Musazzi Umberto M, Santini Benedetta, Selmin Francesca, Marini Valentina, Corsi Fabio, Allevi Raffaele, Ferretti Anna M, Prosperi Davide, Cilurzo Francesco, Colombo Miriam, Minghetti Paola
Department of Pharmaceutilcal Sciences, Università degli Studi di Milano, via G. Colombo, 71, 20133, Milan, Italy.
Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca, Piazza della Scienza, 2, 20126, Milan, Italy.
J Nanobiotechnology. 2017 Feb 17;15(1):14. doi: 10.1186/s12951-017-0249-6.
This work aimed to provide useful information on the incidence of the choice of formulation in semi-solid preparations of iron-oxide nanoparticles (IONs). The appropriate analytical methods to assess the IONs physical stability and the effect of the semi-solid preparations on IONs human skin penetration were discussed. The physical stability of IONs (D = 31 ± 4 nm; ζ = -65 ± 5 mV) loaded in five semi-solid preparations (0.3% w/v), namely Carbopol gel (CP), hydroxyethyl cellulose gel (HEC), carboxymethylcellulose gel (CMC), cetomacrogol cream (Cet) and cold cream was assessed by combining DLS and low-field pulsed NMR data. The in vitro penetration of IONs was studied using human epidermis or isolated stratum corneum (SC).
Reversible and irreversible IONs aggregates were evidenced only in HEC and CMC, respectively. IONs diffused massively through SC preferentially by an intercellular pathway, as assessed by transmission electron microscopy. The semi-solid preparations differently influenced the IONs penetration as compared to the aqueous suspension. Cet cream allowed the highest permeation and the lowest retained amount, while cold cream and CP favored the accumulation into the skin membrane.
Basic cutaneous semi-solid preparations could be used to administer IONs without affecting their permeation profile if they maintained their physical stability over time. This property is better discriminated by low-field pulsed NMR measurements than the commonly used DLS measurements.
本研究旨在提供有关氧化铁纳米颗粒（IONs）半固体制剂中剂型选择发生率的有用信息。讨论了评估IONs物理稳定性的合适分析方法以及半固体制剂对IONs经皮渗透的影响。通过结合动态光散射（DLS）和低场脉冲核磁共振（NMR）数据，评估了负载于五种半固体制剂（0.3% w/v）中的IONs（直径D = 31 ± 4 nm；ζ电位 = -65 ± 5 mV）的物理稳定性，这五种半固体制剂分别为卡波姆凝胶（CP）、羟乙基纤维素凝胶（HEC）、羧甲基纤维素凝胶（CMC）、西托溴铵乳膏（Cet）和冷霜。使用人表皮或离体角质层（SC）研究了IONs的体外渗透情况。
分别仅在HEC和CMC中证实存在可逆和不可逆的IONs聚集体。通过透射电子显微镜评估，IONs主要通过细胞间途径大量扩散穿过SC。与水性悬浮液相比，半固体制剂对IONs渗透的影响不同。Cet乳膏允许最高的渗透率和最低的保留量，而冷霜和CP有利于在皮肤膜中积累。
如果基础皮肤半固体制剂能随时间保持其物理稳定性，则可用于给药IONs而不影响其渗透特性。通过低场脉冲NMR测量比常用的DLS测量能更好地区分这一特性。
