Long acting tariquidar loaded stearic acid-modified hydroxyapatite enhances brain penetration and antitumor effect of temozolomide.

Autor: Yu CP; School of Pharmacy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City 701, Taiwan. Electronic address: s68114021@gs.ncku.edu.tw., Lin SW; School of Pharmacy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City 701, Taiwan. Electronic address: s68071045@gs.ncku.edu.tw., Tsai JC; School of Pharmacy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City 701, Taiwan. Electronic address: jctsai@mail.ncku.edu.tw., Shyong YJ; School of Pharmacy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan City 701, Taiwan. Electronic address: bear901704@gs.ncku.edu.tw.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Apr; Vol. 197, pp. 114231. Date of Electronic Publication: 2024 Feb 19.
DOI: 10.1016/j.ejpb.2024.114231
Abstrakt: Temozolomide (TMZ) is the first line chemotherapy for glioblastoma (GBM) treatment, but the P-glycoprotein (P-gp) expressed in blood-brain barrier (BBB) will pump out TMZ from the brain leading to decreased TMZ concentration. Tariquidar (TQD), a selective and potent P-gp inhibitor, may be suitable for combination therapy to increase concentration of TMZ in brain. Hydroxyapatite (HAP) is a biodegradable material with sustained release characteristics, and stearic acid surface-modified HAP (SA-HAP) can increase hydrophobicity to facilitate TQD loading. TQD-loaded stearic acid surface-modified HAP (SA-HAP-TQD) was prepared with optimal size and high TQD loading efficiency, and in vitro release and cellular uptake of SA-HAP-TQD showed that SA-HAP-TQD were taken up into lysosome and continuously released TQD from macrophages. In vivo studies have found that over 70 % of SA-HAP was degraded and 80 % of TQD was released from SA-HAP-TQD 28 days after administration. SA-HAP-TQD could increase brain penetration of TMZ, but it would not enhance adverse effects of TMZ in healthy mice. SA-HAP-TQD and TMZ combination had longer median survival than TMZ single therapy in GL261 orthotopic model. These results suggest that SA-HAP-TQD has sustained release characteristics and are potential for improving antitumor effect with TMZ treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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