Folic‐Acid‐Targeted Self‐Assembling Supramolecular Carrier for Gene Delivery

A targeting gene carrier for cancer‐specific delivery was successfully developed through a “multilayer bricks‐mortar” strategy. The gene carrier was composed of adamantane‐functionalized folic acid (FA‐AD), an adamantane‐functionalized poly(ethylene glycol) derivative (PEG‐AD), and β‐cyclodextrin‐grafted low‐molecular‐weight branched polyethylenimine (PEI‐CD). Carriers produced by two different self‐assembly schemes, involving either precomplexation of the PEI‐CD with the FA‐AD and PEG‐AD before pDNA condensation (Method A) or pDNA condensation with the PEI‐CD prior to addition of the FA‐AD and PEG‐AD to engage host–guest complexation (Method B) were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the material produced by the Method A assembly scheme has lower cytotoxicity than branched PEI 25 kDa (PEI‐25KD) and that the transfection efficiency is maintained. These findings suggest that the gene carrier, based on multivalent host–guest interactions, could be an effective, targeted, and low‐toxicity carrier for delivering nucleic acid to target cells.     

Gadolinium‐conjugated FA‐PEG‐PAMAM‐COOH nanoparticles as potential tumor‐targeted circulation‐prolonged macromolecular MRI contrast agents

The aim of research is to develop potential tumor‐targeted circulation‐prolonged macromolecular magnetic resonance imaging (MRI) contrast agents without the use of low molecular gadolinium (Gd) ligands. The contrast agents were based on polymer–metal complex nanoparticles with controllable particle size to achieve the active and passive tumor‐targeted potential. In particular, poly (amidoamine) (PAMAM) dendrimer with 32 carboxylic groups was modified with folate‐conjugated poly (ethyleneglycol) amine (FA‐PEG‐NH₂, M_w: 2 k and 4 kDa). FA‐PEG‐PAMAM‐Gd macromolecular MRI contrast agents were prepared by the complex reaction between the carboxylic groups in PAMAM and GdCl₃. The structure of FA‐PEG‐PAMAM‐COOH was confirmed by nuclear magnetic resonance (¹H‐NMR), Fourier transform infrared (FTIR) spectra, and electrospray ionization mass spectra (ESI‐MS). The mass percentage content of Gd (III) in FA‐PEG‐PAMAM‐Gd was measured by inductively coupled plasma‐atomic emission spectrometer (ICP‐AES). The sizes of these nanoparticles were about 70 nm measured by transmission electron microscopy, suggestion of their passive targeting potential to tumor tissue. In comparison with clinically available small molecular Gadopentetate dimeglumine, FA‐PEG‐PAMAM‐Gd showed comparable cytotoxicity and higher relaxation rate, suggestion of their great potential as tumor‐targeted nanosized macromolecular MRI contrast agents due to the overexpressed FA receptor in human tumor cell surfaces. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Polyethylene glycol‐polyethylenimine‐tetrachloroplatinum (IV): A novel conjugate with good abilities of antitumor and gene delivery

It is much importance to develop novel multifunctional delivery systems for the combination therapy of drug and gene. In this work, a novel conjugate, polyethylene glycol‐polyethylenimine‐tetrachloroplatinum (IV) (PEG‐PEI‐Pt), with good abilities of antitumor and gene delivery was proposed by combining PEG (Mw 3400 Da), low molecular weight PEI (Mw 800 Da), and tetrachloroplatinum (IV). The antitumoral and gene transfection activities of PEG‐PEI‐Pt were analyzed in many tumor (A549, A375, HepG‐2, HuH‐7, and B16 cells) and normal (COS‐7 cells) cell lines. Similar to cisplatin (one platinum anticancer drug), PEG‐PEI‐Pt showed much higher sensitivity in tumor cells than in normal cells. More importantly, PEG‐PEI‐Pt had a potential to treat drug‐resistant tumors. Almost no transfection efficiency was observed for PEI (Mw 800 Da) and PEG‐PEI. Very interestingly, PEG‐PEI‐Pt could condense plasmid DNA efficiently, and exhibited good transfection efficiency in B16, HepG‐2, A375 and COS‐7 cells, comparable to even higher than PEI 25 kDa. In addition, PEG‐PEI‐Pt could also effectively deliver siRNA into the cytoplasm of tumor cells. With the good antitumoral and gene delivery abilities, PEG‐PEI‐Pt may have a great potential for combination therapy of drug and gene. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Rheological properties of semidilute solutions of poly(acrylic acid) modified with hydrocarbon and fluorocarbon end‐capped poly(ethylene glycol) macromonomer

