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.     

Synthesis and characterization of temperature‐sensitive block copolymers from poly(N‐isopropylacrylamide) and 4‐methyl‐ε‐caprolactone or 4‐phenyl‐ε‐caprolactone

This study synthesizes thermally sensitive block copolymers poly(N‐isopropylacrylamide)‐b‐poly(4‐methyl‐ε‐caprolactone) (PNIPA‐b‐PMCL) and poly(N‐isopropylacrylamide)‐b‐poly(4‐phenyl‐ε‐caprolactone) (PNIPA‐b‐PBCL) by ring‐opening polymerization of 4‐methyl‐ε‐caprolactone (MCL) or 4‐phenyl‐ε‐caprolactone (BCL) initiated from hydroxy‐terminated poly(N‐isopropylacrylamide) (PNIPA) as the macroinitiator in the presence of SnOct₂ as the catalyst. This research prepares a PNIPA bearing a single terminal hydroxyl group by telomerization using 2‐hydroxyethanethiol (ME) as a chain‐transfer agent. These copolymers are characterized by differential scanning calorimetry (DSC), ¹H‐NMR, FTIR, and gel permeation chromatography (GPC). The thermal properties (T_g) of diblock copolymers depend on polymer compositions. Incorporating larger amount of MCL or BCL into the macromolecular backbone decreases T_g. Their solutions show transparent below a lower critical solution temperature (LCST) and opaque above the LCST. LCST values for the PNIPA‐b‐PMCL aqueous solution were observed to shift to lower temperature than that for PNIPA homopolymers. This work investigates their micellar characteristics in the aqueous phase by fluorescence spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The block copolymers formed micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range of 0.29–2.74 mg L^?1, depending on polymer compositions, which dramatically affect micelle shape. Drug entrapment efficiency and drug loading content of micelles depend on block polymer compositions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

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     

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) graft copolymers and their application as carriers for drug delivery system

Poly(N‐isopropylacrylamide‐co‐hydroxyethyl methacrylate) [P(NIPAM‐co‐HEMA)] copolymer was synthesized by controlled radical polymerization from respective N‐isopropylacrylamide (NIPAM) and hydroxyethyl methacrylate (HEMA) monomers with a predetermined ratio. To prepare the thermosensitive and biodegradable nanoparticles, new thermosensitive graft copolymer, poly(L ‐lactide)‐graft‐poly(N‐isoporylacrylamide‐co‐hydroxyethyl methacrylate) [PLLA‐g‐P(NIPAM‐co‐HEMA)], with the lower critical solution temperature (LCST) near the normal body temperature, was synthesized by ring opening polymerization of L ‐lactide in the presence of P(NIPAM‐co‐HEMA). The amphiphilic property of the graft copolymers was formed by the grafting of the PLLA hydrophobic chains onto the PNIPAM based hydrophilic backbone. Therefore, the graft copolymers can self‐assemble into uniformly spherical micelles ò about 150–240 nm in diameter as observed by the field emission scanning electron microscope and dynamic light scattering. Dexamethasone can be loaded into these nanostructures during dialysis with a relative high loading capacity and its in vitro release depends on temperature. Above the LCST, most of the drugs were released from the drug‐loaded micelles, whereas a large amount of drugs still remains in the micelles after 48 h below the LCST. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Thermoresponsive poly(ϵ‐caprolactone)‐graft‐poly(N‐isopropylacrylamide) graft copolymers prepared by a combination of ring‐opening polymerization and sequential azide–alkyne click chemistry

A straightforward strategy is described to synthesize poly(?‐caprolactone)‐graft‐poly(N‐isopropylacrylamide) (PCL‐g‐PNIPAAm) amphiphilic graft copolymers consisting of potentially biodegradable polyester backbones and thermoresponsive grafting chains. PCL with pendent chlorides was prepared by ring‐opening polymerization, followed by conversion of the pendent chlorides to azides. Alkyne‐terminated PNIPAAm was synthesized by atom transfer radial polymerization. Then, the alkyne end‐functionalized PNIPAAm was grafted onto the PCL backbone by a copper‐catalyzed azide–alkyne cycloaddition. PCL‐g‐PNIPAAm graft copolymers self‐assembled into spherical micelles comprised of PCL cores and PNIPAAm coronas. The critical micelle concentrations of the graft copolymers were in the range 7.8–18.2 mg L^?1, depending on copolymer composition. Mean hydrodynamic diameters of micelles were in the range 65–135 nm, which increased as the length of grafting chains grew. PCL‐g‐PNIPAAm micelles were thermosensitive and aggregated upon heating. © 2014 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     

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

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

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     

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     

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.     

