Easy Access to Supramolecular Gels of the Nonsteroidal Anti‐inflammatory Drug Diflunisal: Synthesis,Characterization, and Plausible Biomedical Applications

By exploiting salt formation, a new series of primary ammonium monocarboxylate salts of a nonsteroidal anti‐inflammatory drug, namely, diflunisal, was synthesized. The majority of the salts thus synthesized turned out to be good gelators of various solvents, including the solvents (e.g., methyl salicylate and pure water) typically used for topical gel formulation. Single‐crystal X‐ray diffraction studies of a few gelator and nongelator salts in the series revealed details of the hydrogen‐bonding networks present in the salts. Furthermore, one such gelator salt, namely, the diflunisal salt of serinol, was found to be biocompatible (MTT assay), and its anti‐inflammatory (PGE₂ assay) response turned out to be as good as that of the parent drug, which is indicative of its potential in biomedical applications.     

Supramolecular Gels by Design: Towards the Development of Topical Gels for Self‐Delivery Application

Following a supramolecular synthon approach, simple salt formation has been employed to gain access to a series of supramolecular gelators derived from the well‐known non‐steroidal anti‐inflammatory drug (NSAID) ibuprofen. A well‐studied gel‐inducing supramolecular synthon, namely primary ammonium monocarboxylate (PAM), has been exploited to generate a series of PAM salts by reacting ibuprofen with various primary amines. Remarkably, all of the salts ( S1 – S7 ) thus synthesized proved to be good to moderate gelators of various polar and nonpolar solvents. Single‐crystal and powder X‐ray diffraction studies established the existence of the PAM synthons in the gel network, confirming the efficacy of the supramolecular synthon approach employed. Most importantly, the majority of the salts ( S2 , S3 , S6 , and S7 ) were capable of gelling methyl salicylate (MS), an important ingredient found in many commercial topical gels. In vitro experiments (MTT and PGE₂ assays) revealed that all of the salts (except S3 and S7 ) were biocompatible (up to 0.5 mm concentration), and the most suited one, S6 , displayed anti‐inflammatory ability as good as that of the parent drug ibuprofen. A topical gel of S6 with methyl salicylate and menthol was found to be suitable for delivering the gelator drug in a self‐delivery fashion in treating skin inflammation in mice. Histological studies, including immunohistology, were performed to further probe the role of the gelator drug S6 in treating inflammation. Cell imaging studies supported cellular uptake of the gelator drug in such biomedical application.     

Multidrug‐Containing,Salt‐Based,Injectable Supramolecular Gels for Self‐Delivery,Cell Imaging and Other Materials Applications

Both molecular and crystal‐engineering approaches were exploited to synthesize a new class of multidrug‐containing supramolecular gelators. A well‐known nonsteroidal anti‐inflammatory drug, namely, indomethacin, was conjugated with six different l ‐amino acids to generate the corresponding peptides having free carboxylic acid functionality, which reacted further with an antiviral drug, namely, amantadine, a primary amine, in 1:1 ratio to yield six primary ammonium monocarboxylate salts. Half of the synthesized salts showed gelation ability that included hydrogelation, organogelation and ambidextrous gelation. The gels were characterized by table‐top and dynamic rheology and different microscopic techniques. Further insights into the gelation mechanism were obtained by temperature‐dependent ¹H NMR spectroscopy, FTIR spectroscopy, photoluminescence and dynamic light scattering. Single‐crystal X‐ray diffraction studies on two gelator salts revealed the presence of 2D hydrogen‐bonded networks. One such ambidextrous gelator (capable of gelling both pure water and methyl salicylate, which are important solvents for biological applications) was promising in both mechanical (rheoreversible and injectable) and biological (self‐delivery) applications for future multidrug‐containing injectable delivery vehicles.     

Exploiting Supramolecular Synthons in Designing Gelators Derived from Multiple Drugs

A simple strategy for designing salt‐based supramolecular gelators comprised of various nonsteroidal anti‐inflammatory drugs (NSAIDs) and amantadine (AMN) (an antiviral drug) has been demonstrated using a supramolecular synthon approach. Single‐crystal and powder X‐ray diffraction established the existence of the well‐studied gel‐forming 1D supramolecular synthon, namely, primary ammonium monocarboxylate (PAM) synthon in all the salts. Remarkably five out of six salts were found to be capable of gelling methyl salicylate (MS)—an important ingredient in commercially available topical gels; one such selected biocompatible salt displayed an anti‐inflammatory response in prostaglandin E₂ (PGE₂) assay, thereby indicating their plausible biomedical applications.     

