Lipid-based formulations: A promising approach for poorly soluble drug delivery via the intestinal lymphatic system

Abstract

Lipid-based formulation (LBF) has attracted more and more attention as it can significantly improve the efficiency of oral delivery of poorly soluble drugs by exploiting the specific absorption pathway of lipids in the intestinal lymphatic system. Based on the structure and function of the intestinal lymphatic system, this article describes the advantages and strategies of oral LBF delivery through this system, highlights the research progress of oral LBF (lipid-based nanocarriers, lipid-based prodrugs) based on this system in recent years, and briefly outlines the experimental model to study the intestinal lymphatic delivery of drugs, providing methods and ideas for the development and utilization of poorly soluble drugs and the rational design of LBF.

Introduction

Currently, more than 50% of marketed drugs [1] and 90% of drug candidates have poor water solubility, and these percentages continue to increase due to the rapid development of drug discovery routes [2]. Oral drug delivery is widely used in the clinic due to its non-invasive nature, high patient compliance, low cost and pain avoidance. Since dissolution is a prerequisite for oral drug absorption, unsuitable solubility always leads to slow dissolution and low bioavailability.

The lymphatic system is a unidirectional transport system parallel to blood circulation and plays an essential role in maintaining fluid homeostasis [3], lipid metabolism [4] and immune regulation [5]. It enables the return of fluid filtered through capillaries to the interstitial space, thus replenishing the circulation and maintaining the volume and composition of functional fluids in various body parts to prevent organ failure [6]. In recent years the role of the lymphatic system in drug delivery has attracted increasingly widespread attention from researchers, especially for oral delivery of poorly soluble drugs. Different types of LBF have been developed to improve the oral delivery of poorly soluble drugs, such as lipid-based nanocarriers and lipid-based prodrugs. Lipid-based nanocarriers can significantly increase the dissolution of poorly soluble medications and promote the absorption of drugs in intestinal lymphatic tissues by using the digestion process of an exogenous lipid matrix. Lipid-based prodrugs can significantly improve the absorption of drugs through the covalent binding of lipids to drugs and the digestion and absorption process of exogenous lipids in intestinal lymphatic tissues, thus improving the efficiency of oral delivery of drugs.

In this article, the structure and function of the ILS and the characteristics of drug delivery through this system are briefly reviewed, as the progress of recent research on lipid-based nanocarriers, lipid-based prodrugs, and drugs delivered in combination with these two forms based on this system is detailed. Several experimental models for evaluating intestinal lymphatic transport are also outlined to provide literature references and design ideas for developing and utilizing poorly soluble drugs and the rational design of LBF.