Biocompatibles UK Limited

Dsm IP Assets B.v.

Isp Investments Inc.

University of Sheffield

Steven Peter Armes

Andrew Lennard Lewis

Osama M Musa

Yinghua Ma

Sean Leo Willis

Jian-Jun Yuan

Emma Janice Lobb

Victoria Jane Cunningham

Jens Christoph Thies

Giuseppe Battaglia

Yuting Li

Nanning Joerg Arfsten

Patrick Wilhelmus Antonius Vrijaldenhoven

Andrew Leonard Lewis

Irene Canton

Pascal Jozef Paul Buskens

Andrew W Lloyd

Nicholas John Warren

Harry Moore

Rebecca Roisin Gibson

Alan Fernyhough

Denis Cecchin

Oliver Johnathan Deane

Jonathan P Salvage

Andrew Lennard Biocompatibles Uk Limited Lewis

Jonathan P University Of Brighton Salvage

Andrew William University Of Brighton Lloyd

ALennard Biocompatibles Uk Limited Lewis

This application provides high molecular weight block copolymers comprising at least one block A comprising repeating units derived from monomers comprising lactam and acryloyl moieties and at least one block B comprising repeating units derived from hydrophilic monomers. The application further provides compositions comprising the block copolymers and applications thereof in various industrial areas including personal care. The application furthermore provides compositions comprising colloidal particles of the block copolymers. The variables x, y, Rand Rare described herein (I). Wherein each x and y is independently an integer having a value from about 10 to about 10000, and each R, and Ris independently selected from the group consisting of hydrogen, methyl, and combinations thereof.

High molecular weight block copolymers comprising repeating units derived from monomers comprising lactam and acryloyl moieties and hydrophilic monomers, compositions, and applications thereof

The invention provides a method for preparation of homopolymers and non-homopolymers comprising polymerizing in an aqueous medium a monomer comprising at least one acryloyl moiety and at least one functionalized or unfunctionalized lactam moiety, and optionally at least one hydrophilic or hydrophobic comonomer, in the presence of at least one chain transfer agent and at least one non-radiation initiator. Exemplary diblock polymers prepared by the method have the structure: where subscripts x, y, and z and variables R, R, Rand Rare described herein.

Methods of synthesis of homopolymers and non-homopolymers comprising repeating units derived from monomers comprising lactam and acryloyl moieties in an aqueous medium

The invention provides block copolymers comprising at least one block A comprising repeating units derived from monomers comprising lactam and acryloyl moieties and at least one block B comprising repeating units derived from hydrophobic monomers. The invention further provides compositions comprising the block copolymers and applications thereof in various industrial areas including personal care. The invention furthermore provides compositions comprising colloidal particles of the block copolymers. The variables x, y, Rand Rare described herein. 

Block copolymers comprising repeating units derived from monomers comprising lactam and acryloyl moieties and hydrophobic monomers, compositions, and applications thereof

The present invention relates to a medium for storing, preserving, culturing, and/or differentiating stem cells. The medium employs a synthetic thermo-responsive copolymer, dispersed in an aqueous vehicle, which allows the medium to be readily 'switched' between a non-gelatinous (fluid) form and a gelatinous form by simply adjusting temperature across the gelling temperature of the medium. As such, stem cells can be easily captured within a 3D gel matrix by simply mixing the stem cells with the non-gelatinous/fluid form of the medium and then gelling the medium by adjusting the temperature across the gelling temperature of the medium. The stem cells encapsulated within the gelatinous form of the medium may then be preserved for a significant time period before either using the stem cells directly within the medium (e.g. in therapy, or in culturing, differentiation, and such like), or after their extraction from the medium.

Media for stem cells

The present invention relates to a composition suitable for forming an optical coating, the composition comprising core-shell nanoparticles, wherein said nanoparticles comprise: (a) core material comprising polymer; and (b) shell material comprising metal oxide.

Core-shell nanoparticles

An aqueous composition comprises an amphiphilic block copolymer, having a hydrophilic block comprising pendant zwitterionic groups and a hydrophobic block, and a biologically active compound associated with the polymer. The polymer is preferably in the form of micelles, and preferably the biological active is a hydrophobic drug. The hydrophilic block is preferably formed from acrylic monomer including phosphorylcholine groups. The hydrophobic group is suitably formed from monomer which has groups which can be ionised at useful pH's, especially tertiary amine groups. Micelles may be formed by dissolving the block copolymer in aqueous solvent at a pH at which the amine groups are protonated then raising the pH to a value at which the amine groups are substantially deprotonated, whereupon micelles spontaneously form. The preformed micelles are then contacted with active, under conditions such that solubilisation of the active occurs. The active may be for tumour treatment.

