In vivo absorption of steroidal hormones from smart polymer based delivery systems

Abstract

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 approximately 4 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. injection.

Figure 1.

Typical MS chromatographs for in vivo study of LNG: A) Blank; B) LNG; C) Oxandrolone

Figure 2.

In vivo absorption of LNG in rabbits after s.c. administration of LNG Formulations A) control solution (12 mg/mL LNG in DMSO); B) Phase sensitive polymer formulations (12 mg/mL LNG, 5% w/v PLA, and 85/15 v/v BB/BA); C) Thermosensitive polymer formulations (12 mg/mL LNG, copolymer PLGA-PEG-PLGA, 30% w/v). All the data points are mean ± s.d. (n=4)

Figure 3.

Calibration curve for TSN in vivo

Figure 4.

In vivo absorption of TSN in rabbits after s.c. administration of TSN formulations (A) Control solution (300 mg/mL TSN in DMSO); (B) Phase sensitive polymer formulations (300 mg/mL TSN, 5% w/v PLA, and 85/15 v/v BB/BA); (C) Thermosensitive polymer formulations (300 mg/mL TSN, copolymer PLGA-PEG-PLGA, 30% w/v)