Microgel particles for the delivery of bioactive materials
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Abstract
Novel microgels, microparticles and related polymeric materials capable of delivering bioactive materials to cells for use as vaccines or therapeutic agents. The materials are made using a crosslinker molecule that contains a linkage cleavable under mild acidic conditions. The crosslinker molecule is exemplified by a bisacryloyl acetal crosslinker. The new materials have the common characteristic of being able to degrade by acid hydrolysis under conditions commonly found within the endosomal or lysosomal compartments of cells thereby releasing their payload within the cell. The materials can also be used for the delivery of therapeutics to the acidic regions of tumors and sites of inflammation.
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Citations
58 Claims
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1-22. -22. (canceled)
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23. A method of delivering a bioactive material to the cellular interior of a cell to control immune response, comprising:
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providing to the cell a microgel composition comprising;
(a) a bisacryloyl acetal crosslinker-linked polymer, wherein said bisacryloyl acetal crosslinker being essentially non-hydrolyzable above pH 7, but hydrolyzable below pH 6, and (b) a bioactive material, whereby hydrolysis within an acidic cellular compartment of the cell cleaves said crosslinker and releases said bioactive material. - View Dependent Claims (24, 25, 26, 34, 35, 36, 37, 38, 39, 40, 41)
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42. A method of vaccination, comprising the step of providing to a cell an acid degradable crosslinked microgel composition, wherein the composition comprises:
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(a) a polymer backbone selected from the group consisting of an acrylic polymer and a dextran polysaccharide crosslinked by an acid hydrolyzable crosslinker, wherein said crosslinker hydrolyzes at pH 4.5 to pH 7.4;
(b) the crosslinker having the formula R2CH(OR1)2, wherein R1 is an acryloyl group; and
R2 is Ar—
X where X is a water solubilizing group selected from hydrogen, methoxy, —
O—
(CH2—
CH2—
O)n—
CH3 wherein n is from 1 to 10, —
O—
CH2—
CH2—
O—
C(O)—
O-Ph-NO2 and —
O—
CH2—
CH2—
CH2—
NH—
CO-(dextran polysaccharide), said dextran polysaccharide having a molecular weight from 300 to 100,000 daltons;
and Ar is an aryl group;
(c) a particle size of the microgel composition between 0.1-10 microns;
(d) cross linkages between 1 and 20 mole percent; and
(e) a bioactive material, whereby hydrolysis cleaves said crosslinker and releases said bioactive material. - View Dependent Claims (43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58)
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Specification