Drug carriers comprising amphilphilic block copolymers

A method of preparing a block copolymer of Formula (B) wherein Prepresents a substantially aqueously soluble polymeric component and Prepresents a substantially aqueously insoluble polymeric component, comprises admixing an aqueously soluble polymer macro-chain transfer agent comprising Pwith a monomer (M) and initiating an aqueous dispersion-type radical addition fragmentation chain transfer (RAFT) polymerization. (P) is derived from a monomer (M) selected from monomers of the Formulae (M), (M) and/or (M) where R, Rand Rrepresent a substituent of (M) or (M) which allows Pto be at least partially aqueously soluble, Rrepresents H, CHor CN, Rrepresents one or more substituents of the aromatic ring effective to allow Pto be at least partially aqueously soluble, and monomer Mis selected from: where Ris a substituent of (M) which allows Pto be substantially aqueously insoluble, and Rand Rindependently represent H or methyl. 

Polymer synthesis

Methods for the preparation of polymer-templated core-shell nanoparticles include the steps of (a) preparing a cationic polymeric core material comprising polymeric micelles, and (b) coating the core material with a silica-comprising shell by depositing the shell onto the polymeric micelles from at least one silica precursor to form the core-shell nanoparticles. Compositions which include the core-shell nanoparticles are adapted to facilitate controlled delivery of at least one active agent into a system in response to controlled changes in the pH of the system.

Nanoparticles

Compositions are described comprising a of a block copolymer having an overall ionic charge and in which one of the blocks has pendant zwitterionic groups and a biologically active compound having a charge opposite that of the polymer. The polymer is preferably a linear diablock copolymer, preferably having a low polydispersity, such as a (tertiary amine group containing monomer) block-(zwitterionic monomer) copolymer. Suitable cationic monomers are dialkyl aminoalkyl(alk)acrylates and -acrylamides and suitable zwitterionic monomers are phosphorylcholine group containing acrylate monomers such as 2-methacyloyloxyetyl-2-trimethyl ammonium ethyl phosphate liner salt. The biologically active compound is generally polyionic and is for instance a nucleic acid, such as DNA, especially plasmid DNA.

Composition of polymers

Block copolymers comprise a core block formed of hydrophilic monomers and have pendant zwitterionic groups, and at least two terminal blocks, comprising stimulus-responsive groups. The core block has a degree of polymerisation of at least 100, whilst the terminal blocks have an average degree of polymerisation of at least 20. A solution of polymer in a liquid may be caused to change its characteristics, for instance rheology, upon being subjected to a stimulus such as a change in temperature or pH. Examples comprise core blocks formed of 2-methacryloyloxyethyl-2'-trimethylammonium ethylphosphate inner salt (MPC) and terminal blocks formed of 2-(diisopropylamino)ethyl methacrylate. Upon changing the pH from around 2 to around 8, an aqueous solution of the block copolymer gels, the solution becoming mobile again upon lowering the pH. The effect is due to deprotonation of a quaternary ammonium pendant ion to form a non-ionised group and subsequent protonation to form an ionised group. This changes the hydrophilicity of the terminal blocks and allowing formation of a network of micellar structures when the pendant groups are not ionised and relatively hydrophobic and associated in micelles.

Block copolymers

Polymers may be made from zwitterionic monomers having controlled architectures and molecular weights, using living polymerisations such as group or atom transfer radical polymerisation. For instance polymers may be formed by atom transfer radical polymerisation using a copper chloride catalyst, a ligand which is water soluble, and a water soluble tertiary alkyl halide initiator to form homopolymers having controlled polydispersities of less than 1.5 and block copolymers with other hydrophilic or hydrophobic monomers. One suitable zwitterionic monomer is 2-methacryloyloxy-2'-trimethylammoniumethyl phosphate inner salt. The block copolymers may spontaneously form micelles, believed to have zwitterionic, for instance phosphorylcholine, groups at the external surface, which may be useful as drug delivery systems with improved biocompatibility.

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Sheffield, United Kingdom

Steven Peter Armes