Biodegradable and thermosensitive micelles of amphiphilic polyaspartamide derivatives containing aromatic groups for drug delivery

The preparation, characterization, release, and in vitro cytotoxicity of a biodegradable polymeric micellar formulation of paclictaxel (PTX) were investigated. The micelles based on thermosensitive and degradable amphiphilic polyaspartamide derivatives containing pendant aromatic structures (phe‐g‐PHPA‐g‐mPEG) were prepared by a quick heating method without using toxic organic solvent. Dynamic light‐scattering results show that the micelles are stable upon dilution under physiological conditions and the destabilization of the micelles is pH‐dependent and the phe‐g‐PHPA‐g‐mPEG polymers are biodegradable. PTX was loaded into the phe‐g‐PHPAs‐g‐mPEG micelles with encapsulation efficiency of >90%, resulting in a high drug loading content (up to 29%). PTX‐loaded micelles had a mean size around 70 nm with narrow size distribution (polydispersity index, <0.1). The PTX‐loaded micelles showed sustained drug release and obvious anticancer activity similar to Taxol against HepG2 cells, whereas blank micelles were nontoxic. The present results suggest that the thermosensitive and biodegradable phe‐g‐PHPA‐g‐mPEG micelles are a promising delivery system for the hydrophobic drugs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3917–3924     

Amphiphilic Block‐Graft Copolymers Poly(ethylene glycol)‐b‐(polycarbonates‐g‐palmitate) Prepared via the Combination of Ring‐Opening Polymerization and Click Chemistry

Amphiphilic block‐graft copolymers mPEG‐b‐P(DTC‐ADTC‐g‐Pal) were synthesized by ring‐opening polymerization of 2,2‐dimethyltrimethylene carbonate (DTC) and 2,2‐bis(azidomethyl)trimethylene carbonate (ADTC) with poly(ethylene glycol) monomethyl ether (mPEG) as an initiator, followed by the click reaction of propargyl palmitate and the pendant azido groups on the polymer chains. Stable micelle solutions of the amphiphilic block‐graft copolymers could be prepared by adding water to a THF solution of the polymer followed by the removal of the organic solvent by dialysis. Dynamic light scattering measurements showed that the micelles had a narrow size distribution. Transmission electron microscopy images displayed that the micelles were in spherical shape. The grafted structure could enhance the interaction of polymer chains with drug molecules and improve the drug‐loading capacity and entrapment efficiency. Further, the amphiphilic block‐graft copolymers mPEG‐b‐P(DTC‐ADTC‐g‐Pal) were low cytotoxic and had more sustained drug release behavior. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

pH‐Triggered Sustained Drug Delivery from a Polymer Micelle having the β‐Thiopropionate Linkage

The synthesis, micellar aggregation, and pH‐triggered intracellular drug delivery ability of an amphiphilic statistical copolymer (P2) are studied. Two methacrylate derivatives, one containing a hydrophilic pendant and the other containing a hydrophobic pendant chain, are copolymerized to produce P2. The hydrophobic pendant chain is linked to the polymer backbone by a β‐thiopropionate linkage, known to undergo slow hydrolysis at mild acidic pH. P2 forms a multimicellar cluster in water with a critical aggregation concentration of 0.02 mg mL⁻¹ and encapsulates a hydrophobic guest such as pyrene, Nile red, or the anti‐cancer drug doxorubicin (Dox). Sustained release of the entrapped Dox (80% after 100 h) is noticed at pH 5.2, while release is significantly slower (35% after 100 h) at pH 7.4. Acidic hydrolysis of the β‐thiopropionate linkage leading to the reduction of the hydrophobicity is established as the cause for micellar disassembly and triggered drug release. Cell‐culture studies with the human breast cancer cell line, MCF‐7, reveal biocompatibility of P2 (below 150 μg mL⁻¹). It is further tested for intracellular delivery of Dox. MCF‐7 cells remain healthy at pH 7.4 but become unhealthy at pH 5.2 when treated with a Dox‐loaded P2 micelles.

