Cristal Delivery B.v.

Octoplus B.v.

Universiteit Utrecht

Other

Umc Utrecht Holding B.v.

Universiteit Utrecht Holding B.v.

Duphar International Research Bv

Nederlandse Organisatie Voor Toegepast-natuurwetenschappelijk Onderzoek

Stichting Voor De Technische Wetenschappen

Rheinisch-westfalische Technische Hochschule (rwth) Aachen

Universiteit Utrecht Introgene B.v.

Universiteit Twente

Rheinisch-westfalische Technische Hochschule Aachen

Chienna B.v.

Wilhelmus Everhardus Hennink

Cornelis Franciscus Van Nostrum

Cristianne Johanna Ferdinand Rijcken

Cornelus Franciscus Van Nostrum

Abraham Bout

Robert Smakman

Okke Franssen

Osamu Soga

Marinus Jacob Van Steenbergen

Karin Gerarda Frederika Gerritsen

Jacobus Adrianus Wilhelmus Jong

Jan Feijen

Isil Altintas

Clemens Antoni Van Blitterswijk

Jeroen Mattijs Bezemer

Leendert Huizer

Hendrik Teunissen

Robertus Matthias Joseph Liskamp

Yang Shi

Jacobus J Zandman

Maria E Van Der Heijden-van Beek

Petra Van De Wetering

Wendelmoed Nelletha Eleonora Van Dijk-Wolthuis

Silvia Johanna De Jong

Johannes Anna Wilhelmus Kruijtzer

Steffen Van Der Wal

Yong Guo

Cristianne Johanna Rijcken

Jacob Hillebrand Goedemoed

Joost Dick De Bruijn

Ilaria Geremia

Dimitrios Stamatialis

The present invention relates to a method for preparing a macromolecular composition comprising indene-derivatives. The invention also relates to the macromolecular compositions per se, and to methods of using the macromolecular compositions. The macromolecular compositions are useful for undergoing subsequent reactions with small molecules.

Macromolecular compositions comprising indene-derivatives, preparation thereof, and use thereof

The present invention provides an amphiphilic block copolymer for drug delivery and a controlled release system comprising the same copolymer. The copolymer comprises at least one hydrophilic block and at least one hydrophobic block, wherein the hydrophobic block is selected from the group consisting of acrylates, methacrylates, acrylamides, methacrylamides, vinylethers and their aromatic derivatives, wherein at least one hydrophobic block contains an aryl group, which is bound to the hydrophobic block with a degradable linker. The controlled release system of the invention shows high stability and high drug retention when administered in vivo enabling accumulation and drug release at the site of action.

Amphiphilic block copolymers for delivery of active agents

The present invention relates to a particular class of biodegradable linkers, ensuring transiently stable conjugation of building blocks and/or bioactive compounds into drug delivery systems (DDS), such as DDS based on polymeric micelles or hydrogels. In addition, the present invention relates to compounds, comprising said linkers, such compounds preferably being prodrugs. Further, the invention is directed to the use of said linkers, and especially said biodegradable linkers, in a drug delivery system. Moreover, the invention relates to controlled release system comprising a polymer matrix, capable of releasing an active ingredient, wherein the active ingredient is covalently linked to the polymer molecules of the polymer matrix through said linkers, as well as to a method of synthesizing these linkers and preparing such controlled release systems.

Tunable, biodegradable linker molecules for transient conjugation of components in drug delivery systems, and drug delivery systems prepared therewith

The present invention relates to a method for the preparation of a controlled release system and especially to a method for entrapment of compounds in polymer carriers for controlled release of active ingredients, preferably bioactive ingredients, such as drugs. This method results in a system for controlled release of active ingredients and especially for controlled drug delivery. In accordance with the present invention, the term 'controlled release' encompasses all kinds of controlled release, including slow release, sustained and delayed release. Particularly, the present invention results in active ingredients, entrapped in or otherwise incorporated in or coupled to polymer carriers or polymeric devices, such as micelles, nanoparticles, microspheres and other types of polymer devices for controlled release; the active ingredients are covalently bonded to the polymer carriers or polymeric devices.

Method for preparation of a controlled release system

The present invention relates to a method for the preparation of a controlled release system and especially to a method for entrapment of compounds in polymer carriers for controlled release of active ingredients, preferably bioactive ingredients, such as drugs. This method results in a system for controlled release of active ingredients and especially for controlled drug delivery. In accordance with the present invention, the tem controlled release' encompasses all kinds of controlled release, including slow release, sustained and delayed release. Particularly, the present invention results in active ingredients, entrapped in or otherwise incorporated in or coupled to polymer carriers or polymeric devices, such as micelles, nanoparticles, microspheres and other types of polymer devices for controlled release; the active ingredients are covalently bonded to the polymer carriers or polymeric devices.

The present invention relates to compositions comprising polymers whose solubility characteristics can be changed by incubation and particularly poly (hydroxyalkyl(meth) acrylamide mono/di-lactate_interpolymers. Another aspect of this invention is the application of such temperature sensitive polymers as release systems of biologically active compounds. The polymers of the present invention comprise monomers, which have modifiable functionality. The functionality of the monomers can for example be modified by the presence of hydrolysable groups. The modification is effected by the incubation, leading to a change of the water solubility characteristics of the polymer. The polymers used in the present invention contain hydrolysable chemical groups. As a result the polymer's solution characteristics, specifically its lower critical solution temperature (LCST), change upon incubation.

