Biodegradable polylactide/poly(ethylene glycol)/polylactide triblock copolymer micelles as anticancer drug carriers

Adriamycin (ADR) was selected as a model drug to evaluate the potential applications of polylactide/poly(ethylene glycol)/polylactide (PLA/PEG/PLA) micelles as drug carriers in parenteral delivery systems. The PLA/PEG/PLA triblock copolymer micelles were characterized by dynamic light scattering and transmission electron microscopy. It was found that the micelle size increased with the increasing of the PLA chain length. The average size of ADR‐loaded micelles was 143.2 nm. The histogram analysis showed that the ADR‐loaded micelles possessed a narrow unimodal size distribution. The ADR loading contents of the micelles and ADR entrapment efficiency were dependent on the PLA chain length and PEG chain length in the copolymer. They increased with the increase of the PLA chain length, but the PEG chain length was identical and decreased with the increase of the PEG chain length; the length of the PLA block was similar. The initial amount of ADR also influenced the drug contents and entrapment efficiency (i.e., the more the initial amount added, the more the drug contents and the higher encapsulation efficiency). The drug release experiments indicated that the ADR‐loaded micelles possessed sustained release characteristics. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1976–1982, 2001     

Self‐assembly of poly(3‐hexyl thiophene)‐b‐poly(ethylene oxide) into cylindrical micelles in binary solvent mixtures

Asymmetric block copolymer based on regioregular poly(3‐hexyl thiophene) (P3HT) and poly(ethylene oxide) (PEO) was synthesized through Heck reactions. The addition of PEO block has no influence in the effective conjugation length of P3HT block and apparently provides colloidal stability for the formation of stable nanostructures. Introduction of poor solvent to good solvent containing P3HT‐b‐PEO will induce the crystallization‐driven assembly of the P3HT into cylindrical micelles with a P3HT core, owing to π–π stacking of the conjugated backbone of P3HT. The absorption spectra of the cylindrical micelles reveal a red shift as compared to the polymer in good solvent, indicating the extension of conjugation length with an improved π–π stacking of the polymer chains within the cylindrical micelles. Our results indicated that cylindrical micelles with varied diameter and length can be obtained when solvent properties were varied using several different binary solvent mixtures. More interestingly, we demonstrate that ultrasonic processing can fragment the cylindrical micelles only when the ratio of poor solvent increases. This provides a facile and effective way to fabricate cylindrical micelles for applications in the area of polymer solar cell as well as organic optoelectronics device. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41186.     

Self‐assembled micelles prepared from poly(ɛ‐caprolactone)–poly(ethylene glycol) and poly(ɛ‐caprolactone/glycolide)–poly(ethylene glycol) block copolymers for sustained drug delivery

A series of poly(?‐caprolactone)–poly(ethylene glycol) (PCL‐PEG) and poly(?‐caprolactone/glycolide)–poly(ethylene glycol) [P(CL/GA)‐PEG] diblock copolymers were prepared by ring‐opening polymerization of ?‐caprolactone or a mixture of ?‐caprolactone and glycolide using monomethoxy PEG (mPEG) as macroinitiator and Sn(Oct)₂ as catalyst. The resulting copolymers were characterized using ¹H‐NMR, gel permeation chromatography, differential scanning calorimetry, and wide‐angle X‐ray diffraction. Copolymer micelles were prepared using the nanoprecipitation method. The morphology of the micelles was spherical or worm‐like as revealed by transmission electron microscopy, depending on the copolymer composition and the length of the hydrophobic block. Introduction of the glycolide component, even in small amounts (CL/GA = 10), disrupted the chain structure and led to the formation of spherical micelles. Interestingly, the micelle size decreased with the encapsulation of paclitaxel. Micelles prepared from mPEG5000‐derived copolymers exhibited better drug loading properties and slower drug release than those from mPEG2000‐derived copolymers. Drug release was faster for copolymers with shorter PCL blocks than for those with longer PCL chains. The introduction of glycolide moieties enhanced drug release, but the overall release rate did not exceed 10% in 30 days. In contrast, drug release was enhanced in acidic media. Therefore, these bioresorbable micelles and especially P(CL/GA)‐PEG micelles with excellent stability, high drug loading content, and prolonged drug release could be promising for applications as drug carriers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45732.     