Supramolecular Synthons in Designing Low Molecular Mass Gelling Agents: L‐Amino Acid Methyl Ester Cinnamate Salts and their Anti‐Solvent‐Induced Instant Gelation

Easy access to a class of chiral gelators has been achieved by exploiting primary ammonium monocarboxylate ( PAM ), a supramolecular synthon. A combinatorial library comprising of 16 salts, derived from 5 l ‐amino acid methyl esters and 4 cinnamic acid derivatives, has been prepared and scanned for gelation. Remarkably, 14 out of 16 salts prepared (87.5 % of the salts) show moderate to good gelation abilities with various solvents, including commercial fuels, such as petrol. Anti‐solvent induced instant gelation at room temperature has been achieved in all the gelator salts, indicating that the gelation process is indeed an aborted crystallization phenomenon. Rheology, optical and scanning electron microscopy, small angle neutron scattering, and X‐ray powder diffraction have been used to characterize the gels. A structure‐property correlation has been attempted, based on these data, in addition to the single‐crystal structures of 5 gelator salts. Analysis of the FT‐IR and ¹H NMR spectroscopy data reveals that some of these salts can be used as supramolecular containers for the slow release of certain pest sex pheromones. The present study clearly demonstrates the merit of crystal engineering and the supramolecular synthon approach in designing new materials with multiple properties.     

Rational Approach Towards Designing Metallogels From a Urea‐Functionalized Pyridyl Dicarboxylate: Anti‐inflammatory,Anticancer, and Drug Delivery

A structural rationale was adopted to design a series of metallogels from a newly synthesized urea‐functionalized dicarboxylate ligand, namely, 5‐[3‐(pyridin‐3‐yl)ureido]isophthalic acid ( PUIA ), that produces metallogels upon reaction with various metal salts (Cu^II, Zn^II, Co^II, Cd^II, and Ni^II salts) at room temperature. The gels were characterized by dynamic rheology and transmission electron microscopy (TEM). The existence of a coordination bond in the gel state was probed by FTIR and ¹H NMR spectroscopy in a Zn^II metallogel (i.e., MG2 ). Single crystals isolated from the reaction mixture of PUIA and Co^II or Cd^II salts characterized by X‐ray diffraction revealed lattice inclusion of solvent molecules, which was in agreement with the hypothesis based on which the metallogels were designed. MG2 displayed anti‐inflammatory response (prostaglandin E₂ assay) in the macrophage cell line (RAW 264.7) and anticancer properties (cell migration assay) on a highly aggressive human breast cancer cell line (MDA‐MB‐231). The MG2 metallogel matrix could also be used to load and release (pH responsive) the anticancer drug doxorubicin. Fluorescence imaging of MDA‐MB‐231 cells treated with MG2 revealed that it was successfully internalized.     

Design and Synthesis of ZnII‐Coordination Polymers Anchored with NSAIDs: Metallovesicle Formation and Multi‐drug Delivery

A series of coordination polymers synthesized from a bis‐pyridyl linker, namely 4,4′‐azopyridine ( L ), selected non‐steroidal‐anti‐inflammatory drugs (NSAIDs), namely diclofenac ( Dic ), ibuprofen ( Ibu ), flurbiprofen ( Flu ), mefenamic acid ( Mefe ), and naproxen ( Nap ), and Zn(NO₃)₂ were characterized by single crystal X‐ray diffraction. One of the coordination polymers, namely CP3 derived from Flu , was able to form metallovesicles in DMSO, DMSO/H₂O and DMSO/DMEM (biological media) as revealed by TEM, AFM and DLS. Metallovesicle formation by CP3 was further supported by loading a fluorescent dye, namely calcein, as well as an anti‐cancer drug, doxorubicin hydrochloride ( DOX ), as revealed by UV‐vis and emission spectra, and fluorescence microscopy. DOX ‐loaded metallovesicles of CP3 ( DOX@CP3‐vesicle ) could be delivered in vitro to a highly aggressive human breast cancer cell line, namely MDA‐MB‐231, as revealed by MTT and cell migration assays, and also cell imaging performed under laser scanning confocal microscope (LSCM). Thus, a proof of concept for developing a multi‐drug delivery system derived from a metallovesicle for delivering an anti‐cancer drug to cancer cells is demonstrated for the first time.     

