Residence structures and related methods

Abstract

Residence structures, systems, and related methods are generally provided. Certain embodiments comprise administering (e.g., orally) a residence structure to a subject (e.g., a patient) such that the residence structure is retained at a location internal to the subject for a particular amount of time (e.g., at least about 24 hours) before being released. The residence structure may be, in some cases, a gastric residence structure. In some embodiments, the structures and systems described herein comprise one or more materials configured for high levels of active substances (e.g., a therapeutic agent) loading, high active substance and/or structure stability in acidic environments, mechanical flexibility and strength in an internal orifice (e.g., gastric cavity), easy passage through the GI tract until delivery to at a desired internal orifice (e.g., gastric cavity), and/or rapid dissolution/degradation in a physiological environment (e.g., intestinal environment) and/or in response to a chemical stimulant (e.g., ingestion of a solution that induces rapid dissolution/degradation). In certain embodiments, the structure has a modular design, combining a material configured for controlled release of therapeutic, diagnostic, and/or enhancement agents with a structural material necessary for gastric residence but configured for controlled and/or tunable degradation/dissolution to determine the time at which retention shape integrity is lost and the structure passes out of the gastric cavity. For example, in certain embodiments, the residence structure comprises a first elastic component, a second component configured to release an active substance (e.g., a therapeutic agent), and, optionally, a linker. In some such embodiments, the linker may be configured to degrade such that the residence structure breaks apart and is released from the location internally of the subject after a predetermined amount of time.

1 . A residence structure, comprising:
 a loadable polymeric component;   an elastic polymeric component associated with at least a portion of the loadable polymeric component; and   wherein:   the loadable polymeric component comprises an antiretroviral,   the residence structure is configured such that the antiretroviral is released from the loadable polymeric material at a particular initial average rate as determined over the first 24 hours of release, and   the antiretroviral is released at an average rate of at least about 1% of the initial average rate as determined over a 24-hour period after the first 24 hours of release.   
     
     
         2 . A residence structure, comprising:
 a loadable polymeric component;   an elastic polymeric component associated with at least a portion of the loadable polymeric component; and   wherein:   the linker is degradable under a set of physiological conditions,   the loadable polymeric component comprises an antiretroviral,   wherein the residence structure is configured such that it is retained at a location internally of a subject for at least about 24 hours.   
     
     
         3 . A method for delivering an antiretroviral, comprising:
 administering, to a subject, a containing structure comprising a residence structure, such that the containing structure releases the residence structure at a location within the subject;   wherein:   the residence structure has a second configuration different than the first configuration within the containing structure,   after the residence structure is released from the containing structure, the residence structure obtains a first configuration such that the residence structure is retained at or in proximity to the location within the subject for at least about 24 hours, and   the residence structure is configured such that an antiretroviral is released from the residence structure at the location within the subject for at least about 24 hours.   
     
     
         4 . A method for delivering an antiretroviral, comprising:
 administering, to a subject, a containing structure comprising a residence structure, such that the containing structure releases the residence structure at a location within the subject;   wherein:   the residence structure has a second configuration different than the first configuration within the containing structure,   the residence structure is configured such that the antiretroviral is released from the residence structure while in the first configuration at a particular initial average rate as determined over the first 24 hours of release, and   the antiretroviral is released at an average rate of at least about 1% of the initial average rate as determined over a 24-hour period after the first 24 hours of release.   
     
     
         5 . A residence structure as in  claim 1 , comprising a linker coupling the loadable polymeric component and the second polymeric component to an elastic polymeric component. 
     
     
         6 . A residence structure as in  claim 1 , wherein the linker is degradable under a set of physiological conditions. 
     
     
         7 . A method as in  claim 2 , wherein the location internal to a subject is the stomach of a subject. 
     
     
         8 . A method as in  claim 2 , wherein the residence structure is configured such that an antiretroviral is released from the residence structure at the location within the subject for at least about 7 days. 
     
     
         9 . A residence structure as in  claim 1 , wherein the second polymeric component comprises polylactide or polyurethane. 
     
     
         10 . A residence structure as in  claim 1 , wherein the loadable polymeric component comprises a polyanhydride or poly(ethylene glycol). 
     
     
         11 . A residence structure as in  claim 1 , wherein the residence structure is configured such that it is retained at a location internally of a subject for at least about 24 hours. 
     
     
         12 . A residence structure as in  claim 1 , wherein the loadable polymeric component comprises greater than or equal to 0.01 wt % and less than or equal to 80 wt % versus the total component weight. 
     
     
         13 . A residence structure as in  claim 1 , wherein the residence structure is characterized by a folding force of at least about 0.2N. 
     
     
         14 . A residence structure as in  claim 1 , wherein the residence structure has an uncompressed cross-sectional dimension of at least about 2 cm.