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

• Published in: Journal of controlled release 2017-06, Vol.255, p.62-72
• Main Authors: Shyong, Yan-Jye, Wang, Mao-Hsien, Kuo, Li-Wei, Su, Chang-Fu, Kuo, Wei-Ting, Chang, Kuo-Chi, Lin, Feng-Huei
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Benzodiazepines - administration & dosage; Benzodiazepines - chemistry; Benzodiazepines - therapeutic use; Benzodiazepines - toxicity; Brain - drug effects; Brain - metabolism; Depression - drug therapy; Depression - metabolism; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - therapeutic use; Drug Carriers - toxicity; Drug Liberation; Durapatite - administration & dosage; Durapatite - chemistry; Durapatite - therapeutic use; Durapatite - toxicity; Hydroxyapatite; Learning and memory abilities; Locomotion - drug effects; Locomotor activities; Male; Maze Learning - drug effects; Porosity; Prolong antidepressant drug carrier; Rats, Wistar; Serotonin; Serotonin - metabolism; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - chemistry; Serotonin Uptake Inhibitors - therapeutic use; Serotonin Uptake Inhibitors - toxicity
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.03.399

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. After IM injection, mesoHAP-OLZ is engulfed by macrophages and the lysosome/endosome hybrid is broken down by osmosis, which facilitates delivery of OLZ into the bloodstream for various analyses. [Display omitted]