Hydrophobic ion pairing-based self-emulsifying drug delivery systems: a new strategy for improving the therapeutic efficacy of water-soluble drugs

ABSTRACT

Introduction

Self-emulsifying drug delivery systems (SEDDS) are formulations consisting of oil phase, emulsifiers, and co-emulsifiers, which can be spontaneously emulsified in the body to form O/W microemulsion. Traditionally, SEDDS are used commercially for the improvement of oral absorption and in vivo performances for poorly water-soluble drugs. However, SEDDS formulations were rarely reported for the delivery of water-soluble drugs. Recent studies have found that SEDDS have the potential for water-soluble macromolecular drugs by the application of the hydrophobic ion pairing (HIP) technology.

Areas covered

This review summarized the characteristics of HIP complexes in SEDDS and introduced their advantages and discussed the future prospects of HIP-based SEDDS in drug delivery.

Expert opinion

Hydrophobic ion pairing (HIP) is a technology that combines lipophilic structures on polar counterions to increase the lipophilicity through electrostatic interaction. Recent studies showed that HIP-based SEDDS offer an effective way to increase the mucosal permeability and improve the chemical stability for antibiotics, proteases, DNA-based drugs, and other water-soluble macromolecular drugs. It is believed that HIP-based SEDDS offer a potential and attractive method capable of delivering hydrophilic macromolecules with ionizable groups for oral administration.

KEYWORDS:

• Self-emulsifying drug delivery systems
• hydrophobic ion pairing
• oral administration
• hydrophilic macromolecules

Article highlights

• As promising drug delivery systems, self-emulsifying drug delivery systems are receiving extensive attention for the delivery of lipid-based drugs.

• Hydrophobic ion pairing technology is a convenient and reversible method to improve the lipophilicity of hydrophilic macromolecules with ionizable groups through electrostatic interaction.

• Delivery of water-soluble macromolecules by SEDDS is realized with the development of HIP technology.

• HIP-based SEDDS provide protective effects against enzymes and improve mucosa permeability for oral hydrophilic macromolecules.

• Antibiotics, proteases, and DNA-based drugs have been loaded into HIP-based SEDDS for oral delivery.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 82173765), the Science Foundation for Outstanding Youth of Liaoning Province (2021-YQ-08), the Natural Science Foundation Funding Program of Liaoning Province (2022-MS-096), the Ningxia Key Research and Invention Program (NO.2021BEG02039), the Basic Research Projects of Liaoning Provincial Department of Education (2020LFW01), the Career Development Program for Young Teachers (ZQN2019003) and the Outstanding Youth Lifting Program (YQ202115) in Shenyang Pharmaceutical University, and the Open Fund (NO. KF2022005) of Key Laboratory of Biotechnology and Bioresources Utilization (Dalian Minzu University), Ministry of Education, China.