     

Temperature and pH dual‐sensitive polyaspartamide derivatives for antitumor drug delivery

The pH‐sensitive tertiary amino groups were introduced to synthesize temperature and pH dual‐sensitive degradable polyaspartamide derivatives (phe/DEAE‐g‐PHPA) containing pendant aromatic structures and ionizable tertiary amino groups. The thermo/pH‐responsive behavior of phe/DEAE‐g‐PHPA polymer can be tuned by adjusting the graft copolymer composition. Due to the pH sensitivity of the phe/DEAE‐g‐PHPA‐g‐mPEG polymer with hydrophilic long PEG chain, the micelles and the anticancer drug‐loaded micelles were prepared by a quick pH‐changing method without using toxic organic solvent. The obtained polymeric micelles, paclitaxel‐loaded micelles and doxorubicin‐loaded micelles were stable under physiological conditions. Both the drug‐loaded micelles showed much faster release at pH 5 than at pH 7.4. The doxorubicin‐loaded micelles showed obvious and better anticancer activity against both HepG2 and HeLa cells than free doxorubicin. Thus these nontoxic, dual thermo‐ and pH‐sensitive phe/DEAE‐g‐PHPA‐g‐mPEG micelles may be a promising anticancer drug delivery system. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 879–888     

Photo‐responsive amphiphilic poly(α‐hydroxy acids) with pendent o‐nitrobenzyl ester constructed via copper‐catalyzed azide‐alkyne cycloaddition reaction

Photo‐responsive block copolymer mPEG‐b‐poly(Tyr)‐g‐NB was prepared by introduction of o‐nitrobenzyl ester group into the side chain of amphiphilic poly(ethylene glycol)‐b‐poly(α‐hydroxy acids) (mPEG‐b‐poly(Tyr)) containing pendent alkynyl group via copper‐catalyzed azide‐alkyne cycloaddition reaction. The amphiphilic mPEG‐b‐poly(Tyr) was synthesized via the ring‐opening polymerization of O‐carboxyanhydrides, with monomethoxy poly(ethylene glycol) (mPEG) as macroinitiator. The molecular structure, self‐assembly, and photo‐controlled release of the obtained mPEG‐b‐poly(Tyr)‐g‐NB were thoroughly investigated. mPEG‐b‐poly(Tyr)‐g‐NB could self‐assemble into spherical micelles in water and showed disassembly under UV light irradiation, which was demonstrated by means of UV‐vis spectroscopy, scan electron microscopes, and dynamic light scattering measurement. Fluorescence emission measurements demonstrated that Nile red, encapsulated by micelles, can be released upon UV irradiation. This study provides a convenient way to construct smart poly(α‐hydroxy acids)‐based nanocarriers for controlled release of hydrophobic drugs. Copyright © 2015 John Wiley & Sons, Ltd.     

An H‐shaped polymer bonding β‐cyclodextrin at branch points: Synthesis and influences of attached β‐cyclodextrins on physical properties

We report on the synthesis of an H‐shaped polymer bonding β‐cyclodextrin (β‐CD) at branch points and influences of attached β‐CD on physical properties. First, a poly(ethylene glycol)(PEG)‐based functional macroinitiator bearing two azidos and four chlorines at chain‐ends (PEG‐2N₃(‐4Cl)) was prepared via terminal modification reactions. Then, PEG‐2N₃(‐4Cl) was applied to initiate the atom transfer radical polymerization of N‐isopropylacrylamide, leading to the synthesis of an H‐shaped block polymer with PEG as the central chain and poly(N‐isopropylacrylamide) (PNIPAM) as side‐arms (PEG‐2N₃(‐4PNIPAM)). Azido groups were at the branch points of the polymer. Finally, the click reaction between PEG‐2N₃(‐4PNIPAM) and alkynyl monosubstituted β‐cyclodextrin (β‐CD) afforded another H‐shaped polymer with two β‐CDs bonding at the polymer branch points (PEG‐2CD(‐4PNIPAM)). The glass transition temperature (T_g) and lower critical solution temperature (LCST) of the H‐shaped polymer increased after the attachment of β‐CD. The self‐assembly and thermal responsive behaviors, as well as the encapsulation behaviors of PEG‐2CD(‐4PNIPAM) were also altered. When temperature was below the LCSTs, PEG‐2N₃(‐2PNIPAM) dissolved in water molecularly, whereas PEG‐2CD(‐4PNIPAM) could self‐assemble into nano‐sized micelles. After the LCST transitions, PEG‐2N₃(‐4PNIPAM) aggregated into micron‐sized unstable particles, whereas PEG‐2CD(‐4PNIPAM) transformed into PNIPAM‐cored nanomicelles. Besides, PEG‐2CD(‐4PNIPAM) can encapsulate doxorubicin below its LCST due to the formation of micelles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Synthesis and pH‐responsive assembly of methoxy poly(ethylene glycol)‐b‐poly(ε‐caprolactone) with pendant carboxyl groups

