Engineered microparticles for macromolecule delivery

Abstract

A method for making a modified release composition, comprising: selecting a desired active agent and polymer matrix for formulating into a modified release composition; assessing degradation effect on release of the active agent from the composition including plotting polymer molecular weight (M wr ) at onset of active agent release vs. active agent molecular weight (M wA ); predicting performance of multiple potential formulations for the composition based on the degradation assessment and average polymer matrix initial molecular weight (M wo ) to define a library of building blocks; determining the optimal ratio of the building blocks to satisfy a specified release profile; and making a modified release composition based on the optimal ratio determination.

1 . A method for making a modified release composition, comprising:
 selecting a desired active agent and polymer matrix for formulating into a modified release composition;   assessing degradation effect on release of the active agent from the composition including plotting polymer molecular weight (M wr ) at onset of active agent release vs. active agent molecular weight (M wA );   predicting performance of multiple potential formulations for the composition based on the degradation assessment and average polymer matrix initial molecular weight (M wo ) to define a library of building blocks;   determining the optimal ratio of the building blocks to satisfy a specified release profile; and   making a modified release composition based on the optimal ratio determination.   
     
     
         2 . The method of  claim 1 , wherein the performance predicting step provides a matrix of M wo  and polymer degradation rates (kC w ). 
     
     
         3 . The method of  claim 1 , wherein the optimal ratio determining step includes performing a non-linear optimization to determine the mass fraction of each formulation of the building blocks;
 redefining the library of building blocks by eliminating the formulation(s) having the lowest mass fraction in each formulation;   repeating the above steps until the result produces a significant deviation.   
     
     
         4 . The method of  claim 1 , further comprising characterizing the produced modified release composition to confirm that model design specifications have been met. 
     
     
         5 . The method of  claim 1 , wherein the modified release composition is a sustained release composition. 
     
     
         6 . The method of  claim 1 , wherein the active agent is a bioactive agent. 
     
     
         7 . The method of  claim 1 , wherein the active agent is a therapeutic agent. 
     
     
         8 . The method of  claim 1 , wherein the polymer matrix is selected from poly(glycolic acid), poly(lactic acid), poly(lactide-co-glycolide), or a mixture thereof. 
     
     
         9 . The method of  claim 1 , wherein the polymer matrix is selected from a polyanhydride, poly(α-hydroxy ester), poly(β-hydroxy ester), poly(ortho ester), or a mixture thereof. 
     
     
         10 . The method of  claim 1 , wherein the composition includes at least two different populations of microparticles wherein each microparticle includes at least one active agent and at least one biodegradable polymer matrix. 
     
     
         11 . A composition comprising three different populations of sustained release microparticles wherein each microparticle includes at least one active agent and at least one biodegradable polymer matrix, wherein:
 the polymer matrix of the first population of microparticles has a M W  of 6.0 to 8.1 kDa and constitutes 15.1 to 33.0% by weight of the composition;   the polymer matrix of the second population of microparticles has a M W  of 9.1 to 12.4 kDa and constitutes 25.7 to 22.8% by weight of the composition; and   the polymer matrix of the third population of microparticles has a M W  of 26.8 to 36.4 kDa and constitutes 59.2 to 44.1% by weight of the composition; and   wherein the composition can sustain a release of the active agent for at least 1 month.   
     
     
         12 . A composition comprising two different populations of sustained release microparticles, wherein each microparticle includes at least one active agent and at least one biodegradable polymer matrix, wherein:
 the polymer matrix of the first population of microparticles has a M W  of 5.1 to 6.8 kDa and constitutes 24.8 to 72.9% by weight of the composition;   the polymer matrix of the second population of microparticles has a M W  of 8.3 to 11.0 kDa and constitutes 75.2 to 27.1% by weight of the composition; and   wherein the composition can sustain a release of the active agent for at least 2 weeks.   
     
     
         13 . The composition of  claim 11 , wherein the biodegradable polymer matrix is selected from poly(glycolic acid), poly(lactic acid), poly(lactide-co-glycolide), or a mixture thereof. 
     
     
         14 . The composition of  claim 11 , wherein the active agent is a bioactive agent. 
     
     
         15 . The composition of  claim 11 , wherein the active agent is a therapeutic agent. 
     
     
         16 . The composition of  claim 11 , wherein the biodegradable polymer matrix comprises 50:50 PLGA.