Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Int J Nanomedicine. 2010 Nov 10;5:943-54. doi: 10.2147/IJN.S12947.
The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r² > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a T(max) of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC₀₋∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.
将天然黄体酮制成肌肉内（IM）注射制剂，将提供比使用半合成黄体酮更安全的解决方案。然而，低溶解度和半衰期短等缺点妨碍了天然黄体酮的使用。在这项研究中，我们将天然黄体酮制成一种可作为 IM 注射的缓释制剂。首先开发了黄体酮纳米混悬剂（PNS），然后将其分散在热敏凝胶基质中。所选纳米颗粒的平均粒径为 267nm，zeta 电位接近-41mV。PNS 从 F127 加甲基纤维素凝胶中的体外释放曲线遵循零级动力学，与凝胶溶解的重量百分比呈线性相关，表明 PNS 的整体释放速率由 F127/甲基纤维素（MC）凝胶的溶解控制（r²>0.99）。与对照黄体酮混悬剂相比，评估了 PNS（6mg/mL）在 F127/MC 凝胶中的药代动力学参数。在 F127/MC 凝胶中给予 PNS 后，在 T（max）为 4.05±0.1h 时达到血清中最大浓度 22.1±1.9ng/mL。半衰期为 12.7±0.8h。注射配方的 AUC₀₋∞为 452.75±42.8ng·h/mL，总平均滞留时间为 18.57±1.44h。PNS 在凝胶中的速率和程度与对照相比差异有统计学意义（P<0.001）。纳米化并制成热敏凝胶的天然黄体酮显著延长了天然黄体酮的作用，使其可以每 36h 而不是每天注射一次。此外，与使用半合成黄体酮相比，该配方有望提供更安全的选择。
