Method of producing submicron particles of a labile agent and use thereof

A method for preparing a composition for the sustained release of a labile agent, comprising the steps of:

• a) forming a suspension comprising the labile agent wherein the labile agent is a protein, polypeptide or oligonucleotide dispersed in a polymer solution comprising a poly(lactide-co-glycolide) polymer and at least one polymer solvent;
• b) wet milling the suspension to achieve submicron particles of the labile agent;
• and
• c) removing the polymer solvent thereby forming a solid polymer matrix having the labile agent dispersed therein.

A method for preparing a composition for the sustained release of a labile agent, comprising the steps of:

• a) forming a suspension comprising the labile agent wherein the labile agent is a protein, polypeptide or oligonucleotide dispersed in a polymer solution comprising at least one biocompatible polymer and a polymer solvent selected from the group consisting of methylene chloride, chloroform, acetone, ethyl acetate, methyl acetate, dimethylsulfoxide, hexafluoroisopropanol and any combinations thereof;
• b) wet milling the suspension to achieve submicron particles of the labile agent;
• and
• c) removing the polymer solvent thereby forming a solid polymer matrix having the labile agent dispersed therein.

A method for preparing a composition for the sustained release of a labile agent, comprising the steps of:

• a) forming a suspension comprising the labile agent wherein the labile agent is a protein, polypeptide or oligonucleotide dispersed in a polymer solution comprising at least one biocompatible polymer and at least one polymer solvent;
• b) wet milling the suspension to achieve submicron particles of the labile agent;
• c) adding a metal cation component to the suspension which modulates the release of the labile agent;
• and
• d) removing the polymer solvent thereby forming a solid polymer matrix having the labile agent dispersed therein.