Manufacture of Thermo-Responsive Hydrogel Composing of Drug-Nanocapsule for Sustainable Release of Ibuprofen, Ofloxacin and Dexamethasone

Technology

This technology is a thermo-responsive hydrogel built from bottlebrush polymers that are liquid at room temperature and undergo solidification into a gel at body temperature. This thermo-responsive transition from solution to gel allows straightforward injection of the hydrogel into the target location. The material then retains the encapsulated therapeutic at the target site through gelation, releasing the therapy slowly with controlled kinetics depending on the bottlebrush polymer structure. The bottlebrush copolymer consists of a backbone with many long polymeric sidechains extending from the backbone. This thermo-responsive hydrogel has three primary types of polymeric side chain sequentially arranged in blocks along the backbone. The three side chain types are polyesters, which are hydrophobic and biodegradable, polyethers, which are hydrophilic, and a safe derivative of polyacrylamides, which performs the sol-gel transition. In aqueous solutions, the bottlebrush copolymers self-assemble into micelles with polyester hydrophobic cores, polyether middles that promote solubility, and polyacrylamide protrusions that facilitate the sol-gel transition. Any hydrophobic drug molecule can be loaded into the bottlebrush copolymer hydrogel, and the inventors describe successful loading of NSAIDs, antibiotics, corticosteroids, chemotherapeutics, and immune modulators. Additionally, multiple drugs can be loaded into the same hydrogel by adding combinations of drug into the aqueous assembly. 

Problem Addressed

Localized drug delivery has the potential to greatly improve patient outcomes by delivering high levels of therapeutics directly to the location in need of treatment while reducing systemic side effects. However, manufacturing, drug loading, and delivery of these sustained release therapeutics remains a challenge. These inventors have designed an innovative thermo-responsive hydrogel based on bottlebrush polymers that overcomes many of the current challenges in the field of sustained release therapeutics. The synthesis is modular and scalable, with a wide range of compatibility with small molecule and biologic agents.

Advantages

• Innovative thermo-responsive hydrogel composed of bottlebrush copolymers for injectable sustained release therapeutics
• Simple assembly of bottlebrush copolymers
• Straightforward drug loading by aqueous self-assembly
• Capable of loading of any hydrophobic drug
• Enables sustained release combination therapy