pH‐responsive methoxy poly(ethylene glycol)‐b‐poly(ε‐caprolactone) bearing pendant carboxyl groups mPEG‐b‐P(2‐CCL‐co‐6‐CCL) was synthesized based on our newly monomer benzyloxycarbonylmethly functionalized ε‐caprolactone. Their structure was confirmed by ¹H NMR, ¹³C NMR, and Fourier transform infrared spectrum spectra. In addition, SEC results indicated that the copolymers had a relatively narrow polydispersity. WXRD and DSC demonstrated that the introduction of carboxymethyl groups had significant effect on the crystallinity of the copolymers. Furthermore, the solution behavior of mPEG‐b‐P(2‐CCL‐co‐6‐CCL) has been studied by various methods. The results indicated that mPEG‐b‐P(2‐CCL‐co‐6‐CCL) had a rich pH‐responsive behavior and the micelles could be formed by pH induction, and the mPEG‐b‐P(2‐CCL‐co‐6‐CCL) could existed as unimers, micelles or large aggregates in different pH range accordingly. The mechanism of which was supposed to depend on the counteraction between the hydrophobic interaction from PCL and the ionization of the carboxyl groups along the polymer chain. Moreover, the mPEG‐b‐P(2‐CCL‐co‐6‐CCL) copolymers displayed good biocompatibility according to the preliminary cytotoxicity study. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 188–199     

Self‐assembly of thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) micelles for drug delivery

Self‐assembled thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) (PAA‐b‐PNIPAM) micelles for entrapment and release of doxorubicin (DOX) was described. Block copolymer PAA‐b‐PNIPAM associated into core‐shell micelles in aqueous solution with collapsed PNIPAM block or protonated PAA block as the core on changing temperature or pH. Complexation of DOX with PAA‐b‐PNIPAM triggered by the electrostatic interaction and release of DOX from the complexes due to the changing of pH or temperature were studied. Complex micelles incorporated with DOX exhibited pH‐responsive and thermoresponsive drug release profile. The release of DOX from micelles was suppressed at pH 7.2 and accelerated at pH 4.0 due to the protonation of carboxyl groups. Furthermore, the cumulative release of DOX from complex micelles was enhanced around LCST ascribed to the structure deformation of the micelles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5028–5035, 2008     

Reduction and pH dual‐responsive block copolymers containing pendent p‐nitrobenzyl carbamate functionalities: Synthesis and self‐assembly behavior

We report on the preparation of reduction‐responsive amphiphilic block copolymers containing pendent p‐nitrobenzyl carbamate (pNBC)‐caged primary amine moieties by reversible addition–fragmentation chain transfer (RAFT) radical polymerization using a poly(ethylene glycol)‐based macro‐RAFT agent. The block copolymers self‐assembled to form micelles or vesicles in water, depending on the length of hydrophobic block. Triggered by a chemical reductant, sodium dithionite, the pNBC moieties decomposed through a cascade 1,6‐elimination and decarboxylation reactions to liberate primary amine groups of the linkages, resulting in the disruption of the assemblies. The reduction sensitivity of assemblies was affected by the length of hydrophobic block and the structure of amino acid‐derived linkers. Using hydrophobic dye Nile red (NR) as a model drug, the polymeric assemblies were used as nanocarriers to evaluate the potential for drug delivery. The NR‐loaded nanoparticles demonstrated a reduction‐triggered release profile. Moreover, the liberation of amine groups converted the reduction‐responsive polymer into a pH‐sensitive polymer with which an accelerated release of NR was observed by simultaneous application of reduction and pH triggers. It is expected that these reduction‐responsive block copolymers can offer a new platform for intracellular drug delivery. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1333–1343     

Design and proof of reversible micelle‐to‐vesicle multistimuli‐responsive morphological regulations

