Sabir Fakhara, Katona Gábor, Ismail Ruba, Sipos Bence, Ambrus Rita, Csóka Ildikó
Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Str. 6, H-6720 Szeged, Hungary.
Department of Applied & Environmental Chemistry, Faculty of Science and Informatics, University of Szeged, Rerrich Béla sqr. 1, H-6720 Szeged, Hungary.
Pharmaceuticals (Basel). 2021 Jul 19;14(7):696. doi: 10.3390/ph14070696.
The objective of the present study was to develop -propyl gallate-loaded solid lipid nanoparticles (PG-SLNs) in a hydrogel (HG) formulation using Transcutol-P (TC-P) as a permeation enhancer. Modified solvent injection technique was applied to produce optimized PG-SLNs via the Quality by Design approach and central composite design. The in vitro mucoadhesion, scavenging activity, drug release, permeation studies of PG from PG-SLNs-loaded HG were evaluated under simulated nasal conditions. Compared with in vitro release behavior of PG from SLNs, the drug release from the PG-SLNs-loaded HG showed a lower burst effect and sustained release profile. The cumulative permeation of PG from PG-SLNs-loaded HG with TC-P was 600 μg/cm within 60 min, which is 3-60-fold higher than PG-SLNs and native PG, respectively. Raman mapping showed that the distribution of PG-SLNs was more concentrated in HG having lower concentrations of hyaluronic acid. The scavenging assay demonstrated increased antioxidant activity at higher concentrations of HG. Due to enhanced stability and mucoadhesive properties, the developed HG-based SLNs can improve nasal absorption by increasing residence time on nasal mucosa. This study provides in vitro proof of the potential of combining the advantages of SLNs and HG for the intranasal delivery of antioxidants.
本研究的目的是使用二乙二醇单乙基醚（Transcutol-P，TC-P）作为渗透促进剂，在水凝胶（HG）制剂中制备载有没食子酸丙酯的固体脂质纳米粒（PG-SLNs）。采用改良溶剂注入技术，通过质量源于设计方法和中心复合设计来制备优化的PG-SLNs。在模拟鼻腔条件下，对载有PG-SLNs的HG的体外黏膜黏附性、清除活性、药物释放和PG渗透进行了研究。与PG从SLNs的体外释放行为相比，载有PG-SLNs的HG的药物释放显示出较低的突释效应和缓释特性。载有PG-SLNs的HG与TC-P一起时，PG在60分钟内的累积渗透量为600μg/cm²，分别比PG-SLNs和天然PG高3至60倍。拉曼映射显示，PG-SLNs的分布在透明质酸浓度较低的HG中更为集中。清除试验表明，在较高浓度的HG下抗氧化活性增强。由于稳定性和黏膜黏附性增强，所开发的基于HG的SLNs可通过增加在鼻黏膜上的停留时间来改善鼻腔吸收。本研究提供了体外证据，证明了结合SLNs和HG的优势用于鼻内递送抗氧化剂的潜力。
