TPE‐conjugated biomimetic and biodegradable polymeric micelle for AIE active cell imaging and cancer therapy

Smart nanocarrier for simultaneous drug delivery and cellular imaging is ideal for both cancer therapy and diagnosis. In this work, polymeric micelles based on the tetraphenylethene (TPE) conjugated poly(N6‐carbobenzyloxy‐l ‐lysine)‐block‐poly(2‐methacryloyloxyethyl phosphorylcholine) (TPE‐PLys‐b‐PMPC) copolymer are successfully prepared. Such biomimetic and biodegradable TPE‐PLys‐b‐PMPC micelles exhibit remarkable aggregation‐induced emission (AIE) feature and great biocompatibility, showing great potential for bioimaging application. In addition, anticancer drug doxorubicin (DOX) can be incorporated into the core of micelles and the intracellular release of DOX can be furthermore traced through the fluorescent imaging of these AIE micelles. As expected, this DOX‐loading polymeric micelle shows significant growth inhibition against HeLa cells and 4T1 cells and such TPE‐PLys‐b‐PMPC micelles would be a promising drug carrier for potential cancer therapy and bioimaging. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45651.     

Construct biomimetic giant vesicles via self‐assembly of poly(2‐methacryloyloxyethyl phosphorylcholine)‐block‐poly(D,L‐lactide)

The poly(2‐methacryloyloxyethyl phosphorylcholine)‐block‐poly(D ,L ‐lactide) (PMPC‐b‐PLA) was specially designed to develop biomimetic giant vesicles (GVs) and giant large compound vesicles via a simple spontaneous assemble in aqueous solution. The weight fraction of the hydrophilic PMPC block (f_PC) was proved to play an important role in the size and morphology control of the self‐assembled aggregates. The GVs with controlled micrometer size and biomimetic PMPC corona have great potential as artificial cell models. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Encapsulation of curcumin by methoxy poly(ethylene glycol‐b‐aromatic anhydride) micelles

Suitable carrier systems for sustained release of curcumin were studied by using the self‐assembled polymeric micelles. Poly(ethylene glycol) methyl ether and poly(aromatic anhydride) were used as the hydrophilic and hydrophobic blocks, respectively, in forming amphiphilic diblock copolymers. Four different types of polymers methoxy poly(ethylene glycol‐ b‐1,3‐bis(p‐carboxyphenoxy)propane) (mPEG₅₀₀₀CPP, mPEG₂₀₀₀CPP), methoxy poly(ethylene glycol‐b‐1,6‐bis(p‐carboxyphenoxy)hexane) (mPEG₅₀₀₀CPH, mPEG₂₀₀₀CPH) were synthesized via melt condensation approach. Micelles were formed at very low polymer concentration with stable hydrophobic cores. The particle sizes of micelles remained stable during degradation period. All four different polymeric micelles showed low cytotoxicity toward human fibroblasts cells and can kill cancer cells in very low concentrations. High loading efficiency and drug content were observed in curcumin‐loaded micelles. Curcumin showed mild initial burst (30% of drug loading in the first 24 h) when released from the micelles and its release was sustained for at least 18 days. These micelles, especially those of mPEG₅₀₀₀CPP, show potential to serve as the delivery vehicles for sustained release of curcumin. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Synthesis and evaluation of biodegradable segmented multiblock poly(ether ester) copolymers for biomaterial applications

Based on 1,4‐succinic acid, 1,4‐butanediol, poly(ethylene glycol)s and dimethyl terephthalate, biodegradable segmented multiblock copolymers of poly[(butylene terephthalate)‐co‐poly(butylene succinate)‐block‐poly(ethylene glycol)] (PTSG) were synthesized with different poly(butylene succinate) (PBS) molar fractions and varying the poly(ethylene glycol) (PEG) segment length, and were evaluated as biomedical materials. The copolymer extracts showed no in vitro cytotoxicity. However, sterilization of the copolymers by gamma irradiation had some limited effect on the cytotoxicity and mechanical properties. A copolymer consisting of PEG‐1000 and 20 mol% PBS, assigned as 1000PBS20 after SO₂ gas plasma treatment, sustained the adhesion and growth of dog vascular smooth muscle cells. The in vivo biocompatibility of this sample was also measured subcutaneously in rats for 4 weeks. The assessments indicated that these poly(ether ester) copolymers are good candidates for anti‐adhesion barrier and drug controlled‐release applications. Copyright © 2004 Society of Chemical Industry     