Hydrocarbon and fluorocarbon end‐capped poly(ethylene glycol) (PEG) macromonomers with 9, 23, and 45 ethylene oxide units were synthesized by the esterification method. Copolymerization of these macromers with acrylic acid (AA) resulted in hydrophobically grafted poly(AA)s (PAAs) containing different lengths of PEG spacers. Their solution properties were investigated by rheological measurements and compared to those without hydrocarbon and fluorocarbon groups and without PEG spacers. Evident hydrophobic association was found to exist in the aqueous solution of these hydrophobically grafted copolymers, and the associating efficiency was improved by the flexible PEG spacer compared to those counterparts without them. However, the intramolecular association became predominant with the spacer length increase and the solution viscosity decreased. A wide viscosity plateau was observed for macromer modified polyelectrolytes in the alkalization process, which was unavailable for hydrophobically modified ones without PEG spacers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 12: 2777–2783, 2003     

Conjugated polyelectrolyte-cisplatin complex nanoparticles for simultaneous in vivo imaging and drug tracking

A molecular brush based on conjugated polyelectrolyte (CPE) grafted with dense poly(ethylene glycol) (PEG) chains was successfully complexed with an anticancer agent, cisplatin, to form cisplatin-loaded nanoparticles (CPE-PEG-Pt). The obtained nanoparticles have high far-red/near-infrared fluorescence and are able to release the drug in a continuous and slow manner. These nanoparticles have not only been used to visualize HepG2 cancer cells, but also served as an in vivo fluorescent imaging probe that simultaneously tracks the in vivo drug distribution in nude mice upon intravenous administration.     

Electropolymerization of p‐phenylenediamine on Pt‐electrode from aqueous acidic solution: Kinetics,mechanism, electrochemical studies,and characterization of the polymer obtained

Ar plasma‐induced graft polymerization of poly(ethylene glycol) (PEG) on Ar plasma pretreated poly(methyl methacrylate) (PMMA) surfaces was carried out to improve the antistatic properties. The surface composition and microstructure of the PEG‐grafted PMMA surfaces from plasma induction were characterized by attenuated total reflectance Fourier transfer infrared (ATR‐FTIR) spectroscopy, water contact angles (CA), and atomic force microscopy (AFM) measurements. The measurements revealed that the antistatic properties can be remarkably improved with the surface resistivity of PEG‐grafted PMMA surface decreasing significantly by 3–6 orders of magnitude, with the optimum condition for polymerization grafted onto the Ar plasma pretreated PMMA surface being 40 W for RF power and 3 min for glow discharge time. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Fluorescent microspheres of poly(ethylene glycol)–poly(lactic acid)–fluorescein copolymers synthesized by Ugi four‐component condensation

Microparticles formed by poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG) diblock copolymers containing fluorescein grafted to the polymer chain were synthesized by a Ugi four‐component condensation (UFCC) reaction. To synthesize these copolymers, lactide was first polymerized by a ring‐opening polymerization with alcohol initiators containing functional groups to give carboxyl‐ and aldehyde‐end‐functionalized PLA. Two different fluorescent block copolymers (FCPs) of PEG–PLA conjugated to fluorescein (FCP 1 and FCP 2) were then synthesized by UFCC; they gave yields in the range 65–75%. These copolymers were characterized well according their chemical structures and thermal properties, and we prepared fluorescent microspheres (FMSs) from them with the single emulsion–solvent evaporation method (FMS 1 and FMS 2). A new application of UFCC in the preparation of biomasked drug‐delivery systems is proposed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42994.     

