TY - JOUR
T1 - Mesoporous Hydroxyapatite as Olanzapine Carrier Provides a Long-Acting Effect in Antidepression Treatment
AU - Shyong, Yan-Jye
AU - Wang, Mao Hsien
AU - Tseng, Hsiang Chien
AU - Cheng, Chen
AU - Chang, Kuo Chi
AU - Lin, Feng Huei
PY - 2015/10/16
Y1 - 2015/10/16
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jmedchem.5b00714
DO - 10.1021/acs.jmedchem.5b00714
M3 - Article
C2 - 26474006
AN - SCOPUS:84947216814
VL - 58
SP - 8463
EP - 8474
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 21
ER -