Division of Oral and Maxillofacial Surgery, Pathology & Anesthesiology, College of Dentistry, The Ohio State University, Columbus, Ohio, USA.
Pharm Res. 2010 Jul;27(7):1224-36. doi: 10.1007/s11095-010-0121-y. Epub 2010 Mar 31.
To determine if solid lipid nanoparticles represent a viable strategy for local delivery of poorly water soluble and unstable chemopreventive compounds to human oral tissues.
Nanoparticle uptake and compound retention evaluations employed monolayer-cultured human oral squamous cell carcinoma (OSCC) cell lines and normal human oral mucosal explants. Feasibility of nanoparticle delivery was also evaluated with respect to the presence of phase-III efflux transporters in normal oral mucosal tissue and OSCC tissues.
Functional uptake assays confirmed significantly greater internalization of nanoparticle-delivered fluorescent probe relative to free-fluorescent probe delivery, while concurrently demonstrating nanoparticle uptake rate differences among the OSCC cell lines and the phagocytic control human monocyte cell line. Mucosal explants exhibited nanoparticle penetration and internalization in the spinous and basal epithelial layers (7/10 specimens), and also exhibited the presence of the phase-III efflux transporters multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP).
These data confirm nanoparticle internalization by OSCC cells and support the premise that nanoparticle-based delivery provides higher final intracellular levels relative to bolus administration. Furthermore, the penetration and subsequent internalization of nanoparticles within the proliferating basal layer cells demonstrates the feasibility of nanoparticle formulations for local delivery and stabilization of oral chemopreventive compounds.
确定固体脂质纳米粒是否代表一种可行的策略，用于将疏水性和不稳定性化学预防化合物局部递送至人体口腔组织。
采用单层培养的人口腔鳞状细胞癌（OSCC）细胞系和正常人口腔黏膜外植体进行纳米颗粒摄取和化合物保留评估。还评估了纳米颗粒递送的可行性，涉及正常口腔黏膜组织和 OSCC 组织中 III 相外排转运蛋白的存在。
功能摄取测定证实，与游离荧光探针递送相比，纳米颗粒递送的荧光探针的内化明显增加，同时还证明了 OSCC 细胞系和吞噬控制的人单核细胞系之间的纳米颗粒摄取率差异。黏膜外植体在棘层和基底上皮层中显示出纳米颗粒的穿透和内化（10 个标本中的 7 个），并且还存在 III 相外排转运蛋白多药耐药相关蛋白 1（MRP1）和乳腺癌耐药蛋白（BCRP）。
这些数据证实了 OSCC 细胞对纳米颗粒的内化，并支持了纳米颗粒给药相对于单次给药可提供更高的最终细胞内水平的前提。此外，纳米颗粒在增殖的基底细胞层内的穿透和随后的内化表明，纳米颗粒制剂可用于局部递送至口腔化学预防化合物并稳定其。