Temperature sensitive polymers

The present invention relates to compositions comprising polymers whose solubility characteristics can be changed by incubation and particularly ploy (hydroxyalkyl (meth) acrylamide mono/di-lactate) interpolymers. Another aspect of this invention is the application of such temperature sensitive polymers as release systems of biologically active compounds. The polymers of the present invention comprise monomers, which have modifiable functionality. The functionality of the monomers can for example be modified by the presence of hydrolysable groups. The modification is effected by the incubation, leading to a change of the water solubility characteristics of the polymer. The polymers used in the present invention contain hydrolysable chemical groups. As a result the polymer's solution characteristics, specifically its lower critical solution temperature (LCST), change upon incubation.

The invention relates to hydrogel compositions, which can be applied as biodegradable materials and to the processes to prepare such hydrogels. The hydrogel of the present invention comprises a stereocomplex gel structure which is the result of the interaction of oligomerized monomers of one chirality with that of oligomerized monomers of the opposite chirality, both grafted to hydrophilic polymers. The grafts form an interaction which is different from a covalent chemical interaction and thus provide the gel with the required coherence.

Stereocomplex hydrogels

The present invention relates to a biodegradable hydrogel comprising bonds which are hydrolyzable under physiological conditions. More particularly, the hydrogel consists of two interpenetrating polymer networks interconnected to one another through hydrolyzable spacers. In addition, the invention relates to a method for the preparation of a hydrogel, wherein macromolecules, e.g., polymers which contain bonds which are hydrolyzable under physiological conditions, are cross-linked in an aqueous solution.

Hydrolysable hydrogels for controlled release

The present invention relates to a biodegradable hydrogel comprising bonds which are hydrolysable under physiological conditions. More particularly, the hydrogel consists of two interpenetrating polymer networks interconnected to one another through hydrolysable spacers. In addition, the invention relates to a method for the preparation of a hydrogel, wherein macromolecules, e.g., polymers which contain bonds which are hydrolysable under physiological conditions, are cross-linked in an aqueous solution.

The invention relates to a method for the preparation of microencapsulated colloidal systems such as liposomes, i.e., microspheres which comprise colloidal systems. These microencapsulated colloidal systems can be used as controlled release systems for the delivery of active ingredients in in vivo and in vitro applications. A method is provided in which the colloidal systems are added to a phase which comprises a water soluble crosslinkable polymer followed by formation of microspheres.

Method for the preparation of microspheres which contain colloidal systems

Water soluble polymers or polymeric hydrogels are used to encapsulate antigen to form vaccines. The antigen is mixed with a polymer solution, microparticles are formed of the polymer and antigen, and, optionally, the polymer is crosslinked to form a stable microparticle. Preferred polymers are alginate and polyphospazenes, and mixtures thereof. Microparticles can be administered parenterally or mucosally. For oral delivery, the microparticles are preferably fifteen microns or less in diameter, and adhere to the mucosal lining of the gastointestinal tract, increasing uptake by the reticuloendothelium.

Poly (organo) phosphazenes for use in synthetic transfection systems

A process for the preparation of a controlled release system, comprising forming of an aqueous two-phase system form at least two water soluble polymers which are incompatible in solution, at least one of these polymers being cross-linkable, the cross-linkable polymer phase being emulsified in the other polymer phase; adding at least one relesable compound which is soluble in the cross-linked polymer phase in the aqueous solution, allowing the releasable compound to diffuse in the cross linkable polymer phase; cross-linking the cross-linkable polymer before or after the releasable compound is added, preferably to a degree that the pores in the cross-liked structure are substantially smaller than the particle size of the releasable compound; and separating the cross-linked structures enclosing the release able compound from the other phase. Further, the invention relates to microspheres, at least 80 wt. % thereof having a particle size of between 100 nanometers and 1000 um, which microspheres are comprised of a degradable, cross-linked polymer encapsulating at least one releasable compound, the pore size of the cross-linked polymer being smaller than the particle size of the releasable compound.

Process for the preparation of a controlled release system

The present invention relates to a synthetic transfection or blocking system comprising as a carrier a cationic, water soluble or water dispersable polyacrylate, a polyacrylamide, a poly(C.sub.1-6 alkyl)acrylate or poly(C.sub.1-6 alkyl)acrylamide. In addition, it relates to a method for introducing DNA fragments in target cells, comprising contacting these DNA fragments with a polyacrylate, a polyacrylamide, a poly(C.sub.1-6 alkyl)acrylate or poly(C.sub.1-6 alkyl)acrylamide, which is at least partially substituted with cationic substituents and subsequently contacting the obtained transfection system with target cells. Finally, the invention involves the use of a polyacrylate, a polyacrylamide, a poly(C.sub.1-6 alkyl)acrylate or poly(C.sub.1-6 alkyl)acrylamide, which is at least partially substituted with cationic substituents as a DNA carrier system.

Cationic polyacrylates and poly(alkyl) acrylates or the corresponding

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Waddinxveen, Netherlands

Wilhelmus Everhardus Hennink