Synthesis and characterization of dual stimuli-responsive block copolymers based on poly(N-isopropylacrylamide)-b-poly(pseudoamino acid)

The current study synthesized amphiphilic thermal/pH-sensitive block copolymers PNiPAAm-b-PHpr by condensation polymerization of trans-4-hydroxy-l-proline (Hpr) initiated from hydroxy-terminated poly(N-isopropylacrylamide) (PNiPAAm) as the macroinitiator in the presence of the catalyst, SnOct₂. ¹H NMR, FTIR, and gel permeation chromatography (GPC) characterized these copolymers. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. The LCST values depended on the polymer composition and the media. With critical micelle concentrations (CMCs) in the range of 1.23-3.73 mg L⁻¹, the block copolymers formed micelles in the aqueous phase owing to their amphiphilic characteristics. Increased hydrophobic segment length or decreased hydrophilic segment length in an amphiphilic diblock copolymer produced lower CMC values. The current work proved the core-shell structure of micelles by ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopy analyzed micelle morphology, showing a spherical core-shell structure. The micelles had an average size in the range of 170˜210 nm (blank), and 195˜280 nm (with drug). Observations showed high drug entrapment efficiency and drug-loading content for the drug micelles.     

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     

Synthesis and morphology transformation of amphiphilic diblock polyurethane copolymers in aqueous solution

Amphiphilic block copolymers possess both hydrophobic and hydrophilic properties and can form versatile micellar structures in aqueous solution. The aim of the research presented was to prepare a series of non‐ionic amphiphilic diblock polyurethane copolymers (PUn) based on isophorone diisocyanate, monoallyl‐end‐capped poly(ethylene oxide) and poly(propylene oxide) (PPO), followed by an investigation of their micellization properties and morphology transformation in aqueous solution. The PUn samples were synthesized by condensation polymerization. These polyurethanes exhibit surface tension as low as 33.7–37.0 mN m^?1. There is an obvious decrease in critical micelle concentration as the hydrophobic PPO molecular weight increases. According to transmission electron microscopy, the morphology of aggregates of the copolymers can be tuned by varying the concentration in aqueous solution rather than organic solvent. For example, for PU7, large compound micelles are produced instead of vesicles. For PU17, the concentration can be used to control the size and thickness of vesicles. Vesicle size increases from 60 to 500 nm and vesicle thickness from 40 to 60 nm with concentration ranging from 0.003 to 0.03 wt%. The study shows that the copolymers in aqueous solution have excellent surface activities. In addition, they can self‐assemble into large compound micelles or vesicles at certain concentrations. Moreover, the synthesis method described allows one to obtain a desired morphology of aggregates by adjusting the composition of hydrophilic and hydrophobic segments, which provides a novel and simple way to obtain particles on the nanometer scale. Copyright © 2010 Society of Chemical Industry     

Star‐shaped amphiphilic block polyurethane with pentaerythritol core for a hydrophobic drug delivery carrier

To obtain polyurethane micelles with excellent stability as a drug delivery carrier, star‐shaped amphiphilic block polyurethane (SAPU) was successfully synthesized by the ‘arm‐first’ method, using methoxypoly(ethylene glycol) and poly(ε‐caprolactone) diol as soft segments, hexamethylene diisocyanate as hard segments and pentaerythritol as the core. The structure of the SAPU was characterized by Fourier transform infrared spectroscopy, ¹H NMR spectroscopy and gel permeation chromatography. The micellization behaviour and micelle properties of SAPU were measured by the pyrene fluorescence probe technique, ¹H NMR, SEM and dynamic light scattering. The results indicated that SAPU could self‐assemble to form nanomicelles in aqueous solution and that the micelles showed excellent stability upon dilution and storage. Indometacin as a model drug could be incorporated into SAPU micelles and be released sustainedly. Meanwhile, the hydrophilic segment content and the molecular weight of SAPU had effects on the micelle properties. In addition, SAPU exhibited good cytocompatibility estimated by methylthiazole‐tetrazolium assay. © 2016 Society of Chemical Industry     

PTPFCBBMA-b-PEG-b-PTPFCBBMA amphiphilic triblock copolymer: Synthesis and self-assembly behavior

