Cytotherapeutics, Inc.

Other

The Governing Council of the University of Toronto

Bonetec Corporation

Matregen Corp.

Neurotech S.a.

Shoichet, Molly S.

Molly S Shoichet

Frank T Gentile

Patrick Aebischer

Joseph P Hammang

Edward J Doherty

Shelley R Winn

Brian M Cain

Laura M Holland

Malcolm Schinstine

John Edward Davies

Michael J Cooke

Chantal E Holy

Jordan H Wosnick

Milton Harris

Paul D Dalton

Robert Daniel Lousenberg

Yakov Lapitsky

Robert D Lousenberg

Yumin Yuan

Derek Van Der Kooy

Ryan Wylie

Dimpy Gupta

Meng Shi

Charles H Tator

Sonja Ing

Malgosia M Pakulska

M Douglas Baumann

Limin Guan

Catherine Elizabeth Kang

Yuanfei Wang

John E Davies

Tasneem Zahir

Stephane G Levesque

Jaclyn M Obermeyer

Irja Elliott Donaghue

Brian Ballios

C Ross Ethier

Arthur J Sit

Catherine E Kang

A bioresorbable, sustained release pharmaceutical composition comprising: 1.8 wt % to 3.0 wt % methylcellulose and 0.1 wt % to 3.0 wt % hyaluronan in the form of a gel polymer matrix, and at least one local anesthetic agent, suitably ropivacaine, which may be administered by injection.

Sustained release local anesthetic hydrogel composition

A method of reducing or limiting tissue adhesion comprises contacting the tissue with an effective amount of a hydrogel composition comprising: 2% to 6% by weight hyaluronan, and 3% to 18% by weight methylcellulose, wherein the combined total amount of hyaluronan and methylcellulose in the hydrogel is between 8 and 24% by weight; and wherein the ratio of hyaluronan:methylcellulose is between 1:1 and 1:5 w/w. The hydrogel composition and may be used to reduce or limit tissue adhesion that is correlated with surgery, and may be used in surgeries wherein the surgery is performed through a small incision or opening.

Anti-adhesive hydrogel composition

The present disclosure provides a delivery system for controlled protein release without encapsulation. Identical, burst-free, extended release profiles for three different protein therapeutics were obtained with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, it was shown that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, tunable release was demonstrated by modifying nanoparticle concentration, nanoparticle size, or environmental pH. Additionally, the utility of this system was demonstrated in vivo for BDNF delivery in a rat model of stroke. These new insights obviate the need for encapsulation and offer promising, translatable strategies for more effective delivery of therapeutic biomolecules.

Encapsulation-free controlled protein release system

The present invention provides a method for the covalent immobilization of biomolecules on polymers for delivery of the biomolecules, which has the advantage of being simple, highly efficient, environmentally friendly and free of side products relative to traditional immobilization techniques. The invention provides a modified micro/nanoparticle system, which uses a functionalized polymer formed into micro or nanoparticles to bind a molecule to the particles using uses facile chemistry, the Diels-Alder cycloaddition between a diene and a dienophile with the polymer being functionalized with one of them and the molecule with the other, or the Huisgen 1,3-dipolar cycloaddition between a terminal alkyne and an azide to bind the molecule to the particle. The molecules and/or other therapeutic agents may be encapsulated within the polymer particles for intravenous therapeutic delivery. The invention also provides a novel synthetic biodegradable polymer, a furan/alkyne-functionalized poly(trimethylene carbonate) (PTMC)-based polymer, whose composition can be designed to meet the defined physical and chemical property requirements. In one example, the particle system self-aggregates from functionalized PTMC-based copolymers containing poly(ethylene glycol) (PEG) segments. The composition of the copolymers can be designed to meet various particle system requirements, including size, thermodynamic stability, surface PEG density, drug encapsulation capacity and biomolecule immobilization capacity.