Multistimuli‐responsive precise morphological control over self‐assembled polymers is of great importance for applications in nanoscience as drug delivery system. A novel pH, photoresponsive, and cyclodextrin‐responsive block copolymer were developed to investigate the reversible morphological transition from micelles to vesicles. The azobenzene‐containing block copolymer poly(ethylene oxide)‐b‐poly(2‐(diethylamino)ethyl methacrylate‐co‐6‐(4‐phenylazo phenoxy)hexyl methacrylate) [PEO‐b‐P(DEAEMA‐co‐PPHMA)] was synthesized by atom transfer radical polymerization. This system can self‐assemble into vesicles in aqueous solution at pH 8. On adjusting the solution pH to 3, there was a transition from vesicles to micelles. The same behavior, that is, transition from vesicles to micelles was also realizable on addition of β‐cyclodextrin (β‐CD) to the PEO‐b‐P(DEAEMA‐co‐PPHMA) solution at pH 8. Furthermore, after β‐CD was added, alternating irradiation of the solution with UV and visible light can also induce the reversible micelle‐to‐vesicle transition because of the photoinduced trans‐to‐cis isomerization of azobenzene units. The multistimuli‐responsive precise morphological changes were studied by laser light scattering, transmission electron microscopy, and UV–vis spectra. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Redox‐Responsive Micelles with Cores Crosslinked via Click Chemistry

Redox‐responsive micelles with cores crosslinked via click chemistry are developed to improve the stability of polymer micelles. Amphiphilic block copolymer mPEG‐b‐P(DTC‐ADTC) with pendant azido groups on the hydrophobic chains is synthesized by the ring‐opening polymerization of 2,2‐bis(azidomethyl)trimethylene carbonate (ADTC) and 2,2‐dimethyltrimethylene carbonate (DTC) with monomethoxy poly(ethylene glycol) (mPEG) as an initiator. mPEG‐b‐P(DTC‐ADTC) self‐assemble to form the micelles in aqueous solution and the cores of the micelles are crosslinked via click chemistry to afford redox‐responsive core‐crosslinked micelles. Core‐crosslinking enhances the stability of the micelles in aqueous solution and improve the drug‐loading property. The redox‐responsive core‐crosslinked micelles can be reduced by the addition of reducing agents such as dithiothreitol (DTT), and thus release the loaded drug quickly in the presence of DTT.

     

β‐Cyclodextrin polymer brushes based on hyperbranched polycarbosilane: Synthesis and characterization

In this article, our main goal is to combine hyperbranched polymer with β‐cyclodextrin (β‐CD) to establish a novel functional polymer species with core‐shell structure and supramolecular system for further application in inclusion technologies and the complex drugs delivery system. Therefore, two β‐CD polymer brushes based on hyperbranched polycarbosilane (HBP) as a hydrophobic core and poly(N,N‐dimethylaminoethyl methacrylate) (PDMA) carrying β‐CD units as a hydrophilic shell were synthesized. Hyperbranched polycarbosilane macroinitiator carrying ? Cl groups (HBP‐Cl) was also prepared by using 1,1,3,3‐tetrmethyldisiloxane, allyl alcohol, and chloroacetyl chloride as reagents. The molecular structures of HBP‐Cl macroinitiator and β‐CD polymer brushes were characterized by Fourier transform infrared spectroscopy (FTIR), ¹H nuclear magnetic resonance (¹H NMR), ¹³C nuclear magnetic resonance (¹³C NMR) spectroscopies, size exclusion chromatography/multi‐angle laser light scattering (SEC/MALLS) and laser particle size analyzer. The results indicate that the grafted chain length of two β‐CD polymer brushes can be controlled by changing the feed ratio. Differential scanning calorimetry (DSC) results show that two β‐CD polymer brushes have two glass transition temperatures (T_gs) from a hydrophobic core part and a hydrophilic shell part, respectively, and the T_g from PDMA is higher than that of HBP‐g‐PDMA. Thermalgravimetric analyzer (TGA) analysis indicates that the thermostability of two β‐CD polymer brushes is higher than that of HBP, but is lower than that of HBP‐g‐PDMA. Using phenolphthalein (PP) as a guest molecule, molecular inclusion behaviors for two β‐CD polymer brushes were studied. It reveals that two β‐CD polymer brushes possess molecular inclusion capability in PP buffer solution with a fixed concentration. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5036–5052, 2008     

Efficient synthesis of ionic triblock copolyesters and facile access to charge‐reversal hybrid micelles

