Crosslinked polymer nano-assemblies and uses thereof

• US 9,592,302 B2
• Filed: 05/22/2012
• Issued: 03/14/2017
• Est. Priority Date: 05/23/2011
• Status: Active Grant

• Current Assignee: University Of Massachusetts
• Original Assignee: University Of Massachusetts
• Inventors: Thayumanavan, Sankaran
• Primary Examiner(s): Shomer, Isaac
• Application Number:
  US14/118,224
• Publication Number:
  US 20140112881A1
• Time in Patent Office: 1,757 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08F 220/20 of polyhydric alcohols or phenols , e.g. 2-hydroxyethyl (meth)acrylate or glycerol mono-(meth)acrylate
• CPC Class Codes: C08F 220/26 Esters containing oxygen in addition to the carboxy oxygen
• CPC Class Codes: C08F 220/385 and containing nitrogen
• CPC Class Codes: C08F 220/387 and containing nitrogen and oxygen
• CPC Class Codes: C08F 226/02 by a single or double bond to nitrogen
• CPC Class Codes: C08F 2810/20 leading to a crosslinking, either explicitly or inherently
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C
• CPC Class Codes: C08J 2333/14 of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08J 3/24 Crosslinking, e.g. vulcanising, of macromolecules mechanical aspects B29C35/00; crosslinking agents C08K
• 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

Abstract

The invention provides a novel system of nano-assemblies and related method for delivery of therapeutic, diagnostic or imaging agent to biological sites. The compositions and methods of the invention enable the syntheses of novel polymeric nano-assemblies (nanoparticles) under non-emulsion conditions with the incorporation of hydrophobic guest molecules. The versatilities and advantages of the polymer nanoparticles of the invention include: (i) the guest molecules (e.g., drug molecules) can be readily incorporated non-covalently within the nanoparticles; (ii) the surface of the nanoparticles are functionalizable; (iii) the non-covalently encapsulated guest molecule (payload) can be released in response to a biologically relevant stimulus at the target site; (iv) the payload is held by the polymeric nanoparticle before being internalized in cells and can be released within the cellular interiors; (v) encapsulating lipophilic small molecules within its crosslinked interiors and binding proteins on its surface through electrostatic interactions; (vi) facile synthetic methods for ligand functionalization that can be utilized to decorate nanogels with cell targeting ligands that facilitate receptor-dependent cellular uptake, and (vii) the payload release kinetics is tunable and controllable.

Claims

1. A nano-assembly for controlled delivery of a therapeutic or diagnostic agent to a biological site, comprising:

a water-soluble polymer host comprising a crosslinked network of a random co-polymer having the structural formula;

2. The nano-assembly of claim 1, wherein the crosslinked network of polymer molecules is crosslinked both inter-molecularly and intra-molecularly.

3. The nano-assembly of claim 1, wherein the de-crosslinking of the crosslinked polymer molecules is due to a biological or chemical stimulus at the biological site.

4. The nano-assembly of claim 3, wherein the stimulus is a pH value at the biological site.

5. The nano-assembly of claim 1, wherein the stimulus is induced by an external light signal.

6. The nano-assembly of claim 1, wherein the loading weight percentage of the guest molecule is from about 2% to about 70%.

7. The nano-assembly of claim 6, wherein the crosslinked network of polymer molecules have a crosslinking density from about 5% to about 60%, relative to the total number of structural units in the polymer.