MICROPARTICLES USEFUL AS ULTRASONIC CONTRAST AGENTS AND FOR DELIVERY OF DRUGS INTO THE BLOODSTREAM
Microparticles are provided comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microparticles contain a gas, liquid or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The microparticles are capable of passing through the capillary systems of a subject.
1 . A composition comprising:
a plurality of microparticles, a majority of which have diameters in the range of about 1 to 10 micrometers, each of which comprises a shell enclosing a gas-filled hollow core, said shell comprising an outer layer composed of a cross-linked amphiphilic protein and an inner layer composed of a biodegradable synthetic polymer; and
a sugar.
2 . The composition of claim 1 in which the sugar is sucrose.
3 . The composition of claim 1 which further comprises a surfactant.
4 . The composition of claim 3 in which the surfactant is a poloxomer.
5 . The composition of claim 1 which further comprises a water-soluble polymer.
6 . The composition of claim 5 in which the water-soluble polymer is a medium molecular weight polyethylene glycol.
7 . The composition of claim 1 in which the gas is nitrogen.
8 . The composition of claim 1 in which the biodegradable polymer is selected from the group consisting of polycaprolactone, polylactide, polyglycolide, polylactide-polyglycolide copolymers, copolymers of lactides and lactones, delta-valerolactone, polyalkylcyanoacrylates, polyamides, polyhydroxybutyrates, polydioxanones, poly-beta-aminoketones, polyanhydrides, poly-(ortho)esters, polyglutamic acid, polyaspartic acid and esters of polyglutamic and polyaspartic acids.
9 . The composition of claim 1 in which the cross-linked amphiphilic protein is a cross-linked human serum albumin.
10 . The composition of claim 1 in which the cross-linked amphiphilic protein is cross-linked with glutaraldehyde.
11 . A composition comprising:
a plurality of microparticles, a majority of which have diameters in the range of about 1 to 10 micrometers, each of which comprises a shell enclosing a gas-filled hollow core, said shell comprising an inner layer composed of polylactide and an outer layer composed of glutaraldehyde cross-linked human serum albumin;
glycine; and
polyethylene glycol 3350.
12 . The composition of claim 11 which is in the form of a dry cake and/or powder.
13 . The composition of claim 11 which is in the form of an aqueous suspension.
14 . The composition of claim 1 in which the microparticles do not contain a drug.
15 . The composition of claim 11 in which the microparticles do not contain a drug.