MICELLAR DRUG DELIVERY VEHICLES AND PRECURSORS THERETO AND USES THEREOF
Anhydrous formulations are formed of a diblock copolymer (X-Y) having a hydrophilic block X comprising residues of monomer x, and a hydrophobic block Y comprising residues of monomer y; an additive selected from a polymer and an organic solvent, where the solvent is water-miscible and biocompatible, and the polymer is hydrophobic or hydrophilic and comprises residues of monomers x and/or y, the polymer optionally having a molecular weight that is less than the molecular weight of the diblock copolymer; and a drug. Upon admixture with water, the anhydrous formulations form drug delivery vehicles, preferably in micellar form. The inclusion of polymer and/or organic solvent provides for the formation of micelles at an enhanced rate, and/or provides the formation of micelles having an enhanced ability to incorporate drug(s), and/or provides the formation of micelles having advantageous physical characteristics, e.g., advantageous viscosity and/or melting point.
1 - 190 . (canceled)
191 . A composition comprising:
(a) a diblock copolymer (X-Y) having a hydrophilic block X comprising residues of monomer x, and a hydrophobic block Y comprising residues of monomer y;
(b) a hydrophilic polymer additive; and
(c) a hydrophobic drug.
192 . The composition of claim 191 wherein the hydrophilic polymer additive comprises residues of monomer x.
193 . The composition of claim 191 wherein the diblock copolymer is present at an amount of about 1-15 parts per one part of the hydrophilic polymer additive.
194 . The composition of claim 191 wherein 100 parts of diblock copolymer comprises 30-90 parts hydrophilic polymer X and 60-10 parts hydrophobic polymer Y.
195 . The composition of claim 191 wherein the hydrophilic block X is a polyether and the hydrophobic block Y is a polyester.
196 . The composition of claim 195 wherein the hydrophilic block X comprises residues of alkylene oxide, and the hydrophobic block X comprises residues of DL-lactide.
197 . The composition of claim 196 wherein the diblock copolymer comprises methoxypoly(ethylene oxide) (MePEG) and poly(DL-lactide).
198 . The composition of claim 197 wherein 100 parts of diblock copolymer comprises about 60 parts of MePEG and 40 parts of poly(DL-lactide).
199 . The composition of claim 191 wherein the hydrophilic polymer additive is MePEG.
200 . The composition of claim 199 wherein the MePEG has s molecular weight of about 2,000 g/mol.
201 . The composition of claim 191 wherein the hydrophobic drug is paclitaxel.
202 . The composition of claim 191 further comprising a phosphate salt.
203 . The composition of claim 202 being anhydrous powders.
204 . A composition prepared by:
heating a hydrophobic drug and a hydrophilic polymer additive to form a molten liquid;
mixing a diblock copolymer with the molten liquid to provide a homogeneous mixture, the diblock copolymer including a hydrophilic block X comprising residues of monomer x, and a hydrophobic block Y comprising residues of monomer y;
dissolving the homogeneous mixture into an aqueous buffer to provide a clear solution; and
lyophilizing the clear solution to form anhydrous powders.
205 . The composition of claim 204 wherein the hydrophilic polymer additive comprises residues of monomer x.
206 . The composition of claim 204 wherein the diblock copolymer is present at an amount of about 1-15 parts per one part of the hydrophilic polymer additive.
207 . The composition of claim 204 wherein 100 parts of diblock copolymer comprises 30-90 parts hydrophilic polymer X and 60-10 parts hydrophobic polymer Y.
208 . The composition of claim 204 wherein the hydrophilic block X is a polyether and the hydrophobic block Y is a polyester.
209 . The composition of claim 208 wherein the hydrophilic block X comprises residues of alkylene oxide, and the hydrophobic block X comprises residues of DL-lactide.
210 . The composition of claim 209 wherein the diblock copolymer comprises methoxypolyethylene glycol (MePEG) and poly(DL-lactide).
211 . The composition of claim 210 wherein 100 parts of diblock copolymer comprises about 60 parts of MePEG and 40 parts of poly(DL-lactide).
212 . The composition of claim 204 wherein the hydrophilic polymer additive is MePEG.
213 . The composition of claim 212 wherein the MePEG has s molecular weight of about 2,000 g/mol.
214 . The composition of claim 204 wherein the hydrophobic drug is paclitaxel.
215 . The composition of claim 204 further comprise a saline solution, wherein the composition forms micelles in the presence of the saline solution.
216 . A method comprising:
heating a hydrophobic drug and a hydrophilic polymer additive to form a molten liquid;
mixing a diblock copolymer with the molten liquid to provide a homogeneous mixture, the diblock copolymer including a hydrophilic block X comprising residues of monomer x, and a hydrophobic block Y comprising residues of monomer y;
dissolving the homogeneous mixture into an aqueous buffer to provide a clear solution; and
lyophilizing the clear solution to form anhydrous powders.
217 . The method of claim 216 further comprising adding a saline solution to the anhydrous powders and forming a clear micellar composition.