We present the synthesis and self-assembly behavior of a new semi-fluorinated amphiphilic triblock copolymer. A series of perfluorocyclobutyl aryl ether-based amphiphilic ABA triblock copolymer containing hydrophilic poly(ethylene glycol) segment as the middle block were synthesized by atom transfer radical polymerization (ATRP). ATRP of 4-(4′-p-tolyloxyperfluorocyclobutoxy)benzyl methacrylate was initiated by PEG-based bifunctional macroinitiators with different molecular weights to obtain the desired copolymers with narrow molecular weight distributions (M_w/M_n ≤ 1.30) and the number of perfluorocyclobutyl linkage can be tuned by the feed ratio and the conversion of the fluorine-containing methacrylic monomer. The critical micelle concentrations of these amphiphilic ABA triblock copolymers in aqueous media were determined by fluorescence probe technique. They could aggregate to form spherical and cylindrical micelles visualized by TEM with varying the content of hydrophobic segment.     

Synthesis and characterization of amphiphilic triblock-graft PEG-(<Emphasis Type="Italic">b</Emphasis>-PαN<Subscript>3</Subscript>CL-<Emphasis Type="Italic">g</Emphasis>-Alkyne)<Subscript>2</Subscript> degradable copolymers

The study proposes a straightforward strategy for synthesizing novel, amphiphilic triblock-graft PEG-(b-PαN₃CL-g-Alkyne)₂ degradable copolymers. First, this investigation performs copolymerization of α-chloro-ε-caprolactone (αClCL) using α,ω-dihydroxyl-terminated macroinitiator poly(ethylene glycol) (PEG) and stannous octoate as the catalyst. In a second step, the current work converts pendent chlorides into azides by reacting with sodium azide. Finally, various kinds of terminal alkynes react with pendent azides by copper-catalyzed Huisgen’s 1,3-dipolar cycloaddition, thus a “click” reaction. These copolymers are characterized by differential scanning calorimetry (DSC), ¹H NMR, IR and gel permeation chromatography. The resulting triblock-graft copolymers exhibit lower crystallinity and melting temperature with respect to the original PEG. The triblock-graft copolymers form micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range of 1.58–8.62 mg L⁻¹, depending on polymer composition. The ¹H NMR spectrum of micelles in D₂O demonstrate only the PEG signal and thus confirm the PCL-g-Alkyne blocks constitute the micelle core, while the central PEG block constitutes the micelle shell. The hydrophilic segment lengths influence the micelle shape. The mean hydrodynamic diameters of micelles from DLS range from 90–200 nm. The work describes drug entrapment efficiency and drug loading content of micelles depending on the composition of triblock-graft polymers.      

A novel well-defined amphiphilic diblock copolymer containing perfluorocyclobutyl aryl ether-based hydrophobic segment

A series of well-defined binary hydrophilic-fluorophilic diblock copolymers were synthesized by successive atom transfer radical polymerization (ATRP) of methoxylmethyl acrylate (MOMA) and 4-(4′-p-tolyloxyperfluorocyclobutoxy)benzyl methacrylate (TPFCBBMA) followed by the acidic selective hydrolysis of the hydrophobic poly(methoxymethyl acrylate) (PMOMA) segment into the hydrophilic poly(acrylic acid) (PAA) segment. ATRP of MOMA was initiated by 2-MBP at 50 °C in bulk to give two different PMOMA homopolymers with narrow molecular weight distributions (M_w/M_n ≤ 1.15). PMOMA-b-PTPFCBBMA well-defined diblock copolymers were synthesized by ATRP of TPFCBBMA at 90 °C in anisole using Br-end-functionalized PMOMA homopolymer as macroinitiator and CuBr/PMDETA as catalytic system. The final PAA-b-PTPFCBBMA amphiphilic diblock copolymers were obtained via the selective hydrolysis of PMOMA block in dilute HCl without affecting PTPFCBBMA block. The critical micelle concentrations (cmc) of PAA-b-PTPFCBBMA amphiphilic copolymers in aqueous media were determined by fluorescence spectroscopy using pyrene as probe and these diblock copolymers showed different micellar morphologies with the changing of the composition.     

