Superoxide dismutase-loaded porous polymersomes as highly efficient antioxidant nanoparticles
View Patent ↗Therapeutic compositions, comprising: an anti-reactive oxygen species agent and a pervious polymersome, the pervious polymersome encapsulating the anti-reactive oxygen species agent, and the pervious polymersome having therein channels defined by a channel diblock copolymer, the channels being arranged so as to retain at least some of the anti-reactive oxygen species agent within the pervious polymersome while allowing reactive oxygen species to pass into the pervious polymersome. Method of treating a patient, comprising: administering an effective amount of a therapeutic composition, the therapeutic composition comprising an anti-reactive oxygen species agent disposed within a pervious polymersome, the pervious polymersome encapsulating the anti-reactive oxygen species agent, and the pervious polymersome having therein channels defined by a channel diblock copolymer, the channels being arranged so as to retain at least some of the anti-reactive oxygen species agent within the pervious polymersome while allowing reactive oxygen species to pass into the pervious polymersome.
1 . A therapeutic composition, comprising:
an anti-reactive oxygen species agent and a pervious polymersome,
the pervious polymersome encapsulating the anti-reactive oxygen species agent, and
the pervious polymersome having therein channels defined by a channel diblock copolymer,
the channels being arranged so as to retain at least some of the anti-reactive oxygen species agent within the pervious polymersome while allowing reactive oxygen species to pass into the pervious polymersome.
2 . The therapeutic composition of claim 1 , wherein the pervious polymersome comprises an amphiphilic diblock copolymer, the amphiphilic diblock copolymer being present as a bilayer.
3 . The therapeutic composition of claim 2 , wherein the amphiphilic diblock copolymer comprises one or more of PEG-PBD, PEG-PCL, PEG-PLA, PEG-PLGA.
4 . The therapeutic composition of claim 3 , wherein the amphiphilic diblock copolymer comprises PEG-PBD.
5 . The therapeutic composition of claim 1 , wherein the channel diblock copolymer comprises a PEG-PPO diblock copolymer.
6 . The therapeutic composition of claim 1 , wherein the anti-reactive oxygen species agent is an enzyme or an enzyme mimic.
7 . The therapeutic composition of claim 6 , wherein the enzyme is at least one of superoxide dismutase or catalase.
8 . The therapeutic composition of claim 7 , wherein the enzyme is superoxide dismutase.
9 . The therapeutic composition of claim 1 , wherein the pervious polymersome defines a diameter of from about 50 to about 500 nm.
10 . The therapeutic composition of claim 1 , wherein, the therapeutic composition is characterized by a retention after 24 hours of the anti-reactive oxygen species agent in a murine myocardium having an ischemia-reperfusion injury that is at least 50% of an initial amount of the anti-reactive oxygen species agent in the murine myocardium having the ischemia-reperfusion injury.
11 . The therapeutic composition of claim 1 , wherein the pervious polymersome has a diameter that changes by less than about 5% after 7 days in phosphate buffered saline.
12 . A method, comprising exogenous administration of a therapeutic composition according to claim 1 to the myocardium of a subject having an ischemic condition.
13 . A method, comprising exogenous administration of a therapeutic composition according to claim 1 to a joint of a subject, the subject optionally having an osteoarthritic condition.
14 . A method, comprising exogenous administration of a therapeutic composition according to claim 1 to a subject having a septic condition, a respiratory condition, or a dermatologic condition.
15 . A method of treating a pathology of a patient in need of treatment thereof, comprising:
administering an effective amount of a therapeutic composition,
the therapeutic composition comprising an anti-reactive oxygen species agent disposed within a pervious polymersome,
the pervious polymersome encapsulating the anti-reactive oxygen species agent, and
the pervious polymersome having therein channels defined by a channel diblock copolymer,
the channels being arranged so as to retain at least some of the anti-reactive oxygen species agent within the pervious polymersome while allowing reactive oxygen species to pass into the pervious polymersome.
16 . The method of claim 15 , further comprising, before administering, identifying a treatment site in the patient, and locally injecting the therapeutic composition at the treatment site.
17 . The method of claim 16 , wherein the treatment site is a joint.
18 . The method of claim 17 , wherein the joint is a knee joint.
19 . The method of claim 16 , wherein the treatment site is the myocardium.
20 . The method of claim 15 , wherein the administrating comprises injecting.
21 . The method of claim 15 , wherein the pervious polymersome comprises a layer of PEG-PBD diblock copolymer, the pervious polymersome optionally comprising a bilayer of PEG-PBD copolymer.
22 . The method of claim 15 , wherein the channel diblock copolymer comprises a PEG-PPO diblock copolymer.
23 . The method of claim 15 , wherein the anti-reactive oxygen species agent is an enzyme or an enzyme mimic.
24 . The method of claim 23 , wherein the enzyme is at least one of superoxide dismutase or catalase.
25 . The method of claim 24 , wherein the enzyme is superoxide dismutase.
26 . The method of claim 15 , wherein the pervious polymersome defines a diameter of from about 50 to about 500 nm.
27 . A kit, the kit comprising a therapeutic composition according to claim 1 and an injector configured to inject the therapeutic composition into a subject.