Free volume,adhesion, and viscoelastic properties of model nanostructured pressure‐sensitive adhesive based on stoichiometric complex of poly(N‐vinyl pyrrolidone) and poly(ethylene glycol) of disparate chain lengths

Positron annihilation lifetime spectroscopy was used to characterize the size and content of subnanoscopic free volume in a model pressure‐sensitive adhesive based on a stoichiometric hydrogen‐bonded network complex of poly(N‐vinyl pyrrolidone) (PVP) and oligomeric poly(ethylene glycol) (PEG). Adhesive properties were examined with peel and probe tack tests, and mechanical properties were studied with tensile test. Nonequimolar stoichiometry and the structure of PVP–PEG model pressure‐sensitive adhesive blends were found to be determined by the length of PEG short chains. The size and number density of free volume domains in the PVP–PEG blends were determined as functions of blend composition and relative humidity of the surrounding atmosphere, which controls the amount of absorbed water. Correlating the free volume, adhesion behaviors, and tensile properties of the blends, the range of free volume favoring pressure‐sensitive adhesion in examined compositions was established. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis of a novel polymer cholesterol‐poly(ethylene glycol) 2000‐glycyrrhetinic acid (chol‐PEG‐GA) and its application in brucine liposome

In this research, a novel polymer cholesterol‐poly(ethylene glycol) 2000‐glycyrrhetinic acid (Chol‐PEG‐GA) was synthesized with four steps of chemical modification and elucidated by FTIR and ¹H‐NMR spectra. To demonstrate the application of this Chol‐PEG‐GA in preparation of liposomes (CPGL), conventional liposome (CL) composed of PC and Chol was prepared and the effects of the quantity of Chol‐PEG‐GA on the physicochemical properties (entrapment efficiency, particle size, stability of storage, and so on) of CPGL were also evaluated. The ability of the sustained release and the liver targeting ability of CPGL were further studied in vivo in rats and mice. The results show that, the AUC and MRT of CPGL were increased 2.31 and 2.11 times when compared with CL, respectively. The CPGL delivered about seven times higher drug into liver as compared with CL. From the targeting parameters of CPGL and CL, we can also conclude that the CPGL is able to improve the liver targeting of brucine. All these results suggested that, the Chol‐PEG‐GA modified liposomes were potential as the sustained and liver targeting drug delivery. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

MODELING MASS TRANSFER OF FITC-LABELED DEXTRAN FROM POLYELECTROLYTE MICROCAPSULES

Layer-by-layer adsorption of oppositely charged polyelectrolytes has been used for the manufacturing of hollow microspheres or capsules for controlled release studies. Using this self-assembly technique, microsphere core material was encapsulated with poly styrenesulfonate (PSS) and poly allylamine (PAH) multilayers or PAH and polyvinyl sulfate (PVS) multilayers and the core dissolved to produce hollow microcapsules. The microspheres were loaded with fluorescein-isothiocyanate (FITC)-labeled dextran of different molecular weights for different lengths of time to quantify the release properties. After loading, the capsules were immersed in water and the FITC-dextran was allowed to diffuse into the mother liquor. The FITC-dextran concentration of the mother liquor was measured over a period of hours and days. In this study, one- and two-compartment models were developed, based on a species mass balance, to predict the concentration of dextran release from the microcapsules over time. The two-compartment model was found to be superior to the one-compartment model in its fit to the observed data. The model was applied to experimental data in order to characterize the release properties of microcapsules with different numbers of layers and constituent architectures.     

