Development of poly(lactic-co-glycolic) acid nanoparticles-embedded hyaluronic acid-ceramide-based nanostructure for tumor-targeted drug delivery

作者：Park Ju Hwan; Lee Jae Young; Termsarasab Ubonvan; Yoon In Soo; Ko Seung Hak; Shim Jae Seong; Cho Hyun Jong^*; Kim Dae Duk

来源：International Journal of Pharmaceutics, 2014, 473(1-2): 426-433.

DOI：10.1016/j.ijpharm.2014.07.038

• Cancer diagnosis
• Docetaxel
• Embedding
• Hyaluronic acid-ceramide
• PLGA nanoparticle
• Tumor targeting

A hyaluronic acid-ceramide (HACE) nanostructure embedded with docetaxel (DCT)-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) was fabricated for tumor-targeted drug delivery. NPs with a narrow size distribution and negative zeta potential were prepared by embedding DCT-loaded PLGA NPs into a HACE nanostructure (DCT/PLGA/HACE). DCT-loaded PLGA and DCT/PLGA/HACE NPs were characterized by solid-state techniques, including Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). A sustained drug release pattern from the NPs developed was observed and negligible cytotoxicity was seen in NIH3T3 cells (normal fibroblast, CD44 receptor negative) and MDA-MB-231 cells (breast cancer cells, CD44 receptor positive). PLGA/HACE NPs containing coumarin 6, used as a fluorescent dye, exhibited improved cellular uptake efficiency, based on the HA-CD44 receptor interaction, compared to plain PLGA NPs. Cyanine 5.5 (Cy5.5)-labeled PLGA/HACE NPs were injected intravenously into a MDA-MB-231 tumor xenograft mouse model and demonstrated enhanced tumor targetability, compared with Cy5.5-PLGA NPs, according to a near-infrared fluorescence (NIRF) imaging study. Considering these experimental results, the DCT/PLGA/HACE NPs developed may be useful as a tumor-targeted drug delivery system.

• 出版日期2014-10-1