Continuous release of protein from biodegradable in situ forming depot

Biodegradable in Situ forming drug delivery systems that solidify of gel in the body from injectable fluids represent effective parenteral depot systems for controlled delivery of proteins. Various pharmaceutical additives were tested on their effectiveness as protein release modifiers and stabilizers. Mono-, di-, poly-saccharides, PEG2K and salting-out salts except cyclodextrins significantly decreased Tg of thermogelling polymers and their decreasing abilities were proportional to the polymer concentration and additive/polymer weight ratio up to solubility limits in aqueous media. For methyl cellulose (MC) gel, sodium carbonate, a strong salting-out salt, decreased Tg by 23 degrees C so that in situ gel can be formed at the body temperature. The incorporation of additives into thermogelling polymers significantly decreased the burst and retarded release kinetics. Although the pH inside gel gradually dropped down due to the polymer degradation, released model protein was confirmed to retain the original conformation.