Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens- University Innsbruck, Innrain 80/82, Innsbruck, Austria.
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens- University Innsbruck, Innrain 80/82, Innsbruck, Austria.
Int J Pharm. 2020 May 15;581:119299. doi: 10.1016/j.ijpharm.2020.119299. Epub 2020 Apr 3.
The aim of this study was to evaluate the impact of a PEG-corona on oily droplets of a nanoemulsion on phosphate cleavage on their surface. A PEG-free nanoemulsion composed of 60% oleic acid, 30% Capmul MCM EP and 10% Span 85 being additionally stabilized by 1% cetyltrimethylammonium bromide (CTAB) and 3% phosphatidic acid (PA) was evaluated regarding phosphate release, zeta potential change and mucus permeation properties. In order to evaluate the impact of PEG-corona on phosphate release 10%, 20% and 30% of polyethoxylated-35 castor oil were incorporated in the nanoemulsion. The developed PEG-free nanoemulsion exhibited the droplet size of 123 nm with PDI of 0.24, whereas the droplet size of the nanoemulsions containing PEG ranged from 166 nm to 128 nm with PDI about 0.26. In case of the PEG-free formulation enzymatically induced phosphate cleavage was 3-fold and 7-fold higher than that from formulations containing 20% and 30% PEG-surfactant, respectively. Accordingly, the zeta potential shift of PEG-free formulation reached ~Δ 40 mV within 4 h, whereas zeta potential of PEG-containing formulations did not show any significant changes remaining constant at ~-30 mV. In contrast, PEG-containing formulations exhibited a 3.3-fold to 4-fold higher mucus permeation than the PEG-free formulation. According to the results, a PEG-corona has a great impact on phosphate cleavage and zeta potential change, which has to be taken into consideration for the development of highly efficient zeta potential changing nanocarriers, as zeta potential constitutes one of the crucial parameter regarding the permeation properties through physiological barriers.
本研究旨在评估 PEG 冠对纳米乳液油滴表面磷酸酯裂解的影响。评估了由 60%油酸、30%Capmul MCM EP 和 10%Span 85 组成的无 PEG 纳米乳液在磷酸盐释放、表面zeta 电位变化和黏液渗透特性方面的情况，该纳米乳液还通过 1%十六烷基三甲基溴化铵（CTAB）和 3%磷脂酸（PA）进行额外稳定。为了评估 PEG 冠对磷酸盐释放的影响，将 10%、20%和 30%的聚氧乙烯-35 蓖麻油加入到纳米乳液中。所开发的无 PEG 纳米乳液的粒径为 123nm，PDI 为 0.24，而含有 PEG 的纳米乳液的粒径范围为 166nm 至 128nm，PDI 约为 0.26。对于无 PEG 配方，酶诱导的磷酸酯裂解比含有 20%和 30%PEG-表面活性剂的配方分别高 3 倍和 7 倍。因此，无 PEG 配方的 zeta 电位变化在 4 小时内达到约 40mV，而含有 PEG 的配方的 zeta 电位没有显示出任何显著变化，保持在约-30mV。相比之下，含有 PEG 的配方的黏液渗透能力比无 PEG 配方高 3.3 倍至 4 倍。根据结果，PEG 冠对磷酸酯裂解和 zeta 电位变化有很大影响，在开发高效 zeta 电位变化纳米载体时必须考虑到这一点，因为 zeta 电位是通过生理屏障渗透特性的关键参数之一。
