New pH-Sensitive Hydrogels for Oral Delivery of Hydrophobic Drugs

A series of acrylic copolymers containing silyl pendant groups was prepared by free radical cross-linking copolymerization. Me₃Si, Et₃Si, and Ph₃Si together with cubane-1,4-dicarboxylic acid (CDA) were covalently linked with 2-hydroxyethyl methacrylate (HEMA). CDA linked to two HEMA group is the cross-linking agent (CA). Free radical cross-linking copolymerization of the methacrylic acid (MAA) and organosilyl monomers with two different molar ratios of CA was carried out at 60–70°C. The compositions of the cross-linked three-dimensional polymers were determined by FT-IR spectroscopy. The glass transition temperature of the network polymers was determined calorimetrically. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). A model hydrophobic drug, the steroid hormone estradiol, was entrapped in these gels, and the in vitro release profiles were established separately in both SGF (pH 1) and SIF (pH 7.4). Incorporation of silyl groups in a new macromolecule system modified network polymers for drug delivery.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Site‐specific reversible immobilization and purification of His‐tagged protein on poly(2‐acetamidoacrylic acid) hydrogel beads

Ni²⁺‐complexed poly(2‐acetamidoacrylic acid) (PAAA) hydrogel beads were developed for the site‐specific reversible immobilization and purification of the histidine‐tagged green fluorescent protein (His‐tagged GFP). PAAA hydrogel beads were prepared by photopolymerization, and significantly improved mechanical properties of PAAA hydrogel beads were observed in comparison with PAAA hydrogel from our previous study. Confocal laser scanning microscopy was used to determine the binding of His‐tagged GFP to the hydrogel beads in three‐dimensional space. Photoluminescence spectroscopy revealed 89% of binding efficiency of His‐tagged GFP to the Ni²⁺‐PAAA hydrogel beads, 51% of yielding recovery. The maximum binding capacity of His‐tagged GFP was estimated to be 0.45 µg/mg of Ni²⁺‐PAAA hydrogel beads. The recombinant His‐tagged GFP from the soluble fraction of E. coli BL21(DE3) cell lysates was purified with Ni²⁺‐PAAA hydrogel beads. The major advantage of the Ni²⁺‐PAAA hydrogel beads system was simple preparation procedures of producing the matrix, because PAAA hydrogel beads had relatively enhanced mechanical strength than soft hydrogels. Copyright © 2012 John Wiley & Sons, Ltd.     

Injectable Graphene Oxide/Graphene Composite Supramolecular Hydrogel for Delivery of Anti-Cancer Drugs

Injectable hydrogels have attracted a lot of attention in drug delivery, however, their capacity to deliver water-insoluble or hydrophobic anti-cancer drugs is limited. Here, we developed injectable graphene oxide/graphene composite supramolecular hydrogels to deliver anti-cancer drugs. Pluronic F-127 was used to stabilize graphene oxide (GO) and reduced graphene oxide (RGO) in solution, which was mixed with α-cyclodextrin (α-CD) solution to form hydrogels. Native hydrogel was used as control. GO or RGO slightly shortened gelation time. The storage and loss moduli of the hydrogels were tracked by dynamic force measurement. The storage modulus of GO or RGO composite hydrogels was larger than that of the native hydrogel. Hydrogels were unstable in solution and eroded gradually. GO or RGO in Pluronic F-127 solution could potentially improve the solubility of the water-insoluble anti-cancer drug camptothecin (CPT), especially with large drug-loaded CPT amount. Drug release behaviors from solutions and hydrogels were characterized. The nanocomponents (GO or RGO) were able to bind more drug molecules either for CPT or for doxorubicin hydrochloride (DXR) in solution. Therefore, GO or RGO composite hydrogel could potentially enable better controlled and gentler drug release (for both CPT and DXR) than native hydrogel.     

Study on Biological Safety of Polyvinyl Alcohol/Collagen Hydrogel as a Tissue Substitute (II)

Physically crosslinked polyvinyl alcohol/collagen composite hydrogels were prepared by a cyclic freezing-drying technique. The biological properties of the hydrogels, including hemolysis, anaphylaxis, pyrogen and acute systemic toxicity tests and implantation in-vivo, were investigated. The hemolysis test suggested that the polyvinyl alcohol/collagen, with a hemolysis index of 1.19%, did not have an obvious hemolysis reaction. There was no toxicosis or death cases observed in the acute systemic toxicity test, and the hydrogel showed no anaphylaxis or pyrogen response. The composite hydrogel showed a good histological compatibility in the in-vivo study. The results indicated that the polyvinyl alcohol/collagen composite hydrogels have promising applications for pharmaceutical and biomedical fields.     

