Fig. 1

SHAP-CLB preparation and mechanism of drug release. (A) First, mesoporous hydroxyapatite (mesoHAP) was synthesized to an appropriate size using a co-precipitation method. Subsequently, several hydrophobic surface modifications were performed using stearic acid to load clenbuterol (CLB) through physical absorption to produce SHAP-CLB. (B) Owing to the hydrophobic nature of CLB, it was not efficiently released from SHAP-CLB in an aqueous environment. However, once it was taken up by macrophages, the lysosome/endosome hybrid ruptured as a result of changes in osmotic pressure, leading to the release of CLB into the cytoplasm. CLB was then exocytosis to the extracellular space, where the high concentration of calcium ions (Ca²⁺) facilitated its transfer to the bloodstream. This approach can provide a useful treatment strategy for achieving long-term drug release through a single intramuscular injection, which can solve the problem of nonadherence to medication intake that frequently arises in AD therapy