Synthesis and characterization of a novel hydroxypropyl chitosan-graft-β-Cyclodextrin copolymer as potential drug carrier

Abstract

One of the most attractive fields in drug delivery is the design of nanoparticles that could be used to transport drugs into the target place at appropriate time. This paper describes the preparation of a novel hydroxypropyl chitosan-graft-β-cyclodextrin (HPCS-g-β-CD) copolymer using the 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) promoted condensation reaction. Structural characterization was finished with FTIR and ¹H NMR spectra, which confirmed the grafting of β-cyclodextrin (β-CD) onto hydroxypropyl chitosan (HPCS). The thermal properties were studied based on DSC and TGA analyses, which revealed the fact that grafting of β-CD onto HPCS resulted in obvious enhancement of the decomposition temperature of the copolymer. Aqueous solution of HPCS-g-β-CD copolymer was stable at pH 7-8 based on the Zeta potential test. The morphological characteristics were investigated by SEM, TEM and AFM analysis, and the results indicated that this copolymer had three-dimensional structure which was suitable for loading drugs.     

Synthesis,characterization and complexation studies of bis-oxy biphenyl based novel diamides

A series of bis-oxy biphenyl based diamides have been synthesized and characterized from spectral and XRD data. All the diamides form charge-transfer (CT) complex with 7,7,8,8-tetracyanoquinodimethane (TCNQ).     

Synthesis and characterization of novel amphiphilic copolymer stearic acid-coupled F127 nanoparticles for nano-technology based drug delivery system

Pluronic, F127, amphiphilic block copolymers, are used for several applications, including drug delivery systems. The critical micelle concentration (CMC) of F127 is about 0.26-0.8 wt% so that the utility of F127 in nano-technology based drug delivery system is limited since the nano-sized micelles could dissociate upon dilution. Herein, stearic acid (SA) was simply coupled to F127 between the carboxyl group of SA and the hydroxyl group of F127, which formed a novel copolymer named as SA-coupled F127, with significantly lower CMC. Above the CMC 6.9 × 10(-5)wt%, SA-coupled F127 self-assembled stable nanoparticles with Zeta potential -36 mV. Doxorubicin (DOX)-loaded nanoparticles were made, with drug loading (DL) 5.7 wt% and Zeta potential -36 to -39 mV, and the nanoparticles exhibited distinct shape with the size distribution from 20 to 50 nm. DOX-loaded nanoparticles were relatively stable and exhibited DOX dependant cytotoxicity toward MCF-7 cells in vitro. These results suggest that SA-coupled F127 potentially could be applied as a nano-technology based drug delivery method.     

Synthesis of a novel phosphate‐containing highly transparent PMMA copolymer with enhanced thermal and flame retardant properties

A novel poly(methyl methacrylate) (PMMA)‐based copolymer (PMMA‐co‐BDPA) rich in aromatic rings was synthesized via radical copolymerization between a phosphorus‐containing acrylic monomer (BDPA) and methyl methacrylate (MMA). UV‐vis spectroscopy demonstrated that the copolymer had high transparency. Thermogravimetric analysis (TGA) and a differential scanning calorimeter (DSC) were used to test the thermal properties of the composites. Additionally, the PMMA‐co‐BDPA‐15 copolymer exhibited a 23% increase in the limited oxygen index (LOI) value. A cone calorimeter test indicated that the peak heat release rate (pk‐HRR) of PMMA‐co‐BDPA was reduced by 29.2% compared with that of pure PMMA, and the carbon yield of burning was obviously increased. The combined test results demonstrated that the prepared copolymer material had good transparency, thermal stability, and flame retardancy.     