All‐trans retinoic acid release from polyion‐complex micelles of methoxy poly(ethylene glycol) grafted chitosan

We synthesized a methoxy poly(ethylene glycol) grafted chitosan (ChitoPEG) copolymer to prepare a retinoic acid (RA) encapsulated polymeric micelle. The RA‐encapsulated polymeric micelle of the ChitoPEG copolymer had a particle size of 100–500 nm and a spherical shape when observed by transmission electron microscopy. In a ¹H‐NMR study, the specific peaks of RA and chitosan as a drug‐carrying inner core disappeared in deuterium oxide, and only the specific peak of methoxy poly (ethylene glycol) (MPEG) was observed, whereas specific peaks of MPEG, RA, and chitosan appeared in dimethyl sulfoxide. This indicated that the RA/ChitoPEG ion complexes were composed of a polymeric micelle with a core–shell structure and that free drug did not exist in the polymeric micelle formulations. Other evidence of drug incorporation into the polymeric micelle was witnessed in a differential scanning calorimetry analysis. The melting peaks of RA and chitosan were 182 and 220°C, respectively. The melting peak of the polymeric micelle was 200°C, whereas the melting peaks of the physical mixtures were those of both RA and the ChitoPEG copolymer. The lyophilized polymeric micelle was successfully reconstituted into phosphate‐buffered saline without the aid of cryoprotectants. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Composition and properties of complexes between anionic liposomes and diblock copolymers with cationic and poly(ethylene oxide) blocks

A series of cationic diblock copolymers were synthesized via sequential anionic polymerization of 2‐vinylpyridine and ethylene oxide and further quaternization of the resulting diblock copolymers with dimethyl sulfate. Diblock copolymers with a degree of polymerization (DP) of the cationic block equal to 40 and DP of the poly(ethylene oxide) (PEO) block equal to 45, 210 and 450, as well as a cationic homopolymer with DP = 40 (control), were adsorbed on the surface of anionic liposomes of 40–60 nm in diameter. The liposomes were constructed with egg lecithin admixed with 0.1 mole fraction of a doubly anionic lipid, cardiolipin. The liposome–polymer complexes were characterized using electrophoretic mobility measurements, dynamic light scattering, conductivity, fluorescence and UV spectroscopy, and differential scanning calorimetry. Adsorption of the polymers causes the liposomes to aggregate; the only exception is the diblock copolymer with DP of the PEO block of 450, which shows an aggregation‐preventing effect. In all cases, the integrity of liposomes is retained upon their complexation with polymers. The diblock copolymer with a short PEO block induces clustering of anionic lipid in the outer leaflet of the membrane; this effect becomes less pronounced with increasing DP of the PEO block. The differences in behaviour of the diblock copolymers are explained in terms of copolymer cluster formation via hydrogen bonding between neighbouring PEO blocks. These observations are important for interpretation of biological effects produced by cationic polymers and selection of cationic polymers for biomedical applications. © 2017 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     

Self‐assembly and drug delivery behaviors of thermo‐sensitive poly(t‐butyl acrylate)‐b‐poly(N‐isopropylacrylamide) micelles

Self‐assembly of thermo‐sensitive poly (t‐butyl acrylate)‐b‐poly(N‐isopropylacrylamide) (PtBA‐ b‐PNIPAM) micelles in aqueous medium and its applications in controlled release of hydrophobic drugs were described. PtBA‐b‐PNIPAM was synthesized by atom transfer radical polymerization and aggregated into thermo‐sensitive core‐shell micelles with regular spheres in water, which was confirmed by ¹H‐NMR, fluorescence spectroscopy, transmission electron microscopic (TEM), and UV–vis spectroscopic techniques. The critical micelle concentration of micelles decreased with the increase of the hydrophobic components. The anti‐inflammation drug naproxen (NAP) was loaded as the model drug into polymeric micelles, which showed a dramatic thermo‐sensitive fast/slow switching behavior around the lower critical solution temperature (LCST). When the temperature was enhanced above LCST, release of NAP from core‐shell micelles was accelerated ascribed to the temperature‐induced deformation of micelles. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and self‐assembly of amphiphilic star‐block copolymers consisting of polyethylene and poly(ethylene glycol) segments

