Design and analysis of a liposomal melatonin formulation for intravenous administration

Introduction. Cerebrovascular accident is one of the major causes of death worldwide. This group of diseases frequently leads to incapacity, disability, and a poor quality of life and requires long-term treatment and rehabilitation. The use of antioxidants that include melatonin among others is a promising treatment for cerebral circulatory disorders. In view of the proven efficacy of melatonin for these disorders, it is rational to design its parenteral formulation for accelerated drug delivery to the patient's body, especially in the situations where this drug cannot be administered orally. The liposomal formulation of melatonin allows its intravenous injection and is likely to promote its passage through the blood-brain barrier. Objective: to develop a procedure to prepare a liposomal melatonin formulation for parenteral administration and to investigate the resulting dosage form. Material and methods. Liposomes were obtained by hydration of the lipid film prepared from phospholipids and cholesterol, by using a rotary evaporator. Melatonin was incorporated into the lipid membrane, after dissolving the agent in chloroform. The size of liposomes was measured by dynamic light scattering. The liposomes were purified from unincorporated melatonin by dialysis through a semipermeable membrane. The efficiency of melatonin incorporation into the liposomes was determined using UV spectrophotometry. Results. A liposomal melatonin formulation with a particle size of 66.6±10-nm was obtained. The drug concentration in this preparation was 1.8±0.01 mg/ml. The efficiency of incorporating melatonin into liposomes was 87.8±0.5%. The ratio of the incorporated melatonin to phospholipids was 0.035. Conclusion. The obtained liposomes with melatonin can be suitable for intravenous administration, and, if they can penetrate the blood-brain barrier, provide the targeted delivery of high-concentration melatonin to the central nervous system, where melatonin will exert its therapeutic effect.

cerebrovascular accident, melatonin, liposomes