Synthesis of three-dimensional hydrogels based on poly(glycidyl methacrylate-alt-maleic anhydride): Characterization and study of furosemide drug release

In the present work, three-dimensional drug carriers were synthesized via chemical modification of poly (glycidyl methacrylate-alt-maleic anhydride) P(GMA-alt-MA) by isopropylamine (IPA) and ethylenediamine (EDA) with different molar ratios. Then furosemide drug (FR) was loaded on the hydrogels and studied for its slow release in phosphate-buffered saline (PBS) solution (pH = 7.41) at 37 °C. According to the obtained results, the sample with the lowest amount of crosslinking agent (Sample A) showed the highest swelling ratio in comparison to the others. By increasing the rigidity of carrier in the result of increasing the crosslinker density, the amount of the released drug was decreased. However, the release rate for all of samples (slope of the profiles) were rather similar. All the synthesized carriers have shown pH dependent properties and the maximum release rate was shown in basic pH. Also, the drug release experiments in different temperatures showed almost thermal sensitivity properties for synthesized carriers and release rate become faster by increasing the medium temperature. The FT-IR, TGA, and FE-SEM analyses were carried out for characterization of prepared samples and the swelling behavior of prepared hydrogels were measured too. Investigation of the release data with different mathematical models showed the highest adaption with the Higuchi model for all samples.     

Synthesis of a PEG-PNIPAm thermosensitive dendritic copolymer and investigation of its self-association

A Novel thermosensitive dendritic copolymer based on polyethylene glycol(PEG) and poly(Nisopropylacrylamide)(PNIPAm) with a cloud point(CP) around 36 ?C was successfully synthesized by preparation of a dendritic polyol and followed by atom transfer radical polymerization(ATRP) of N-isopropylacrylamide. The dendritic copolymer was characterized using gel-permeation chromatography(GPC), FTIR and 1H-NMR spectroscopy. The selfassociation behavior of the copolymer in aqueous medium was investigated by dynamic light scattering(DLS) and transmission electron microscopy(TEM). These investigations confirmed that the dendritic copolymer showed different association behaviors at various temperatures.     

Biocompatible amphiphilic conetwork based on crosslinked star copolymers: A potential drug carrier

A series of amphiphilic conetworks (APCNs) is synthesized through crosslinking of well‐defined tri‐arm star diblock copolymers via atom transfer radical polymerization. A new three‐arm initiator is synthesized to initiate the polymerization of 2‐hydroxyethyl methacrylate (HEMA) via “core‐first” method. The resulting star HEMA homopolymers with well‐defined molecular weight and narrow polydispersity are used as macroinitiator to incorporate allyl methacrylate to get the star diblock copolymers. Then, the precursors with allyl pendant groups are fully crosslinked with polyhydrosiloxanes through hydrosilylation. The so‐prepared APCNs exhibit unique properties of microphase separation of hydrophilic (HI) and hydrophobic (HO) phases with small channel size, a variable swelling capacity, excellent biocompatibility, and outstanding mechanical strength (2 ± 0.5 MPa). The properties of APCNs depend on the ratio of HI to HO, which can be regulated via precise synthesis of the star diblock copolymers. The APCNs show well‐controlled drug release to choline theophyllinate, suggesting a promising intelligent drug carrier for controlled release. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2537–2545     

Synthesis and characterization of novel core-shell colloidal particles ZnO/poly(ethylcyanoacrylate)

Here we report the synthesis and physicochemical characterization of novel hybrid core/shell type ZnO/poly(ethylcyanoacrylate) colloidal particles. It is expected that coating ZnO colloidal particles with biocompatible and biodegradable poly(alkylcyanoacrylates) will pave the way toward the potential application of ZnO colloidal particles in biomedical research. Recent findings of cell selective toxicity indicate a potential utilization of ZnO colloidal particles in the treatment of cancer. For this purpose, ZnO colloidal particles have to be selectively delivered to the site of action by a suitable biocompatible and biodegradable carrier system. Toward this goal, poly(alkylcyanoacrylates) meet ideally the requirements for carrier systems in drug delivery due to their biocompatibility, biodegradability, low toxicity, and ability to overcome the multidrug resistance in cancer cells.     

Synthesis and characterization of a starch‐modified hydrogel as potential carrier for drug delivery system

