Stock material or miscellaneous articles – Coated or structually defined flake – particle – cell – strand,... – Particulate matter
Reexamination Certificate
1997-10-17
2001-09-04
Le, Hoa T. (Department: 1773)
Stock material or miscellaneous articles
Coated or structually defined flake, particle, cell, strand,...
Particulate matter
C424S001210, C424S001290, C424S450000, C424S484000, C424S486000, C424S489000, C424S490000, C424S491000, C424S497000, C424S498000, C428S407000
Reexamination Certificate
active
06284375
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a lipid vesicle system that is useful in a variety of biomedical applications including drug delivery, vaccine targeting, drug distribution and uptake, membrane protein reconstitution, enzyme immobilization and construction of artificial cells such as blood cells.
BACKGROUND OF THE INVENTION
Artificial particulate systems such as polymeric beads and liposomes are finding a variety of biomedical applications in drug delivery, drug targeting, protein separation, enzyme immobilization and blood cell substitution (
1
-
6
). Liposomes have a flexible, cell-like lipid bilayer surface which acts as a permeability barrier such that compounds can be entrapped in their aqueous interior. However, liposomes can be mechanically unstable and their loading capacity limited by the water solubility of the material to be loaded (
7
). Polymeric beads, although mechanically more stable and having a larger loading capacity then liposomes, lack many of the useful surface properties of a lipid bilayer shell.
Lipid bilayers supported on various solid surfaces, such as glass (
8
), plastic (
5
), and metal (
9
) as well as modified polymers (
10
) have previously been shown to provide a stable and well defined cell membrane-like environment that has found a number of basic and applied uses (
11
,
12
). Gao and Huang reported that encapsulation of hydrogel particles into liposomes enhanced the loading capacity and overall mechanical strength of the liposomal structure (
13
). However, in that system the unanchored bilayer is still somewhat unstable and the system could only be formed with specific lipid mixtures and only with polymer cores of certain sizes and shapes. The inventors have developed a hydrogel anchored lipid vesicle in which these limitations have been overcome.
SUMMARY OF THE INVENTION
The present inventors have developed a new hybrid lipid vesicle system with structural similarity to natural cells that combines complementary advantages of liposomes and polymeric beads. The system consists of a lipid shell that is anchored on the surface of a polymer matrix which acts like a cytoskeleton. Anchoring is provided by fatty acids covalently attached to the surface of the polymer matrix. These hydrophobic chains drive spontaneous assembly of a lipid shell on the modified polymer matrix when exposed to a suspension of liposomes. The bilayer is stable and acts as a permeability barrier to any compound loaded onto the polymer matrix. Lipid mobility in the shell is similar to that found in other unanchored lipid bilayers. The system has potential application in drug delivery and for functional reconstitution of membrane proteins.
Broadly stated, the present invention relates to a lipid vesicle composition comprising a lipid shell attached to a polymer matrix. Preferably, the lipid shell is covalently attached to the polymer matrix.
The invention also contemplates a method for preparing a lipid vesicle composition comprising:
(a) providing a modified polymer matrix having hydrophobic functional groups covalently attached to the polymer matrix; and
(b) mixing the modified polymer core with a lipid suspension to form an anchored lipid shell on the matrix.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples while indicating preferred embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.
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Jin Tuo
Lee Ping I.
Pennefather Peter
Bereskin & Parr
Gravelle Micheline
Le Hoa T.
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