Novel thermosensitive in situ gel based on poloxamer for uterus delivery.

Side effects and drug residues are major concerns affecting hormone therapy of bovine reproductive diseases. Fertility-promoting intrauterine infusion liquid (FPL), an effective alternative to hormone therapy, is associated with short retention time and low therapeutic efficacy. To address these problems, we developed a thermosensitive in situ gel based on poloxamer 407 for local uterine administration. To achieve the desired gelling temperature and enhance local retention property, we added poloxamer 188 and HPMC to the formulation containing poloxamer 407 and FPL. After screening was performed, the optimized formulation showed good temperature sensitivity in vitro and in vivo. Gelation temperature was approximately 27°C. In vitro release tests showed that icariin (the major active compound in FPL) was slow released from in situ forming gel. After the gel was locally administered, uterine and ovarian indexes were significantly increased in the gel group compared with the control group (P<0.05). The serum estradiol level of the gel group was significantly higher than that of the control group (P<0.01). Histological evaluation did not show mucosa irritation in the gel group. Therefore, the proposed in situ forming gel system based on poloxamer 407 is a promising local drug delivery system to treat bovine uterine diseases.