We report on the synthesis and self‐assembly in water of well‐defined amphiphilic star‐block copolymers with a linear crystalline polyethylene (PE) segment and two or three poly(ethylene glycol) (PEG) segments as the building blocks. Initially, alkynyl‐terminated PE (PE‐?) is synthesized via esterification of pentynoic acid with hydroxyl‐terminated PE, which is prepared using chain shuttling ethylene polymerization with 2,6‐bis[1‐(2,6‐dimethylphenyl) imino ethyl] pyridine iron (II) dichloride/methylaluminoxane/diethyl zinc and subsequent in situ oxidation with oxygen. Then diazido‐ and triazido‐terminated PE (PE‐(N₃)₂ and PE‐(N₃)₃) are obtained by the click reactions between PE‐? and coupling agents containing triazido or tetraazido, respectively. Finally, the three‐arm and four‐arm star‐block copolymers, PE‐b‐(PEG)₂ and PE‐b‐(PEG)₃, are prepared by click reactions between PE‐(N₃)₂ or PE‐(N₃)₃ and alkynyl‐terminated PEG. The self‐assembly of the resultant amphiphilic star‐block copolymers in water was investigated by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. It is found that, in water, a solvent selectively good for PEG blocks; these star‐block copolymer chains could self‐assemble to form platelet‐like micelles with insoluble PE blocks as crystalline core and soluble PEG blocks as shell. The confined crystallization of PE blocks in self‐assembled structure formed in aqueous solution is investigated by differential scanning calorimetry. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Amphiphilic star‐shaped poly(ε‐caprolactone)‐block‐poly(l‐lysine) copolymers with porphyrin core: Synthesis,self‐assembly,and cell viability assay

Star‐shaped copolymers poly(ε‐caprolactone)‐bolck‐poly(ε‐benzyloxycarbonyl‐l ‐lysine) (SPPCL‐b‐PZLLs) with porphyrin core were synthesized by a sequential ring‐opening polymerization (ROP) of CL and Nε‐Benzyloxycarbonyl‐l ‐lysine N‐Carboxyanhydride. After the deprotection of benzyloxycarbonyl groups in polylysine blocks, the star‐shaped amphiphilic copolymers SPPCL‐b‐PLLs were obtained. These amphiphilic copolymers can self‐assemble into micelles or aggregates in aqueous solution. Investigation shows that the morphology of micelles/aggregates varied according to the change of pH values of media, indicating the pH‐responsive property of SPPCL‐b‐PLL copolymers. Furthermore, associated with conjugated porphyrin cores, the SPPCL‐b‐PLL copolymers micelles showed a certain degree of Photodynamic Therapy (PDT) effects on tumor cells, suggesting its potential application as carrier for hydrophobic drug with additional therapeutic ability of inherent porphyrin segments. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40097.     

Synthesis of double‐hydrophilic poly(methylacrylic acid)–poly(ethylene glycol)–poly(methylacrylic acid) triblock copolymers and their micelle formation

The aim of the work reported was to synthesize a series of double‐hydrophilic poly(methacrylic acid)‐block‐poly(ethylene glycol)‐block‐poly(methacrylic acid) (PMAA‐b‐PEG‐b‐PMAA) triblock copolymers and to study their self‐assembly behavior. These copolymeric self‐assembly systems are expected to be potential candidates for applications as carriers of hydrophilic drugs. Bromo‐terminated difunctional PEG macroinitiators were used to synthesize well‐defined triblock copolymers of poly(tert‐butyl methacrylate)‐block‐poly(ethylene glycol)‐block‐poly(tert‐butyl methacrylate) via reversible‐deactivation radical polymerization. After the removal of the tert‐butyl group by hydrolysis, double‐hydrophilic PMAA‐b‐PEG‐b‐PMAA triblock copolymers were obtained. pH‐sensitive spherical micelles with a core–corona structure were fabricated by self‐assembly of the double‐hydrophilic PMAA‐b‐PEG‐b‐PMAA triblock copolymers at lower solution pH. Transmission electron microscopy and laser light scattering studies showed the micelles were of nanometric scale with narrow size distribution. Solution pH and micelle concentration strongly influenced the hydrodynamic radius of the spherical micelles (48–310 nm). A possible reason for the formation of the micelles is proposed. Copyright © 2010 Society of Chemical Industry     

