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Mesoporous hydroxyapatite as a carrier of olanzapine for long-acting antidepression treatment in rats with induced depression

Shyong, Yan-Jye, Wang, Mao-Hsien, Kuo, Li-Wei, Su, Chang-Fu, Kuo, Wei-Ting, Chang, Kuo-Chi, Lin, Feng-Huei
Journal of Controlled Release 2017 v.255 pp. 62-72
antidepressants, biomarkers, drug therapy, hippocampus, hydroxyapatite, in vivo studies, locomotion, magnetic resonance imaging, memory, porous media, rats, serotonin
An antidepressant carrier, mesoporous hydroxyapatite olanzapine (mesoHAP-OLZ), was designed to maintain 3weeks of constant medication release. The carrier was intramuscularly (IM) injected, where cellular activity played a role in achieving the goal of constant release. The efficiency of the treatment was evaluated from 3 perspectives in in vivo studies: locomotor activities, biomarkers, and learning and memory ability. MesoHAP-OLZ can increase the locomotor activity in rats with induced depression determined by open field test (OFT) and forced swim test (FST). Serotonin (5-HT), one of the most important biomarker in depression can also be increased by mesoHAP-OLZ, leading to increased hippocampus activity as measured by functional magnetic resonance imaging (fMRI). MesoHAP-OLZ can also improve learning and memory ability in rats with induced depression during Morris water maze (MWM) test. Our findings further show that mesoHAP-OLZ can provide long-term drug release with a single IM injection, helping to solve the problem of non-adherent medication intake that often occurs in antidepressant therapy.