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<sup>®</sup> M 1944 CS (liquid oil) and Precirol<sup>®</sup> ATO 5 (solid lipid)....
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-10-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/10/4/199 |
| _version_ | 1817990220982779904 |
|---|---|
| author | Chang Hyun Kim Si Woo Sung Eun Seok Lee Tae Hoon Kang Ho Yub Yoon Yoon Tae Goo Ha Ra Cho Dong Yoon Kim Myung Joo Kang Yong Seok Choi Sangkil Lee Young Wook Choi |
| author_facet | Chang Hyun Kim Si Woo Sung Eun Seok Lee Tae Hoon Kang Ho Yub Yoon Yoon Tae Goo Ha Ra Cho Dong Yoon Kim Myung Joo Kang Yong Seok Choi Sangkil Lee Young Wook Choi |
| author_sort | Chang Hyun Kim |
| collection | DOAJ |
| description | As a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil<sup>®</sup> M 1944 CS (liquid oil) and Precirol<sup>®</sup> 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. |
| first_indexed | 2024-04-14T00:56:27Z |
| format | Article |
| id | doaj.art-a20cfec89b524f2a95b9f2384d0b13ab |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T00:56:27Z |
| publishDate | 2018-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-a20cfec89b524f2a95b9f2384d0b13ab2022-12-22T02:21:35ZengMDPI AGPharmaceutics1999-49232018-10-0110419910.3390/pharmaceutics10040199pharmaceutics10040199Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and BiodistributionChang Hyun Kim0Si Woo Sung1Eun Seok Lee2Tae Hoon Kang3Ho Yub Yoon4Yoon Tae Goo5Ha Ra Cho6Dong Yoon Kim7Myung Joo Kang8Yong Seok Choi9Sangkil Lee10Young Wook Choi11College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, KoreaCollege of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, KoreaCollege of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, KoreaCollege of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, KoreaCollege of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, KoreaCollege of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, KoreaCollege of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 330-714, KoreaCollege of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 704-701, KoreaCollege of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, KoreaAs a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil<sup>®</sup> M 1944 CS (liquid oil) and Precirol<sup>®</sup> 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.https://www.mdpi.com/1999-4923/10/4/199nanostructured lipid carrierRIPL peptidecellular uptakesteric stabilizationcytotoxicitybiodistribution |
| spellingShingle | Chang Hyun Kim Si Woo Sung Eun Seok Lee Tae Hoon Kang Ho Yub Yoon Yoon Tae Goo Ha Ra Cho Dong Yoon Kim Myung Joo Kang Yong Seok Choi Sangkil Lee Young Wook Choi Sterically Stabilized RIPL Peptide-Conjugated Nanostructured Lipid Carriers: Characterization, Cellular Uptake, Cytotoxicity, and Biodistribution Pharmaceutics nanostructured lipid carrier RIPL peptide cellular uptake steric stabilization cytotoxicity 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 | nanostructured lipid carrier RIPL peptide cellular uptake steric stabilization cytotoxicity biodistribution |
| url | https://www.mdpi.com/1999-4923/10/4/199 |
| work_keys_str_mv | AT changhyunkim stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT siwoosung stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT eunseoklee stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT taehoonkang stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT hoyubyoon stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT yoontaegoo stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT haracho stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT dongyoonkim stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT myungjookang stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT yongseokchoi stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT sangkillee stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution AT youngwookchoi stericallystabilizedriplpeptideconjugatednanostructuredlipidcarrierscharacterizationcellularuptakecytotoxicityandbiodistribution |