Management of Diabetes and its Oral Manifestations With Nanotechnology-Based Treatment.

Objectives: Devastating oral complications of Type 2 diabetic mellitus (T2DM) such as delayed wound healing, caries, neurosensory disorders, xerostomia, and periodontitis are preventable with optimal glycemic control. The main drawback of the FDA-approved glucagon like peptide 1 analogue Exendin 4 (Ex4) is its short half-life, thus requiring frequent administrations. Here we aimed to overcome this limitation and prolong Ex4 half-life, by developing a sustained release drug delivery system (DDS) based on liposomes.
Methods: Liposomes loaded with Ex4 (Lipo-Ex4) were prepared and characterized for the drug level of encapsulation and kinetics by Reversed-phase chromatography. For bioactivity, the glucose clearance of mice treated with free-Ex4 or Lipo-Ex4 was evaluated with intra peritoneal glucose tolerance test (IPGTT). The original model, in which treatments were administrated daily, was modified to administration every 2-3 days, to allow clearance of the free drug.
Mice body weight (BW) was monitored to examine toxicity.
To determine whether our formulation is effective, we performed the modified IPGTT in diabetic (DB/DB) mice.
Results: In-vitro. Lipo-Ex4 exhibited high encapsulation (75%) and sustained release (2 weeks vs. 1d).
In-vivo, the released Ex4 was biologically active.
Lipo-Ex4 exhibited prolonged half-life and plasma presence, compared to free Ex-4, ((8h vs. 2.5h and 6h vs. 24h, respectively). The modified IPGTT showed that Lipo-Ex4 improved glucose clearance compared to free-Ex4 (23% reduction in blood glucose levels vs. 0%, respectively). All mice gained weight, but mice treated with Lipo-Ex4 gained less weight compared to free-Ex4.
Ex4-LMVV improved fasting glucose in diabetic mice compared to free-Ex4 (198 vs. 388 mg/dL, respectively).
Conclusions: We developed a novel sustained release DDS by encapsulating Ex-4 in liposomes, which prolonged the Ex-4 half-life and was able to treat T2DM in mice. Our approach will reduce treatment frequency, improve patients’ compliance and safety. Optimal glycemic control will also improve oral health.