Synthesis and characterization of a new hydrogel were carried out using a chemically modified starch (starch‐M) consisting of coupling C?C bounds coming from glycidil methacrylate (GMA) onto the polysaccharide structure. ¹³C NMR, ¹H NMR, and FT‐IR spectroscopies were used to confirm the incorporation of such groups onto the starch‐M. The hydrogel was prepared by a crosslinking polymerization of starch‐M using sodium persulfate as an initiating agent. The starch‐M hydrogel shows morphology clearly different from that of the raw starch film due to the presence of voids on its surface. The swelling process of the starch‐M hydrogel was not significantly affected by changes on the temperature or on pH of the surrounding liquid, indicating the such behavior can be then understood by a diffusional process, resulting from its physical–chemical interactions with the solvent. The values of the diffusional exponent n were on the order of 0.45–0.49 for the range of pHs investigated, demonstrating that the water transport mechanism of starch‐M hydrogel is more dependent on Fickian diffusion, that is, controlled by water diffusion. Such starch‐M hydrogel is a promising candidate to be used in transporting and in preserving acid‐responsive drugs, such as corticoids, for the treatment of colon‐specific diseases, for example, Crohn's disease. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2567–2574, 2008     

Preparation and characterization novel polymer-coated magnetic nanoparticles as carriers for doxorubicin

The poly(lactide-co-glycolide)-coated magnetic nanoparticles (PLGA MNPs) were prepared as carriers of doxorubicin (PLGA-DOX MNPs) through water-in-oil-in-water (W/O/W) emulsification method. The characteristics of PLGA-DOX MNPs were measured by using transmission electron microscopy (TEM) and vibrating-sampling magnetometry (VSM). It was found that the synthesized nanoparticles were spherical in shape with an average size of 100 ± 20 nm, low aggregation and good magnetic responsivity. Meanwhile, the drug content and encapsulation efficiency of nanoparticles can be achieved by varying the feed weight ratios of PLGA and DOX particles. These PLGA-DOX MNPs also demonstrated sustained release of DOX at 37 °C in buffer solution. Besides, influence of drug-loaded nanoparticles on in vitro cytotoxicity was determined by MTT assay, while cellular apoptosis was detected by Annexin V-FITC apoptosis detection kit. The results showed that PLGA-DOX MNPs retained significant antitumor activities. Therefore, PLGA-DOX MNPs might be considered a promising drug delivery system for cancer chemotherapy.     

Synthesis and characterization of grafted/crosslinked proton conducting membranes based on amphiphilic PVDF copolymer

A novel graft copolymer consisting of a poly(vinylidene fluoride‐co‐chlorotrifluoroethylene) backbone and poly(glycidyl methacrylate) side chains, that is, P(VDF‐co‐CTFE)‐g‐PGMA, was synthesized through atom transfer radical polymerization (ATRP) using CTFE units as a macroinitiator. Successful synthesis and microphase‐separated structure of the polymer were confirmed by ¹H NMR, FTIR spectroscopy, and TEM. As‐synthesized P(VDF‐co‐CTFE)‐g‐PGMA copolymer was sulfonated by sodium bisulfite, followed by thermal crosslinking with sulfosuccinic acid (SA) via the esterification to produce grafted/crosslinked polymer electrolyte membranes. The IEC values continuously increased with increasing SA content but water uptake increased with SA content up to 10 wt %, above which it decreased again as a result of competitive effect between crosslinking and hydrophilicity of membranes. At 20 wt % of SA content, the proton conductivity reached 0.057 and 0.11 S/cm at 20 and 80 °C, respectively. The grafted/crosslinked P(VDF‐co‐CTFE)‐g‐PGMA/SA membranes exhibited good mechanical properties (>400 MPa of Young's modulus) and high thermal stability (up to 300 °C), as determined by a universal testing machine (UTM) and TGA, respectively. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1110–1117, 2010     

Synthesis and characterization of biodegradable materials： PDLLA-（MAh-Diol）n-PDLLA copolymer

The novel biodegradable copolymer PDLLA-(MAH-Diol)_n-PDLLAwith unsaturated bond was synthesized by copolymerizing lactide and prepolymer, which was prepared by the polycondensation of maleic anhydride and poly(ethylene glycol), using p- toluene sulphonic acid as catalyst. The new copolymer has improved hydrophilicity and fexibility. The structure and properties of the novel polymers were studied by FTIR, NMR, GPC-MALLS and DSC.     