In vitro degradability and stability of hydrophobically modified pH‐sensitive micelles using MPEG‐grafted poly(β‐amino ester) for efficient encapsulation of paclitaxel

Methoxypoly(ethylene glycol)‐grafted poly(β‐amino ester) was synthesized for the fabrication of pH‐sensitive micelles, and these micelles were modified with deoxycholic acid to facilitate the hydrophobic interaction between the micellar core and paclitaxel. The micelle properties were studied by dynamic light scattering and fluorescence spectrometry. An in vitro degradation study showed that the synthesized polymers degraded hydrolytically within 24 h under physiological conditions. The stability of paclitaxel‐loaded pH‐sensitive micelles was evaluated in vitro. The introduced deoxycholic acid more stabilized the micelles at pH 7.4 compared to the micelles without modification. But the pH‐sensitive region of the micelles was lowered from pH 6.8 to pH 5.8. These results indicate that pH‐sensitive micelles with improved stability have great potential as hydrophobic drug carriers for tumor targeting. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Poly(methyl methacrylate)/poly(ethylene glycol)/poly(ethylene glycol dimethacrylate) micelles: Preparation,characterization, and application as doxorubicin carriers

A crosslinked amphiphilic copolymer [poly(ethylene glycol) (PEG)–poly(methyl methacrylate) (PMMA)–ethylene glycol dimethacrylate (EGDM)] composed of PMMA, PEG, and crosslinking units (EGDM) was synthesized by atom transfer radical polymerization to develop micelles as carriers for hydrophobic drugs. By adjusting the molar ratio of methyl methacrylate and EGDM, three block copolymer samples (P0, P1, and P2) were prepared. The measurement of gel permeation chromatography and ¹H‐NMR indicated the formation of crosslinked structures for P1 and P2. Fluorescence spectroscopy measurement indicated that PEG–PMMA–EGDM could self‐assemble to form micelles, and the critical micelle concentration values of the crosslinked polymer were lower than those of linear ones. The prepared PEG–PMMA–EGDM micelles were used to load doxorubicin (DOX). The drug‐loading efficiencies of P1 and P2 were higher than that of P0 because the crosslinking units enhanced the micelles' stability. With increasing drug‐loading contents, DOX release from the micelles in vitro was decreased, and in the crosslinked formulations, the release rate was also slower. An in vitro release study indicated that DOX release from the micelles for the linear samples was faster than that for crosslinked micelles. The drug feeding amount increased and resulted in an increase in the drug‐loading content, and the loading efficiency decreased. These PEG–PMMA–EGDM micelles did not show toxicity in vitro and could reduce the cytotoxicity of DOX in the micelles; this suggested that they are good candidates as stable drug carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39623.     

Vesicular and micellar self‐assembly of stimuli‐responsive poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) amphiphilic diblock copolymers

