Novel biodegradable polymers as gene carriers

This study investigated two new biodegradable polymers as gene controlled-released coatings for gene transfer. Poly(ethylene glycol)-co-poly(D,L-lactic acid) (PELA) and poly(ethylene glycol)-co-poly(lactic acid)-co-poly(glycolic acid) random copolymer (PELGA) were synthesized and used as microspheres matrices with encapsulated plasmid pCH110. The plasmid loading efficiency, cytotoxicity, transfection efficiency and in vitro degradation and release profiles of microsphere complexes were evaluated in details. The biodegradable polymers showed high DNA loading efficiency and low cytotoxicity as gene controlled-released coatings, and the poly(ethylene glycol) (PEG) contents of polymer matrices influenced the diameter, loading efficiency and transfection efficiency of plasmid DNA within the microspheres. The average diameters of PELA and PELGA microspheres were between 0.5 and 1.5 microm, and the plasmid loading efficiency was 62 and 73% for PELA and PELGA microspheres with 10% PEG content, respectively. In vitro testing showed a gradual release profile of DNA from polymeric matrices. The polymers/DNA microspheres had high transfection efficiency and early gene expression and maintenance of gene expression level for up to 96 h, although transfection efficiency were slightly lower than that of liposome in the initial 24 h. The biodegradable polymeric materials possess potential superiority as gene carriers.     

Supramolecular polymers

The study of polymeric-sized supramolecules constructed by non-covalent self-assembly or self-organization ([1]Moore JS: Molecular architecture and supramolecular chemistry. Curr Opin Solid State Mater Sci 1996, 1:777–788) continues to be a growing activity leading to interesting materials with unique features. An evolving theme is the self-organization of large covalent objects (shape-controlled mesomolecules) having high-definition molecular surfaces. The folding of polymer molecules into conformationally ordered states is a new vista on the horizon.     

Nanoparticles act as protein carriers during cellular internalization

Two-colour fluorescence microscopy was used to track the cellular internalization of nanoparticles exposed to extracellular serum proteins. Single particle tracking revealed that nanoparticles and serum proteins are internalized and transported through the cell as a single complex. This study demonstrates the importance of nanoparticle-protein interactions in cellular applications.     

Aqueous sec analysis of cationic polymers as gene carriers

Cationic polymers have been receiving much attention as non-viral gene vectors.The aqueous mobile phase was optimized in combination with Shodex OHpak SB columns for size-exclusion chromatography(SEC)analysis of disulfide-containing poly(ethylene imine)(PEI)derivatives used in gene delivery.Addition of acetonitrile in mobile phase was shown to be able to suppress the hydrophobic interactions between polymer analytes and the stationary phase.The absolute molecular weights and distributions of the cationic polymers were determined directly from online SEC-MALS(multi-angle light scattering)/RI(refractive index detector).The results demonstrate that a good SEC separation of disulfide-containing PEI derivatives used in gene delivery with little band broadening was achieved.     

Supramolecular polymers based on cyclodextrins

Two types of supramolecular polymers based on cyclodextrins were prepared. One was a host–guest type, and the other was a polyrotaxane type. When a guest part was covalently attached to cyclodextrin, they formed supramolecular dimers, a cyclic daisy chain, supramolecular oligomers, and polymers. t-Boc-cinnamamide-α-cyclodextrin was found to form chiral supramolecular polymers in aqueous solutions. Supramolecular poly[2]rotaxane polymers and supramolecular α,β-cyclodextrin copolymers were obtained. Polyrotaxanes containing β-cyclodextrin or γ-cyclodextrin were prepared. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5113–5119, 2006     

Synthetic and natural polymers as drug carriers for tuberculosis treatment

Drug forms based polymer carriers of prolong action were created for toxicologic effect of drug to be reduced in spite of long treatment of diseases. In present work a number of synthesis and natural polymers have been studied as carriers of antituberculous drugs for controlled delivery application. Following as drugs as isoniazid and ethionamide were incorporated into polymeric matrix (segmented polyurethanes, polyvinyl alcohol) and chemically bound with the polymer chain by covalent or electrostatic forces (aldehyde- and carboxymethylderivatives of polysaccharides). Biodegradation of polymeric systems and the release of drugs were studied by various physico-chemical methods. It was shown that the drug release depends of method of the immobilization, type of the drug/polymer bonding, drug loading. The bacteriostatic activity of obtained systems was determined. The possibility of tuberculosis treatment was proved in experiments of animals.     

