Oral delivery of
proteins has opened a new perspective for the treatment of different diseases. However, advances of oral
protein formulation are usually hindered by
protein susceptibility and suboptimal absorption in the gastrointestinal tract (GIT). Polymeric
nano drug delivery systems are considered revolutionary candidates to solve these issues, which can be preferably tunable against specific delivery challenges. Herein, a tailored family of
lysine-based poly(
ester amide)s (Lys-aaPEAs) is designed as a general oral
protein delivery platform for efficient
protein loading and protection from degradation.
Insulin, as a model
protein, can achieve effective internalization by epithelial cells and efficient transport across the intestinal epithelium layer into the systemic circulation, followed by controlled release in physiological environments. After the
oral administration of
insulin carried by Lys-aaPEAs with ornamental
hyaluronic acid (HA), mice with
type 1 diabetes mellitus showed an acceptable
hypoglycemic effect with alleviated complications. A successful oral
insulin delivery is associated with patient comfort and convenience and simultaneously avoids the risk of
hypoglycemia compared with
injections, which is of great feasibility for daily diabetes
therapy. More importantly, this versatile Lys-aaPEAs polymeric library can be recognized as a universal vehicle for oral biomacromolecule delivery, providing more possibilities for treating various diseases.