In Vivo Absorption of Steroidal Hormones from Smart Polymer Based Delivery Systems

作者：Chen Sibao; Pederson Daniel; Oak Mayura; Singh Jagdish^*

来源：Journal of Pharmaceutical Sciences, 2010, 99(8): 3381-3388.

DOI：10.1002/jps.22098

• controlled release
• biodegradable polymers
• pharmacokinetics
• polymeric drug delivery systems, poly(DL-lactic) acid
• bioavailability, levonorgestrel
• testosterone
• phase sensitive, thermosensitive

The purpose of this study was to develop smart polymer based controlled delivery systems to deliver steroidal hormones after single subcutaneous (s.c.) injection at predetermined rates over extended period of time. In vivo absorption and pharmacokinetics of levonorgestrel (LNG) and testosterone (TSN) were investigated from the thermosensitive and phase sensitive polymeric controlled delivery systems A selective, reliable, and rapid method for determination of serum LNG concentration was developed using high-performance liquid chromatography tandom mass spectrometry with atmospheric pressure chemical ionization interface (HPLC MS MS with APCI), while TSN in serum samples was detected and quantified by a competitive immunoassay The delivery systems controlled the absorption of LNG in rabbits up to 6 weeks from thermosensitive and weeks from phase sensitive polymeric delivery systems. In vivo study of TSN delivery systems in castrated rabbits controlled the release of TSN for at least 2 months from both thermosensitive and phase sensitive polymers. Thermosensitive and phase sensitive polymer formulations significantly (p < 0.05) increased relative bioavailability of steroidal hormones compared to control In conclusion, thermosensitive and phase sensitive polymer based delivery systems controlled the release in vivo in rabbits for longer duration after single s.c.

• 出版日期2010-8