assemble into spherical core‐shell micelles in aqueous media independent on drug loading. Physicochemical properties of the blank and drug‐loaded micelles were examined by surface tension, fluorescence spectroscopy, UV‐vis, transmission electron microscope, and dynamic light scattering measurements. The copolymer micelles exhibited thermo‐triggered phase transition, with low critical solution temperature of 33.7 and 34.6°C, varying with copolymer compositions. The critical aggregate concentrations were 11.62 and 47.61 mg L^?1, and hydrodynamic diameters from 200 to 220 nm. Water‐insoluble 10‐hydroxycamptothecine was encapsulated into the micelle aggregates to investigate the change in the resulting physicochemical parameters, thermo‐triggered in vitro drug release, and the applicability as drug targeting release carriers. MTT assays were carried out to uncover cytotoxicity of the newly developed micelle‐based drug formulations. © 2014 American Institute of Chemical Engineers AIChE J, 61: 35–45, 2015     

Two‐component “Onionlike” micelles with a PPO core,a PDMAEMA shell and a PEO corona: formation and crosslinking

BACKGROUND: Chemical or physical crosslinking of supramolecular assemblies gives them stability in a wide range of environments. Much attention is paid to multilayer (onion‐like) polymeric micelles because their functionality is higher than classic core‐shell micelles. This work reports on the formation and crosslinking of onion‐like micelles prepared by mixing two different block copolymers containing a crosslinkable poly(dimethylaminoethyl methacrylate) (PDMAEMA) block. RESULTS: Block copolymers of a crosslinkable PDMAEMA block were synthesized by atom transfer radical polymerization of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) from poly(propylene oxide) (PPO) or poly(ethylene oxide) (PEO) macroinitiators. The (PDMAEMA₁₃)‐block‐PPO₆₉‐block‐(PDMAEMA₁₃) triblock formed wormlike core‐shell micelles, which were converted into ellipsoidal onion‐like micelles on mixing with the PEO₄₅‐block‐P(DMAEMA₈‐co‐MMA₄) diblock. Onion‐like micelles were crosslinked by quaternization of DMAEMA units. CONCLUSION: Formation of onion‐like micelles by mixing two different AB (ABA) and B′C block copolymers and their subsequent crosslinking is a valuable approach towards stabilized supramolecular assemblies of a higher complexity and functionality than the individual constitutive components. Copyright © 2008 Society of Chemical Industry     

Synthesis of amphiphilic temperature‐sensitive poly(N‐isopropylacrylamide)‐block‐poly(tetramethylene carbonate) block copolymers and micellar characterization

Amphiphilic thermally sensitive poly(N‐isopropylacrylamide)‐block‐poly(tetramethylene carbonate) block copolymers were synthesized by ring‐opening polymerization of tetramethylene carbonate with hydroxyl‐terminated poly(N‐isopropylacrylamide) (PNiPAAm) as macro‐initiator in the presence of stannous octoate as catalyst. The synthesis involved PNiPAAm bearing a single terminal hydroxyl group prepared by telomerization using 2‐hydroxyethanethiol as a chain‐transfer agent. The copolymers were characterized using ¹H NMR and Fourier transform infrared spectroscopy and gel permeation chromatography. Their solutions show reversible changes in optical properties: transparent below the lower critical solution temperature (LCST) and opaque above the LCST. The LCST depends on the polymer composition and the media. Owing to their amphiphilic characteristics, the block copolymers form micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range 1.11–22.9 mg L^?1. Increasing the hydrophobic segment length or decreasing the hydrophilic segment length in the amphiphilic diblock copolymers produces lower CMCs. A core‐shell structure of the micelles is evident from ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopic analyses of micelle morphology show a spherical structure of both blank and drug‐loaded micelles. The blank and drug‐loaded micelles have an average size of less than 130 nm. Observations show high drug‐entrapment efficiency and drug‐loading content for the drug‐loaded micelles. Copyright © 2010 Society of Chemical Industry     

Preparation and characterization of enalapril maleate–loaded nanoparticles using amphiphilic diblock copolymers

