Radiation polymerization of thermo-sensitive poly (N-vinylcaprolactam)

Temperature-sensitive poly (N-vinylcaprolactam) both in water-soluble state and in gel was prepared by γ-radiation polymerization. The effects of radiation dose, radiation dose rate and monomer concentration on polymerization and the low critical solution temperature characteristics of the polymer were studied. The results show that the polymer prepared within certain radiation dose (beyond 2 kGy) and dose rate range (2–14 Gy/min) has good temperature sensitivity and uniformity.     

Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery

Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL₁₀-b-PDMS₆₅-b-PVCL₁₀ vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg⁻¹ single dose) of PVCL₁₀-PDMS₆₅-PVCL₁₀ vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research.     

New Approach to Determine the Phase Transition Temperature,Cloud Point,of Thermoresponsive Polymers

In this study, a novel method to determine the cloud point temperature variation in aqueous solutions of thermoresponsive homo- and copolymers was developed. Poly(N-vinylcaprolactam) (PVCL) and triblock copolymers of poly(t-butyl acrylate-co-acrylic acid)-b-poly(N-vinylcaprolactam)-b-(t-butyl acrylate-co-acrylic acid) (P[(tBA-co-AA)-b-PVCL-b-P(tBA-co-AA)] were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and used as models. The incorporation of AA units (hydrophilic segments) into the polymeric chain of PVCL influenced the phase transition, increasing the cloud point temperature of the final copolymer. The cloud point temperatures of the PVCL and the triblock copolymer P(tBA-co-AA)-b-PVCL-b-P(tBA-co-AA) were determined by measuring the transmittance of aqueous solutions of the polymers in a Turbiscan Lab instrument in the range of 29 to 40 C. This is the first study in which Turbiscan Lab is used to determine the cloud point temperature.     

Reactivities of Dialkyl Dithiol Mesaconates in Radical Copolymerization with Styrene

Nine novel types of dialkyldithiol mesaconates (DRTM, M₁) were synthesized and copolymerized with styrene (Ma) in tetrahydro-furan at 60 °C in order to clarify the polymerization behavior of DRTM and the substituent effects on the copolymerization. From the results obtained, the monomer reactivity ratio r₁, r₂ and Q₁, e₁ values were determined. It was found that the relative reactivities l/r₂ of DRTM toward an attack by polystyryl radical were correlated only by the polar substituent constant σ? of the alkyl group in DRTM, but not by the steric substituent constant E, in Taft's equation: log (l/r₂) = σ?σ? + ΔE_s. It was also observed that the Q₁ and e₁ values for DRTM were correlated by Taft's σ? constant. The number-average molecular weights of the DRTM-ST copolymer were found to be between 5.0 × 10³ and 1.2 × 10⁴.     

Polymerization of N-Vinylcaprolactam and Characterization of Poly(N-Vinylcaprolactam)

Poly(N-vinylcaprolactam), PNVCL, is a nonionic, nontoxic, water soluble, thermally sensitive and biocompatible polymer. It contains hydrophilic carboxylic and amide groups with hydrophobic carbon-carbon backbone suitable for biomedical applications. In this study, N-vinylcaprolactam was polymerized by free radical polymerization at 50, 60 and 70°C. The synthesized polymers were white powder, soluble in water and common organic solvents. The percent conversion vs. time plot is almost linear up to about 60% conversion without induction period. The activation energy of polymerization was calculated as 108.4 kJ/mol from the Arrhenius plot. FTIR and NMR results showed that polymerization takes place by opening of carbon-carbon double bond without any change in the caprolactam ring. Polymer was characterized by FTIR, ¹H-NMR and ¹³C -NMR, DSC, TGA and XRD techniques. The DSC thermogram of monomer has shown a melting point at 37.3°C. The polymer has T_g value at 1.8°C and softening temperature at 68.8°C. It was determined from the X-Ray powder pattern that the polymerization proceed in the b-crystallographic axis direction.     

Mild and Simple Access to Diverse 4-Amino-substituted 2-Phenyl-1,2,3,4-tetrahydroquinolines and 2-Phenylquinolines Based on a Multicomponent Imino Diels–Alder Reaction

A straightforward synthesis of new 1-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones/azepan-2-one from N-vinyl caprolactam/N-vinylpyrrolidin-2-one and N-benzylideneaniline via the imino Diels–Alder reaction has been reported for the first time. Antimony(III) chloride has been shown to effectively catalyze imino-Diels–Alder reaction to afford both 2-phenylquinoline and 2-phenyl-1,2,3,4-tetrahydroquinolin derivatives in excellent yields at ambient temperature. The cis diastereoselectivity to give cis 2-phenyl-1,2,3,4-tetrahydroquinolines is also highlighted in this reaction.     

Stability and thermosensitive properties of various poly (N-vinylcaprolactam) microgels

Thermally responsive microgels have been synthesised by polymerising N-vinylcaprolactam under various conditions. Stabilisation of the latices was of special interest and, thus, electrostatically, sterically, and electrosterically stabilised particles were prepared. Electrostatic stabilisation was achieved by the use of an ionic initiator and/or an ionic detergent. Steric stabilisation was realised through a macromonomer technique, where polymerisable poly(ethylene oxide)-containing macromonomers were utilised as a detergent. Capillary electrophoresis was used to compare the electrokinetic properties of the polymer particles. All the product particles show thermal behaviour typical of poly(vinylcaprolactam), but sterically stabilised ones are superior in the stability against added electrolytes. Received: 24 April 2001 Accepted: 13 August 2001     

Optimization of adsorption conditions of BSA on thermosensitive magnetic composite particles using response surface methodology

Thermosensitive core-shell magnetic composite particles with a magnetic silica core and a rich poly (N-vinylcaprolactam) (PNVCL) shell layer were developed for studying the adsorption of bovine serum albumin (BSA) in a batch system. Various analytical and spectroscopic techniques including SEM, FT-IR, VSM and DSC were used to characterize the adsorbents prepared in this study. The combined effects of operating parameters such as initial temperature, pH and initial BSA concentration on the adsorption were analyzed using response surface methodology. The optimum conditions were 40°C, pH 4.68, and initial BSA concentration 2.0 mg/mL. Desorption experiments were conducted by altering the system temperature where a high recovery rate of protein was obtained. The separation process developed here indicates that the dual-responsive smart adsorbent could be an ideal candidate for the separation of protein.