Recognition-mediated hydrogel swelling controlled by interaction with a negative thermoresponsive LCST polymer

Most polymeric thermoresponsive hydrogels contract upon heating beyond the lower critical solution temperature (LCST) of the polymers used. Herein, we report a supramolecular hydrogel system that shows the opposite temperature dependence. When the non-thermosesponsive hydrogel NaphtGel, containing dialkoxynaphthalene guest molecules, becomes complexed with the tetra cationic macrocyclic host CBPQT4+, swelling occurred as a result of host–guest complex formation leading to charge repulsion between the host units, as well as an osmotic contribution of chloride counter-ions embedded in the network. The immersion of NaphtGel in a solution of poly(N-isopropylacrylamide) with tetrathiafulvalene (TTF) end groups complexed with CBPQT4+ induced positive thermoresponsive behaviour. The LCST-induced dethreading of the polymer-based pseudorotaxane upon heating led to transfer of the CBPQT4+ host and a concomitant swelling of NaphtGel. Subsequent cooling led to reformation of the TTF-based host–guest complexes in solution and contraction of the hydrogel

Hyaluronic Acid-Poly(N-acryloyl glycinamide) Copolymers as Sources of Degradable Thermoresponsive Hydrogels for Therapy

One-pot free-radical polymerization of N-acryloyl glycinamide in the presence of hyaluronic acid as transfer-termination agent led to new copolymers in high yields without any chemical activation of hyaluronic acid before. All the copolymers formed thermoresponsive hydrogels of the Upper Critical Solution Temperature-type in aqueous media. Gel properties and the temperature of the reversible gel ↔ sol transition depended on feed composition and copolymer concentration. Comparison with mixtures of hyaluronic acid-poly(N-acryloyl glycinamide) failed in showing the expected formation of graft copolymers conclusively because poly(N-acryloyl glycinamide) homopolymers are also thermoresponsive. Grafting and formation of comb-like copolymers were proved after degradation of inter-graft hyaluronic acid segments by hyaluronidase. Enzymatic degradation yielded poly(N-acryloyl glycinamide) with sugar residues end groups as shown by NMR. In agreement with the radical transfer mechanism, the molar mass of these released poly(N-acryloyl glycinamide) grafts depended on the feed composition. The higher the proportion of hyaluronic acid in the feed, the lower the molar mass of poly(N-acryloyl glycinamide) grafts was. Whether molar mass can be made low enough to allow kidney filtration remains to be proved in vivo. Last but not least, Prednisolone was used as model drug to show the ability of the new enzymatically degradable hydrogels to sustain progressive delivery for rather long periods of time in vitro

Affinity Chromatography as a Tool to Analyze Polyanion–Polycation Complexes: the Case of Poly(Llysine Citramide)–Poly(L-lysine) Systems

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Poly[(N-acryloyl glycinamide)-co-(N-acryloyl l-alaninamide)] and Their Ability to Form Thermo-Responsive Hydrogels for Sustained Drug Delivery

In the presence of water, poly(N-acryloyl glycinamide) homopolymers form highly swollen hydrogels that undergo fast and reversible gel↔sol transitions on heating. According to the literature, the transition temperature depends on concentration and average molecular weight, and in the case of copolymers, composition and hydrophilic/hydrophobic character. In this article, we wish to introduce new copolymers made by free radical polymerization of mixtures of N-acryloyl glycinamide and of its analog optically active N-acryloyl l-alaninamide in various proportions. The N-acryloyl l-alaninamide monomer was selected in attempts to introduce hydrophobicity and chirality in addition to thermo-responsiveness of the Upper Critical Solubilization Temperature-type. The characterization of the resulting copolymers included solubility in solvents, dynamic viscosity in solution, Fourrier Transform Infrared, Nuclear Magnetic Resonance, and Circular Dichroism spectra. Gel→sol transition temperatures were determined in phosphate buffer (pH = 7.4, isotonic to 320 mOsm/dm3). The release characteristics of hydrophilic Methylene Blue and hydrophobic Risperidone entrapped in poly(N-acryloyl glycinamide) and in two copolymers containing 50 and 75% of alanine-based units, respectively, were compared. It was found that increasing the content in N-acryloyl-alaninamide-based units increased the gel→sol transition temperature, decreased the gel consistency, and increased the release rate of Risperidone, but not that of Methylene Blue, with respect to homo poly(N-acryloyl glycinamide). The increase observed in the case of Risperidone appeared to be related to the hydrophobicity generated by alanine residues

Roles of hydrophobicity and charge density on the dynamics of polyelectrolyte complex formation and stability under modeled physicochemical blood conditions

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Dynamics of polyelectrolyte complex formation and stability when a polycation is progressively added to a polyanion under physico-chemical conditions modeling blood