Synthesis and characterization of poly(d,l-lactide-co-glycolide) modified by maleic anhydride and 1,4-butanediamine

Bone tissue engineering is sought to apply strategies for bone defects healing biodegradable porous scaffolds without limitations and shortcomings. In this work, we have developed a novel maleic anhydride (MAH) and 1,4-butanediamine modified poly(lactide-co-glycolide) polymer (BMPLGA). The synthesized polymer was characterized by Fourier transform infrared spectrometry (FTIR), Nuclear magnetic resonance spectra (¹H NMR), gel permeation chromatography (GPC) and contact angle measurements. In addition, cell morphologies in the extracts and cell cytotoxity were also studied. The results showed that the BMPLGA was successfully obtained by introducing MAH and 1,4-butanediamine into PLGA in bulk. The introduction of anhydride and amino groups improved the hydrophilicity of PLGA. Fibroblastic cells showed normal morphologies in BMPLGA extracts, and the BMPLGA materials showed no cell cytotoxicity. The synthetic BMPLGA material may have potentials for biomedical applications due to improving hydrophilicity.     

Synthesis and characterization of novel poly（aryl ether sulfone ketone）s containing phthalazinone and biphenyl moieties

A novel series of poly（aryl ether sulfone ketone）s （PPESKs） containing phthalazinone and biphenyl moieties were prepared by two-step nucleophilic polycondensation reaction. The ^-Mw values of these copolymers were between 38,330 and 67,900. The glass transition temperatures （Tg） and 5% decomposition temperatures were ranged in 253-269 ℃ and 488-500 ℃, respectively, The structures of these copolymers were confirmed by FT-IR and ^1H NMR. Moreover, all the resultant copolymers were amorphous determined by wide angle X-ray diffraction （WAXD）.     

Synthesis and characterization of graft copolymers containing poly(p-phenylene) main chains and mesogen-jacketed liquid-crystalline polystyrene side chains

A series of novel comblike mesogen-jacketed liquid-crystalline graft copolymers, poly(p-phenylene)-g-poly{2,5-bis[(4-methoxyphenyl)oxycarbonyl]styrene} (PPP-g-PMPCS) copolymers, have been designed and successfully synthesized by a Yamamoto coupling reaction and subsequent atom transfer radical polymerization (ATRP). ¹H NMR spectroscopy, ultraviolet–visible spectra, and gel permeation chromatography (GPC) have been used to confirm the molecular structure of the macroinitiator and the copolymers. A study of the polymerization kinetics of ATRP has shown that the molecular weight of the copolymer increases linearly with the conversion of the monomer, whereas the polydispersity remains narrow (≤1.28), indicating that the ATRP of 2,5-bis[(4-methoxyphenyl)oxycarbonyl]styrene is well controlled. Thermogravimetric analysis and differential scanning calorimetry (DSC) measurements have indicated that the PPP-g-PMPCS copolymers have better thermal stabilities than the macroinitiator, and their thermal stabilities increase with increasing molecular weight. The liquid-crystalline behavior has been examined with polarized optical microscopy, DSC, one-dimensional wide-angle X-ray diffraction (1D WAXD), and two-dimensional wide-angle X-ray diffraction (2D WAXD). The results show that all the comblike copolymers exhibit obvious liquid-crystalline behaviors, even though the GPC molecular weight of the segments of poly{2,5-bis[(4-methoxyphenyl)oxycarbonyl]styrene} (PMPCS) have been determined to be far less than the critical value of linear PMPCS. Moreover, 1D WAXD measurements show that the temperature at which the comblike mesogen-jacketed liquid-crystalline copolymers can transform into a liquid-crystalline phase is low; about 20 °C in comparison with the linear ones. 2D WAXD analysis has revealed that these comblike copolymers should be assigned to a hexatic columnar nematic (Φ_HN) phase. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2543–2555, 2007     

Synthesis and characterization of novel push-pull oligomer based on naphthodithiophene-benzothiodiazole for OFETs application

A novel push-pull oligomeric semiconductor, ENBT based on naphthodithiophene-benzothiodiazole was successfully designed and synthesized. ENBT was fully characterized by ¹H NMR, MS, thermogravimetric analysis (TGA), UV–vis spectra, and cyclic voltammetry (CV). Furthermore, ENBT-based OFETs were fabricated by solution-processed dip-coating technique and its charge transporting property was investigated. The film of ENBT exhibited a hole mobility as high as 1.4?×?10^?2?cm²/(Vs) with a current on/off ratio of 10⁶–10⁷ after annealed at 160?°C. In order to give an insight to the transporting property of ENBT films, thin film morphologies after annealing at different temperatures were also studied by atomic force microscopy (AFM).     

