Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1997-03-04
1999-07-13
Glass, Margaret W.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424499, 424497, 424493, 424489, 424501, 424451, 424 7808, 5147721, 5147723, 514951, 514963, 42840224, 428403, 428407, 42840221, A61K 950
Patent
active
059223570
DESCRIPTION:
BRIEF SUMMARY
The invention relates to colloidal particles, particularly polymer microspheres which are suitable for biomedical applications and to a method of producing these microspheres. The invention also relates to a method of modifying the surface of polymer microspheres and other polymer surfaces used for clinical and diagnostic applications so that they are rendered more biocompatible.
The term "microsphere" is generally employed to describe a substantially spherical particle having a diameter in the range 10 nm to 2 mm. Particles having a diameter of less than 12 m are sometimes called "nanospheres". Microspheres made from a very wide range of natural and synthetic polymers have been prepared and have found use in a variety of biomedical applications. They can be labelled with markers (labels or sensing devices) and transported through various media both in vitro and in-vivo. The labels may be chemical, fluorescent, magnetic or radio-active and thus they may, by appropriate sensing equipment, be observed when in use. They may be manufactured so that they degrade after their job is complete or they may be recovered. The sort of applications for which microspheres can be used are diagnostic screening, cell separation, immunoassays, studies of phagocytosis and blood flow, studies of cell motility, haemoperfusion and extracorporeal therapy, drug delivery devices, targeted drug delivery, cell encapsulation, endovascular embolisation and vaccines.
A major problem associated with medical uses of polymers in general is that the natural surface characteristics of the polymer favour the binding of proteins. Thus, in the case of microspheres, for example, introduced into the circulatory system, plasma components known as opsonins bind to the surface of the microsphere and render it vulnerable to phagocytosis by macrophages and other phagocytic cells of the reticulo-endothelial system. In certain in-vivo applications of microspheres it is important to retain the microspheres in the circulatory system long enough for them to discharge their function. Therefore a considerable amount of research has been carried out into methods of modifying the surface of microspheres and other polymers suitable for medical use, so as to reduce protein uptake.
The general approach has been to attempt to incorporate into the surface of these polymers, materials with hydrophilic properties which will not therefore favour the uptake of proteins. For example polyethylene glycol, polyvinyl pyrrolidone and polyethyl oxazoline have been incorporated into commonly used biomedical polymers such as polyethylene terephthalate, polyurethanes and polymethylmethacrylate (Desai et al, Biomaterials 12 1991, 144-153). This work has shown polyethylene glycol to have quite a dramatic effect in reducing protein adherence at the polymer surface.
Apart from modifying the surface of the microsphere to reduce protein uptake other alterations in the surface characteristics may be desirable such as attraction of particular molecules or ligands. The surface of a microsphere can be afforded a desired characteristic by the grafting or adsorption of particular materials, functional groups or targeting ligands.
There are various known methods for the preparation of polymeric microspheres and some of these include manipulation of the surface of the final product for a particular purpose. For example, they may be prepared directly by co-polymerisation of suitably functionalized monomers as described by Arshady in Biomaterials 14 No 1, 1993, 5-15. It is also known from U.S. Pat. No. 4,785,030 and U.S. Pat. No. 4,734,445 to produce microspheres with a hydrophilic surface using amphiphilic di-block polymers comprising a hydrophobic tail for chemical attachment to a non-water soluble core polymer. Alternatively microspheres may be generated by dissolving a suitable polymer in a solvent, dispersing the polymer solution so formed in a second liquid immiscible with the polymer solvent so as to form a dispersed phase and a continuous phase and then evaporating and/or extracting the
REFERENCES:
patent: 5468526 (1995-11-01), Allen et al.
patent: 5545823 (1996-08-01), Kuo et al.
patent: 5565215 (1996-10-01), Gref et al.
patent: 5714159 (1998-02-01), Shalaby
patent: 5795864 (1998-08-01), Amstutz et al.
Coombes Allan Gerald Arthur
Davis Stanley Stewart
Schacht Etienne Honore
Glass Margaret W.
University of Gent
University of Nottingham
LandOfFree
Polymer microspheres and a method of production thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polymer microspheres and a method of production thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polymer microspheres and a method of production thereof will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2273737