Supramolecular polymers having chiral interactions

Poly(L-glutamate) having amphiphilic side chains was designed as membrane materials for optical resolution of α-amino acids. Solvent-cast films of the poly(glutamate) (PLG) had a self-ordered structure containing α-helix of the poly(L-glutamate). Optical resolutions of various amino acids were carried out through the thin membranes of the amphiphilic poly(L-glutamate). Racemic mixtures of Tryptophan were completely separated through the membrane. Mechanism of the optical resolutions was investigated in terms of molecular recognitions of racemic Tryptophan by the ordered structure of the membrane. Polymers having pendant PLG and α-amino acids were synthesized and their permeation behaviors were investigated.     

Supramolecular polymerization from polypeptide-grafted comb polymers

The helical and tubular structures self-assembled from proteins have inspired scientists to design synthetic building blocks that can be "polymerized" into supramolecular polymers through coordinated noncovalent interactions. However, cooperative supramolecular polymerization from large, synthetic macromolecules remains a challenge because of the difficulty of controlling the structure and interactions of macromolecular monomers. Herein we report the synthesis of polypeptide-grafted comb polymers and the use of their tunable secondary interactions in solution to achieve controlled supramolecular polymerization. The resulting tubular supramolecular structures, with external diameters of hundreds of nanometers and lengths of tens of micrometers, are stable and resemble to some extent biological superstructures assembled from proteins. This study shows that highly specific intermolecular interactions between macromolecular monomers can enable the cooperative growth of supramolecular polymers. The general applicability of this strategy was demonstrated by carrying out supramolecular polymerization from gold nanoparticles grafted with the same polypeptides on the surface.     

Supramolecular polymers formed by cinnamoyl cyclodextrins

6-Cinnamoyl α-cyclodextrin (6-CiO-α-CD) and 6-cinnamoyl β-cyclodextrin (6-CiO-β-CD) were prepared. 6-CiO-α-CD formed intermolecular complexes to give supramolecular oligomers. 6-CiO-β-CD formed insoluble supramolecular complexes in the solid state. The structures of these complexes are discussed. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3519–3523, 2003     

Supramolecular star polymers with compositional heterogeneity

We present the synthesis of supramolecular star polymers with heterogeneous chemical compositions through potassium cation‐templated assembly of guanosine end‐functionalized random, diblock, and Y‐shaped copolymers. The assembly and disassembly processes of the synthesized star polymers have been systematically examined on changing the concentration, the temperature, the solvent, and the amount of cation using ¹H NMR, UV/vis, and CD spectroscopy. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Vinyl polymers as non-viral gene delivery carriers: current status and prospects

Since the first application of polymers as non-viral gene delivery systems in 1965 by Vaheri and Pagano using functionalised dextran (A. Vaheri and J. S. Pagano, "Infectious poliovirus RNA: a sensitive method of assay", Virology 1965, 27, 434-6), a large number of different polymers have been developed, studied and compared for application as DNA carriers. Vinyl-based polymers are one type of polymers that have gained considerable interest. The interest in developing this particular type of polymer is partly related to the straightforward way in which large amounts of these polymers can be prepared by radical (co)polymerisation. This opens up a path for establishing a wide range of structure-property relations using polymer libraries. The present review aims to give an overview of past and ongoing research using vinyl-based gene delivery systems. The application of cationic, neutral and zwitterionic polymers as DNA carriers is summarised and discussed. [structure: see text] Chemical structure of DEAE-functionalised dextran.     

Doubly hydrophilic multiarm hyperbranched polymers with acylhydrazone linkages as acid-sensitive drug carriers

A novel type of drug carrier capable of controlled drug release is proposed. It consists of an acid-sensitive doubly hydrophilic multiarm hyperbranched copolymer with a hyperbranched polyamidoamine core and many linear poly(ethylene glycol) arms. Using pH-sensitive acylhydrazone linkages, the polymer forms unimolecular micelles that can encapsulate hydrophobic drugs. Due to their amphiphilicity, the drug-loaded unimolecular micelles can self-assemble into multimolecular micelles that show acid-triggered intracellular delivery of the hydrophobic drugs.     

Supramolecular polymers based on dative boron-nitrogen bonds

Heteroditopic monomers containing an arylboronate ester and a dialkyl-4-aminopyridine group aggregate via dative boron-nitrogen bonds to give main chain supramolecular polymers. The degree of polymerization can be tuned by changing the electronic and steric properties of the boronate ester.     

Amphiphilic comb-like polymers based on poly(oxyethylene)s as drug-delivery carriers

Comb-like polymers with biocompatible oxyethylene backbones and amphiphilic side groups were synthesized via polymer-analogous reactions. Using these polymers, indomethacin-loaded polymeric micelles were fabricated with various drug-to-polymer weight ratios using the oil-in-water emulsion technique. In addition, the size, size distribution, CMC, drug-loading content, and entrapment efficiency of the polymeric micelles were analyzed. The volume-weighted diameters of polymeric micelles ranged from 10 to 140 nm and were narrowly distributed for passive targeting drug delivery. The CMCs were lower (approximately 10(-8) M) than for conventional surfactants and block copolymers.     

