Biodegradable stealth polymeric particles fabricated using the macromonomer approach by free radical dispersion polymerization

Patent metadata

Field	Value
Publication number	US-9675556-B2
Application number	US-201414575517-A
Country	US
Kind code	B2
Filing date	Dec 18, 2014
Priority date	Nov 23, 2010
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

The present invention is directed to a crosslinked or non-crosslinked polymer particle, wherein the crosslinked polymer particle comprises a copolymer of poly(alklyene glycol-graft-lactate) that is crosslinked by at least one hydrolysable monomer. Another embodiment of the present invention is a polymer particle comprising a crosslinked polymer particle that is a product of starting materials comprising (a) a hydrophilic monomer, (b) a hydrophobic monomer, and (c) a hydrolysable crosslinking agent. Another embodiment of the present invention is a polymer particle comprising, a crosslinked copolymer comprises structures represented by Formulas (I), (II), and (III), where Formulas (I), (II) and (III) are defined in the specification. Yet other embodiments of the present invention include a method of preparing a methacrylate terminated macromonomer, a method of preparing a crosslinking agent, and a method of preparing a therapeutic agent loaded nanosphere by dispersion polymerization.

First claim

The invention claimed is:

1. A method of preparing a therapeutic agent loaded nanosphere by dispersion polymerization, wherein the method comprises the steps of:
(i) reacting a hydrophilic macromonomer with a hydrophobic macromonomer with or without a crosslinker in an organic solvent/water solvent system;
(ii) adding NPDEA and BPO at predetermined intervals to the reaction mixture of step (i) under a nitrogen atmosphere;
(iii) dissolving the therapeutic agent in an organic phase containing the hydrophobic monomers;
(iv) recovering the therapeutic agent loaded nanospheres.

2. The method of claim 1 , wherein the therapeutic agent is Paclitaxel.

3. The method of claim 1 , wherein the hydrophilic and hydrophobic macromonomers are selected from the group consisting of polyglycolide (PGA) macromonomer, polylactide (PLA) macromonomer, polycaprolactone (PCL) macromonomer, poly(lactide-co-glycolide) (PLGA) macromonomer, poly(propylene fumarate) PFF, methacryloyl-terminated PMMA macromonomer, methacrylate-terminated/functionalized poly(dimethylsiloxane) macromonomer (PDMS-MA), methacryloylpolystyrene (MA-Pst), (vinylbenzyl)polystyrene (VB-Pst), 2-oxyethylmethacrylate-terminated PLLA macromonomer (MC), vinylbenzyl-terminated polyisoprene (PI) macromonomers, poly(ethylene glycol)-copoly(α-hydroxyacid) diacrylate macromers, oligocaprolactone vinyl ether macromonomer, PEG-PLA macromer, PEG-PLA-PEG macromer, poly(ethylene oxide) (PEO) block functionalized with styryl, methacryloyl, thiol, maleate, vinyl, p-vinylphenylalkyl reactive end groups, methacryloxypropyl- and vinyl-terminal polysiloxanes, w-methacryloylpoly(E-caprolactone) (PCL) macromonomer, poly(glycolide) macromonomers, HEMA terminated oligo(L-lactide) or oligo(D-lactide) macromonomers, oligoNIPAAm and polyNIPAAm macromonomers, poly(n-butylacrylate) macromonomers, n-butyl acrylate, methyl acrylate (MA), methyl methacrylate (MMA), N,N′-dimethyl acrylamide (DMA); N-vinyl pyrrolidone (VP), hydroxyethyl methacrylate, n-butyl methacrylate, acrylamide, hydrophilic N-(2-hydroxypropylmethacrylamide) (HPMA), methyl-, ethyl-butyl-, octylcyanoacrylates to form poly(alkylcyanoacrylates)(PACA), acrylic acid, 2-hydroxypropyl methacrylate (HPMA), N,N-dimethylaminoethyl methacrylate (DMAEMA), hydrophilic polymers or macromonomers, poly(vinyl pyrrolidone), (hydroxypropyl) cellulose (HPC), poly(acrylic acid), poly[N-(2-hydroxypropyl) methacrylamide] (PHMPA), dextran-10, -40, -70, poloxamer-188, -184, -237, polyethylene glycol (PEG), polyethylene oxide (PEO) and PEO macromonomers with p-vinylbenzyl and methacrylate end groups, poloxamine, polysorbates, methacryloyl-terminated poly(ethylene oxide) macromonomer, poly(2-alkyl-2-oxazolin), poly(methacrylic acid), poly(acrylic acid) macromonomers, bifunctional vinyl urethane macromonomers, vinyl terminus polysiloxane macromonomer, poly(vinyl alcohol), polyacrylamide, and poly(glutaraldehyde).

4. The method of claim 1 , wherein the hydrophobic macromonomer is poly (L-lactic acid-hydroxyethyl methacrylate).

5. The method of claim 1 , wherein the hydrophilic macromonomer is polyethylene glycol-monomethyl ether monomethacrylate.

6. The method of claim 1 , wherein the organic solvent/water solvent system is dioxane:dimethylsulfoxide:water in a ratio of 12:5:2.5.

7. The method of claim 1 , wherein an encapsulation efficiency is greater than or equal to 31.9%.

8. The method of claim 1 , wherein a drug loading is greater than or equal to 0.25% w/w.

Assignees

• Univ Howard

Inventors

• Akala Emmanuel Oyekanmi
• Adesina Simeon Kolawole

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• B82Y15/00

  Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors · CPC title

• A61K9/5153

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61K31/7034

  attached to a carbocyclic compound, e.g. phloridzin · CPC title