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     

An in vitro focus on doxorubicin hydrochloride delivery of novel pH‐responsive poly(2‐succinyloxyethylmethacrylate) and poly[(N‐4‐vinylbenzyl),N,N‐diethylamine] diblock copolymers

Novel pH‐responsive poly(2‐succinyloxyethylmethacrylate)‐b‐poly[(N‐4‐vinylbenzyl),N,N‐diethylamine] [poly(SEMA‐b‐VEA)] diblock copolymers were synthesized via reversible addition fragmentation transfer (RAFT) polymerization to investigate their self‐assembly micellar behavior. The self‐assembly behaviors of synthesized diblock copolymers with distinct molecular weights (labeled (1) to) were confirmed by ¹H NMR spectroscopy, TEM and dynamic light scattering measurements. Doxorubicin hydrochloride (DOX) loading capacity was evaluated, and the in vitro cytotoxicity effect of DOX‐loaded diblock copolymer was also studied by assessing the survival rate of the breast cancer cell line MCF‐7 with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results exhibited remarkable controlled release in the MTT assay. The DOX encapsulation efficiency was calculated to be 96.4%. The size and zeta potential of DOX‐loaded poly(SEMA‐b‐VEA) diblock copolymers were 204 nm and +5.7 mV at a pH of 7.4. DOX release values after 440 h at pH 7.4, 5.4 and 4 were 22.15%, 31.43% and 47.06%, respectively. The released values of DOX‐loaded poly(SEMA‐b‐VEA) and at pH 7.4 were 22.15%, 20.5% and 17.5%, respectively. Cell survival ratios were 18.9%, 23.16% and 16.92% after 72 h. Poly(SEMA‐b‐VEA) copolymers can be considered in nanomedicine applications due to their excellent pH‐responsive micellar behavior. © 2017 Society of Chemical Industry     

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.     

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     

Intracellular pH‐sensitive dextran‐based micelles as efficient drug delivery platforms

As drug delivery systems, stimuli‐responsive polymer micelles hold great potential in cancer chemotherapeutics to improve therapeutic efficiency and eliminate organism adverse effects. Here, pH‐sensitive polymeric micelles based on dextran‐g‐benzimidazole were designed and used for intracellular anticancer drug delivery. The anticancer drug doxorubicin (DOX) was effectively loaded into the micelles via hydrophobic interactions. In vitro release studies demonstrated that the release of loaded DOX was greater and faster under acid conditions such as in carcinomatous areas (pH < 6.8) than in physiological conditions (pH 7.4). MTT assays and flow cytometric analyses showed that DOX‐loaded micelles had higher cellular proliferation inhibition towards HeLa and HepG2 cells than pH‐insensitive controls. These pH‐sensitive micelles with significant efficiency for intracellular drug release will be beneficial to the future of in vivo biomedical applications. © 2014 Society of Chemical Industry     

Synthesis and characterization of PEG–PCL–PEG triblock copolymers as carriers of doxorubicin for the treatment of breast cancer

Triblock copolymers of monomethoxy poly(ethylene glycol) (mPEG) and ε‐caprolactone (CL) were prepared with varying lengths of poly(ε‐caprolactone) (PCL) compositions and a fixed length of mPEG segment. The molecular characteristics of triblock copolymers were characterized by ¹H NMR, gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), and differential scanning calorimetry (DSC). These amphiphilic linear copolymers based on PCL hydrophobic chain and hydrophilic mPEG ending, which can self‐assemble into nanoscopic micelles with their hydrophobic cores, encapsulated doxorubicin (DOX) in an aqueous solution. The particle size of prepared micelles was around 40–92 nm. The DOX loading content and DOX loading efficiency were from 3.7–7.4% to 26–49%, respectively. DOX‐released profile was pH‐dependent and faster at pH 5.4 than pH 7.4. Additionally, the cytotoxicity of DOX‐loaded micelles was found to be similar with free DOX in drug‐resistant cells (MCF‐7/adr). The great amounts of DOX and fast uptake accumulated into the MCF‐7/adr cells from DOX‐loaded micelles suggest a potential application in cancer chemotherapy. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation of new dendrimer‐like star‐shaped amphiphilic poly(ethylene glycol)–poly(ϵ‐caprolactone) copolymers for biocompatible and high‐efficiency curcumin delivery

