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

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 mononuclea...

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Autores principales: Kim, Chang Hyun, Sung, Si Woo, Lee, Eun Seok, Kang, Tae Hoon, Yoon, Ho Yub, Goo, Yoon Tae, Cho, Ha Ra, Kim, Dong Yoon, Kang, Myung Joo, Choi, Yong Seok, Lee, Sangkil, Choi, Young Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321264/
https://www.ncbi.nlm.nih.gov/pubmed/30360549
http://dx.doi.org/10.3390/pharmaceutics10040199
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author Kim, Chang Hyun
Sung, Si Woo
Lee, Eun Seok
Kang, Tae Hoon
Yoon, Ho Yub
Goo, Yoon Tae
Cho, Ha Ra
Kim, Dong Yoon
Kang, Myung Joo
Choi, Yong Seok
Lee, Sangkil
Choi, Young Wook
author_facet Kim, Chang Hyun
Sung, Si Woo
Lee, Eun Seok
Kang, Tae Hoon
Yoon, Ho Yub
Goo, Yoon Tae
Cho, Ha Ra
Kim, Dong Yoon
Kang, Myung Joo
Choi, Yong Seok
Lee, Sangkil
Choi, Young Wook
author_sort Kim, Chang Hyun
collection PubMed
description 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.
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spelling pubmed-63212642019-01-11 Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution Kim, Chang Hyun Sung, Si Woo Lee, Eun Seok Kang, Tae Hoon Yoon, Ho Yub Goo, Yoon Tae Cho, Ha Ra Kim, Dong Yoon Kang, Myung Joo Choi, Yong Seok Lee, Sangkil Choi, Young Wook Pharmaceutics Article 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. MDPI 2018-10-23 /pmc/articles/PMC6321264/ /pubmed/30360549 http://dx.doi.org/10.3390/pharmaceutics10040199 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Chang Hyun
Sung, Si Woo
Lee, Eun Seok
Kang, Tae Hoon
Yoon, Ho Yub
Goo, Yoon Tae
Cho, Ha Ra
Kim, Dong Yoon
Kang, Myung Joo
Choi, Yong Seok
Lee, Sangkil
Choi, Young Wook
Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution
title Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution
title_full Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution
title_fullStr Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution
title_full_unstemmed Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution
title_short Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution
title_sort sterically stabilized ripl peptide-conjugated nanostructured lipid carriers: characterization, cellular uptake, cytotoxicity, and biodistribution
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321264/
https://www.ncbi.nlm.nih.gov/pubmed/30360549
http://dx.doi.org/10.3390/pharmaceutics10040199
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