Phenylboronic Acid Appended Pyrene‐Based Low‐Molecular‐Weight Injectable Hydrogel: Glucose‐Stimulated Insulin Release

A pyrene‐containing phenylboronic acid (PBA) functionalized low‐molecular‐weight hydrogelator was synthesized with the aim to develop glucose‐sensitive insulin release. The gelator showed the solvent imbibing ability in aqueous buffer solutions of pH values, ranging from 8–12, whereas the sodium salt of the gelator formed a hydrogel at physiological pH 7.4 with a minimum gelation concentration (MGC) of 5 mg mL^?1. The aggregation behavior of this thermoreversible hydrogel was studied by using microscopic and spectroscopic techniques, including transmission electron microscopy, FTIR, UV/Vis, luminescence, and CD spectroscopy. These investigations revealed that hydrogen bonding, π–π stacking, and van der Waals interactions are the key factors for the self‐assembled gelation. The diol‐sensitive PBA part and the pyrene unit in the gelator were judiciously used in fluorimetric sensing of minute amounts of glucose at physiological pH. The morphological change of the gel due to addition of glucose was investigated by scanning electron microscopy, which denoted the glucose‐responsive swelling of the hydrogel. A rheological study indicated the loss of the rigidity of the native gel in the presence of glucose. Hence, the glucose‐induced swelling of the hydrogel was exploited in the controlled release of insulin from the hydrogel. The insulin‐loaded hydrogel showed thixotropic self‐recovery property, which hoisted it as an injectable soft composite. Encouragingly, the gelator was found to be compatible with HeLa cells.     

Unusual Salt‐Induced Color Modulation through Aggregation‐Induced Emission Switching of a Bis‐cationic Phenylenedivinylene‐Based π Hydrogelator

The synthesis, hydrogelation, and aggregation‐induced emission switching of the phenylenedivinylene bis‐N‐octyl pyridinium salt is described. Hydrogelation occurs as a consequence of π‐stacking, van der Waals, and electrostatic interactions that lead to a high gel melting temperature and significant mechanical properties at a very low weight percentage of the gelator. A morphology transition from fiber‐to‐coil‐to‐tube was observed depending on the concentration of the gelator. Variation in the added salt type, salt concentrations, or temperature profoundly influenced the order of aggregation of the gelator molecules in aqueous solution. Formation of a novel chromophore assembly in this way leads to an aggregation‐induced switch of the emission colors. The emission color switches from sky blue to white to orange depending upon the extent of aggregation through mere addition of external inorganic salts. Remarkably, the salt effect on the assembly of such cationic phenylenedivinylenes in water follow the behavior predicted from the well‐known Hofmeister effects. Mechanistic insights for these aggregation processes were obtained through the counterion exchange studies. The aggregation‐induced emission switching that leads to a room‐temperature white‐light emission from a single chromophore in a single solvent (water) is highly promising for optoelectronic applications.     

Supramolecular Chirality in Organo‐, Hydro‐, and Metallogels Derived from Bis‐amides of L‐(+)‐Tartaric Acid: Formation of Highly Aligned 1D Silica Fibers and Evidence of 5‐c Net SnS Topology in a Metallogel Network

A series of bis‐amides derived from L ‐(+)‐tartaric acid was synthesized as potential low‐molecular‐weight gelators. Out of 14 bis‐amides synthesized, 13 displayed organo‐, hydro‐, and ambidextrous gelation behavior. The gels were characterized by methods including circular dichroism, differential scanning calorimetry, optical and electron microscopy, and rheology. One of the gels derived from di‐3‐pyridyltartaramide ( D‐3‐PyTA ) displayed intriguing nanotubular morphology of the gel network, which was exploited as a template to generate highly aligned 1D silica fibers. The gelator D‐3‐PyTA was also exploited to generate metallogels by treatment with various Cu^II/Zn^II salts under suitable conditions. A structure–property correlation on the basis of single‐crystal and powder X‐ray diffraction data was attempted to gain insight into the structures of the gel networks in both organo‐ and metallogels. Such study led to the determination of the gel‐network structure of the Cu^II coordination‐polymer‐based metallogel, which displayed a 2D sheet architecture made of a chloride‐bridged double helix that resembled a 5‐c net SnS topology.     