Formation of microcapsules of medicines by the rapid expansion of a supercritical solution with a nonsolvent

The rapid expansion from a supercritical solution with a nonsolvent (RESS‐N) was applied to the formation of polymeric microcapsules containing medicines such as p‐acetamidophenol, acetylsalicylic acid, 1,3‐dimethylxanthine, flavone, and 3‐hydroxyflavone. A suspension of medicine in carbon dioxide (CO₂) containing a cosolvent and dissolved polymer was sprayed through a nozzle to atmospheric pressure. The pre‐expansion pressure was 10–25 MPa, and the temperature was 308–333 K. The polymers were poly(L ‐lactic acid) (molecular weight = 5000), poly(ethylene glycol) (PEG; PEG4000, molecular weight = 3000; PEG6000, molecular weight = 7500; and PEG20000, molecular weight = 20,000), poly(methyl methacrylate) (molecular weight = 15,000), ethyl cellulose (molecular weight = 5000), and PEG–poly(propylene glycol)–PEG triblock copolymer (molecular weight = 13,000). The solubilities of the polymers as coating materials and these medicines as core substance were very low in CO₂. However, the solubilities of these polymers in CO₂ significantly increased with the addition of low molecular weight alcohols as cosolvents. After RESS‐N, polymeric microcapsules were formed according to the precipitation of the polymer caused by a decrease in the solvent power of CO₂. This method offered three advantages: (1) enough of the coating polymers, which were insoluble in pure CO₂, dissolved; (2) the microparticles of the medicine were encapsulated without adhesion between the particles because a nonsolvent was used as a cosolvent and the cosolvent remaining in the mixture was removed by the gasification of CO₂; and (3) the polymer‐coating thickness was controlled with changes in the feed composition of the polymer for drug delivery. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 742–752, 2003     

Effect of the inclusion of PEG on the solid‐state properties and drug release from polylactic acid films and microcapsules

The use of poly(lactic acid) (PLA) for controlled drug delivery applications was limited by unfavorable physical properties such as hydrophobicity, high intrinsic crystallinity, low permeability, and high glass transition temperatures. This research used polyethylene glycols (PEGs) of varying molecular weights (300–18,500 g/mol) and concentrations (0–50% w/w) to modify the permeability, intrinsic crystallinity, glass transition temperature, residual solvent levels, and release of a model drug, 5‐flurouracil (5FU), from monolithic films and microcapsules fabricated with PLA. The films were fabricated by solvent casting from methylene chloride. The microcapsules were formed by a coacervation method by using a methylene chloride/hexane solvent/nonsolvent system. Compared to PLA films, all PLA : PEG films showed the following: (1) a glass transition temperature between 40 and 55°C, (2) 5–8% lower residual solvent levels, and (3) enhanced permeability to 5FU. These results suggested that the incorporation of PEG improves the physical properties of PLA films to enable fabrication of controlled release delivery systems. Similar to the films, incorporation of PEG also enhanced the permeability of PLA microcapsules to 5FU. However, high intrinsic crystallinity, dual endothermal character for PLA melting, and significant burst release of 5FU in PLA : PEG microcapsules may limit their development for controlled drug delivery applications. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2025–2030, 2004     

Bovine serum albumin gel/polyelectrolyte complex of hyaluronic acid and chitosan based microcarriers for Sorafenib targeted delivery

The development of systems for targeted delivery of Sorafenib in unresectable hepatocellular carcinoma to reduce the systemic toxicity is a challenge. In our article, we successfully prepared core-shell microcapsules based on bovine serum albumin gel with polyelectrolyte complex multilayer shell of polysaccharides with opposite charges, hyaluronic acid, and chitosan, encapsulating Sorafenib, as targeting delivery system for improved hepatocellular carcinoma therapy. A bovine serum albumin gel core was formed by a method based on a sacrificial CaCO₃ template, followed by the multilayer shell build-up of Ca²⁺ cross-linked hyaluronic acid hydrogel, and subsequently alternating multilayers of the polyelectrolyte complex formed between hyaluronic acid and chitosan. The following techniques: Fourier-transform infrared and UV–Vis spectroscopy, X-ray diffraction, differential scanning calorimetry, confocal laser scanning microscopy, atomic force microscopy, and scanning electron microscopy were used for the physicochemical characterization. These tests revealed the spherical shape of core-shell type, the micro-size, as well as the composition of microcapsules after their synthesis and proved the successful encapsulation and release of the drug. The promising results regarding encapsulation efficiency, Sorafenib release profile and cytotoxicity on HepG2 and mesenchymal stem cells, recommend Sorafenib loaded microcapsules as suitable targeted drug carriers for further in vivo studies for hepatocellular carcinoma therapy.     