Dually responsive amphiphilic diblock copolymers consisting of hydrophilic poly(N‐isopropyl acrylamide) [poly(NIPAAm)] and hydrophobic poly(9‐anthracene methyl methacrylate) were synthesized by reversible addition fragmentation chain‐transfer (RAFT) polymerization with 3‐(benzyl sulfanyl thiocarbonyl sulfanyl) propionic acid as a chain‐transfer agent. In the first step, the poly(NIPAAm) chain was grown to make a macro‐RAFT agent, and in the second step, the chain was extended by hydrophobic 9‐anthryl methyl methacrylate to yield amphiphilic poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) block copolymers. The formation of copolymers with three different hydrophobic block lengths and a fixed hydrophilic block was confirmed from their molecular weights. The self‐assembly of these copolymers was studied through the determination of the lower critical solution temperature and critical micelle concentration of the copolymers in aqueous solution. The self‐assembled block copolymers displayed vesicular morphology in the case of the small hydrophobic chain, but the morphology gradually turned into a micellar type when the hydrophobic chain length was increased. The variations in the length and chemical composition of the blocks allowed the tuning of the block copolymer responsiveness toward both the pH and temperature. The resulting self‐assembled structures underwent thermally induced and pH‐induced morphological transitions from vesicles to micelles and vice versa in aqueous solution. These dually responsive amphiphilic diblock copolymers have potential applications in the encapsulation of both hydrophobic and hydrophilic drug molecules, as evidenced from the dye encapsulation studies. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46474.     

α‐cyclodextrin assisted self‐assembly of poly(ethylene glycol)‐block‐poly(N‐isopropylacrylamide) in aqueous media

Poly(ethylene glycol)‐block‐poly(N‐isopropylacrylamide) (PEG‐b‐PNIPAM) block copolymers were synthesized by atom transfer radical polymerization, and the α‐cyclodextrin (α‐CD) induced self‐assembly characteristics of the system were elucidated. Below the lower critical solution temperature (LCST) of PNIPAM, CD threaded onto the PEG segments and induced micellization to form rod‐shaped nanostructures comprising of a PEG/α‐CD condensed phase and a PNIPAM shell. Increasing the temperature of system above the LCST caused the PNIPAM segments to collapse, which resulted in the dethreading of the CD. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Synthesis of perfluorohexyl‐terminated poly(ethylene oxide) using maghnite‐h as clay catalyst

Activated monomer cationic ring‐opening polymerization of ethylene oxide initiated with 1H,1H,2H, 2H‐perfluorooctan‐1‐ol, using acid exchanged montmorillonite clay called Maghnite‐H⁺ (Mag‐H⁺) as an effective catalyst, was carried out to obtain the corresponding homopolymers with narrow polydispersity ratios. The molecular weights of the obtained polymers could be controlled with the feed ratio of the monomer and initiator. The effect of amount of catalyst and time on the polymerization yield and viscosity of the polymers were studied. The structure was confirmed by ¹H‐NMR and MALDI‐TOF‐MS. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation of poly(butylene succinate)‐poly[2‐(dimethylamino)ethyl methacrylate] copolymers and their applications as carriers for drug delivery

Copolymers of poly[2‐(dimethylamino)ethyl methacrylate]–poly(butylene succinate)–poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA–PBS–PDMAEMA, PDBD) were synthesized through a chain‐extension reaction. The thermal properties characterized using differential scanning calorimetry showed that the introduction of PDMAEMA chains slightly decreased the melting temperature of PBS. The water contact angle of PDBD copolymer films with media of various pH decreased with a decrease of pH. This should be ascribed to the conformational transition of PDMAEMA blocks from a compact coil to an expanding shape in accordance with the variation of the pH of the surroundings. The results of dynamic light scattering and scanning electron microscopy revealed that PDBD copolymers could form spherical micelles with small particle size and narrow particle size distribution. Furthermore, drug loading (loading content, ca 10%; encapsulation efficiency, ca 60%) and release experiments were conducted using doxorubicin as a hydrophobic model drug. The results of release experiments of copolymer nanomicelles showed that these micelles had pH‐responsive properties. © 2018 Society of Chemical Industry     

Synthesis and characterization of poly(dimethylamino ethyl methacrylate)–poly(ethylene oxide)–poly(dimethylamino ethyl methacrylate) triblock copolymers

Novel, monodispersed, and well‐defined ABA triblock copolymers [poly(dimethylamino ethyl methacrylate)–poly(ethylene oxide)–poly(dimethylamino ethyl methacrylate)] were synthesized by oxyanionic polymerization with potassium tert‐butanoxide as the initiator. Gel permeation chromatography and ¹H‐NMR analysis showed that the obtained products were the desired copolymers with molecular weights close to calculated values. Because the poly(dimethylamino ethyl methacrylate) block was pH‐ and temperature‐sensitive, the aqueous solution behavior of the polymers was investigated with ¹H‐NMR and dynamic light scattering techniques at different pH values and at different temperatures. The micelle morphology was determined with transmission electron microscopy. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