Cationic amphiphilic copolymers: synthesis,characterization, self‐assembly and drug‐loading capacity

Amphiphilic copolymers with cationic hydrophilic moieties and different ratios of hydrophobic portion to hydrophilic portion were designed and synthesized via the combination of hydrosilylation reactions and quaternization reactions. The structures were characterized through Fourier transform infrared spectroscopy, ¹H NMR , ¹³C NMR and gel permeation chromatography. The measurements of critical micelle concentrations, electrical conductivities and zeta potentials indicated that the copolymers could self‐assemble into nanoparticles with charges around the surface in aqueous solution. The sizes of the micelles were between 67 nm and 104 nm detected by dynamic light scattering. The self‐assembled micelles were used as drug carriers to encapsulate a model drug (tocopherol), and their drug‐loading content (DLC ) and efficiency (DLE ) were determined by UV ?visible spectra, resulting in considerable drug‐loading capacity to a tocopherol maximum up to 17.2% (DLC ) and 80.3% (DLE ) with a size of 90 nm. The blank micelles and drug‐loaded micelles displayed a spherical shape detected by transmission electron microscopy, which demonstrated not only the self‐assembly behaviors but also the drug‐loading performances of the cationic amphiphilic copolymers. All the results demonstrated that the cationic amphiphilic copolymers could be used as potential electric‐responsive drug carriers. © 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‐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.     

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.     

Synthesis of thermoresponsive polymeric micelles of PNIPAAm‐b‐OMMA as a drug carrier for loading and controlled release of prednisolone

We synthesized a drug delivery system of poly(N‐isopropylacrylamide)‐b‐oligo(methyl methacrylate) (PNIPAAm‐b‐OMMA) via polycondensation of two homopolymers in 1,4‐dioxane. The products are characterized by FT‐IR and ¹H‐NMR spectra and TEM. The PNIPAAm‐b‐OMMA copolymer micelles in aqueous solution present the same lower critical solution temperature (LCST) as the unmodified PNIPAAm, owing to the formation of a core–shell micellar structure that the hydrophilic shell shields the hydrophobic inner OMMA core from interacting with water. The micelle carriers exhibit two heterogeneous microdomains: a hydrophobic inner core capable of highly solubilizing hydrophobic prednisolone molecules, plus a hydrated outer shell that stabilizes this micellar structure below its LCST. Moreover, the micelle carriers show reversible thermoresponsive aggregation/dispersion in response to temperature cycles through the LCST. By using the antiinflammation drug prednisolone as model drug, it is found that the PNIPAAm‐b‐OMMA drug carrier could prolong the release time and control the release amount by changing the temperature. Accordingly, this copolymer micelle may provide as an effective drug carrier for drug control and release. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Thermosensitive poly(N-isopropylacrylamide)-b-poly(ε-caprolactone) nanoparticles for efficient drug delivery system

To investigate thermosensitive polymeric nanoparticle, amphiphilic block copolymers of poly(N-isopropylacrylamice)-b-poly(ε-caprolactone) (PNPCL) with different PCL block lengths were synthesized by hydroxy-terminated poly(N-isopropyoacrylamide) (PNiPAAm) initiated ring opening polymerization of ε-caprolactone. Owing to their amphiphilic characteristics, the block copolymers formed self-assembled polymeric nanoparticles in aqueous milieus with thermosensitive PNiPAAm shell compartment. The characterizations of the nanoparticles revealed that the PNPCL nanoparticles showed PCL block length dependent physicochemical characters such as particle sizes, critical aggregation concentrations, and core hydrophobicities. Moreover, the thermosensitive PNiPAAm shells conferred unique temperature responsive properties such as phase transitions with temperature elevation over its lower critical solution temperature (LCST). The temperature induced phase transition resulted in the formation of PNiPAAm hydrogel layer on the PNPCL nanoparticle surface. The drug release tests revealed that the formation of thermosensitive hydrogel layer resulted in the enhanced sustained drug release patterns by acting as an additional diffusion barriers. Therefore, the introduction of thermosensitive polymers on polymeric nanoparticles might be a potential approaches to modulate drug release behaviors.     