Performance of melamine modified urea–formaldehyde microcapsules in a dental host material

Urea–formaldehyde (UF) microcapsules filled with dicyclopentadiene (DCPD) show potential for making self‐healing dental restorative materials. To enhance the physical properties of the capsules, the urea was partially replaced with 0–5% melamine. The microcapsules were analyzed by different microscopic techniques. DSC was used to examine the capsule shell, and the core content was confirmed by ¹H NMR spectroscopy. Capsules in the range of 50–300 μm were then embedded in a dental composite matrix consisting of bisphenol‐A‐glycidyl dimethacrylate (Bis‐GMA) and triethylene‐glycol dimethacrylate (TEGDMA). Flexural strength, microhardness, and nanoindentation hardness measurements were performed on the light‐cured specimens. Optical microscopy (OM) examination showed a random distribution of the microspheres throughout the host material. The incorporation of small amounts of the microcapsules did not affect the performance of the matrix material. Scanning electron microscopy (SEM) analysis revealed excellent bonding of the microcapsules to the host material which is a characteristic of utter importance for maintaining the very good mechanical properties of a dental composite with self‐healing ability. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Drug release from electrospun fibers of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) grafted with poly(N‐vinylpyrrolidone)

Poly(N‐vinylpyrrolidone) (PVP) groups were grafted onto poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) backbone to modify the properties of PHBV and synthesize a new novel biocompatible graft copolymer. Based on these graft copolymers, electrospun fiber mats and commonly cast films were explored as drug delivery vehicles using tetracycline hydrochloride as a model drug. Toward that end, the fibers were electrospun and the films were cast from chloroform solutions containing a small amount of methanol to solubilize the drug. The Brookfield viscosities of the solution were determined to achieve the optimal electrospinning conditions. The vitro release of the tetracycline hydrochloride from these new drug delivery systems was followed by UV–vis spectroscopy. To probe into the factors affected on the release behavior of these drug delivery systems, their water absorbing abilities in phosphate buffer solution were investigated, together with their surface hydrophilicity, porosity and crystallization properties were characterized by water contact angles, capillary flow porometer, DSC, and WAXD, respectively. The morphological changes of these drug delivery vehicles before and after release were also observed with SEM. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Surface modification of polythiophene and poly(3‐methyl thiophene) films by graft copolymerization

Polythiophene (PTH) and poly(3‐methyl thiophene) (PMT) films were electrochemically polymerized in an electrolyte solution of boron fluoride–ethyl ether. Ozone‐pretreated PTH and PMT films were subjected to UV‐light‐induced graft copolymerization with different monomers, including poly(ethylene glycol) monomethacrylate, acrylic acid, and glycidyl methacrylate. Surface grafting with the hydrophilic polymers gave rise to more hydrophilic PTH and PMT films. The structure and chemical composition of each copolymer surface were studied by X‐ray photoelectron spectroscopy. The surface grafting with the hydrophilic polymers resulted in a more hydrophilic PTH film. The dependence of the density of surface grafting and the conductivities of the grafted PTH and PMT films on the ozone pretreatment was also studied. A large amount of the grafted groups at the surface of the PTH and PMT films remained free for further surface modification and functionalization. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation and biodegradation of hydroxyl terminated poly(fumaric acid‐co‐diethylene glycol) and its segmented polyurethane

