Lipid-based nanoparticles as oral drug delivery systems: overcoming poor gastrointestinal absorption and enhancing bioavailability of peptide/protein-based drugs

Abstract

Delivery and formulation of oral therapeutic peptide/protein-based biotechnological drugs have always been a challenge for the pharmaceutical industry. The bioavailability of oral biopharmaceuticals mainly relies on their gastrointestinal solubility and permeability which are affected by their poor membrane penetration, high molecular weight and proteolytic (chemical and enzymatic) degradation resulting in limited delivery and therapeutic efficacy. The present review article highlights the challenges and limitations of oral delivery of therapeutic peptide/protein-based drugs focusing on the application, potential and importance of solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) as lipid-based drug delivery systems (LBDDSs) and their advantages and drawbacks. LBDDSs, due to their lipid-based matrix can encapsulate both lipophilic and hydrophilic drugs, and by reducing the first-pass effect and avoiding proteolytic degradation offer improved drug stability, dissolution rate, absorption, bioavailability and controlled drug release. Furthermore, their small size, high surface area and surface modification increase their mucosal adhesion, tissue-targeted distribution, physiological function and half-life. Properties such as simple preparation, high-scale manufacturing, biodegradability, biocompatibility, prolonged half-life, lower toxicity, lower adverse effects, lipid-based structure, higher drug encapsulation rate and various drug release profile compared to other similar carrier systems makes LBDDSs a promising drug delivery system. Nevertheless, undesired physicochemical features of peptide/protein drug development and discovery such as plasma stability, membrane permeability and circulation half-life remain a serious challenge which should be addressed in future.