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Recent progress in hydrophobic ion-pairing and lipid-based drug delivery systems for enhanced oral delivery of biopharmaceuticals

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Abstract

Background

The biopharmaceuticals market has grown rapidly in recent years owing to the low toxicity and high therapeutic efficacy of peptide and protein drugs. However, due to their low stability, biopharmaceuticals have to be administrated via invasive routes, and there is an unmet need for alternative routes. The most familiar and preferred alternative route of administration is the oral route; however, peptide and protein drugs are readily affected by the harsh gastrointestinal environment, resulting in low oral bioavailability. Lipid-based drug delivery systems (LDDSs) for oral administration protect the incorporated drugs and enhance their absorption in the GI tract. However, only lipophilic substances can be stably incorporated in LDDSs, and hydrophilic peptides and proteins require lipidation via, e.g., hydrophobic ion pairing (HIP).

Area covered

This review discusses the issues that hamper the oral administration of peptides and proteins and introduces HIP and LDDSs as strategies to overcome these. The principle of HIP complexation, the parameters to be considered for complexation, and the various counterions used are described. As for LDDSs, the advantages of self-emulsifying drug delivery systems (SEDDSs), which are suitable for oral peptide and protein delivery, and in vivo study results are described.

Expert opinion

HIP complexes are prepared based on an understanding of the characteristics of drugs and counterions. HIP complexes of peptides and proteins in the oil phase of SEDDSs are protected from the GI environment and therefore, improved absorption is expected. Although their fundamental mechanisms remain unclear and require further study, HIP-incorporated SEDDSs provide a potential strategy for oral peptide and protein delivery.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Sciences, ICT & Future Planning (NRF-2016R1D1A1B01015369), and the Ministry of Education (NRF-2016R1A6A1A03011325).

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  1. Gyubin Noh and Taekwang Keum have contributed equally to this work.

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  1. College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu, 42601, Korea

    Gyubin Noh, Taekwang Keum, Santosh Bashyal, Jo-Eun Seo, Lamichhane Shrawani, Jeong Hwan Kim & Sangkil Lee

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Noh, G., Keum, T., Bashyal, S. et al. Recent progress in hydrophobic ion-pairing and lipid-based drug delivery systems for enhanced oral delivery of biopharmaceuticals. J. Pharm. Investig. 52, 75–93 (2022). https://doi.org/10.1007/s40005-021-00549-5

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