Hydroxyl terminated poly(fumaric acid‐co‐diethylene glycol), poly(FA‐co‐DEG) was prepared by melt polycondensation. The resultant unsaturated aliphatic polyester was characterized by Fourier transform infrared (FTIR) spectroscopy, hydroxyl value, acid value, and intrinsic viscosity. Its enzymatic degradation and crosslinking behavior as well as the effect of crosslinking degree on enzymatic degradation were also investigated. The crosslinking degree and reduction of carbon–carbon double bonds revealed excellent self‐crosslinking nature of poly(FA‐co‐DEG) at high temperature. The results of enzymatic degradation showed that poly(FA‐co‐DEG) has excellent biodegradability and that the biodegradation can be controlled by the crosslinking degree. Polyurethane was prepared by the reaction of poly(FA‐co‐DEG), 2,4‐toluene diisocyanate (TDI), and 1,4‐butanediol (BD). It was found that the biodegradation of the obtained polyurethane was slower than that of the original unsaturated aliphatic polyester poly(FA‐co‐DEG). The peeling strength of the polyurethane was very high, supporting better adhesion property with enhanced crosslinking. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Multifunctional hybrid magnetite nanoparticles with pH‐responsivity,superparamagnetism and fluorescence

Multifunctional hybrid nanoparticles, Fe₃O₄@poly[(2‐dimethylamino)ethyl methacrylate]‐block‐poly(2‐hydroxyethyl methacrylate)‐graft‐carbazole, with pH‐responsivity, superparamagnetism and fluorescence for targeted drug delivery and release have been synthesized. The nanoparticles have a core‐shell structure as determined from transmission electron microscopy, pH‐responsivity as determined from hydrodynamic radius analysis, superparamagnetism as determined from vibrating sample magnetometry and fluorescence as determined from fluorescence spectroscopy and fluorescence microscopy. The release behavior of model drug progesterone indicates that the release rate can be effectively controlled by altering the pH of the environment. The multifunctional nanoparticles could be applied extensively in targeted drug delivery and release, and with fluorescence they can serve as efficient tracers to record magnetic targeting routes. Copyright © 2011 Society of Chemical Industry     

The synthesis of fulvic acid–thiourea amide derivates grafted polystyrene and its effect on the crystallization and performance of poly(lactic acid)

Fulvic acid–thiourea amide derivates (FA‐T) was synthesized via amidation with FA and thiourea, and its optimum reaction conditions were 7 h of reaction time, 1 wt% of sodium methylate, 130°C of reaction temperature, and 2 g of thiourea. Then, FA‐T grafted polystyrene (FA‐T‐PS) was synthesized by activators generated by electron transfer for atom transfer radical polymerization. Fourier transform infrared spectroscopy, static contact angle analysis, and X‐ray photoelectron spectroscopy confirmed that the synthesis of FA‐T‐PS. Then, poly(lactic acid)/FA‐T‐PS(PLA/FA‐T‐PS) composites were prepared by the melt blending with FA‐T‐PS as fillers. Mechanical test demonstrated that FA‐T‐PS increased the flexibility and ductility of PLA composites. Dynamic mechanical analysis revealed that FA‐T‐PS reduced friction and loss between PLA chain and filler, and further reformed had higher interfacial compatibility with PLA. Differential scanning calorimetric results and polarized optical microscopy analysis displayed that FA‐T‐PS had strong heterogeneous nucleation effect, which effectively enhanced the crystallization rate and the crystallinity of PLA. Friedman thermal decomposition kinetics presented that E _a of PLA/FA‐T‐PS (0.3 wt%) was increased by 52.94% compared with PLA, which demonstrated that FA‐T‐PS significantly enhanced the thermal stability of PLA. Therefore, FA‐T‐PS effectively improved the comprehensive performance of PLA. POLYM. ENG. SCI., 59:1787–1798, 2019. © 2019 Society of Plastics Engineers