International audienceThe formation of polyelectrolyte complexes is known to depend on many factors, especially pH, temperature, and ionic strength, as well as acid-base properties and mixing conditions. In an approach aimed at by-passing the complexity of blood, the formation and the stability of complexes between oppositely charged polymers were studied in salted media (0.15N NaCl and 0.13 M, pH 7.4 PBS) at room temperature. Different molar masses of poly(L-lysine) were reacted with polyanions with different chemical structures and charge densities, namely: poly(acrylic acid), poly(L-lysine citramide), poly(L-lysine citramide imide), and poly(malic acid). A stepwise protocol was used to investigate the fractionation phenomena reported previously. After each addition, the precipitate was separated and analyzed. The polyanion macromolecules were fractionated according to their structure; no significant fractionation was observed for the polycation. The NaCl concentration, required to destabilize the complexes in the isolated fractions, was found to depend on the polycation molar mass and to vary linearly with log(polyanion Mw). Based on these data, the possible fate of polycationic species, and of polycation-based polyelectrolytic complex, when injected into blood, are addressed

Degradability of poly(L-lysine) and poly(DL-aminoserinate) complexed with a polyanion under conditions modelling physico-chemical characteristics of body fluids

International audiencePoly(L-lysine), (PLL), and poly(DL-amino serinate), (PSA), are respectively enzymatically and hydrolytically degradable polycations. This work was aimed at investigating their degradability when they are complexed with polyanions, namely poly(acrylic acid) and poly(L-lysine citramide), taken as simple models of DNA in polyplexes. Comparison was made with degradation characteristics of the same polycations in solution in the absence of polyanion on the basis of size exclusion chromatography and capillary zone electrophoresis. Complexed PLL remained enzymatically degradable by trypsin, an endopeptidase, but was no longer degradable by aminopeptidase, an exopeptidase. Trypsin yielded a mixture of trilysin and tetralysin. Complexed PSA remained hydrolytically degradable in aqueous media. The hydrolysis of PSA led to DL-serine. However, traces of anionic species were also detected that were identified as residues of constituting repeating units issued from the N-benzyloxycarbonyl polyaminoserinate precursor (PSAZ)

Dynamics of polyelectrolyte complex formation and stability as a polyanion is progressively added to a polycation under modeled physicochemical blood conditions

International audienceTo understand the fate of anionic macromolecular species when injected into blood, poly(acrylic acid) and poly(L-lysine citramide) polyanions, with better charge densities, and the poly(L-lysine) polycation were used as models of negatively charged polymer-drug conjugates and positively charged blood proteins, respectively. To mimic an intravenous injection, the polyanion was added to the poly(L-lysine) stepwise at room temperature. The polyelectrolyte complexes formed as precipitates and the molar mass fractionation was observed from one fraction to the other, especially in the case of largely polydispersed poly(L-lysine). The salt concentration necessary to return each fraction of complexed polyelectrolyte back to solution varied linearly with the logarithm of the molar mass of the polycation component. The physicochemical characteristics data of the polyelectrolytes and the media are compared to previously reported reverse mixing mode when the polycation is introduced into a solution of polyanions

A physico-chemical approach of polyanion-polycation interactions aimed at better understanding the in vivo behaviour of polyelectrolyte-based drug delivery and gene transfection.

International audiencePolyanions and polycations are known to interact electrostatically and form soluble or insoluble polyelectrolyte complexes. Body fluids, blood and cells are composed of many polyelectrolytic systems such as proteins, glycoproteins, poly(glycosamino glycane)s, polynucleotides, etc. under physiological conditions. Nowadays synthetic polyelectrolytes are proposed as carriers of bioactive compounds, such as drugs and genes, and are thus to be injected into body fluids. For the sake of better understanding the complex behaviour of such artificial polyelectrolytic systems in the pool of natural polyelectrolytes forming living systems, interactions of bi- and multi-components mixtures of synthetic polyanions with the same synthetic polycation, namely poly[(dimethylaminoethyl) methacrylate], HCl, were investigated under the conditions imposed by physiological media, namely pH = 7.4, ionic strength mu = 0.15 and T = 37 degrees C. The selected artificial polyanions were the sodium salts of poly(acrylic acid), poly(methacrylic acid), poly(L-lysine citramide) and poly(styrene sulfonic acid) which have different acid strength, charge density and ionogenic group. The influence of ionic strength and pH on complex formation and stability was investigated by turbidimetry at lambda = 520 nm. Phase separation occurred regardless of ionic strength in the case of sodium polystyrene sulfonate. For the other polyanions, redissolution was observed at critical NaCl concentrations much higher than the physiological ionic strength. In the case of mixtures of two or three polyanions with the polycation, the complex formation appeared polyanion-selective at physiological ionic strength. Data are discussed with regard to phenomena that can occur in vivo