Melatonin loaded phytosomes for enhanced therapy against ethanol-induced gastric ulcer: formulation, optimization and in vitro/in vivo evaluation.

Abstract

Healing of gastric ulcer (GU) can terminate the progression into more serious deteriorations. A promising and versatile vesicular nanoformulation, namely; phytosomes (PHY), was fabricated to maximise the GU healing efficacy of the naturally occurring bioactive component; melatonin (MLT). The solvent evaporation-hydration process ensnared MLT in the phytosomal complex, namely; melatonin loaded phytosomes (MLT-loaded PHY), that were fully described. A randomised full factorial design (2³) was applied with three independent key parameters (IKPs) at two levels. The optimal formulation, melatonin soybean phosphatidylcholine loaded chitosan coated phytosomes (MLT-SPC100 loaded/CS-coated PHY (F6)), was the most convenient one with acceptable MLT percentage entrapment efficiency (EE %, 69.467 ± 2.901%) and particle size (PS, 248.200 ± 03.830 nm) values, besides highest zeta potential (ZP, +30.267 ± 0.981 mV) one. Thereafter, it was further characterised with regard to its mucoadhesion efficiency, solid state characterisation, morphology, in vitro dissolution, physical stability, protein adsorption (opsonization) resistance, cytotoxicity, and finally in vivo healing efficacy against ethanol-induced GU in rats. Amongst the treated groups, the healing efficacy of the optimal formulation (F6) was noteworthy, as demonstrated by histological, immunohistochemical (IHC), and biochemical investigations. Hence, the aforementioned formulation deserves consideration as a promising GU remedial strategy.