RESIDENCE STRUCTURES AND RELATED METHODS
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 .- 79 . (canceled)
80 . A method for delivering a residence structure, comprising:
administering, to a subject, a containing structure comprising a residence structure having a second configuration;
allowing the containing structure to release the residence structure at a location internally of the subject, whereupon the residence structure obtains a first configuration, the first configuration having a convex hull at least about 10% less than a convex hull of the second configuration and/or the first configuration having a largest cross-sectional dimension at least about 10% less than a largest cross-sectional dimension of the second configuration;
retaining the residence structure at or in proximity to the location within the subject and releasing the active substance from the residence structure at the location internally of the subject at a particular initial average rate as determined over the first 24 hours of release and at an average rate of at least about 1% of the initial average rate over a 24 hour period after the first 24 hours of release,
wherein the residence structure is constructed and arranged to undergo elastic recoil upon release from the containing structure, the residence structure having a first configuration when contained within the containing structure and a second configuration after release from the containing structure.
81 . A method as in claim A, wherein the active substance is configured to be released at a rate of at least about 1% of the initial average rate on the fifth day of release.
82 . A method as in claim A, wherein the residence structure is retained for at least 24 hours after obtaining the second configuration.
83 . A method as in claim A, wherein the location internal of the subject is the stomach.
84 . A method as in claim A, wherein the residence structure comprises a linker coupling a loadable polymeric component to a second polymeric component.
85 . A method as in claim A, wherein the residence structure is characterized by a folding force of at least about 0.2 N.
86 . A method as in claim 84 , wherein the linker is degradable under a set of physiological conditions.
87 . A method for delivering a residence structure, comprising:
administering, to a subject, a containing structure comprising a residence structure, such that the containing structure releases the residence structure in a stomach of the subject;
wherein the residence structure has a second configuration within the containing structure;
wherein, after the residence structure is released from the containing structure, the residence structure obtains a first configuration such that the residence structure is retained within the stomach of the subject for at least about 24 hours.
88 . A method as in claim 87 , wherein the location internal of the subject is a gastric cavity.
89 . A method as in claim 87 , wherein the residence structure comprises a degradable linker coupling a loadable polymeric component to a second polymeric component.
90 . A method as in claim 87 , wherein the residence structure is characterized by a folding force of at least about 0.2 N.
91 . A method as in claim 89 , wherein the degradable linker is degradable under a set of physiological conditions.
92 . A method for delivering a residence structure, 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 within the containing structure;
the residence device comprises a loadable polymeric component that comprises an active substance;
the residence structure is configured such that the active substance is released from the residence structure at an initial average rate over the first 24 hours of release; and
the active substance is released at an average rate of at least about 1% of the initial average rate on the fifth day of release.
93 . A method as in claim 92 , wherein the residence structure comprises an elastic polymeric component and a loadable polymeric component mechanically coupled to the elastic polymeric component; and
wherein the residence structure has a folding force of at least about 0.2 N.
94 . A method as in claim 92 , wherein the second configuration has a convex hull at least about 10% less than a convex hull of the first configuration and/or wherein the second configuration has a largest cross-sectional dimension at least about 10% less than a largest cross-sectional dimension of the first configuration.
95 . A method as in claim 92 , wherein the residence structure is loaded with the at least one of a therapeutic agent, a diagnostic agent, and an enhancement agent before administering the residence structure to the subject.
96 . A method as in claim 95 , wherein between 0.05 wt % to 99 wt % of the active substance is released between 24 hours and 1 year after the administering step.
97 . A method as in claim 92 , wherein the location internally of the subject is an internal cavity and is wherein the residence structure is retained within the cavity by an internal orifice.
98 . A method as in claim 97 , wherein the residence structure does not substantially restrict flow of liquids through the internal orifice during a time period over which the residence structure is retained within the cavity.
99 . A method as in claim 98 , wherein the internal orifice is the gastric pyloric orifice.
100 . A method as in claim 92 , wherein the residence structure comprises at least one degradable linker coupled with the loadable polymeric component.
101 . A method as in claim 92 , wherein after the residence structure is released from the containing structure, the residence structure releases the active substance at an average rate over a continuous 24 hour period measured at least one point in time between 48 hours and about 1 year after the initial release of between about 1% and about 99% of an initial average release rate, as measured over an initial 24 hour period beginning immediately after release.