Intraperitoneally administered native and lauroyl-modified hyaluronan films: Pharmacokinetic and metabolism studies.

Hyaluronan is being investigated extensively as a biocompatible and biodegradable material for use in biomedical applications. While the derivatization of hyaluronan broadens its potential therapeutic use, the pharmacokinetics and metabolization of the derivatives must be thoroughly investigated. The fate of intraperitoneally-applied native and lauroyl-modified hyaluronan films with varying degrees of substitution was investigated in-vivo employing an exclusive stable isotope-labelling approach and LC-MS analysis. The materials were gradually degraded in peritoneal fluid, lymphatically absorbed, preferentially metabolized in the liver and eliminated without any observable accumulation in the body. Hyaluronan acylation prolongs its presence in the peritoneal cavity depending on the degree of substitution. The safety of acylated hyaluronan derivatives was confirmed via a metabolic study that revealed its degradation into non-toxic metabolites, i.e. native hyaluronan and free fatty acid. Stable isotope-labelling with LC-MS tracking comprises a high-quality procedure for the investigation of the metabolism and biodegradability of hyaluronan-based medical products in-vivo.

Lauroyl hyaluronan films for local drug delivery: Preparation and factors influencing the release of small molecules.

Lauroyl derivatives of hyaluronan are safe and biodegradable materials that seem promising for application in medicine. However, their potential in the field of drug delivery was not yet explored. We thus prepared lauroyl hyaluronan films loaded with various drugs and studied the effects of lauroyl hyaluronan properties, drug hydrophobicity and medium composition on the drug release. Since biomolecules will always be present in real clinical applications, media supplemented by albumin were also included. The amphiphilic character of lauroyl hyaluronan enabled convenient loading of the films by both hydrophilic and hydrophobic drugs. Dominant factors influencing drug release were drug hydrophobicity and the presence of albumin. Hydrophilic diclofenac was released rapidly in all cases, while triclosan with medium hydrophobicity exhibited slower release sensitive to other parameters, reaching equilibrium values in the used experimental setup. The release of hydrophobic octenidine into pure buffer was almost negligible, but the addition of albumin did promote its release. The strong effect of albumin highlights the importance of considering biomolecules in the design of release experiments.