In vitro evaluation of efficacy of dihydroartemisinin‐loaded methoxy poly(ethylene glycol)/poly(l‐lactic acid) amphiphilic block copolymeric micelles

Dihydroartemisinin (DHA)‐loaded methoxy poly(ethylene glycol)/poly(l ‐lactic acid) (mPEG₅₀₀₀—PLLA₃₂₀₀) amphiphilic block copolymeric micelles (DHA‐CM) have been prepared using modified solvent evaporation method. Physicochemical properties of DHA‐CM were investigated by using dynamic light scattering, transmission electron microscopy, high‐performance liquid chromatography, and Fourier transform infrared. Polymers formed stable, spherical, and worm‐like micelles with mean sizes smaller than 130 nm. In vitro release experiments revealed that DHA‐CM provided a more solubilizing effect than DHA suspension; in addition, it was showed that drug release profiles highly depended on pH values of dissolution media. Various types of lyoprotectants were tested to improve the redispersion performance of the freeze‐dried products. 3‐(4, 5‐dimethyl‐ thiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide assay was used to evaluate the cytotoxicity of micellar solutions of freeze‐dried DHA‐CM. The results showed that the IC₅₀ values of DHA‐CM and DHA suspension for KB cell lines were 18.70 and 24.55 μM, respectively. However, DHA‐CM had little cytotoxicity for L02 cell lines. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Self‐assembly and degradation of poly[(2‐methacryloyloxyethyl phosphorylcholine)‐block‐(D,L‐lactide)] diblock copolymers: large compound micelles to vesicles

Biodegradable poly[(2‐methacryloyloxyethyl phosphorylcholine)‐block‐(D ,L ‐lactide)] (PMPC‐b‐PLA) diblock copolymers with various hydrophilic PMPC weight fractions (f_PC) will spontaneously self‐assemble into well‐defined vesicles and large compound micelles (LCMs) in water. Transmission electron microscopy, scanning electron microscopy, dynamic light scattering and fluorescence microscopy were used to observe their aggregate morphologies. The degradation of the LCMs was investigated and the loss of molecular weight of PLA blocks was confirmed using ¹H NMR analysis. The hydrolysis of PLA increases f_PC and consequently shifts the preferred morphology from LCMs to vesicles. Such degradation‐induced morphological transitions mean that the biocompatible and biodegradable LCMs have great application potential in drug delivery. Copyright © 2010 Society of Chemical Industry     

Structure–property relationship of pH‐sensitive (PCL)2(PDEA‐b‐PPEGMA)2 micelles: Experiment and DPD simulation

The experiment and dissipative particle dynamics simulation were carried out on four polymers with different block ratios for the investigation of the structure–property relationship of (poly(ε‐caprolactone)₂‐[poly(2‐(diethylamino)ethyl methacrylate)‐b‐poly(poly(ethylene glycol) methyl ether methacrylate)]₂ [(PCL)₂(PDEA‐b‐PPEGMA)₂] micelles. The miktoarm star polymers assembled into spherical micelles composed of PCL core, pH‐sensitive PDEA mesosphere and poly (ethylene glycol) methyl ether methacrylate (PPEGMA) shell. When decreasing pH from 7.4 to 5.0, the hydrodynamic diameter and transmittance of (PCL)₂(PDEA‐b‐PPEGMA)₂ micelles increased along with globule‐uneven‐extended conformational transitions, owing to the protonation of tertiary amine groups of DEA at lower pH conditions. Doxorubicin (DOX) was mainly loaded in the pH‐sensitive layer, and more DOX were loaded in the core when increasing drug concentrations. The in vitro DOX release from the micelles was significantly accelerated by decreasing pH from 7.4 to 5.0. The results demonstrated that the pH‐sensitive micelles could be used as an efficient carrier for hydrophobic anticancer drugs, achieving controlled and sustained drug release. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3634–3646, 2014