Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids
Non-lamellar liquid crystal (NLLC) structures have gained increasing attention for the controlled release of entrapped drugs. In the present study, an in situ NLLC structure-forming depot formulation through contact with water was developed using a ternary mixture system of soya phosphatidyl choline...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Drug Delivery |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fddev.2023.1270584/full |
| _version_ | 1827162296718196736 |
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| author | Hiroaki Todo Rina Niki Akie Okada Ibuki Narita Kazuya Inamura Ayu Ito Shoko Itakura Ichiro Hijikuro Kenji Sugibayashi Kenji Sugibayashi |
| author_facet | Hiroaki Todo Rina Niki Akie Okada Ibuki Narita Kazuya Inamura Ayu Ito Shoko Itakura Ichiro Hijikuro Kenji Sugibayashi Kenji Sugibayashi |
| author_sort | Hiroaki Todo |
| collection | DOAJ |
| description | Non-lamellar liquid crystal (NLLC) structures have gained increasing attention for the controlled release of entrapped drugs. In the present study, an in situ NLLC structure-forming depot formulation through contact with water was developed using a ternary mixture system of soya phosphatidyl choline (SPC), 1, 2-dioleoyl-sn-glycero-3-phosphoglycerol sodium salt (DOPG), and sorbitan trioleate (Span 85), and the long-term release of an entrapped model drug, leuprolide acetate (LA), was investigated using evaluation of in vitro release and in vivo blood concentration–time profiles. Polarized images and small angle X-ray scattering analysis were used to confirm the presence of NLLC structures by contacting the prepared formulation with water. In addition, LA release and blood concentration–time profiles were investigated using in vitro and in vivo experiments, respectively. In situ NLLC constructed formulations by contacting water were achieved using a ternary mixture of SPC, DOPG, and Span 85. In particular, negative curvature was increased with an increase in the amount of Span 85 in the formulation, and an Fd3m structure was obtained with a sustained release of LA. A maintained blood concentration of LA over 21 days was confirmed by subcutaneous (s.c.) administration of the formulation. No retained administered formulation at the injection site was confirmed 28 days after administration without any signs of irritation, inflammation, or other apparent toxicity confirmed by visual observation. This result may be helpful for the development of a lipid-based formulation of peptides and proteins with sustained drug release. |
| first_indexed | 2024-03-11T17:24:05Z |
| format | Article |
| id | doaj.art-c9c6b2ca48e54baf8776b7e15015be95 |
| institution | Directory Open Access Journal |
| issn | 2674-0850 |
| language | English |
| last_indexed | 2025-03-21T00:42:34Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Drug Delivery |
| spelling | doaj.art-c9c6b2ca48e54baf8776b7e15015be952024-08-03T06:10:46ZengFrontiers Media S.A.Frontiers in Drug Delivery2674-08502023-10-01310.3389/fddev.2023.12705841270584Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipidsHiroaki Todo0Rina Niki1Akie Okada2Ibuki Narita3Kazuya Inamura4Ayu Ito5Shoko Itakura6Ichiro Hijikuro7Kenji Sugibayashi8Kenji Sugibayashi9Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFarnex Incorporated, Yokohama Joint Research Center, Yokohama, JapanFaculty of Pharmacy and Pharmaceutical Sciences, Josai University, Sakado, JapanFaculty of Pharmaceutical Sciences, Josai International University, Togane, JapanNon-lamellar liquid crystal (NLLC) structures have gained increasing attention for the controlled release of entrapped drugs. In the present study, an in situ NLLC structure-forming depot formulation through contact with water was developed using a ternary mixture system of soya phosphatidyl choline (SPC), 1, 2-dioleoyl-sn-glycero-3-phosphoglycerol sodium salt (DOPG), and sorbitan trioleate (Span 85), and the long-term release of an entrapped model drug, leuprolide acetate (LA), was investigated using evaluation of in vitro release and in vivo blood concentration–time profiles. Polarized images and small angle X-ray scattering analysis were used to confirm the presence of NLLC structures by contacting the prepared formulation with water. In addition, LA release and blood concentration–time profiles were investigated using in vitro and in vivo experiments, respectively. In situ NLLC constructed formulations by contacting water were achieved using a ternary mixture of SPC, DOPG, and Span 85. In particular, negative curvature was increased with an increase in the amount of Span 85 in the formulation, and an Fd3m structure was obtained with a sustained release of LA. A maintained blood concentration of LA over 21 days was confirmed by subcutaneous (s.c.) administration of the formulation. No retained administered formulation at the injection site was confirmed 28 days after administration without any signs of irritation, inflammation, or other apparent toxicity confirmed by visual observation. This result may be helpful for the development of a lipid-based formulation of peptides and proteins with sustained drug release.https://www.frontiersin.org/articles/10.3389/fddev.2023.1270584/fulllipid-based depot formulationin situ forming systemsustained releasenon-lamellar liquid crystallong-acting drug delivery system |
| spellingShingle | Hiroaki Todo Rina Niki Akie Okada Ibuki Narita Kazuya Inamura Ayu Ito Shoko Itakura Ichiro Hijikuro Kenji Sugibayashi Kenji Sugibayashi Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids Frontiers in Drug Delivery lipid-based depot formulation in situ forming system sustained release non-lamellar liquid crystal long-acting drug delivery system |
| title | Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids |
| title_full | Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids |
| title_fullStr | Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids |
| title_full_unstemmed | Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids |
| title_short | Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids |
| title_sort | development of a depot formulation with an in situ non lamellar liquid crystal forming system with phospholipids |
| topic | lipid-based depot formulation in situ forming system sustained release non-lamellar liquid crystal long-acting drug delivery system |
| url | https://www.frontiersin.org/articles/10.3389/fddev.2023.1270584/full |
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