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[0033]In another embodiment of the controlled-release system of the invention, the polymeric matrix is surrounded by a lipid monolayer shell. In one embodiment, the lipid
Problems solved by technology
Targeted delivery for diagnosis and therapeutic applications has until recently largely been limited to receptor ligands such as antibodies, modified-antibodies and nucleic acids.
The large size of antibody molecules can be advantageous for bimodal binding mechanisms but it may also lead to poor solid penetration and slow elimination from the blood circulation.
Unfortunately, slow elimination kinetics can cause myelotoxicity.
In addition, its in vivo application has be
Method used
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example 1
Amphiphilic Nanoparticle with Aptamer
[0238]In one embodiment, the A10 RNA aptamer which binds to the Prostate Specific Membrane Antigen (PSMA) on the surface of prostate cancer cells is conjugated to DSPE (1,2-Distearoyl-sn-glycero-3-phosphoethanolamine)-PEG-COOH using EDC / NHS chemistry with a conjugate concentration of 0.7 mg / mL. 0.21 mg of this DSPE-PEG-aptamer bioconjugate is mixed with 0.07 mg lecithin in 2 mL aqueous solution containing 4% ethanol. 1 mg poly(D,L-lactic-co-glycolic acid) (PLGA, Mw=100 kD) is dissolved in 1 mL tetrahydrofuran (THF) solvent, to which 5% docetaxel of the mass of PLGA is added. This PLGA solution is then mixed with the aqueous solution of lecithin / DSPE-PEG-Aptamer. These mixtures are vortexed for 3 minutes, followed by stirring for 2 hours. In order to remove all organic solvents, these mixtures are then dialyzed for another 4 hours against PBS buffer. This procedure would yield nanoparticles targeting to prostate cancer cells expressing PSMA antige...
example 2
Amphiphilic Nanoparticle with CREKA
[0242]The peptide CREKA is conjugated to DSPE-PEG-Maleimide before formulating nanoparticles using the protocol of Example 1. This peptide will target the delivery and uptake of the nanoparticles to extracellular basement membranes which are exposed under the leaky endothelial layer covering atherosclerotic plaques.
example 3
Amphiphilic Nanoparticle with AXYLZZLN
[0243]The peptide AXYLZZLN, or conservative variants or peptidomimetics thereof, wherein X and Z are variable amino acids, can be conjugated to DSPE-PEG-Maleimide before formulating nanoparticles using the protocol of Example 1. This peptide will target the delivery and uptake of the nanoparticles to extracellular basement membranes which are exposed under the leaky endothelial layer covering atherosclerotic plaques.
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Abstract
The present invention generally relates to polymers and macromolecules, in particular, to polymers useful in particles such as nanoparticles. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. In some cases, the nanoparticle may contain a drug. Other aspects of the invention are directed to methods using nanoparticle libraries.
Description
RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 60 / 910,097, Attorney Docket No. BBZ-011-1, filed Apr. 4, 2007, titled “Amphiphilic compound assisted polymeric particles for targeted delivery;” U.S. Provisional Application No. 60 / 985,104, Attorney Docket No. BBZ-011-2, filed Nov. 2, 2007, titled “Lipid-Stabilized Polymeric Nanoparticles for Targeted Drug Delivery;” U.S. Provisional Application No. 60 / 938,590, Attorney Docket No. BBZ-012-1, filed May 17, 2007, titled “Poly(Amino Acid)-Targeted Drug Delivery;” U.S. Provisional Application No. 60 / 986,202, Attorney Docket No. BBZ-012-2, filed Nov. 7, 2007, titled “Poly(Amino Acid)-Targeted Drug Delivery;” and U.S. Provisional Application No. 60 / 990,250, Attorney Docket No. BBZ-012-3, filed Nov. 26, 2007, titled “Poly(Amino Acid)-Targeted Drug Delivery;” all of which are incorporated herein by reference in their entirety. Additionally, the contents of any patents, patent applications, and ref...
Claims
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Application Information
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Inventor ALEXIS, FRANKZHANG, LIANGFANGRADOVIC-MORENO, ALEKSANDAR F.GU, FRANK X.BASTO, PAMELALEVY-NISSENBAUM, ETGARCHAN, JULIANALANGER, ROBERT S.FAROKHZAD, OMID C.
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