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Tricaprin as a membrane permeability regulator: sustained small hydrophilic substance release from liposomes

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Abstract

Purpose

Incorporating fatty acids into the phospholipid bilayer affects membrane packing order and permeability. We recently demonstrated that incorporating triglyceride into liposomes may alter membrane packing order and hydrophobic drug encapsulation capacity. This work investigated the effect of the saturated fatty acid-based triglyceride incorporation into liposomes carrying hydrophilic drugs.

Methods

Effects of tricaprin (TC) incorporation on the physicochemical properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based liposomes encapsulated with small or large hydrophilic model drugs were investigated in terms of dithionite permeability, phase transition temperature, drug encapsulation efficiency, drug release rate, storage stability and cellular uptake of liposomes.

Results

TC incorporation into liposomes decreased dithionite permeability and raised phase transition temperatures of DMPC, indicating TC reduced membrane permeability. TC-induced thermogram changes in small hydrophilic drug model fluorescein-5-(and-6)-sulfonic acid (5-FSA)-encapsulated liposomes were comparable to those in drug-free/TC-incorporated liposomes. In contrast, they were significantly altered in large hydrophilic drug model FITC-BSA-encapsulated liposomes, suggesting macromolecule-induced membrane rearrangement. TC decreased the release rate of 5-FSA but increased that of FITC-BSA. Further, TC improved 5-FSA-encapsulated liposomes’ storage and freeze-drying stability. TC incorporation did not affect the cellular uptake of 5-FSA encapsulated in liposomes.

Conclusion

Our work demonstrates that saturated fatty acid-based triglyceride incorporation provides multiple benefits for liposomes carrying small, but not large, hydrophilic drugs by improving membrane properties.

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Data Availability

Studies are still ongoing and data are not available yet.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2021R1A2C1004343) to S.J. Lim.

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Authors and Affiliations

  1. Department of Integrated Bioscience and Biotechnology, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, 05006, Korea

    So-Youn Ro, Hyeon-Muk Choi, Seung-Ho Choi & Soo-Jeong Lim

  2. Research and Development Center of Yooyoung Pharmaceutical Co., Ltd, 38-21, Digital-ro 31-gil, Guro-gu, Seoul, 08376, Korea

    Sa-Won Lee

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  1. So-Youn Ro
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Correspondence to Soo-Jeong Lim.

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All authors S.‑Y. Ro, H.‑M. Choi, S.‑H. Choi, S.-W. Lee, and S.‑J. Lim declare that they have no conflict of interest.

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Ro, SY., Choi, HM., Choi, SH. et al. Tricaprin as a membrane permeability regulator: sustained small hydrophilic substance release from liposomes. J. Pharm. Investig. 53, 539–548 (2023). https://doi.org/10.1007/s40005-023-00621-2

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  • DOI: https://doi.org/10.1007/s40005-023-00621-2

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