Remarkable Regioisomer Control in the Hydrogel Formation from a Two‐Component Mixture of Pyridine‐End Oligo(p‐phenylenevinylene)s and N‐Decanoyl‐L‐alanine

N‐Decanoyl‐L ‐alanine (DA) was mixed with either colorless 4,4′‐bipyridine (BP) or various derivatives such as chromogenic oligo(p‐phenylenevinylene) (OPV) functionalized with isomeric pyridine termini in specific molar ratios. This mixtures form salt‐type gels in a water/ethanol (2:1, v/v) mixture. The gelation properties of these two‐component mixtures could be modulated by variation of the position of the ′′N′′ atom of the end pyridyl groups in OPVs. The presence of acid–base interactions in the self‐assembly of these two‐component systems leading to gelation was probed in detail by using stoichiometry‐dependent UV/Vis and FTIR spectroscopy. Furthermore, temperature‐dependent UV/Vis and fluorescence spectroscopy clearly demonstrated a J‐type aggregation mode of these gelator molecules during the sol‐to‐gel transition process. Morphological features and the arrangement of the molecules in the gels were examined by using scanning electron microscopy (SEM), atomic force microscopy (AFM), and X‐ray diffraction (XRD) techniques. Calculation of the length of each molecular system by energy minimization in its extended conformation and comparison with the XRD patterns revealed that this class of gelator molecules adopts lamellar organizations. Rheological properties of these two‐component systems provided clear evidence that the flow behavior could be modulated by varying the acid/amine ratio. Polarized optical microscopy (POM), differential scanning calorimetry (DSC), and XRD results revealed that the solid‐phase behavior of such two‐component mixtures (acid/base=2:1) varied significantly upon changing the proton‐acceptor part from BP to OPV. Interestingly, the XRD pattern of these acid/base mixtures after annealing at their associated isotropic temperature was significantly different from that of their xerogels.     

Exploring Orthogonal Hydrogen Bonding towards Designing Organic‐Salt‐Based Supramolecular Gelators: Synthesis,Structures, and Anticancer Properties

A series of primary ammonium monocarboxylate (PAM) salts derived from β‐alanine derivatives of pyrene and naphthalene acetic acid, along with the parent acids, were explored to probe the plausible role of orthogonal hydrogen bonding resulting from amide???amide and PAM synthons on gelation. Single‐crystal X‐ray diffraction (SXRD) studies were performed on two parent acids and five PAM salts in the series. The data revealed that orthogonal hydrogen bonding played an important role in gelation. Structure–property correlation based on SXRD and powder X‐ray diffraction data also supported the working hypothesis upon which these gelators were designed. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and cell migration assay on a highly aggressive human breast cancer cell line, MDA‐MB‐231, revealed that one of the PAM salts in the series, namely, PAA.B2 , displayed anticancer properties, and internalization of the gelator salt in the same cell line was confirmed by cell imaging.     

Screening and identification of Caulis Sinomenii bioactive ingredients with dual‐target NF‐κB inhibition and β2‐AR agonizing activities

Caulis Sinomenii (CS) is a valuable traditional medicine in China. Its extract can act as an anti‐inflammatory agent and a vascular smooth muscle relaxant. However, the underlying mechanisms remain unknown. In this study, we developed a simple dual‐target method based on ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry combined with a dual‐target bioactive screening assay for anti‐inflammatory and antispasmodic activities to characterize the chemical structure of various bioactive compounds of CS rapidly. Seven potential NF‐κB inhibitors were identified, including laudanosoline‐1‐O‐xylopyranose, 6‐O‐methyl‐laudanosoline‐1‐O‐glucopyranoside, menisperine, sinomenine, laurifoline, magnoflorine and norsinoacutin. Furthermore, IL‐6 and IL‐8 assays confirmed the anti‐inflammatory effects of these potential NF‐κB inhibitors, in which laudanosoline‐1‐O‐d ‐xylopyranose and menisperine were revealed as novel NF‐κB inhibitors. Among the seven identified alkaloids, three potential β₂‐adrenergic receptor agonists, including sinomenine, magnoflorine and laurifoline, were characterized using a luciferase reporter system to measure for the activity of β₂‐adrenergic receptor agonists. Finally, sinomenine, magnoflorine and laurifoline were identified not only as potential NF‐κB inhibitors but also as potential β₂‐adrenegic receptor agonists, which is the first time this has been reported. Molecular dynamic simulation and docking results suggest that the three dual‐bioactive constituents could not only inhibit Pseudomonas aeruginosa PAK strain‐induced inflammatory responses via a negative regulation of the Braf protein that participates in MAPK signaling pathway but also activate the β₂‐adrenegic receptor. These results suggest that CS extract has dual signaling activities with potential clinical application as a novel drug for asthma.     

