Hydrophobically Modified Polymer/α-Cyclodextrin Thermoresponsive Hydrogels for Use in Ocular Drug Delivery

We report herein on the preparation of thermoresponsive hydrogels by taking advantage of the interaction of cyclodextrins (CDs) and a hydrophobically modified polymer. A hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC) gel formed thermoresponsive hydrogels when small amounts of α-CD were added to the solution. The HM-HPMC/α-CD showed reversible sol-gel transition in the physiological temperature range that was completely opposite to the temperature dependency shown by the original HM-HPMC. The thermoresponsive gelation was attributed to the temperature dependency of the interaction between α-CD and the hydrophobic moiety of HM-HPMC. The potency of the HM-HPMC/α-CD sol-gel transition system in ophthalmic formulation was tested on the eyes of a rabbit. The use of HM-HPMC/α-CD significantly improved the ocular absorption of a drug, diclofenac sodium, by virtue of the rapid formation of a gel on the ocular surface. That is, the HM-HPMC/α-CD was in a low viscous sol state at room temperature, which made administration easy, but it rapidly formed a viscous hydrogel on the ocular surface at physiological temperature. The thermoresponsive hydrogel based on the hydrophobically modified polymer and CD promises to have widespread applications in drug delivery.