Phospholipid complex based nanoemulsion system for oral insulin delivery: preparation, in vitro, and in vivo evaluations

Xiong-Bin Hu,^1–3 Tian-Tian Tang,^1–3 Yong-Jiang Li,^1–3 Jun-Yong Wu,^1–3 Jie-Min Wang,^1–3 Xin-Yi Liu,^1–3 Da-Xiong Xiang<sup>1–3

1</sup>Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; ²Institute of Clinical Pharmacy, Central South University, Changsha 410011, Hunan, People’s Republic of China; ³Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan Province, 410011, People’s Republic of China

Purpose: The aim of this research was to develop a phospholipid complex based nanoemulsion system for oral insulin delivery.
Methods: Insulin-phospholipid complex (IPC) was firstly prepared by an anhydrous co-solvent lyophilization method, and then encapsulated into the oil phase of nanoemulsion to obtain the IPC-based nanoemulsion (IPC-NE). Both water-in-oil (W/O) IPC-NE and oil-in-water (O/W) IPC-NE were formulated and evaluated for comparison.
Results: The obtained W/O IPC-NE and O/W IPC-NE were both spherical in shape with a mean particle size of 18.6±0.79 nm and 27.3±1.25 nm, respectively. While both IPC-NEs exhibited enhanced Caco-2 cell monolayers permeability than IPC and insulin solution, W/O IPC-NE showed relatively greater protective effects against enzymatic degradation than O/W IPC-NE. Moreover, oral administration of W/O IPC-NE exhibited significant hypoglycemic effects, with 12.4-fold and 1.5-fold higher oral bioavailability compared with insulin solution and O/W IPC-NE, respectively.
Conclusion: IPC-NEs, especially the W/O IPC-NE showed promising efficiency in vitro and in vivo, thus could be a potential strategy for oral insulin delivery.

Keywords: insulin, phospholipid complex, oral drug delivery, nanoemulsion, hypoglycemic effect