Melatonin releasing PLGA micro/nanoparticles and their effect on osteosarcoma cells

Abstract

Melatonin loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles and microparticles in the diameter of ∼200 nm and 3.5 μm, respectively, were prepared by emulsion-diffusion-evaporation method. Melatonin entrapment into the particles was significantly improved with the addition of 0.2% (w/v) melatonin into the aqueous phase and encapsulation efficiencies were found as 14 and 27% for nanoparticles and microparticles, respectively. At the end of 40 days, ∼70% of melatonin was released from both of particles, with high burst release. Both blank and melatonin loaded PLGA nanoparticles caused toxic effect on the MG-63 cells due to their uptake by the cells. However, when 0.05 mg microparticle that is carrying ∼1.7 μg melatonin was added to the cm(2) of culture, inhibitory effect of melatonin on the cells were obviously observed. The results would provide an expectation about the usage of melatonin as an adjunct to the routine chemotherapy of osteosarcoma by encapsulating it into a polymeric carrier system.

Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

“…Melatonin modulates anti-apoptotic processes in normal cells and activates bone cell proliferation and differentiation at 1 nM-1 µM concentrations [82], whereas it inhibits the proliferation of bone cancer cells to trigger pro-apoptotic signals at 4-10 mM concentrations [65]. The idea of encapsulating the drugs inside a micro/nanoparticle, fabricated from biodegradable polymers for drug delivery systems, to control drug release at desired sites, has become very intriguing [83]. Owing to the relatively short half-life (30-57 min) of melatonin in the blood [84], melatonin loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and microparticles have been employed to fortify the inhibitory effect of human osteosarcoma MG-63 cell proliferation, providing an expectation about the usage of melatonin as an adjunct to the routine chemotherapy of osteosarcoma [83].…”

“…The idea of encapsulating the drugs inside a micro/nanoparticle, fabricated from biodegradable polymers for drug delivery systems, to control drug release at desired sites, has become very intriguing [83]. Owing to the relatively short half-life (30-57 min) of melatonin in the blood [84], melatonin loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and microparticles have been employed to fortify the inhibitory effect of human osteosarcoma MG-63 cell proliferation, providing an expectation about the usage of melatonin as an adjunct to the routine chemotherapy of osteosarcoma [83]. Moreover, 9 mM of melatonin concentration released from the melatonin/2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex loaded chitosan scaffolds causes time dependent cell death by reducing the proportion of the cells in the G2/M phase rather than the S phase, so the inclusion complex can be considered an alternative system for human osteosarcoma therapy [85].…”

Development and characterization of oxaceprol‐loaded poly‐lactide‐co‐glycolide nanoparticles for the treatment of osteoarthritis

“…It describes the release mechanism based on both diffusion and erosion. Notably, the diffusion could be ascribed to the generation of potential gradient of drug molecule, while erosion attributed to stress conditions (Altındal & Gümüşderelioğlu, ).…”

Production and Drug Release Assesment of Melatonin Loaded Alginate/Gum Arabic Beads

“…The most important task of melatonin molecule is to regulate circadian rhythm and sleep-wake cycle in humans. Melatonin also provides positive effects on immune system, reduction of tumor growth, antioxidative protection, and homeostasis (6). Low melatonin release may cause sleep disorder, tiredness, and memory impairment.…”

“…The solubility and stability of drugs as well as increased pharmacologic efficiency can be enhanced by entrapping them in drug carriers (6). Melatonin has a short half-life, therefore, developing a controlled release system may be useful (12).…”