title: Mesoporous Hydroxyapatite as Olanzapine Carrier Provides a Long-Acting Effect in Antidepression Treatment.
abstract: An antidepressant carrier was designed to maintain over 2 weeks of constant medication release. The carrier was injected into muscle, where cellular activity was employed to achieve the goal of constant release. Mesoporous hydroxyapatite (mesoHAP) was synthesized into an adequate size by a coprecipitation method; it then went through a series of hydrophobic surface modifications for olanzapine (OLZ) loading by physical absorption to produce mesoHAP-OLZ. Because of its hydrophobic nature, OLZ was not effectively released from mesoHAP-OLZ in an aqueous environment. However, once engulfed by macrophages, the lysosome/endosome hybrid ruptured due to alterations in osmotic pressure, resulting in the release of OLZ into the cytoplasm. OLZ was then exocytosed to the extracellular space due to a high calcium ion (Ca(2+)) concentration and finally reached the blood circulation. Our findings provide a useful treatment strategy to achieve long-term drug release with a single intramuscular (IM) injection, helping to solve the problem of nonadherent medication intake that often occurs in antidepressant therapy.
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University , No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Yan-Jye
authors.initials: YJ
authors.lastname: Shyong
authors.affiliation: Department of Anesthesia, En Chu Kon Hospital , Sanshia District, New Taipei City 23702, Taiwan ROC.
authors.forename: Mao-Hsien
authors.initials: MH
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital , Taipei 11101, Taiwan ROC.
authors.forename: Hsiang-Chien
authors.initials: HC
authors.lastname: Tseng
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University , No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Chen
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Chemical Engineering and Biotechnology, National Taipei University of Technology , No. 1, Sec. 3, Chung-Hsiao East Road, Taipei 10608, Taiwan.
authors.forename: Kuo-Chi
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University , No. 1, Section 4, Roosevelt Road, Taipei 10617, Taiwan.|Institute of Biomedical Engineering and Nanomedicine, National Health Research Institute , No. 35, Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D000077152:Olanzapine; D016062:Porosity; D017208:Rats, Wistar
chemical_list: D000928:Antidepressive Agents; D004337:Drug Carriers; D001569:Benzodiazepines; D017886:Durapatite; D000077152:Olanzapine