Porous hydroxyapatite carrier enables localized and sustained delivery of honokiol for glioma treatment

• Published in: European journal of pharmaceutics and biopharmaceutics 2023-08, Vol.189, p.224-232
• Main Authors: Lin, Feng-Huei, Hsu, Yu-Chen, Chang, Kuo-Chi, Shyong, Yan-Jye
• Format: Article
• Language: English
• Subjects: Drug Delivery Systems; Durapatite - chemistry; Glioblastoma; Glioma - drug therapy; Honokiol; Humans; Hydroxyapatite; Local drug delivery; Porosity; Sustained drug release
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2023.06.016

[Display omitted] The objective of this study is to develop hydroxyapatite (HAp) particles for targeted delivery of honokiol to tumor sites after glioma surgical management. Honokiol is released from the HAp-honokiol particles inside cancer cells through endocytosis and subsequent acid lysosomal dissolution. HAp is synthesized using a co-precipitation method, and egg white is added to create porous structures. The HAp is then surface-modified with stearic acid to enhance its hydrophobicity and loaded with honokiol to form HAp-honokiol particles. The synthesized particles are of appropriate size and characteristics for cancer cell uptake. Honokiol remains attached on to the HAp particles in neutral environments due to its hydrophobic nature, but undergoes rapid burst release in acidic environments such as lysosomes. The HAp-honokiol treatment shows a delayed effect on cell viability and cytotoxicity, indicating sustained drug release without compromising drug efficacy. Flow cytometry analysis demonstrates the apoptosis pathway induced by HAp-honokiol in ALTS1C1 glioma cells. In the in vivo study using a mouse glioma model, MRI results showed a 40% reduction in tumor size after HAp-honokiol treatment. These findings suggest that HAp-honokiol particles have potential as an effective drug delivery system for the treatment of glioma.