Design of Chitosan-5Fu Conjugate Exhibiting Antitumor Activity

In order to provide a macromolecular prodrug of 5-fluorouracil (5FU) reducing the side effects, having an affinity for tumor cells, and exhibiting strong antitumor activity, the covalent attachments of 5FUs to chitosan and chitosamino-oligosaccharide (COS) through hexamethylene spacer groups via urea, urea bonds were carried out. The effect of prolongation of life was tested in vivo against p388 lyrnphocytic leukemia in female CDF, mice by intra-peritoneal (i.p.) transplantation/i.p. injection and the growth-inhibitory effect on Meth-A fibrosarcoma or MH-134Y heputoma was evaluated in vivo in SPF-C3H/He scl male or Balb/c male mice by subcutaneous (s.c.) implantation/intravenous (i.v.) injection. The effects of the degree of polymerization of chitosan and     

The Preparation,Characterization and Properties of Catalase Immobilized on Crosslinked Gellan

In the present paper, the reaction of chemical immobilization of catalase on a crosslinked macromolecular carrier of a polysaccharide structure (gellan) is studied. The influence of some reaction parameters (enzyme/carrier, activator/carrier ratios, duration) on the activity of enzymatic products is analyzed. The kinetics of the biocatalytic process, stability under different pH and temperature conditions, and the inhibitors effect were studied for the immobilized enzymes.     

Application Properties of Stimuli-Responsive Polyglycerol Hydrogels

Transient state swelling behavior and swelling kinetics of novel stimuli-responsive polyglycerol hydrogels were studied at 293, 310 and 333 K. Depending on temperature, Fickian or anomalous diffusion behavior was observed. Mechanical properties of the hydrogels in the swollen and dry states were investigated and the average molecular weight between crosslinks was calculated. To assess the potential for biodegradation of hydrogels, initial swelling behavior in phosphate buffered saline (PBS) solution and mass loss profiles as a function of degradation time were investigated over a period of 30 days. All swelling behavior, mechanical properties and degradations were clearly affected by the degree of cross-linking. The hydrophilicity and biodegradability of polyglycerol hydrogels make them suitable for pharmaceutical, biomedical and biotechnological applications. They could potentially serve as a substitute for common fossil-based hydrogels such as poly(ethylene glycol) and poly(vinyl alcohol) hydrogels.     

Preparation of PEO-b-PPO-b-PEO/α-cyclodextrin supramolecular hydrogels hybridized with exfoliated graphite nanoplates

Abstract

In this work, an effective method was developed to prepare novel PEO-b-PPO-b-PEO (EPE)/α-cyclodextrin (α-CD) supramolecular hydrogels containing exfoliated graphite nanoplates (xGNPs) by mixing an aqueous solution of α-CD with an aqueous dispersion of xGNPs at the presence of amphiphilic EPE copolymer. The EPE copolymer played three important roles in the preparation process: (1) as an exfoliating agent to break expanded graphites into xGNPs under ultrasonication, (2) as a dispersant to stabilize xGNPs in the aqueous solution, and （3）as a component to form the inclusion complexes with α-CD. The resultant xGNPs/EPE/α-CD hybridized hydrogels were characterized by scanning electron microscopy, wide-angle X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy, which confirmed not only the formation of supramolecular hydrogel structure but also the homogenous dispersion of xGNPs in the hydrogel matrix. It was found that the existence of xGNPs can accelerate the speed of gel formation in comparison with that of the native EPE/α-CD hydrogel. Additionally, the water-retention ability and the release behavior of vancomycin hydrochloride for the xGNPs/EPE/α-CD hybridized hydrogels were investigated.     

Search for a Steric Penultimate Effect: Copolymerization of 2,3,4-Trimethyl-3-pentyl Methacrylate with Styrene

The hindered monomer, 2,3,4-trimethyl-3-pentyl methacrylate (I), was synthesized for penultimate effect studies. Since it readily homopoiymerized (km¹¹¹≠ 0) and readily copolymerized with styrene, copolymerizations of I with styrene were carried out at 60°C in benzene with AIBN as initiator. The conversion to copolymer and the copolymer composition were determined by using GLC techniques. Composition-conversion data was analyzed by performing a computerized nonlinear least-squares fitting to the integrated form of the penultimate model equation. The experimental design included the use of optimized M¹°/M²° ratios. The penultimate reactivity ratios calculated from these data were r¹′ = 0.23, r¹′= 0.59, r² = 0.59, r²′ = 1.34. Thus, when I is the penultimate unit, a terminal styryl radical prefers to add styrene, whereas when styrene is the penultimate unit, terminal styryl radicals prefer to add I. These results constitute the best evidence for a steric penultimate effect yet available in the literature from composition-conversion studies. However, the case is not yet proved. Further studies to strengthen this conclusion are proposed.