Glycerol-based soft vesicular systems for nose to brain delivery of 131I-melatonin: Synthesis, characterization, biodistribution and Pharmacokinetic investigations

Recently, glycerol has shown several pharmaceutical merits, particularly in intranasal brain delivery. In the present manuscript, advanced glycerol-based soft vesicular systems (glycerosomes, Gs) encompassing melatonin (MLT), a pineal gland hormone, were formulated and characterized in this regard. The prepared vesicles were tested for their particle size (PS), zeta potential (ZP), encapsulation efficiency (EE%) as well as storage stability. Besides, the drug release pattern, surface morphology, viscosity and pH measurements, and permeability through sheep nasal mucosa were conducted on the selected preparations. Bio-distribution along with pharmacokinetic investigations were conducted employing the radioiodinated-MLT (¹³¹I-MLT) to assess the in-vivo behavior of intravenous solutions (Vs), intranasal solutions (Ns), and intranasal given glycerosomes (NGs). Results revealed that MLT-loaded vesicles showed PS ranging from 202 to 538 nm, negative ZP values varying from −13.10 to −19.26 mV, superior EE% values possessing a range of 84.21–96.53 % and good stability properties manifested by insignificant change in their colloidal properties. In addition, the optimized formulation(s) displayed spherical shape, prolonged drug release reaching ≈100 % throughout 24 h and augmented permeation of approximately 4-fold higher relative to MLT ethanolic solution. The findings of the in-vivo study showed that during the first 5 min, brain/blood ratio (B/B) of NGs was 11.0 and 2.8 times greater compared to Vs and Ns of ¹³¹I-MLT, respectively. Accordingly, the results demonstrated the possibility of employing Gs as a secure and reliable platform for MLT intranasal brain delivery.