Lipolysis and structure controlled drug release from reversed hexagonal mesophase

The present work investigates a system composed of a ternary reversed hexagonal mesophase (HII) loaded with a lipase for modulating drug delivery capabilities of the system. Thermomyces lanuginosa lipase was solubilized into HII mesophase for the benefits of continuing lipolysis of the lipids, consequently disordering and decomposing the hexagonal mesophase and thereby enhancing the diffusion of the encapsulated drug.A single transition from the HII structure to a random micellar phase was detected during the lipolysis. In the first lipolysis stage the hexagonal system (glycerol monooleate, tricaprylin, and water) preserved its symmetry within ca. 200 min. During this step about 40–60% molar of the lipids were hydrolyzed, and a gradual shrinking of the HII cylinders (decrease of 8 Å in lattice parameter) was detected. In the second lipolysis stage, the HII mesophase gradually disintegrated (faster rate) and the release of a model drug (sodium diclofenac) was significantly enhanced, which was assumed to be lipolysis rate-controlled. After about 15 h the HII mesophase was disintegrated into two dispersed immiscible phases.The release obeyed two-step Higuchi kinetics with two consecutive linear correlations of the drug release.

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► TLL and sodium diclofenac were solubilized in HII mesophases based on monoolein and tricaprylin.
► A single transition from the HII structure to a random micellar phase was detected during the lipolysis.
► The sodium diclofenac release obeyed two-step Higuchi kinetics with two consecutive linear correlations of the drug release.