US 9,789,195 B2 · Particulate drug delivery methods

Abstract

Methods for efficient preparation of drug-polymer (or oligomer) conjugates useful in the preparation of particles, including microparticles and nanoparticles, for delivery of the drug in vivo for therapeutic applications are provided. The invention also provides nanoparticles prepared by nanoprecipitation using drug-polymer/oligomer conjugates of the invention. The drug conjugates are formed during polymerization of the polymer or oligomer in which the drug is employed as an initiator of the polymerization of the monomers which form the polymer and/or oligomer. More specifically, the drug conjugates are formed by ring-opening polymerization of cyclic monomers in the presence of an appropriate ring-opening polymerization catalyst and the initiator (the drug). The method is particularly useful for formation of polymer/oligomer conjugates with drugs and other chemical species containing one or more hydroxyl groups or thiol groups.

Claims26

Dependent claims

A method for preparing particles for in vivo delivery of a drug comprising:

(a) providing a drug, the structure of which comprises one or more hydroxyl or thiol groups;
(b) conducting ring-opening polymerization of one or more cyclic monomers, wherein the cyclic monomers are cyclic esters, cyclic carbonates, cyclic phosphate, cyclic silicone, cyclic peptides or amino acid derivatives, or cyclic phosphazane, or a combination thereof, in an anhydrous, water-miscible solvent in the presence of (i) the drug as a polymerization initiator, and (ii) a polymerization catalyst, to form a covalent drug-oligomer or drug-polymer conjugate in the water-miscible solvent, wherein the water-miscible solvent is dimethylformamide (DMF) or tetrahydrofuran (THF), wherein the incorporation efficiency of the drug into the oligomer or polymer is greater than 98%;
and
(c) forming particles comprising the drug-oligomer or drug-polymer conjugate by combining the drug-oligomer or drug-polymer conjugate in the water-miscible solvent with water or ether to form the particles, wherein the particles are about 2 nanometers to about 400 micrometers in diameter.

1 more element

Dependencies are inferred from the claim text.

Particulate drug delivery methods

Life of this patent

Particulate drug delivery methods

Life of this patent

Abstract

Claims26