Self‐Assembled Fibers Containing Stable Organic Radical Moieties: Alignment and Magnetic Properties in Liquid Crystals

Macroscopically oriented stable organic radicals have been obtained by using a liquid–crystalline (LC) gel composed of an l ‐isoleucine‐based low molecular weight gelator containing a 2,2,6,6‐tetramethylpiperidine 1‐oxyl moiety. The LC gel has allowed magnetic measurements of the oriented organic radical. The gelator has formed fibrous aggregates in liquid crystals via intermolecular hydrogen bonds. The fibrous aggregates of the radical gelator are formed and oriented on cooling by applying a magnetic field to the mixture of liquid crystals and the gelator. Superconducting quantum interference device (SQUID) measurements have revealed that both oriented and nonoriented fibrous aggregates exhibited antiferromagnetic interactions, in which super‐exchange interaction constant J is estimated as ?0.89 cm^?1.     

In Situ Gel‐to‐Crystal Transition and Synthesis of Metal Nanoparticles Obtained by Fluorination of a Cyclic β‐Aminoalcohol Gelator

A new fluorinated version of a cyclic β‐aminoalcohol gelator derived from 1,2,3,4‐tetrahydroisoquinoline is presented. The gelator is able to gel various nonprotic solvents through OH???N hydrogen bonds and additional CH???F interactions due to the introduction of fluorine. A bimolecular lamellar structure is formed in the gel phase, which partly preserves the pattern of molecular organization in the single crystal. The racemate of the chiral gelator shows lower gelation ability than its enantiomer because of a higher tendency to form microcrystals, as shown by X‐ray diffraction analysis. The influence of fluorination on the self‐assembly of the gelator and the properties of the gel was investigated in comparison to the original fluorine‐free gel system. The introduction of fluorine brings two new features. The first is good recognition of o‐xylene by the gelator, which induces an in situ transition from gels of o‐xylene and of an o‐xylene/toluene mixture to identical single crystals with unique tubular architecture. The second is the enhanced stability of the toluene gel towards ions, including quaternary ammonium salts, which enables the preparation of a stable toluene gel in the presence of chloroaurate or chloroplatinate. The gel system can be used as a template for the synthesis of spherical gold nanoparticles with a diameter of 5 to 9 nm and wormlike platinum nanostructures with a diameter of 2 to 3 nm and a length of 5 to 12 nm. This is the first example of a synthesis of platinum nanoparticles in an organogel medium. Therefore, the appropriate introduction of a fluorine atom and corresponding nonbonding interactions into a known gelator to tune the properties and functions of a gel is a simple and effective tactic for design of a gel system with specific targets.     

Solution 1H and 13C NMR of new chiral 1,4‐oxazepinium heterocycles and their intermediates from the reaction of 2,4‐pentanedione with α‐L‐amino acids and (R)‐(—)‐2‐phenylglycinol

The reaction of 2,4‐pentanedione ( 1 ) with (R)‐(—)‐2‐phenylglycine methyl ester ( 2 ), (R)‐(—)‐2‐phenylglycinol ( 3 ) and the proteinogenic amino acids (2S,3R)‐(—)‐2‐amino‐3‐hydroxybutyric acid (L ‐threonine) ( 4 ) and (R)‐(—)‐2‐amino‐3‐mercaptopropionic acid (L ‐cysteine) ( 5 ) methyl esters was investigated. The corresponding enamines 6 , 7 and 8 were isolated and characterized spectroscopically whereas 9 , which is unstable, was transformed in situ into 13 . Treatment of 7 , 8 and 9 with boron trifluoride etherate afforded the new [1,4]oxazepines 10 , 11 and [1,4]thiazepine ( 12 ) as their BF₃O^? salts. The structures of the enamines and their corresponding seven‐membered heterocycles were assessed by 1D and 2D NMR spectroscopy. Variable‐temperature experiments revealed different molecular mobility behavior among these heterocycles. Copyright © 2003 John Wiley & Sons, Ltd.     

Remarkable Shape‐Sustaining,Load‐Bearing,and Self‐Healing Properties Displayed by a Supramolecular Gel Derived from a Bis‐pyridyl‐bis‐amide of L‐Phenyl Alanine

A series of bis‐amides decorated with pyridyl and phenyl moieties derived from L ‐amino acids having an innocent side chain (L ‐alanine and L ‐phenyl alanine) were synthesized as potential low‐molecular‐weight gelators (LMWGs). Both protic and aprotic solvents were found to be gelled by most of the bis‐amides with moderate to excellent gelation efficiency (minimum gelator concentration=0.32–4.0 wt. % and gel–sol dissociation temperature T_gel=52–110 °C). The gels were characterized by rheology, DSC, SEM, TEM, and temperature‐variable ¹H NMR measurements. pH‐dependent gelation studies revealed that the pyridyl moieties took part in gelation. Structure–property correlation was attempted using single‐crystal X‐ray and powder X‐ray diffraction data. Remarkably, one of the bis‐pyridyl bis‐amide gelators, namely 3,3‐Phe (3‐pyridyl bis‐amide of L ‐phenylalanine) displayed outstanding shape‐sustaining, load‐bearing, and self‐healing properties.     

