Technologie Servier, 27 rue Eugène Vignat, Orléans, France.
Inserm, U1144, F-75006, Paris, France.
Pharm Res. 2018 Mar 5;35(4):82. doi: 10.1007/s11095-018-2358-9.
Oral drug delivery using NPs is a current strategy for poorly absorbed molecules. It offers significant improvement in terms of bioavailability. However, the encapsulation of proteins and peptides in polymeric NPs is a challenge. Firstly, the present study focused on the double emulsion process in order to encapsulate the OXY peptide. Then the technique was challenged by a one-step simplified process, the simple emulsion.
In order to study the influence of formulation and process parameters, factorial experimental designs were carried on. The responses observed were the NP size (<200 nm in order to penetrate the intestinal mucus layer), the suspension stability (ZP < |30| mV) and the OXY loading.
It was thus found that the amount and the nature of surfactant, the ratio between the phases, the amount of PLA-PEG polymer and OXY, the presence of a viscosifying agent, and the duration of the sonication could significantly influence the responses. Finally, OXY-loaded NPs from both processes were obtained with NP size of 195 and 226 nm and OXY loading of 4 and 3.3% for double and simple emulsions, respectively.
The two processes appeared to be suitable for OXY encapsulation and comparable in term of NP size, peptide drug load and release obtained.
利用纳米粒子（NPs）进行口服药物递送是一种提高生物利用度的策略，尤其适用于那些不易被吸收的分子。然而，将蛋白质和肽类药物封装在聚合物 NPs 中是一个挑战。本研究首先聚焦于双重乳液法来包裹 OXY 肽，然后再用简化的一步法（简单乳液法）来挑战该技术。
为了研究配方和工艺参数的影响，进行了析因实验设计。观察到的响应是 NP 尺寸（<200nm，以便穿透肠道黏液层）、悬浮液稳定性（ZP<|30|mV）和 OXY 载药量。
研究发现，表面活性剂的用量和种类、相比例、PLA-PEG 聚合物和 OXY 的用量、增稠剂的存在以及超声时间均会显著影响响应。最后，从双重乳液和简单乳液两种工艺中均获得了载有 OXY 的 NPs，其 NP 尺寸分别为 195nm 和 226nm，OXY 载药量分别为 4%和 3.3%。
这两种工艺似乎都适合 OXY 的封装，在 NP 尺寸、肽类药物负载和释放方面具有可比性。
