Programmable stimuli-responsive polymeric formulations

A delivery system, comprising:

• a mixture of a di-block copolymer and a tri-block copolymer;
• wherein the di-block copolymer comprises a hydrophilic segment and a hydrophobic segment comprising a first stimulus-responsive cleavable site, and the tri-block copolymer comprises two substantially identical hydrophobic segments each comprising a second stimulus-responsive cleavable site and a hydrophilic segment therebetween;
• wherein the delivery system is in the form of self-assembled micelles or fibers that transform to micelles upon hydration;
• wherein the first stimulus-responsive cleavable site undergoes cleavage upon exposure to a first stimulus thereby invoking a first phase transition from micelles to a hydrogel, and the second stimulus-responsive cleavable sites undergo cleavage upon exposure to a second stimulus thereby disassembling the hydrogel and invoking a second phase transition to dissolved polymers and fragments thereof.

A method of delivering a cargo to a target site, the method comprising:

• providing a delivery system comprising a mixture of a di-block copolymer and a tri-block copolymer, wherein the di-block copolymer comprises a hydrophilic segment and a hydrophobic segment comprising a first stimulus-responsive cleavable site, and the tri-block copolymer comprises two substantially identical hydrophobic segments each comprising a second stimulus-responsive cleavable site and a hydrophilic segment therebetween, and a cargo encapsulated within or attached thereto, wherein the delivery system is in the form of self-assembled micelles or fibers which transform to micelles upon hydration;
• applying a first stimulus to induce cleavage of the first stimulus-responsive cleavable site thereby invoking a first phase transition from micelles to a hydrogel;
• and
• applying a second stimulus to induce cleavage of the second stimulus-responsive cleavable sites and disassembly of the hydrogel thereby invoking a second phase transition to dissolved polymers and fragments thereof and releasing the cargo at the target site.