Nitrosation of Sugar Oximes: Preparation of 2‐Glycosyl‐1‐hydroxydiazene‐2‐oxides

Oximes of glucose, xylose, lactose, fructose, and mannose have been prepared. Nitrosation of the oximes of glucose, xylose, and lactose with NaNO₂/HCl afforded 2‐(β‐glycopyranosyl)‐1‐hydroxydiazene‐2‐oxides, which were isolated as salts 13 , 22 , and 28 . Nitrosation of fructose oxime 29 furnished fructose, whereas nitrosation of mannose oxime 30 with NaNO₂/HCl afforded the 1‐hydroxy‐2‐(β‐d‐ mannopyranosyl)diazene‐2‐oxide 32 , from which the p‐anisidinium salt 31 and the sodium salt 33 were prepared. However, nitrosation of 30 with isopentyl nitrite in aqueous solutions of CsOH or KOH resulted in the formation of the 2‐(α‐D ‐mannofuranosyl)‐1‐hydroxydiazene‐2‐oxide salts 34 and 35 , respectively. Methylation of the ammonium 2‐(β‐D ‐glucopyranosyl)‐1‐hydroxydiazene‐2‐oxide 13 yielded the 1‐methoxy compound, which was benzoylated to afford the tetra‐O‐benzoate 14 a , the structure of which was confirmed by X‐ray diffraction analysis. From the glucose O‐methyloximes 15 and 16 the N‐methoxy‐N‐nitroso‐2,3,4,6‐tetra‐O‐acetyl‐β‐D ‐glucopyranosylamine 18 was prepared. The structure of this compound was confirmed by X‐ray diffraction analysis. Treatment of acetobromoglucose with cupferron furnished the 1‐(2,3,4,6‐tetra‐O‐acetyl‐β‐D ‐glucopyranosyloxy)‐2‐phenyldiazene‐2‐oxide 20 .     

An Organocatalyzed Efficient One‐pot Synthesis,Biological Evaluation,and Molecular Docking Studies of 4,4′‐(Arylmethylene)bis‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ols)

The synthesis of 4,4′‐(arylmethylene)bis‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ol) derivatives catalyzed by ʟ‐proline is a simple, versatile, and efficient method. In vitro antioxidant, anti‐inflammatory, and antimicrobial activities of compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j were studied. Furthermore, to rationalize the observed anti‐inflammatory activity data, molecular docking study has been performed against COX‐2 enzyme which revealed a good binding affinity for these molecules and could provide an insight into the various bonded and non‐bonded interactions guiding their binding affinity.     

Hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer and their nanoparticles as paclitaxel delivery system

A new hyperbranched poly (amine‐ester)‐poly (lactide‐co‐glycolide) copolymer (HPAE‐co‐PLGA) was synthesized by ring‐opening polymerization of D , L ‐lactide (DLLA) glycolid and branched poly (amine‐ester) (HPAE‐OHs) with Sn(Oct)₂ as catalyst. The chemical structures of copolymers were determined by FT‐IR, ¹H‐NMR(¹³C NMR), TGA and their molecular weights were determined by gel permeation chromatography (GPC). Paclitaxel‐loaded copolymer nanoparticles were prepared by the nanoprecipitation method. Their physicochemical characteristics, e.g. morphology and nanoparticles size distribution were then evaluated by means of fluorescence spectroscopy, environmental scanning electron microscopy (ESEM), and dynamic light scattering (DLS). Paclitaxel‐loaded nanoparticles assumed a spherical shape and have unimodal size distribution. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticles size, drug‐loading content, and drug release behavior. As the molar ratio of DL ‐lactide/glycolide to HPAE increased, the nanoparticles size and drug‐loading content increased, and the drug release rate decreased. The antitumor activity of the paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles against human liver cancer H7402 cells was evaluated by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The paclitaxel‐loaded HPAE‐co‐PLGA nanoparticles showed comparable anticancer efficacy with the free drug. Copyright © 2010 John Wiley & Sons, Ltd.