Synthesis and characterization of a novel amphiphilic poly (ethylene glycol)–poly (ε-caprolactone) graft copolymers

A series of amphiphilic graft copolymers PEO-g-PCL with different poly (ε-caprolactone) (PCL) molecular weight were successfully synthesized by a combination of anionic ring-opening polymerization (AROP) and coordination-insertion ring-opening polymerization. The linear PEO was produced by AROP of ethylene oxide (EO) and ethoxyethyl glycidyl ether initiated by 2-(2-methoxyethoxy) ethoxide potassium, and the hydroxyl groups on the backbone were deprotected after hydrolysis. The ring-opening polymerization of CL was initiated using the linear poly (ethylene oxide) (PEO) with hydroxyl group on repeated monomer as macroinitiator and Sn(Oct)₂ as catalyst, then amphiphilic graft copolymers PEO-g-PCL were obtained. By changing the ratio of monomer and macroinitiator, a series of PEO-g-PCL with well-defined structure, molecular weight control, and narrow molecular weight distribution were prepared. The expected intermediates and final products were confirmed by ¹H NMR and GPC analyzes. In addition, these amphiphilic graft copolymers could form spherical aggregates in aqueous solution by self-assemble, which were characterized by transmission electron microscopy, and the critical micelle concentration values of graft copolymers PEO-g-PCL were also examined in this article.     

Synthesis and solution properties of novel nonionic functional polyurethane surfactants

A series of novel nonionic functional polyurethane surfactants were synthesized by the polycondensation of 2,4‐toluene diisocyanate with poly(propylene oxide) (weight‐average molecular weight = 400, 1000, or 2000) and monoallyl‐end‐capped poly(ethylene oxide). The chemical structure of the polyurethane surfactants was determined by Fourier transform infrared and ¹H‐NMR, and the effects of the concentration, salt, rest time, and temperature on the surface tension were investigated. These polymeric surfactants exhibited excellent surface activity. Sample III, which was synthesized with monoallyl‐end‐capped poly(ethylene oxide) (number‐average molecular weight = 1000), poly(propylene oxide) (number‐average molecular weight = 2000), and tolylene diisocyanate, could reduce the surface tension to 37.6 mN/m at a concentration of 0.06 mol/L at 25°C. All polyurethane surfactants synthesized in this study had low critical micelle concentrations (ca. 10^?4 to 10^?5 mol/L) and could reduce the surface tension even at very low concentration levels. Moreover, the surface tension decreased with an increase in the temperature or the concentration of the polyurethane surfactants. The addition of salt resulted in a decrease in the surface tension, and it took some time for the polyurethane surfactants to reach a constant surface tension value. UV spectra were found to be very useful for determining the critical micelle concentration. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2956–2962, 2006     

Well-defined poly(2-hydroxyethyl methacrylate) and its amphiphilic block copolymers via acidolysis of anionically synthesized poly(2-vinyloxyethyl methacrylate)

Summary A novel approach to a well-defined poly(2-hydroxyethyl methacrylate) [poly(HEMA)] and to its amphiphilic block copolymers was developed. The selective living anionic polymerization of the methacryloyl group of the bifunctional monomer 2-vinyloxyethyl methacrylate (VEMA) generated a functional polymer with a controlled molecular weight and a narrow molecular weight distribution (M_w/M_n= 1.05–1.09). This polymer is very stable under normal conditions. Being soluble in the common organic solvents, its characterization could be carried out easily. The unreacted vinyl groups in the side chains of the resulting polymer were further reacted with hydrochloric acid. This acidolysis changed poly(VEMA) to a well-defined poly(HEMA). In addition, the anionic block copolymerization of VEMA with styrene or methyl methacrylate also proceeded smoothly, generating the corresponding block copolymers. After acidolysis, these copolymers were turned into amphiphilic block copolymers containing a hydrophilic poly(HEMA) block. Received: 22 June 2001/Revised version: 15 August 2001/Accepted: 15 August 2001     

Synthesis and properties of acrylate‐acrylic acid‐acrylate triblock copolymers with gemini structure by RAFT polymerization

