Mechano-sensitive microcapsules for drug delivery

Abstract

Embodiments of the present invention relate to mechanically-activated microcapsules (MAMCs) for controlled drug-delivery, wherein the MAMCs release one or more active ingredients in response to mechanical stimuli in a subject's body. The MAMCs provide a platform for stimulating biological regeneration, biological repair, modifying disease, and/or controlling disease in mechanically-loaded musculoskeletal tissues.

What is claimed is: 
     
         1 . A method of tuning the rupture profiles of mechanically-activated microcapsules to deliver a therapy to a subject comprising:
 identifying one or more rupture profiles that will provide a therapy to a subject by enabling the mechanically-activated microcapsules to rupture in response to one or more mechanical loads that are expected to be applied to the mechanically-activated microcapsules after they have been administered to the subject, and   creating mechanically-activated microcapsules that have said one or more rupture profiles,   wherein each mechanically-activated microcapsule comprises one or more active ingredients encapsulated inside a shell,   wherein said mechanically-activated microcapsules are designed to rupture and release a therapeutically effective amount of said one or more active ingredients when the one or more mechanical loads are applied to said mechanically-activated microcapsules.   
     
     
         2 . The method according to  claim 1 , wherein creating the mechanically-activated microcapsules comprises providing shell thicknesses that enable the mechanically-activated microcapsules to rupture and release the therapeutically effective amount of said one or more active ingredients when the one or more mechanical loads are applied to said mechanically-activated microcapsules. 
     
     
         3 . The method according to  claim 1 , wherein creating the mechanically-activated microcapsules comprises adding one or more plasticizers to the shell. 
     
     
         4 . The method according to  claim 1  further comprising embedding the mechanically-activated microcapsules within a matrix material. 
     
     
         5 . The method according to  claim 1 , wherein one or more of the administered mechanically-activated microcapsules are designed to rupture and release the therapeutically effective amount of said one or more active ingredients after a plurality of mechanical loads is applied over time. 
     
     
         6 . The method according to  claim 5 , wherein the plurality of mechanical loads applied over time is at least one of a regimen of different mechanical loads applied over time, or a regimen of identical loads repeated over time. 
     
     
         7 . A method of using mechanically-activated microcapsules for drug delivery comprising:
 delivering the mechanically-activated microcapsules (MAMCs) to a region of a subject's body,   wherein the mechanically-activated microcapsules have one or more rupture profiles that enable the mechanically-activated microcapsules to rupture in response to one or more mechanical loads in said region of the subject's body.   
     
     
         8 . The method according to  claim 7 , wherein delivering the MAMCs to said region of the subject's body comprises injecting the MAMCs into said region. 
     
     
         9 . The method according to  claim 7  comprising delivering the MAMCs to a joint. 
     
     
         10 . The method according to  claim 7  comprising delivering the MAMCs to a knee joint, elbow joint, shoulder joint, wrist joint, ankle joint or hip joint. 
     
     
         11 . The method according to  claim 7  comprising delivering the MAMCs to non-joint tissue. 
     
     
         12 . The method according to  claim 7 , wherein the MAMCs are embedded within a matrix material, and wherein delivering the MAMCs to said region of the subject's body comprises implanting the matrix material into said region. 
     
     
         13 . The method according to  claim 7 , wherein the MAMCs have a plurality of different rupture profiles. 
     
     
         14 . The method according to  claim 7 , wherein the one or more rupture profiles of the MAMCs enable the MAMCs to rupture after exposure to a single mechanical load. 
     
     
         15 . The method according to  claim 7 , wherein the one or more rupture profiles of the MAMCs enable the MAMCs to rupture after each of multiple exposures to mechanical loads. 
     
     
         16 . The method according to  claim 7 , wherein the MAMCs comprise one or more active therapeutics , wherein the active therapeutics comprise anti-catabolic compounds, anabolic compounds, anti-inflammatory compounds, chondrogenic factors, and growth factors. 
     
     
         17 . The method according to  claim 16 , wherein the active therapeutics comprise at least one of transforming growth factors, fibroblast growth factors, connective tissue growth factors, insulin-like growth factors, or bone morphogenetic proteins. 
     
     
         18 . The method according to  claim 7 , wherein the MAMCs comprise polymeric shells comprising poly(lactic-co-glycolic)acid (PLGA). 
     
     
         19 . The method according to  claim 11 , wherein the MAMCs delivered to non-joint tissue comprise one or more active ingredients for wound healing. 
     
     
         20 . The method according to  claim 16 , wherein the active therapeutics are designed to control or modify a disease in mechanically-loaded musculoskeletal tissues. 
     
     
         21 . A composition comprising a mixture of mechanically-activated microcapsules having a plurality of rupture profiles. 
     
     
         22 . The composition according to  claim 21 , wherein the mechanically-activated microcapsules have more than one shell thickness and/or more than one shell composition. 
     
     
         23 . The composition according to  claim 21 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         24 . The composition according to  claim 21 , wherein the composition further comprises one or more excipients. 
     
     
         25 . The composition according to  claim 21 , wherein the composition is embedded within a matrix material. 
     
     
         26 . A method of making the composition of  claim 21  comprising mixing the mechanically-activated microcapsules with a pharmaceutical carrier and one or more optional excipients.