Drug Delivery Systems
The present invention relates to microparticles comprising a gel body, wherein the gel body comprises a synthetic polymer and a drug, wherein the microparticles have an average diameter in the range 40 to 1500 μm, wherein the polymer is cross-linked by groups comprising disulfide linkages and is in the form of a hydrogel.
1 . Microparticles comprising a gel body, wherein the gel body comprises a synthetic polymer and a drug, wherein the microparticles have an average diameter in the range 40 to 1500 μm, wherein the polymer is cross-linked by groups comprising disulfide linkages and is in the form of a hydrogel.
2 . Microparticles according to claim 1 for use in a method of treatment by embolisation, wherein in the treatment drug is released.
3 . Microparticles according to claim 2 , wherein in the method of treatment of embolisation, the microparticles are exposed to a hypoxic environment, in which the disulfide linkages are cleaved, facilitating release of the drug.
4 . Microparticles according to claim 2 , wherein the method of treatment by embolisation is treatment of a tumour.
5 . Microparticles according to claim 1 , wherein the drug is selected from the group consisting of anti-tumour drugs, anti-angiogenesis drugs, anti-fungal drugs, antiviral drugs, anti-inflammatory drugs, anti-bacterial drugs, anti-histamine drugs, antineoplastic drugs, enzymes and anti-allergenic drugs, and is preferably an anthracycline or camptothecin compound.
6 . Microparticles according to claim 1 , wherein the microparticles are microspheres.
7 . Microparticles according to claim 1 , wherein the polymer is an acrylic-based polymer.
8 . Microparticles according to claim 1 , wherein the polymer is a vinyl alcohol polymer.
9 . Microparticles according to claim 1 which have an average diameter in the range 40-300 μm.
10 . Microparticles according to claim 1 , wherein the polymer is anionic, and the drug is cationic, and electrostatically associated with the polymer.
11 . Microparticles according to claim 10 , wherein the groups which cross-link the polymer contribute to the anionic charge on the polymer.
12 . Microparticles according to claim 1 , wherein the polymer has been cross-linked using a reagent comprising a disulfide linkage which comprises two cationically or anionically charged groups at physiological pH, symmetrically arranged either side of the disulfide linkage.
13 . Microparticles according to claim 12 , wherein the two cationically or anionically charged groups are electrostatically associated with the drug.
14 . Microparticles according to claim 1 , wherein the polymer is formed from a PVA macromer.
15 . Microparticles according to claim 1 , wherein the microparticles are biodegradable.
16 . A pharmaceutical composition comprising microparticles according to claim 1 .
17 . A composition according to claim 16 further comprising a pharmaceutically acceptable liquid vehicle, preferably comprising physiological saline and/or a contrast agent visible by imaging devices, for instance x-ray.
18 . Use of microparticles as defined in claim 1 in the manufacture of an embolic composition for use in a method of treatment by embolisation wherein the drug is released from the microparticle.
19 . Use according to claim 18 , wherein the method of treatment is of a tumour, preferably wherein the drug is released from the microparticle in a hypoxic environment.