Targeted delivery via biodegradable polymers
First Claim
1. A method for delivery of biologically active molecules to a targeted site in the vascular system of an animal where treatment is needed, the method comprisingselecting microparticles comprising a synthetic biodegradable polymer and biologically active molecules and having a diameter that causes the microparticles to lodge at the targeted site, wherein the diameter is between one and 100 microns andadministering the microparticles to the animal so that the microparticles selectively lodge at the targeted site within the vascular system of the animal where release is desired for a sufficient amount of time to permit controlled release of a therapeutically effective amount of the biologically active molecules,wherein the biologically active molecules are selected from the group consisting of growth factors, cytokines, angiogenesis factors, immunosuppressant molecules, peptide fragments thereof, and nucleic acid constructs capable of synthesizing these compounds andwherein the synthetic polymer is biodegradable and is made from a polymerizable macromer having a solubility of at least about 1 g/100 ml in an aqueous solution comprising at least one water soluble region, at least one degradable region which is hydrolyzable under in vivo conditions, and free radical polymerizable end groups having the capacity to form additional covalent bonds resulting in macromer interlinking, wherein the polymerizable end groups are separated from each other by at least one degradable region.
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Abstract
Delivery of bioactive molecules such as nucleic acid molecules encoding a protein can be significantly enhanced by immobilization of the bioactive molecule in a polymeric material adjacent to the cells where delivery is desired, where the bioactive molecule is encapsulated in a vehicle such as liposomes which facilitates transfer of the bioactive molecules into the targeted tissue. Targeting of the bioactive molecules can also be achieved by selection of an encapsulating medium of an appropriate size whereby the medium serves to deliver the molecules to a particular target. For example, encapsulation of nucleic acid molecules or biologically active proteins within biodegradable, biocompatible polymeric microparticles which are appropriate sized to infiltrate, but remain trapped within, the capillary beds and alveoli of the lungs can be used for targeted delivery to these regions of the body following administration to a patient by infusion or injection.
869 Citations
13 Claims
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1. A method for delivery of biologically active molecules to a targeted site in the vascular system of an animal where treatment is needed, the method comprising
selecting microparticles comprising a synthetic biodegradable polymer and biologically active molecules and having a diameter that causes the microparticles to lodge at the targeted site, wherein the diameter is between one and 100 microns and administering the microparticles to the animal so that the microparticles selectively lodge at the targeted site within the vascular system of the animal where release is desired for a sufficient amount of time to permit controlled release of a therapeutically effective amount of the biologically active molecules, wherein the biologically active molecules are selected from the group consisting of growth factors, cytokines, angiogenesis factors, immunosuppressant molecules, peptide fragments thereof, and nucleic acid constructs capable of synthesizing these compounds and wherein the synthetic polymer is biodegradable and is made from a polymerizable macromer having a solubility of at least about 1 g/100 ml in an aqueous solution comprising at least one water soluble region, at least one degradable region which is hydrolyzable under in vivo conditions, and free radical polymerizable end groups having the capacity to form additional covalent bonds resulting in macromer interlinking, wherein the polymerizable end groups are separated from each other by at least one degradable region.
Specification