Method of biomolecule immobilization on polymers using click-type chemistry

The present invention relates to a composite hydrogel comprising a blend of an aqueous solution of an anionic polysaccharide or a derivative thereof, such as hyaluronan (also commonly referred to as hyaluronic acid) or a derivative thereof and an aqueous solution of methylcellulose or another water soluble cellulose derivative thereof, having dispersed polymeric particles, such as polymeric hydrophobic particles therein selected from micro particles and nanoparticles, and wherein the stability of the hydrogel is enhanced relative to the stability of the hydrogel alone. The polymeric particles may contain at least one therapeutic agent, in which case each therapeutic agent exhibits a linear sustained release rate that can be tuned or altered by selecting the appropriate polymer formulation of the micro particles and/or nanoparticles. The composite may be injectable, and in the absence of a therapeutic agent may be used as a bulking agent for reconstructive and cosmetic surgery or may act as a platform for subsequent delivery of therapeutic agents.

Enhanced stability of inverse thermal gelling composite hydrogels

The incorporation of polymeric excipients into an injectable hydrogel matrix, for example, methyl cellulose in the case of a hydrogel matrix comprising hyaluronan and methylcellulose (HAMC) has been found to increase the solubility of sparingly soluble hydrophobic drugs and tune their rate of release. The hydrogel matrix may also include other sparingly soluble hydrophobic food or cosmetic agents.

Tunable sustained release of a sparingly soluble hydrophobic therapeutic agent from a hydrogel matrix

This invention provides a polymer composition comprising at least one thermal gelling polymer and at least one anionic polymer for cell delivery applications. These injectable polymer compositions are shear-thinning, thixotropic and resorbable. More specifically there is described a hyaluronan (HA) and methylcellulose (MC) based thermogelling cell delivery system (HAMC) that promotes cell survival both in vitro and in vivo. Importantly, HAMC (relative to media alone) enhances survival of transplanted stem/progenitor cells in the injured CNS. HAMC provides a minimally-invasive cell delivery strategy where the microenvironment can be further defined and the differentiation and regenerative capacity further explored. This hydrogel system has applications for minimally-invasive cell delivery to other tissues/organs in the body as well.

Injectable polymer composition for use as a cell delivery vehicle

A chemically patterned modified hydrogel formed from a modified hydrogel is provided. The hydrogel is conjugated with a multiphoton photocleavable molecule. The molecule has a multiphoton-labile protective group and a protected group. The protective group is cleavable upon multiphoton excitation to deprotect the protected group, without substantial polymerization of the hydrogel. The chemically patterned modified hydrogel is formed by exposing the modified hydrogel to multiphoton excitation to deprotect a portion of the protected groups.

Chemically patterned hydrogels, manufacture and use thereof

A physical blend of inverse thermal gelling and shear-thinning, thixotropic polymers that has a lower gelation temperature than the thermal gelling polymer alone is provided. The blend results in an injectable hydrogel that does not flow freely at room temperature, but is injectable due to its shear-thinning properties. The thermal-gelling properties of the polymer promote a more mechanically stable gel at body temperature than at room temperature. The polymer matrix gel has inherent therapeutic benefit and can also be used as a drug delivery vehicle for localized release of therapeutic agents.

Blends of temperature sensitive and anionic polymers for drug delivery

A polymer scaffold is provided comprising an extensively interconnected macroporous network. The polymer scaffold embodies macropores having a diameter in a range of 0.5-3.5 mm, and preferably in a range of about 1.0-2.0 mm. The polymer scaffold is prepared using a novel process which advantageously combines the techniques of particulate leaching and phase inversion to render a process that provides amplified means by which to control the morphology of the resulting polymer scaffold. The polymer scaffold has utility in the area of tissue engineering, particularly as a scaffold for both in vitro and in vivo cell growth. The polymer scaffold may be produced using pure polymer or alternatively a composite material may be formed consisting of a macroporous polymer scaffold and osteoclast-resorbable calcium phosphate particles with a binding agent binding the calcium phosphate particles to the polymer scaffold.