Novel carboxyl‐ and amino‐functionalized copolyesters, based on poly(ε‐caprolactone)‐block‐poly(butylene fumarate)‐block‐poly(ε‐caprolactone), were efficiently synthesized via Michael‐type thiol‐ene click chemistry. The resulting amphiphilic copolyesters with controllable molecular weights and abundant positively or negatively charged groups could spontaneously form pH‐sensitive micelles in aqueous solutions, as confirmed by transmission electron microscopy, dynamic light scattering, fluorescence probing technique, and zeta potential analyses. Importantly, charge‐reversal hybrid micelles can be obtained by co‐assembly of carboxyl‐ and amino‐functionalized copolyesters. The surface charges of hybrid micelles reversed rapidly from negative to positive at isoelectric point via protonation of surface carboxyl and amino groups. Interestingly, the hybrid micelles showed apparent pH‐triggered Nile red‐release behavior in acidic condition resembling tumor intracellular environment, which is fairly desirable for drug delivery. Our work indicates that co‐assembly is a facile but efficient way to prepare charge‐reversal micelles, which have great potential to be used as intelligent drug delivery systems for cancer therapy. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1259–1267     

Biocompatible Micelles Based on Comb‐like PEG Derivates: Formation,Characterization, and Photo‐responsiveness

A novel comb‐like derivative CPEG‐g‐DNQ was prepared by incorporating light responsive 2‐diazo‐1,2‐naphthoquinone (DNQ) groups into the structure of comb‐like poly(ethylene glycol) (CPEG). DLS and TEM results showed that CPEG‐g‐DNQ self‐assembled into spherical micelles with an average size of about 135 nm in water. Upon exposure to light, the micelles could be disrupted because of the conversion of hydrophobic DNQ to hydrophilic 3‐indenecarboylic acid. Additionally, hydrophobic coumarin 102 was successfully loaded into the micelles and photo‐induced ON‐OFF release was demonstrated by fluorescence spectroscopy. MTT assay revealed that the micelles are biocompatible. These photo‐responsive micelles might have great potential for controlled release of hydrophobic drugs.

     

Thermosensitive and photocleavable polyaspartamide derivatives for drug delivery

The development of novel thermo‐ and photo‐dual‐responsive biodegradable polymeric micelles based on amphiphilic polyaspartamide derivatives (NB‐g‐PHPA‐g‐mPEG) for anticancer drug delivery is reported. The obtained polymers containing hydrophobic photocleavable o‐nitrobenzyl groups exhibit thermo‐ and photosensitivity. The micelles and paclitaxel‐loaded micelles based on the thermo‐ and photo‐dual‐sensitive polymers were prepared by a quick heating method without using toxic organic solvent. The paclitaxel release from the drug‐loaded micelles can be triggered under photoirradiation. Enhancement of the anticancer activity against HeLa cells was observed for paclitaxel‐loaded NB‐g‐PHPA‐g‐mPEG micelles after light irradiation, while the empty NB‐g‐PHPA‐g‐mPEG micelles with or without irradiation did not show any toxicity. Therefore, the thermo‐ and photo‐dual‐responsive NB‐g‐PHPA‐g‐mPEG micelles have a promising future applied as a light controlled drug delivery system for anticancer drugs. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2855–2863     

Lactic acid‐ and carbonate‐based crosslinked polymeric micelles for drug delivery

Our objective was to synthesize and evaluate lactic acid‐ and carbonate‐based biodegradable core‐ and core‐corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)‐b‐poly(carbonate‐co‐lactide‐co‐5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxane‐2‐one) [mPEG‐b‐P(CB‐co‐LA‐co‐MAC)] and methoxy poly(ethylene glycol)‐b‐poly(acryloyl carbonate)‐b‐poly(carbonate‐co‐lactide) [mPEG‐b‐PMAC‐b‐P(CB‐co‐LA)] copolymers were synthesized by ring‐opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8‐diazabicycloundec‐7‐ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.8–1 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG₁₁₄‐b‐P(CB₈‐co‐LA₃₅‐co‐MAC_2.5) had a higher drug encapsulation efficiency (78.72% ± 0.15%) compared to mPEG₁₁₄‐b‐PMAC_2.5‐b‐P(CB₉‐co‐LA₃₉) (20.29% ± 0.11%).¹H NMR and IR spectroscopy confirmed successful crosslinking (～70%) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide‐loaded crosslinked micelles were more potent compared to non‐crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Thiol‐responsive micelles based on nonionic gemini surfactants with a cystine disulfide spacer