A class of gemini structure block copolymers with a trithiocarbonate ester spacer group had been synthesized with S, S′‐bis (R, R′‐dimethylacetic acid) trithiocarbonate as reversible addition fragmentation chain transfer agents and acrylic acid as the second monomer. These triblock copolymers were characterized by ¹H NMR spectroscopy, gel permeation chromatography in terms of their compositions, molecular weights and behaviour at the air–water interface. The results showed that the weight‐average molecular weight was larger than theoretical molecular as the acrylate side chain increased. The polymer neutralized by sodium hydroxide solution had low critical micelle concentration which was <10^?2 mol L^?1 in water. TEM and DLS showed that it formed a special micelle structure with large pore structure which might lead to low surface tension and critical micelle concentration in water. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43017.     

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     

Synthesis and self-assembly behaviors of three-armed amphiphilic block copolymers via RAFT polymerization

The novel trifunctional reversible addition-fragmentation chain transfer (RAFT) agent, tris(1-phenylethyl) 1,3,5-triazine-2,4,6-triyl trithiocarbonate (TTA), was synthesized and used to prepare the three-armed polystyrene (PS₃) via RAFT polymerization of styrene (St) in bulk with thermal initiation. The polymerization kinetic plot was first order and the molecular weights of polymers increased with the monomer conversions with narrow molecular weight distributions (M_w/M_n ≤ 1.23). The number of arms of the star PS was analyzed by gel permeation chromatography (GPC), ultraviolet visible (UV-vis) and fluorescence spectra. Furthermore, poly(styrene-b-N-isopropylacrylamide)₃ (PS-b-PNIPAAM)₃, the three-armed amphiphilic thermosensitive block copolymer, with controlled molecular weight and well-defined structure was also successfully prepared via RAFT chain extension method using the three-armed PS obtained as the macro-RAFT agent and N-isopropylacrylamide as the second monomer. The copolymers obtained were characterized by GPC and ¹H nuclear magnetic resonance (NMR) spectra. The self-assembly behaviors of the three-armed amphiphilic block copolymers (PS-b-PNIPAAM)₃ in mixed solution (DMF/CH₃OH) were also investigated by high performance particle sizer (HPPS) and transmission electron microscopy (TEM). Interestingly, the lower critical solution temperature (LCST) of aqueous solutions of the three-armed amphiphilic block copolymers (PS-b-PNIPAAM)₃ decreased with the increase of relative length of PS in the block copolymers.     

Synthesis of poly(acrylic acid)-g-polystyrene copolymer by successive ATRP

A series of well-defined amphiphilic graft copolymers consisting of hydrophilic poly(acrylic acid) backbone and hydrophobic polystyrene side chains were synthesized by hydrolysis of poly(methyl acrylate)-g-polystyrene under basic condition. The backbone and the side chains were synthesized by atom transfer radical polymerization (ATRP), so the molecular weight could be tuned by the variation of the feed ratio or monomer conversion, and the molecular weight distributions of amphiphilic graft copolymers were kept low (PDI < 1.35). The products were characterized by FT-IR, ¹H NMR, ¹³C NMR, and gel permeation chromatography (GPC). The study of self-assembly behavior can benefit the formation of the well-defined structures of the products.     

Synthesis of amphiphilic pseudopolyamino acid‐containing ABC‐triblock copolymers and micellar characterizations

This study describes the synthesis of amphiphilic ABC‐triblock copolymers comprising a central pseudopoly(4‐hydroxy‐L ‐proline) segment and terminal hydrophilic poly(ethylene glycol)methyl ether as well as hydrophobic poly(ε‐caprolactone) blocks. Differential scanning calorimetry, ¹H‐NMR spectroscopy, and gel permeation chromatography are used to characterize the copolymers. The thermal properties (T_g and T_ms) of the triblock copolymers depend on the composition of polymers. Larger amounts of ε‐CL incorporated into the macromolecular backbone increased T_g and T_ms. Fluorescence spectroscopy, transmission electron microscopy, and dynamic light scattering are utilized to investigate their micellar characteristics in the aqueous phase. Observations showed a higher critical micelle concentration with higher hydrophilic components in the copolymers. The micelle exhibited a core‐shell‐corona and/or vesicle shape, and the average size was less than 300 nm. Drug entrapment efficiency and drug loading of micelles depending on the composition of block polymers are also described. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis and micellization of an amphiphilic biodegradable β-cyclodextrin/poly(γ-benzyl L-glutamate) copolymer

