Mesoporous Hydroxyapatite as Olanzapine Carrier Provides a Long-Acting Effect in Antidepression Treatment

Yan-Jye Shyong, Mao Hsien Wang, Hsiang Chien Tseng, Chen Cheng, Kuo Chi Chang, Feng Huei Lin

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 (Ca2+) 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.

Original languageEnglish
Pages (from-to)8463-8474
Number of pages12
JournalJournal of Medicinal Chemistry
Volume58
Issue number21
DOIs
Publication statusPublished - 2015 Oct 16

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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