Novel amphiphilic star‐shaped terpolymers comprised of hydrophobic poly(?‐caprolactone), pH‐sensitive polyaminoester block and hydrophilic poly(ethylene glycol) (M_n = 1100, 2000 g mol^?1) were synthesized using symmetric pentaerythritol as the core initiator for ring‐opening polymerization (ROP) reaction of ?‐caprolactone functionalized with amino ester dendrimer structure at all chain ends. Subsequently, a second ROP reaction was performed by means of four‐arm star‐shaped poly(?‐caprolactone) macromer with eight ‐OH end groups as the macro‐initiator followed by the attachment of a poly(ethylene glycol) block at the end of each chain via a macromolecular coupling reaction. The molecular structures were verified using Fourier transform infrared and ¹H NMR spectroscopies and gel permeation chromatography. The terpolymers easily formed core–shell structural nanoparticles as micelles in aqueous solution which enhanced drug solubility. The hydrodynamic diameter of these agglomerates was found to be 91–104 nm, as measured using dynamic light scattering. The hydrophobic anticancer drug curcumin was loaded effectively into the polymeric micelles. The drug‐loaded nanoparticles were characterized for drug loading content, encapsulation efficiency, drug–polymer interaction and in vitro drug release profiles. Drug release studies showed an initial burst followed by a sustained release of the entrapped drug over a period of 7days at pH = 7.4 and 5.5. The release behaviours from the obtained drug‐loaded nanoparticles indicated that the rate of drug release could be effectively controlled by pH value. Altogether, these results demonstrate that the designed nanoparticles have great potential as hydrophobic drug delivery carriers for cancer therapy. © 2015 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     

Drug release from poly(ortho esters)–poly(ethylene glycol) polyblend

A polyblend of poly(ortho esters)–poly(ethylene glycol) (POE–PEG) was prepared. The release behavior of the acetanilide‐loaded film of the POE–PEG polyblend was studied. Blending POE with water‐soluble PEG can promote the release of drug in pH 7.4 PBS buffer at 37°C, while POE has plasticizing effect on PEG. Infrared and X‐ray diffraction studies reveal that there is some interaction between POE and acetanilide. The SEM micrographs disclose that the porosity of the drug‐loaded film enhances with an increase immersing time. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 303–309, 1999     

Bioinspired photo-degradable amphiphilic hyperbranched poly(amino ester)s: Facile synthesis and intracellular drug delivery

A novel amphiphilic photo-degradable hyperbranched polymer was reported at the first time. The hyperbranched o-nitrobenzyl containing poly(amino ester)s (HPAE) were prepared by one-pot Michael addition polymerization. The photo-induced degradation of hyperbranched poly(amino ester)s was confirmed by gel permeation chromatography (GPC) and UV-vis spectra. Bioinspired phosphorylcholine grafted HPAE (HPAE-PC) was synthesized via thiol-ene click chemistry. HPAE-PC can self-assemble to micelles and the micelles could be disassembled under UV irradiation because of the photo-degradation of HPAE. HPAE-PC micelles were used to load anticancer drug Doxorubicin (DOX). In vitro drug release studies showed that the release of DOX was much faster in the presence of UV irradiation than that without UV irradiation. The fluorescence microscope results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Moreover, the DOX-loaded HPAE-PC micelles under UV irradiation exhibited better anticancer activity against A549 cells than that of the nonirradiated ones. The novel amphiphilic photo-degradable hyperbranched polymers can be used to construct spatiotemporal on-demand drug delivery system for cancer therapy.     

