Nano-encapsulation of melatonin into polydiacetylene-phospholipid assembly for sustained-release and enhanced bone formation in zebrafish

Abstract

The low bioavailability of melatonin limits its effective antiosteoporosis activity. In the present study, the polymer-supported liposome is used to encapsulate the melatonin in order to enhance its bone formation activity. More specifically, the melatonin drug has enwrapped into a polymer/lipid hybrid nanovesicle (Lip-mel) by the self-assembly of 10,12-pentacosadiynoic acid (PCDA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) through thin-film hydration method. The liposome-encapsulated melatonin was characterised well by UV–Vis absorption spectroscopy, fluorescence microscopy, energy-dispersive X-ray analysis (EDX), and dynamic light scattering (DLS) measurements. The conjugated yne-ene chain of polymeric backbone of polydiacetylene (PDA) facilitates the formation of stable nanoaggregate from which only 50% of the encapsulated melatonin was leached out even after 72 h under physiological conditions. The Lip-mel shows alkaline phosphatase activity (ALP) and calcium deposition in mouse mesenchymal stem cells more efficient than non-encapsulated melatonin. Furthermore, the Lip-mel elevated the expression of key transcription factors (Runx2, type1 col mRNAs) and secretion of extracellular matrix proteins that are related to osteoblast differentiation. Interestingly, the bone formation in zebrafish model was also enhanced after exposure of Lip-mel compared to melatonin. Thus, the nano formulation of melatonin could be developed as efficient antiosteoporosis drug with better pharmacokinetic properties than that of free form of melatonin.