Dendrimer-like supramolecular nanovalves based on polypseudorotaxane and mesoporous silica-coated magnetic graphene oxide: a potential pH-sensitive anticancer drug carrier

In the present research, two types of drug carriers based on mesoporous silica-coated magnetic graphene oxide, Fe₃O₄@GO@mSiO₂, were synthesised and the pH-responsive behaviour for doxorubicin release was investigated. One type of the carrier was dendrimer-like multi ethylene amine grafted on Fe₃O₄@GO@mSiO₂ and the other was dendrimer-like supramolecular polypseudorotaxane. Herein, α-cyclodextrin was used in the structure of supramolecular nanoparticles as a gatekeeper to inhibit the drug from escaping at neutral pH (the pH of healthy tissue). The drug release profile showed that the supramolecular nanocarrier was more sensitive to the pH changes. The content of drug release was about 100% at pH 5.5 (endosomal pH) during 48 h; but it was zero at pH 7.4. Also, the dendrimer structure facilitated the triggered release of doxorubicin.     

新型有机电双稳态材料的设计和性质

本文旨在突破传统的TCNQ和TTF的分子架构，通过分子剪裁保留这两个分子中的核心功能基团，同时引入新的螺环分子骨架以提高分子的热稳定性，从而获得全新的具有电子授受性质的有机化合物，并研究其电荷转移配合物的电双稳性质。     

Synthesis and characterization of a thiadiazole/benzoimidazole‐based copolymer for solar cell applications

In this study, we synthesized a new polymer, PCTDBI , containing alternating carbazole and thiadiazole‐benzoimidazole (TDBI) units. This polymer (number‐average molecular weight = 25,600 g mol^?1), which features a planar imidazole structure into the polymeric main chain, possesses reasonably good thermal properties (T_g = 105 °C; T_d = 396 °C) and an optical band gap of 1.75 eV that matches the maximum photon flux of sunlight. Electrochemical measurements revealed an appropriate energy band offset between the polymer's lowest unoccupied molecular orbital and that of PCBM, thereby allowing efficient electron transfer between the two species. A solar cell device incorporating PCTDBI and PCBM at a blend ratio of 1:2 (w/w) exhibited a power conversion efficiency of 1.20%; the corresponding device incorporating PCTDBI and PC₇₁BM (1:2, w/w) exhibited a PCE of 1.84%. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis,characterization, and bulk properties of amphiphilic copolymers containing fluorinated methacrylates from sequential copper‐mediated radical polymerization

The partly fluorinated monomers, 2,2,2‐trifluoroethyl methacrylate (3FM), 2,2,3,3,4,4,5,5‐octafluoropentyl methacrylate (8FM), and 1,1,2,2‐tetrahydroperfluorodecyl methacrylate (17FM) have been used in the preparation of block copolymers with methyl methacrylate (MMA), 2‐methoxyethyl acrylate (MEA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA) by Atom Transfer Radical Polymerization. A kinetic study of the 3FM homopolymerization initiated with ethyl bromoisobutyrate and Cu(I)Br/N‐(n‐propyl)‐2‐pyridylmethanimine reveals a living/controlled polymerization in the range 80–110 °C, with apparent rate constants of 1.6 · 10⁻⁴ s⁻¹ to 2.9 · 10⁻⁴ s⁻¹. Various 3FM containing block copolymers with MMA are prepared by sequential monomer addition or from a PMMA macroinitiator in all cases with controlled characteristics. Block copolymers of 3FM and PEGMA resulted in block copolymers with PDI < 1.22, whereas block copolymers from 3FM and MEA have less controlled characteristics. The block copolymers based on MMA with 8FM and 17 FM have PDI's < 1.30. The glass transition temperatures of the block copolymers are dominated by the majority monomer, as the sequential monomer addition results in too short pure blocks to induce observable microphase separation. The thermal stability of the fluorinated poly((meth)acrylate)s in inert atmosphere is less than that of corresponding nonfluorinated poly((meth)acrylate)s. The presence of fluorinated blocks significantly increases the advancing water contact angle of thin films compared to films of the nonfluorinated poly((meth)acrylate)s. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 8097–8111, 2008