Enhanced loading of doxorubicin into polymeric micelles by a combination of ionic bonding and hydrophobic effect,and the pH-sensitive and ligand-mediated delivery of loaded drug

Folate-conjugated micelles were fabricated from amphiphilic diblock copolymers with poly(ethylene glycol) as the hydrophilic block and a random copolymer of n-butyl methacrylate and methacrylic acid as the hydrophobic block. Doxorubicin (DOX), a model drug that contains an amine group and hydrophobic moiety, was loaded with a high loading capacity into micelles by a combination of ionic bonding and hydrophobic effect. The combined interactions imparted a pH-sensitive delivery property to the system. The release rate of loaded DOX was slow at pH 7.4 (i.e., mimicking the plasma environment) but increased significantly at acidic pH (i.e., mimicking endosome/lysosome conditions). Acid-triggered drug release resulted from the carboxylate protonation of poly(methacrylic acid), which dissociated the ionic bonding between the micelles and DOX. Cellular uptake by folate receptor-overexpressing HeLa cells of the DOX-loaded folate-conjugated micelles was higher than that of micelles without folate conjugation. Thus, the DOX-loaded folate-conjugated micelles displayed higher cytotoxicity to HeLa cells.     

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     

Micelles formed by self‐assembly of hyperbranched poly[(amine‐ester)‐co‐(D,L‐lactide)] (HPAE‐co‐PLA) copolymers for protein drug delivery

BACKGROUND: The aim of the work presented was to synthesize a series of amphiphilic hyperbranched poly[(amine‐ester)‐co‐(D ,L ‐lactide)] (HPAE‐co‐PLA) copolymers and study the formation of copolymeric micelles. These copolymeric micelle systems are expected to be potential candidates for applications in protein drug delivery. RESULTS: The chemical structures of the copolymers were confirmed by Fourier transform infrared spectroscopy, ¹³C NMR and thermogravimetric analysis. Fluorescence spectroscopy and dynamic light scattering confirmed the formation of copolymeric micelles of the HPAE‐co‐PLA copolymers. The maintenance of stability of bovine serum albumin (BSA) during release from micelles in vitro was also measured using circular dichroism and fluorescence spectrometry. CONCLUSION: Novel hyperbranched HPAE‐co‐PLA copolymers have been synthesized. Conjugation of PLA to HPAE was proved to be an available method for the preparation of micelles for protein delivery. The BSA‐loaded micelles showed enhanced encapsulation efficiency and the structural stability of BSA was retained during the release process. The hyperbranched polymeric micelles could be useful as drug carriers for protein drug delivery systems. Copyright © 2008 Society of Chemical Industry     

Functional poly(p-phenylene)s as targeting and drug carrier materials

Polymers have a substantial attention in drug delivery systems owing to the diverse intrinsic advantages. It is important to carry the drug to the target site and release to exert its effects. Herein, poly(p-phenylene)s with amino and poly(ethylene glycol) substituents (PPP-NH₂-g-PEG) were used as a carrier for doxorubicin (DOX), an anticancer drug, and haloperidol, a sigma receptor targeting ligand. Both human cervix adenocarcinoma cell line (HeLa) and human keratinocyte cell line (HaCaT) having different Sigma receptor 1 (SigmaR1) expression levels were compared. HeLa was found to express twofold SigmaR1 compared to HaCaT cells. Cell imaging studies showed that, DOX cell uptake was higher in HeLa cells when targeted with haloperidol.     

Lipase-catalyzed synthesis of pH-responsive poly(β-thioether ester)-b-poly(ethylene glycol)-b-poly(β-thioether ester) amphiphilic triblock copolymers for drug delivery

Novel amphiphilic triblock copolymers poly(β-thioether ester)-b-poly(ethylene glycol)-b-poly(β-thioether ester) (PTE-b-PEG-b-PTE) were designed for the first time and used as carriers for the sustained release of the hydrophobic drug curcumin (Cur). These BAB-type triblock copolymers were synthesized via one-step enzymatic polycondensation with catalysis by immobilized lipase B from Candida antarctica (CALB). The copolymers could self-assemble to form flower-like nanosized micelles in aqueous solution. The pH-triggered disassembly behaviors of the micelles were evaluated from the changes of the micellar size and molecular weight due to the acid-degradable β-thiopropionate groups in the hydrophobic PTE core. Cur was encapsulated into the micelles and showed faster release at pH 5.0 than pH 7.4. In vitro experiments indicated that the copolymers were non-cytotoxic, while the Cur-loaded micelles effectively inhibited the proliferation of HeLa cells. All these findings demonstrated the potential of PTE-b-PEG-b-PTE triblock copolymers as a promising pH-responsive nanocarrier for controlled drug delivery.     

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