Macroporous polymer scaffold containing calcium phosphate particles

A variety of hollow structures with unique morphologies were manufactured with a rotational spinning technique. Phase separation of soluble solutions or emulsions was induced within a filled mold as it was being rotated about one of its axis. The density difference between phases results in sediment at the inner lumen of the mold under centrifugal forces. After or during sedimentation, gelation of the phase-separated particles fixes the hollow structure morphology and the solvent remains in the center of the mold. The solvent is removed from the mold resulting in a coating or tube. By controlling the rotational speed and the formulation chemistry, the tube dimensions and wall morphology can be manipulated. This technique offers a new approach to the manufacture of polymeric tubes. It requires small quantities of starting material, permits multi-layering of tubes, is applicable to diverse polymers and can result in highly diffusive hollow structures while maintaining good mechanical strength.

Method of producing structures using centrifugal forces

A polymer scaffold is provided comprising an extensively interconnected macroporous network. The polymer scaffold embodies macropores having a diameter in a range of 0.5-3.5 mm, and preferably in a range of about 1.0-2.0 mm. The polymer scaffold is prepared using a novel process which advantageously combines the techniques of particulate leaching and phase inversion to render a process that provides amplified means by which to control the morphology of the resulting polymer scaffold. The polymer scaffold has utility in the area of tissue engineering, particularly as a scaffold for both in vitro and in vivo cell growth.

Process for growing tissue in a biocompatible macroporous polymer scaffold and products therefrom

Hollow polymeric structures with unique morphologies are manufactured with a rotational spinning technique wherein phase separation of soluble solutions is induced within a filled mold as it is rotated. As phase-separation occurs, an increase in density of one phase results in sediment at a periphery under centrifugal forces and after or during sedimentation, gelation of phase-separated particles fixes a tube morphology. By controlling the rotational speed and the formulation chemistry, the tube dimensions and wall morphology can be manipulated. The method requires small quantities of starting material, permits multi-layering of tubes, is applicable to diverse polymers and results in highly diffusive hollow structures while maintaining good mechanical strength.

Linear copolymers of fluorocarbon and hydrocarbon monomers. The present invention provides linear copolymers and terpolymers of fluorocarbon and hydrocarbon monomers, and particularly the invention provides a linear copolymers, of fluoromonomers, such as tetrafluoroethylene, chlorotrifluoroethylene, or vinylidene fluoride, with hydrocarbon monomers, such as vinyl acetate, acrylic acid ethyl acetate or tertiary butyl acrylate. The copolymers were synthesized by polymerization by a free radical mechanism in supercritical carbon dioxide and they are linear because of synthesis in carbon dioxide. The copolymer composition was controlled by the monomer feed concentration to have between 7 and 71 mol % TFE. Additionally, new and predominantly linear co- and terpolymers were prepared by hydrolysis and trans-esterification of the latter copolymers. Furthermore, neither surfactants nor dispersing agents are required to produce the linear copolymers, but may be used.

Linear copolymers of fluorocarbon-hydrocarbon monomers synthesized in carbon dioxide

A bioinert implantable shunt device useful for controlling internal pressure includes a valve apparatus, a device for attaching the valve apparatus and an inlet tube. The valve apparatus includes an inlet port, an outlet port, a flexible tube connected therebetween and a pressurized enclosure. The flexible tube is positioned inside the pressurized enclosure whereby fluid flow from the inlet port to the outlet port is dependent on a differential pressure between a pressure in the flexible tube and a pressure outside the flexible tube in the pressurized enclosure. The inlet tube is connected to the inlet port of the valve apparatus. The pressurized enclosure may include a housing and a semi-permeable membrane in a wall of the housing whereby fluid can pass through the semi-permeable membrane into the pressurized enclosure thereby increasing the pressure in the pressurized enclosure. The implantable shunt device may be for use in the treatment of glaucoma. Further, there is provided a method of reducing intraocular pressure including the, steps of attaching a biocompatible implantable shunt device to the scleral surface of an eye and inserting an inlet tube into the anterior chamber of the eye.

Implantable shunt device

Growing community of inventors

Toronto, Canada

Molly S Shoichet