Polymer micellar aggregates of novel amphiphilic biodegradable graft copolymer composed of poly(aspartic acid) derivatives: Preparation,characterization, and effect of pH on aggregation

Novel amphiphilic biodegradable graft copolymer based on poly(aspartic acid) was prepared by attaching monomethoxy polyethylene glycol (mPEG) as hydrophiphic segment to poly(aspartic acid‐g‐octadecylamine) (PASP‐g‐ODA) as hydrophobic backbone. The chemical structures of amphiphilic copolymers were confirmed by FTIR and ¹H NMR spectroscopy. The polymeric micelles were prepared with solvent evaporation and their physicochemical properties in aqueous media were characterized by dynamic light scattering (DLS) and fluorescence spectroscopy. These micelles were confirmed to be pH‐sensitive by measuring optical transmittance of micelle solution and the size of micellar aggregates. The number average diameter of polymeric micelles prepared in medium at pH 2.5 was larger than that in neutral and basic medium and showed a bimodal size distribution because of the protonation of carboxyl groups in backbone. Furthermore, the polymeric micelle can load water‐insoluble drug (podophyllotoxin), and the drug release from micelles showed a pH‐dependency. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

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 functional poly(carbonate‐b‐ester) copolymers and micellar characterizations

Functional poly(carbonate‐b‐ester)s were synthesized in buck by ring‐opening polymerization of the carbonate (TMC, MBC, or BMC) with tert‐butyl N‐(2‐hydroxyethyl) carbamate as an initiator, and then with ε‐CL (or ε‐BCL) comonomer. Subsequently, the PMMC‐b‐PCL with pendent carboxyl groups and the PTMC‐b‐PHCL with pendent hydroxyl groups were obtained by catalytic debenzylation. DSC analysis indicated that only one T_g at an intermediate temperature the T_gs of the two polymer blocks. A decrease T_g was observed when an increase contents of ε‐CL incorporated into the copolymers. In contrast, two increased T_ms were observed with increasing PCL content. The block copolymers formed micelle in aqueous phase with critical micelle concentrations (cmcs) in the range of 2.23–14.6 mg/L and with the mean hydrodynamic diameters in the range of 100–280 nm, depending on the composition of copolymers. The drug entrapment efficiency and hydrolytic degradation behavior of micelle were also evaluated. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Synthesis,characterization, and application of novel amphiphilic poly(D‐gluconamidoethyl methacrylate)‐b‐polyurethane‐b‐ poly(D‐gluconamidoethyl methacrylate) triblock copolymers

Novel amphiphilic ABA‐type poly(D ‐gluconamidoethyl methacrylate)‐b‐polyurethane‐b‐poly(D ‐gluconamidoethyl methacrylate) (PGAMA‐b‐PU‐b‐PGAMA) tri‐block copolymers were successfully synthesized via the combination of the step‐growth and copper‐catalyzed atom transfer radical polymerization (ATRP). Dihydroxy polyurethane (HO‐PU‐OH) was synthesized by the step‐growth polymerization of hexamethylene diisocyanate with poly(tetramethylene glycol). PGAMA‐b‐PU‐b‐PGAMA block copolymers were synthesized via copper‐catalyzed ATRP of GAMA in N, N‐dimethyl formamide at 20°C in the presence of 2, 2′‐bipyridyl using Br‐PU‐Br as macroinitiator and characterized by ¹H‐NMR spectroscopy and GPC. The resulting block copolymer forms spherical micelles in water as observed in TEM study, and also supported by ¹H NMR spectroscopy and light scattering. Miceller size increases with increase in hydrophilic PGAMA chain length as revealed by DLS study. The critical micellar concentration values of the resulting block copolymers increased with the increase of the chain length of the PGAMA block. Thermal properties of these block copolymers were studied by thermo‐gravimetric analysis, and differential scanning calorimetric study. Spherical Ag‐nanoparticles were successfully synthesized using these block copolymers as stabilizer. The dimension of Ag nanoparticle was tailored by altering the chain length of the hydrophilic block of the copolymer. A mechanism has been proposed for the formation of stable and regulated Ag nanoparticle using various chain length of hydrophilic PGAMA block of the tri‐block copolymer. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013