β-Cyclodextrin/poly(γ-benzyl L-glutamate) (β-CD-PBLG) copolymers were synthesized by ring-opening polymerization of N-carboxy-γ-benzyl L-glutamate anhydride (BLG-NCA) in N,N-dimethylformamide(DMF) initiated by mono-6-amino-β-cyclodextrin(H₂N-β-CD). The structures of the copolymers were determined by IR, ¹H NMR and GPC. The fluorescence technique was used to determine the critical micelle concentration (CMC) of copolymer micelle solution. The diameter and the distribution of micelles were characterized by dynamic light scattering(DLS) and its shape was observed by transmission electron microscopy(TEM). The results showed that BLG-NCA could be initiated by H₂N-β-CD to produce copolymer. These copolymers showed an amphiphilic nature and could self-assemble into nano-micelles in water. The CMC of copolymer solution and the size of micelle reduced with the increasing of the proportion of hydrophobic parts. TEM images demonstrated the micelles are all spherical. Such copolymers could be expected to find applications in drug delivery systems and other biomedical domains.     

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     

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.     

Comparison of micelles formed by amphiphilic poly(ethylene glycol)‐b‐poly(trimethylene carbonate) star block copolymers

In this article, we describe the synthesis and solution properties of PEG‐b‐PTMC star block copolymers via ring‐opening polymerization (ROP) of trimethylene carbonate (TMC) monomer initiated at the hydroxyl end group of the core PEG using HCl Et₂O as a monomer activator. The ROP of TMC was performed to synthesize PEG‐b‐PTMC star block copolymers with one, two, four, and eight arms. The PEG‐b‐PTMC star block copolymers with same ratio of between hydrophobic PTMC and hydrophilic PEG segments were obtained in quantitative yield and exhibited monomodal GPC curves. The amphiphilic PEG‐b‐PTMC star block copolymers formed spherical micelles with a core–shell structure in an aqueous phase. The mean hydrodynamic diameters of the micelles increased from 17 to 194 nm with increasing arm number. As arm number increased, the critical micelle concentration (CMC) of the PEG‐b‐PTMC star block copolymers increased from 3.1 × 10^?3 to 21.1 × 10^?3 mg/mL but the partition equilibrium constant, which is an indicator of the hydrophobicity of the micelles of the PEG‐b‐PTMC star block copolymers in aqueous media, decreased from 4.44 × 10⁴ to 1.34 × 10⁴. In conclusion, we confirmed that the PEG‐b‐PTMC star block copolymers form micelles and, hence, may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermoresponsive and acid-cleavable amphiphilic copolymer micelles for controlled drug delivery

Thermoresponsive and acid-cleavable amphiphilic block copolymers poly(N-isopropylacrylamide)-acetal-poly(4-substituted-ε-caprolactones) (PNiPAAm-a-PXCLs) containing an acidic-cleavable acetal linkage at the junction between the temperature-sensitive hydrophilic PNiPAAm and the degradable hydrophobic block PXCL were synthesized through ring-opening polymerization and electrophilic addition reactions. These polymer solutions showed reversible changes in optical properties and a lower critical solution temperature in the range of 32.0–46.4°C. The copolymers formed micelles in aqueous solution with critical micelle concentrations in the range of 0.83–15.95?mg?L^?1 had hydrodynamic sizes of <200?nm and were spherical. Under the combined stimulation of temperature and pH, the micellar nanoparticles could be dissociated; the loaded molecules could be released from the assemblies more efficiently than that under only one stimulus or without stimulus. In addition, the nanoparticles exhibited low toxicity against human cervical cancer (HeLa) cells at concentrations ≤1000?µg?mL^?1. Doxorubicin-loaded PNiPAAm₁₁-a-PCL₂₈ micelles also effectively inhibited the proliferation of HeLa cells with a half-maximal inhibitory concentration (IC₅₀) of 1.60?µg?mL^?1.