Novel strategies to oral delivery of insulin: Current progress of nanocarriers for diabetes management

Abstract

Diabetes mellitus is one of the most serious public health problems in the world. Repeated daily injections of subcutaneous insulin is the standard treatment for patients with type 1 diabetes mellitus; however, subcutaneous insulin injections can potentially cause local discomfort, patient noncompliance, hypoglycemia, failure to regulate glucose homeostasis, infections, and fat deposits at the injection sites. In recent years, numerous attempts have been made to produce safe and efficient nanoparticles for oral insulin delivery. Oral administration is considered the most effective alternative route to insulin injection, but it is accompanied by several challenges related to enzymatic proteolysis, digestive breakdown, and absorption barriers. A number of natural and synthetic polymeric, lipid‐based, and inorganic nanoparticles have been investigated for use. Although improvements have recently been made in potential oral insulin delivery systems, these require further investigation before clinical trials are conducted. In this review, new approaches to oral insulin delivery for diabetes treatment are discussed, including polymeric, lipid‐based, and inorganic nanoparticles, as well as the clinical trials performed for this purpose.

Exploring mesoporous silica nanoparticles as oral insulin carriers: In-silico and in vivo evaluation

“…An efficient and non-toxic oral insulin delivery system could revolutionize the management of type 1 diabetes for patients, providing them with greater ease and comfort in controlling their blood glucose levels compared to traditional methods [ 31 , 32 ]. This study aimed to achieve two goals.…”

Polymeric nanoparticles (PNPs) for oral delivery of insulin

“…The optimized nanocarriers not only enhance the bioavailability of docked drugs but also their absorption, allowing for more effective insulin delivery [ 38 ]. The following factors largely influence drug release from NPs: pH, solubility, temperature, drug diffusion across the nanomaterial matrix, nanomaterial degradation, the drug incorporation process, and drug adsorption [ 39 , 40 ]. In brief, targeted drug release relies mainly on the stimuli-responsive of the PNPs.…”

“…Chitosan (CS) is a non-toxic, cationic, linear, heteropolysaccharide derived from deacetylated chitin and composed of d -glucosamine and n -acetyl- d -glucosamine monomers linked by β-(1–4) glycosidic bonds [ 39 , 76 , 77 ]. The amino functional groups in CS play a vital role in regulating biochemistry and electrostatic interactions in nanodrug delivery systems, as well as offering solubility in slightly acidic solutions.…”

Interactions between Nanoparticles and Intestine

“…ORMD-0801 is an example of human insulin NPs that underwent several clinical trials, among which the phase II NCT02496000 study. During this trial, patients with Type 2 Diabetes were treated with insulin-NPs, observing an important reduction in insulin without hypoglycaemic side effects [179,180].…”