Supramolecular polymers constructed by crown ether-based molecular recognition

Supramolecular polymers, polymeric systems beyond the molecule, have attracted more and more attention from scientists due to their applications in various fields, including stimuli-responsive materials, healable materials, and drug delivery. Due to their good selectivity and convenient enviro-responsiveness, crown ether-based molecular recognition motifs have been actively employed to fabricate supramolecular polymers with interesting properties and novel applications in recent years. In this tutorial review, we classify supramolecular polymers based on their differences in topology and cover recent advances in the marriage between crown ether-based molecular recognition and polymer science.     

Supramolecular recognition of estrogens via molecularly imprinted polymers

The isolation and preconcentration of estrogens from new types of biological samples (acellular and protein-free simulated body fluid) by molecularly imprinted solid-phase extraction has been described. In this technique, supramolecular receptors, namely molecularly imprinted polymers (MIPs) are used as a sorbent material. The recognition sites of MIPs were prepared by non-covalent multiple interactions and formed with the target 17β-estradiol as a template molecule. High-performance liquid chromatography with spectroscopic UV, selective, and a sensitive electrochemical CoulArray detector was used for the determination of 17β-estradiol, estrone, and estriol in simulated body fluid which mimicked human plasma.     

Supramolecular helical mesomorphic polymers. Chiral induction through H-bonding

The work described here concerns a challenge of general interest in supramolecular chemistry: the achievement of chiral helical organizations with controlled structures. This work provides a strategy to obtain supramolecular polymers in which a chiral helical conformation has been induced by a noncovalent association, that is, through hydrogen bonding. Polycatenar 2,4,6-triarylamino-1,3,5-triazines, which organize into columnar mesophases and are susceptible to H-bonding interactions, were chosen as a starting point to build up the chiral supramolecular structure. The stacking of these mesogens has been forced to wind in a helical way by means of H-bond association with (R)-3-methyladipic acid, within the mesophase. The optically active columnar organization has been studied in depth by optical microscopy, differential scanning calorimetry (DSC), X-ray diffraction, and circular dichroism. Formation of stable complexes between the triazine units and (R)-3-methyladipic acid has also been investigated by means of NMR diffusion-ordered spectroscopy (DOSY) experiments in chloroform.     

Supramolecular pseudorotaxane polymers from complementary pairs of homoditopic molecules

Self-assembly of supramolecular pseudorotaxane polymers from complementary homoditopic building blocks comprised of bis(dibenzo-24-crown-8) esters derived from the hydroxymethyl crown ether and aliphatic diacid chlorides (CxC, x = number of methylene units in the diacid segment) and 1,10-bis[p-(benzylammoniomethyl)phenoxy]alkane bis(hexafluorophosphate)s (AyA, y = number of methylene units in the linker) has been studied. (1)H NMR spectroscopic studies of bis[(2-dibenzo-24-crown-8)methyl] sebacate (C8C) with dibenzylammonium hexafluorophosphate (6) showed that the two binding sites of the ditopic host are equivalent and independent (no positive or negative cooperativity). Likewise the binding sites in 1,10-bis[p-(benzylammoniomethyl)phenoxy]decane bis(hexafluorophosphate) (A10A) were shown to behave independently with dibenzo-24-crown-8 (1a). Then using (1)H NMR spectroscopy on dilute equimolar solutions (<1 mM) of CxC and AyA association constants were estimated for the formation of the linear (lin-CxC*AyA) and cyclic (cyc-CxC*AyA) dimers, thus enabling effective molarities to be estimated for the various systems. Finally (1)H NMR spectroscopy was used to semiquantitatively or qualitatively demonstrate the formation of linear supramolecular polymers lin-[CxC*AyA](n) in more concentrated solutions (up to 2.0 M) of the complementary pairs of CxC and AyA. The sizes of the assemblies (n values) are not as great as the dilute solution studies predict; this is attributed to the deleterious effect of ionic strength and exo complexation at high concentrations. However, as expected from the dilute solution results, linear extension is indeed favored with the longer building blocks, meaning that "monomer" end-to-end distance is a key factor in reducing the amount of cyclic species that form. Viscosity experiments clearly demonstrate the formation of large noncovalent polymers lin-[CxC*AyA](n) in concentrated solutions. Cohesive film and fiber formation also indicate that supramolecular polymers of sufficient size to enable entanglement self-assemble in these solutions.