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US 9,173,840 B2Granted
Multifunctional self-assembling polymeric nanosystems
AssigneeNortheastern University
InventorsMansoor M. Amiji, Arun K. Iyer
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Abstract
Libraries of nanoparticles comprising therapeutic agents and/or imaging agents are disclosed, as well as methods of making, customizing, and using such libraries of nanoparticles.
Claims15
A method of making a combinatorial formulation library comprising a plurality of therapeutic agent-loaded polymeric nanoparticulate delivery systems, the method comprising:
- a) determining the partition coefficient of a therapeutic agent, wherein the therapeutic agent is selected from an siRNA and an anticancer drug;
- wherein the anticancer drug is selected from the group consisting of tamoxifen, paclitaxel, doxorubicin, camptothecin, topotecan, irinotecan, KRN 5500 (KRN), dexamethasone, methylprednisone, prednisone, prednisolone, ellipticin;
- b) solubilizing the therapeutic agent in an aqueous solution;
- c) combinatorially combining the solubilized therapeutic agent with each of a first plurality of derivatized water-soluble polymers encapsulating the therapeutic agent to form a plurality of nanoparticle cores by self-assembly;
- d) combinatorially combining each of the plurality of nanoparticle cores with each of a second plurality of derivatized water-soluble polymers to form a plurality of hydrogel-encapsulated nanoparticles by self-assembly;
- wherein if the therapeutic agent is an siRNA, each of the first plurality of derivatized water-soluble polymers is selected from thiolated dextran derivatives and each of the second plurality of derivatized water-soluble polymers is selected from lipid-modified dextran derivatives;
- wherein if the therapeutic agent is an anticancer drug, each of the first plurality of derivatized water-soluble polymers is selected from lipid-modified dextran derivatives and each of the second plurality of derivatized water-soluble polymers is selected from thiolated dextran derivatives;
- and
- wherein if the partition coefficient is less than 100, then the lipid-modified dextrans are derived from a fatty acid selected from the group consisting of a C2-C14;
- wherein if the partition coefficient is greater than 100, then the lipid-modified dextrans are derived from a fatty acid selected from the group consisting of a C14-C28;
- e) combinatorially combining each of the plurality of hydrogel-encapsulated nanoparticles with a plurality of activated PEG derivatives to form a plurality of therapeutic agent-loaded polymeric nanoparticulate delivery systems;
- wherein each of the therapeutic agent-loaded polymeric nanoparticulate delivery systems differs from one another by at least one of:
- (i) the weight ratio of therapeutic agent to first derivatized water-solubilized polymer to second derivatized water-soluble polymer to activated PEG derivative;
- (ii) the identity of at least one of:
- (1) the first derivatized water-solubilized polymer;
- (2) the second derivatized water-soluble polymer;
- and
- (3) the activated PEG derivative;
- thereby making a combinatorial formulation library comprising a plurality of therapeutic agent-loaded polymeric nanoparticulate delivery systems.
16 more elements
Dependencies are inferred from the claim text.