Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution

• Main Authors: Chang Hyun Kim (Author), Si Woo Sung (Author), Eun Seok Lee (Author), Tae Hoon Kang (Author), Ho Yub Yoon (Author), Yoon Tae Goo (Author), Ha Ra Cho (Author), Dong Yoon Kim (Author), Myung Joo Kang (Author), Yong Seok Choi (Author), Sangkil Lee (Author), Young Wook Choi (Author)
• Format: Book
• Published: MDPI AG, 2018-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1999-4923; 10.3390/pharmaceutics10040199
• Keywords: nanostructured lipid carrier; RIPL peptide; cellular uptake; steric stabilization; cytotoxicity; biodistribution; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 10, Iss 4, p 199 (2018)

As a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil^® M 1944 CS (liquid oil) and Precirol^® ATO 5 (solid lipid). In this study, to prevent the recognition by the mononuclear phagocyte system, polyethylene glycol (PEG)-modified RIPL-NLCs (PEG-RIPL-NLCs) were prepared using PEG3000 at different grafting ratios (1, 5, and 10 mole %). All prepared NLCs showed a homogeneous dispersion (130⁻280 nm), with zeta potentials varying from −18 to 10 mV. Docetaxel (DTX) was successfully encapsulated in NLCs: encapsulation efficiency (93⁻95%); drug-loading capacity (102⁻109 µg/mg). PEG-RIPL-NLCs with a grafting ratio of 5% PEG or higher showed significantly reduced protein adsorption and macrophage phagocytosis. The uptake of PEG(5%)-RIPL-NLCs by cancer cell lines was somewhat lower than that of RIPL-NLCs because of the PEG-induced steric hindrance; however, the uptake level of PEG-RIPL-NLCs was still greater than that of plain NLCs. In vivo biodistribution was evaluated after tail vein injection of NLCs to normal mice. Compared to RIPL-NLCs, PEG(5%)-RIPL-NLCs showed lower accumulation in the liver, spleen, and lung. In conclusion, we found that PEG(5%)-RIPL-NLCs could be a promising nanocarrier for selective drug targeting with a high payload of poorly water-soluble drugs.