Hydrophobic Drug Loading into Thermosensitive Hydrogels Impacts Rheological Properties

Severe burn wounds lead to a weakened immune system and increased risk of exposure to various common microbes found in hospitals, leading to severe infection. Current treatment includes spreading an antimicrobial ointment or cream on the wound, which can be painful. We have been developing sprayable, antimicrobial, polymer treatments that can be applied to an infected wound as a cold liquid but will transition to a gel state when in contact with the warmer tissue. This thermosensitive hydrogel has the advantages of being applied without pressure, reducing application pain, in addition to providing a cooling effect and the ability to prolong drug release.

Differences in final gel properties were noted in our prior work when the drug was added at different times during the formulation process. Therefore, we aimed to understand how these changes in drug addition timing impacted gel viscosity, viscoelastic behavior, transition temperature, and gel stability in this work. Three methods of addition of a hydrophobic drug (diclofenac salt) were tested: 1) preparation of the bare gel (Pluronic F127, a triblock copolymer with a hydrophobic central block, in water) followed by addition of diclofenac the following day, 2) combining the Pluronic F127 and diclofenac in water followed by an overnight resting period, and 3) preparing the bare gel using ¾ of the water and a drug slurry using the remaining ¼ of the water, followed by the combination of the two mixtures the following day.

These methods were tested for Pluronic percentages of 15, 17, and 20 w/w%; and diclofenac salt percentages of 0.5, 1.0, 1.5, and 2.0 w/v%. Bare gels were also tested for methods one and three to compare gel strength with and without later hydration. Gelation of the Pluronic’s occurs due to micellization of the polymers followed by micelle packing when heated. Depending on when the drug is added during the gelation process, it can enter into or be excluded from the micelles. The three methods tested the addition of diclofenac salt once the micelles have been completely formed, as they are forming, and after formation but with additional hydration. Preliminary results show a minor difference in gelation temperature, up to 2.0 °C, but more significant differences in storage modulus or gel rigidity between methods. Future work will include micelle imaging, sizing, and drug release studies.