Thiol‐responsive micelles consisting of novel nonionic gemini surfactants with a cystine disulfide spacer are reported. The gemini surfactants, (C₁₈‐Cys‐mPEG)₂ and ((C₁₈)₂‐Lys‐Cys‐mPEG)₂, were synthesized from polyethylene glycol, cysteine, and stearic acid, and their structures were confirmed by ¹H NMR and gel permeation chromatography. (C₁₈‐Cys‐mPEG)₂ and ((C₁₈)₂‐Lys‐Cys‐mPEG)₂ formed micelles with average diameters of 13 and 22 nm above the critical micelle concentration of 6.5 and 4.7 µg mL^?1, respectively. The micelles of ((C₁₈)₂‐Lys‐Cys‐mPEG)₂ containing more stearoyl groups showed encapsulated more hydrophobic indomethacin (IMC) with higher entrapment efficiencies than those of (C₁₈‐Cys‐mPEG)₂. The gemini surfactant micelles exhibited an accelerated release of encapsulated IMC with the concentration of the reducing agent, glutathione (GSH), whereas they were unaffected by the presence of reduced GSH (GSSG). The 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)?2‐(4‐sulfophenyl)?2H‐tetrazolium studies revealed the noncytotoxic nature of the gemini surfactant micelles. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 582–589     

β‐cyclodextrin‐based polymeric nano‐receptor: the self‐assembly of cyclodextrin‐appended comb‐copolymer

Well‐defined β‐cyclodextrin (β‐CD)‐appended biocompatible comb‐copolymer ethyl cellulose‐graft‐poly (ε‐caprolactone) (EC‐g‐PCL) was synthesized via the combination of ring‐opening polymerization (ROP) and click chemistry. The resulting products were characterized by ¹H NMR, FT‐IR spectroscopy, and GPC. The synthesized comb‐copolymer could assemble to micelles, with the surface covered by β‐CD. The inclusion with ferrocene derivation was investigated by cyclic voltammetric (CV) experiments, which indicated the potential application of the micelles as nano‐receptors for molecule recognization and controlled drug release. Copyright © 2011 John Wiley & Sons, Ltd.     

“Supramolecular” Amphiphiles Created by Wrapping Poly(styrene) with the Helix‐Forming β‐1,3‐Glucan Polysaccharide

We have demonstrated that giant polymer micelles with a uniform diameter (ca. 200 nm) can be fabricated by “supramolecular wrapping” of poly(styrene) (PS) with the β‐1,3‐glucan polysaccharide, with the β‐1,3‐glucan fastening the PS chains together in a noncovalent fashion to facilitate the formation of a supramolecular polymer network on the O/W emulsion surface. Various spectroscopic and microscopic investigations have revealed that the inner cores of the micelles are comprised of a hydrophobic PS network, whereas the surfaces consist of a hydrophilic β‐1,3‐glucan layer. Accordingly, functional guest molecules can easily be encapsulated inside the cavity through hydrophobic interactions. The encapsulated molecules can simply be released from the micelle cores by peeling off the β‐1,3‐glucan shell in a supramolecular manner. As functional groups can be introduced into the glucose side‐chain unit in a straightforward manner by chemical modification, the micellar surface can acquire further functions useful for molecular recognition. These results show that the micelles obtained could have applications as novel soft nanoparticles, which would be indispensable not only for nanotechnologies, but also for biotechnologies aimed at gene or drug delivery systems.     

Synthesis and characterization of biodegradable pH and reduction dual‐sensitive polymeric micelles for doxorubicin delivery

Novel pH and reduction dual‐sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy‐poly(ethylene glycol)‐b‐poly[(benzyl‐l ‐aspartate)‐co‐(N‐(3‐aminopropyl) imidazole‐l ‐aspartamide)] [mPEG‐SS‐P(BLA‐co‐APILA), MPBA] synthesized by a combination of ring‐opening polymerization and side‐chain reaction. The pH/reduction‐responsive behavior of MPBA was observed by both dynamic light scattering and UV–vis experiments. The polymeric micelles and DOX‐loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX‐loaded micelles showed retarded drug release in phosphate‐buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX‐loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX‐loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual‐responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 1771–1780