Polymers for functional particles

• US 9,688,812 B2
• Filed: 02/13/2015
• Issued: 06/27/2017
• Est. Priority Date: 05/15/2006
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated, Massachusetts Institute of Technology
• Original Assignee: Brigham and Women's Hospital Incorporated, Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Gu, Frank X., Teply, Benjamin A., Farokhzad, Omid C.
• Primary Examiner(s): Shomer, Isaac
• Application Number:
  US14/621,551
• Publication Number:
  US 20150157737A1
• Time in Patent Office: 865 Days
• Field of Search: None
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61K 47/6937 the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 51/1244 microparticles or nanoparticles, e.g. polymeric nanoparticles
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C08G 63/664 derived from hydroxy carboxylic acids
• CPC Class Codes: C08G 63/912 derived from hydroxycarboxylic acids
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/906 Drug delivery
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

A 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. The nanoparticle may contain a drug. The moiety may include a polypeptide or a polynucleotide, such as an aptamer. The moiety may be a targeting moiety, an imaging moiety, a chelating moiety, a charged moiety, or a therapeutic moiety. Another aspect is directed to systems and methods of producing such polymeric conjugates. In some embodiments, a solution containing a polymer is contacted with a liquid, such as an immiscible liquid, to form nanoparticles containing the polymeric conjugate. Other methods use such libraries, use or administer such polymeric conjugates, or promote the use of such polymeric conjugates. Kits involving such polymeric conjugates are also described.

Claims

1. A method of making particles, comprising:

providing a solution comprising

(i) a first population of an amphiphilic macromolecule comprising a biocompatible hydrophobic polymer at one end and a biocompatible hydrophilic polymer at the other end, and

(ii) a second population of a second macromolecule comprising a biocompatible hydrophobic polymer;

wherein one or more of the first or second macromolecule further comprises a moiety selected from the group consisting of a targeting moiety, an imaging moiety, a chelating moiety, a moiety having multiple charge groups, and a therapeutic moiety; and

contacting the solution with a polymer nonsolvent for the macromolecules under conditions wherein the macromolecules orient to form particles having hydrophobic polymer ends of the amphiphilic macromolecule on the inside of the particles and hydrophilic polymer ends of the amphiphilic macromolecules on the surface of the particles,

wherein the ratio between the first population of the amphiphilic macromolecule and the second population of the second macromolecule is controlled to form particles with a specific surface density of moieties.

2. The method of claim 1, wherein the particles are nanoparticles.

3. The method of claim 1, wherein one or more of the first or second macromolecule comprises an antigenic moiety.

4. The method of claim 1, further comprising adding a therapeutic, prophylactic, or diagnostic agent prior to forming the particles so that the agent is encapsulated within the particles.

5. The method of claim 1, wherein the hydrophobic polymers of the amphiphilic macromolecule and the second macromolecule have a different molecular structure.

6. The method of claim 1, wherein the hydrophobic polymers of the amphiphilic macromolecule and the second macromolecule have the same molecular structure.

7. The method of claim 5, wherein the hydrophobic polymers of the amphiphilic macromolecule and the second macromolecule comprise a polyester.

8. The method of claim 6, wherein the hydrophobic polymers of the amphiphilic macromolecule and the second macromolecule comprise a polyester.

9. The method of claim 8, wherein the hydrophilic polymer of the amphiphilic macromolecule comprises a poly(alkylene glycol).

10. The method of claim 9, wherein the polyester is selected from the group consisting of poly(lactide-co-glycolide), poly(lactide), and poly(glycolide).

11. The method of claim 10, wherein the poly(alkylene glycol) is poly(ethylene glycol).

12. The method of claim 4, wherein the agent is an immunosuppressive agent.