Pessaries containing nanostructured lipid carriers (NLC) for prolonged vaginal delivery of progesterone
Pessaries containing nanostructured lipid carriers (NLC) for prolonged vaginal delivery of progesterone
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DOI：
10.1016/j.ejps.2020.105475
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发表时间：
2020-10-01
影响因子：
4.6
通讯作者：
Silva, A. C.
中科院分区：
文献类型：
--
作者：
Correia, A.;Costa, C. P.;Silva, A. C.
孕激素（PRG）在女性生殖系统中起着至关重要的作用，阴道途径是最适合其给药的途径，因为这种药物具有广泛的肝脏首过效应。尽管如此，阴道PRG剂型引起立即药物释放，并且需要重复施用，这是令人不快的。因此，有必要开发替代的交付系统，延长阴道释放PRG. This工作的目的是发展阴道托延长阴道交付PRG。研究开始于制备PRG负载的NLC（NLC_PRG）的水性分散体，然后使用三种不同的方法（中性红摄取、刃天青还原和磺酰罗丹明B测定）评价其在人永生化角质形成细胞（HaCat细胞）中的生物相容性。最后，将NLC_PRG掺入阴道栓剂中，根据欧洲药典对其进行进一步表征以评估其延长PRG通过阴道途径释放的适用性，结果显示，制备后，90%的NLC_PRG具有等于或小于315.60 +/- 0.01 nm的尺寸，并且EE为96.42 +/-0.00%。用于评估NLC_PRG生物相容性的所有试验均显示，浓度高达10 μ g/mL时，对HaCaT细胞无细胞毒性。在所有的细胞毒性试验中，仅观察到浓度等于或高于25 μ g/mL的细胞毒性作用，这提供了在所获得的results.The结果的高度置信度，本研究的结果表明，使用含有PRG负载的NLC的持续药物释放，这是一种创新的治疗策略，并构成了一个有前途的替代阴道使用PRG的子宫托的适用性。然而，在达到临床使用之前，需要进一步的离体和体内研究来充分阐明药代动力学和毒理学特征。
Progesterone (PRG) plays a crucial role in the female reproductive system, being the vaginal route the most adequate for its administration, as this drug has an extensive hepatic first pass effect. Nonetheless, vaginal PRG dosage forms originate immediate drug release and requires repeated administrations, which is unpleasant. Thereby, it is necessary to develop alternative delivery systems for prolonged vaginal release of PRG.The objective of this work was the development of pessaries for the prolonged vaginal delivery of PRG. Studies began with the preparation of an aqueous dispersion of PRG-loaded NLC (NLC_PRG), followed by the evaluation of its biocompatibility in human immortalized keratinocytes (HaCat cells), using three different methods (neutral red uptake, resazurin reduction and sulforhodamine B assays). Finally, the NLC_PRG was incorporated into pessaries, which were further characterized according to the European Pharmacopoeia to assess their suitability to prolong PRG release through the vaginal route.The results showed that, after preparation, 90% of the NLC_PRG had sizes equal or lower than 315.60 +/- 0.01 nm, and an EE of 96.42 +/- 0.00%. All the assays used to assess the biocompatibility of NLC_PRG showed the absence of cytotoxicity towards HaCaT cells for concentrations up to 10 mu g/mL. In all cytotoxicity assays, a cytotoxic effect was only observed for concentrations equal or higher than 25 mu g/mL, which provides high confidence in the obtained results.The outcomes of this study suggest the suitability of using pessaries containing PRG-loaded NLC for sustained drug release, which is an innovative therapeutic strategy and constitutes a promising alternative for the vaginal use of PRG. However, further ex vivo and in vivo studies are needed to fully clarify the pharmacokinetic and toxicological profile before reaching the clinical use.