Ethoxysilane-capped PEO-PPO-PEO triblocks: a new family of reverse thermo-responsive polymers.

New reverse thermo-responsive polymers systems combining reverse thermal gelation behavior and a gradual increase in the mechanical properties, were created by crosslinking ethoxysilane-capped poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblocks in aqueous solutions at physiological conditions. Pluronic F127 (PEO(99)-PPO(67)-PEO(99)) was functionalized with (3-isocyanatopropyl) triethoxysilane (IPTS) by reacting its terminal hydroxyl groups with the isocyanate. The silane-capped PEO-PPO-PEO triblock was characterized by (1)H-NMR, GPC, FT-IR and DSC and the rheological behavior of its aqueous solutions were studied. The silane-containing triblock retained the reverse thermo-responsive characteristics displayed by the original Pluronic. Over time, the ethoxysilane groups hydrolysed and created silanol moieties that subsequently condensated, crosslinking the material and generating hydrogels that exhibited gradually increasing mechanical properties. It was found that the higher the pH, the faster the process and the higher the viscosity levels attained. Finally, the ability of these gels to perform as matrices for drug delivery was exemplified by releasing metronidazole and methylene blue. Findings showed that while a 30% F127 gel at 37 degrees C delivered all the drug within less than 3 days, F127di-IPTS gels completed the process at a much slower rate (up to 15 days).

[1]  D. Cohn,et al.  Novel reverse thermoresponsive injectable poly(ether carbonate)s , 2003, Journal of materials science. Materials in medicine.

[2]  C. Bunel,et al.  Low molar mass polybutadiene made crosslinkable by the introduction of silane moities via urethane linkage: 1. Synthesis and kinetic study , 1998 .

[3]  D. Avnir,et al.  Early stages of the silicon alkoxide sol/gel polymerization as detected by dynamic light scattering , 1987 .

[4]  H. Hoffmann,et al.  Phase Diagrams and Aggregation Behavior of Poly(oxyethylene)-Poly(oxypropylene)-Poly(oxyethylene) Triblock Copolymers in Aqueous Solutions , 1994 .

[5]  C. Booth,et al.  Micellisation and gelation of triblock copoly(oxyethylene/oxypropylene/oxyethylene), F127 , 1992 .

[6]  B. Cantor,et al.  Poloxamer 407 as an Intraperitoneal Barrier Material for the Prevention of Postsurgical Adhesion Formation and Reformation in Rodent Models for Reproductive Surgery , 1991, Obstetrics and gynecology.

[7]  D. Cohn,et al.  Poly(ethylene glycol)-poly(epsilon-caprolactone) block oligomers as injectable materials , 2003 .

[8]  A. Banga,et al.  Controlled release of human growth hormone following subcutaneous administration in dogs , 1997 .

[9]  C. Booth,et al.  Thermodynamics of micellisation and gelation of oxyethylene/oxypropylene diblock copolymers in aqueous solution studied by light scattering and differential scanning calorimetry , 1992 .

[10]  J. Seppälä,et al.  Biodegradable crosslinked polymers based on triethoxysilane terminated polylactide oligomers , 2001 .

[11]  G. Abraham,et al.  Crosslinkable PEO-PPO-PEO-based reverse thermo-responsive gels as potentially injectable materials , 2003, Journal of biomaterials science. Polymer edition.

[12]  A. Zhu,et al.  Preparation and characterization of novel silica-butyrylchitosan hybrid biomaterials* , 2003, Journal of materials science. Materials in medicine.

[13]  M. Yokoyama Block copolymers as drug carriers. , 1992, Critical reviews in therapeutic drug carrier systems.

[14]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[15]  Alexander V. Kabanov,et al.  A new class of drug carriers: micelles of poly(oxyethylene)-poly(oxypropylene) block copolymers as microcontainers for drug targeting from blood in brain☆ , 1992 .

[16]  A S Hoffman,et al.  "Intelligent" polymers in medicine and biotechnology. , 1995, Artificial organs.

[17]  Sung Wan Kim,et al.  Biodegradable block copolymers as injectable drug-delivery systems , 1997, Nature.

[18]  You Han Bae,et al.  Thermosensitive sol-gel reversible hydrogels. , 2002, Advanced drug delivery reviews.

[19]  Allan S. Hoffman,et al.  Applications of thermally reversible polymers and hydrogels in therapeutics and diagnostics , 1987 .

[20]  K. Br,et al.  Current status of DNA vaccines in veterinary medicine. , 2000 .

[21]  S. Hill,et al.  Measurement of the rheology of polysaccharide gels by penetration , 1999 .

[22]  G. Daculsi,et al.  General properties of silated hydroxyethylcellulose for potential biomedical applications. , 2002, Biopolymers.

[23]  Daniel Cohn,et al.  Improved reverse thermo-responsive polymeric systems. , 2003, Biomaterials.

[24]  P. Alexandridis,et al.  Small-Angle Neutron Scattering Investigation of the Temperature-Dependent Aggregation Behavior of the Block Copolymer Pluronic L64 in Aqueous Solution† , 2000 .

[25]  David Avnir,et al.  Enzymes and Other Proteins Entrapped in Sol-Gel Materials , 1994 .

[26]  D. Avnir,et al.  One-pot sequences of reactions with sol-gel entrapped opposing reagents: an enzyme and metal-complex catalysts. , 2002, Journal of the American Chemical Society.

[27]  T. A. Hatton,et al.  Poly(ethylene oxide)-poly(propylene oxide )-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling , 1995 .

[28]  L. Reeve The Poloxamers: their chemistry and medical applications , 1998 .

[29]  R. Nalbandian,et al.  Artificial skin. II. Pluronic F-127 Silver nitrate or silver lactate gel in the treatment of thermal burns. , 1972, Journal of biomedical materials research.

[30]  N. Peppas,et al.  Hydrogels in Pharmaceutical Formulations , 1999 .

[31]  C. Nastruzzi,et al.  Comparative analysis of tetracycline-containing dental gels: Poloxamer- and monoglyceride-based formulations , 1996 .