Nanoparticles with the dimensions of circa 50 nm prepared from the micellar aggregation of diblock copolymers of poly(ethylene oxide) and polycaprolactone (PEO–b–PCL) were explored as a parenteral carrier system for water‐soluble organic drugs in salt form. Enalapril maleate (EPM), developed for hypertension and congestive heart failure, was used as a model drug. The nanoparticles from three block copolymers with compositions of 5k–7.5k, 5k–5k, and 5k–2.5k (PEO–b–PCL) exhibited drug‐loading efficiency of 38%, 47%, and 26%, respectively, for an equivalent amount of EPM in a 1% (w/v) micelle solution. Particularly, 5k–5k micelles could be incorporated with the model drug up to 47% (w/w) of polymer. Furthermore, these nanoparticles possess drug‐retaining capability at 25°C or below even after free EPM was eliminated from the aqueous phase by dialysis. A temperature‐responsive release behavior was displayed upon heating to the physiological temperature, 37°C. Drug release from the micelles proceeded in a fairly linear fashion for a duration of about 4–7 days, depending on the composition of the block copolymers. Daily average fractional release was consistent regardless of drug contents in the nanoparticles. In a preliminary animal toxicity test the EPM‐loaded micelle solutions were intravenously administered to mice of the ICR strain through the tail vein. The animal subjects received 0.7 mL of EPM micelle solution up to six times and showed normal weight gain and food consumption. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2856–2867, 1999     

PEGylated polylysine derived copolymers with reduction‐responsive side chains for anticancer drug delivery

Reduction‐responsive drug delivery systems have recently gained intense attention in intracellular delivery of anticancer drugs. In this study, we developed a PEGylated polypeptide, poly(ethylene glycol)‐block‐poly(?‐propargyloxycarbonyl‐l ‐lysine) (PEG₁₁₃‐b‐PPAL), as a novel clickable substrate for conjugation of reduction‐responsive side chains for antineoplastic drug delivery. PEG₁₁₃‐b‐PPAL was synthesized through ring‐opening polymerization of alkyne‐containing N‐carboxyanhydride monomers. A designed disulfide‐containing side chain was introduced onto the PEGylated polypeptide by click reaction. The obtained copolymer PEG₁₁₃‐b‐P(Lys‐DSA) formed micelles by self‐assembly, which exhibited reduction‐responsive behavior under the stimulus of 10 mmol L^–1 glutathione (GSH) in water. A small molecule intermediate, compound 2 , was used as a model to investigate the thiol reduction mechanism of PEG₁₁₃‐b‐P(Lys‐DSA) copolymers. The anticancer drug doxorubicin (DOX) was then loaded into the micelles with a drug loading content of 6.73 wt% and a loading efficiency of 40.3%. Both the blank and the drug‐loaded micelles (DOX‐loaded polylysine derived polymeric micelles (LMs/DOX)) adopted a spherical morphology, with average diameters of 48.0 ± 13.1 and 63.8 ± 20.0 nm, respectively. The in vitro drug release results indicated that DOX could be released faster from the micelles by the trigger of GSH in phosphate buffered saline. Confocal laser scanning microscopy and flow cytometer analysis further proved the intracellular delivery of DOX by LMs/DOX and their GSH‐sensitive release behavior. A 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay showed that the polymers exhibited negligible cytotoxicity towards normal L929 cells or cancer MCF‐7 cells with a treated concentration up to 1.0 mg mL^–1. In conclusion, our synthesized biocompatible and biodegradable PEGylated polypeptides hold great promise for intracellular antineoplastic drug delivery. © 2019 Society of Chemical Industry     

High‐Molecular‐Weight Polyoxirane Copolymers and their Use in High‐Performance Dye‐Sensitized Solar Cells

Low‐crystalline random and gradient P(EO‐co‐PO) copolymers and amorphous PPO and PBO of high molecular weight were synthesized by anionic coordination polymerization. Polymer gel electrolytes based on these (co)polymers were prepared and tested for long‐term performance of DSSC. The DSSC based on P(EO‐co‐PO) copolymers have longer life time compared to the homo‐PEO‐ and homo‐PPO‐based DSSC, respectively. The cells containing the chemically crosslinked copolymer gel exhibited a high efficiency of 6% after 25 d performance, whereas the solar cells based on physically crosslinked copolymer gel showed fast degradation.