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

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.

Drug delivery of extracellular vesicles: Preparation, delivery strategies and applications.

Extracellular vesicles (EV) are cell-originated vesicles exhibited with characteristics similar to the parent cells. Several studies have suggested the therapeutic potential of EV since they played as an intercellular communicator and modulate disease microenvironment, and thus EV has been widely studied in cancer management and tissue regeneration. However, merely application of EV revealed limited therapeutic outcome in different disease scenario and co-administration of drugs may be necessary to exert proper therapeutic effect. The method of drug loading into EV and efficient delivery of the formulation is therefore important. In this review, the advantages of using EV as drug delivery system compared to traditional synthetic nanoparticles will be emphasized, followed by the method of preparing EV and drug loading. The pharmacokinetic characteristics of EV was discussed, together with the review of reported delivery strategies and related application of EV in different disease management.