Preparation, Characterization, Pharmacokinetic, and Therapeutic Potential of Novel 6-Mercaptopurine-Loaded Oral Nanomedicines for Acute Lymphoblastic Leukemia

Preparation, Characterization, Pharmacokinetic, and Therapeutic Potential of Novel 6-Mercaptopurine-Loaded Oral Nanomedicines for Acute Lymphoblastic Leukemia

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Yaru Zou,1,2,* Dong Mei,1,* Jinjie Yuan,1,2 Jiaqi Han,1 Jiamin Xu,1 Ning Sun,1 Huan He,1 Changqing Yang,2 Libo niner rkt 9 rdo 2023 Zhao1 1Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China*These authors contributed equally to this workCorrespondence: Libo ZhaoClinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of ChinaTel +86-010-59617018Email libozhao2011@163.comBackground: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children.It requires a long and rigorous course of chemotherapy treatments.

6-Mercaptopurine (6-MP) is one of the primary drugs used in chemotherapy.Unfortunately, its efficacy has been limited due to its insolubility, poor bioavailability and serious adverse effects.To overcome these drawbacks, we constructed 6-mercaptopurine (6-MP)-loaded nanomedicines (6-MPNs) with biodegradable poly(lactide-co-glycolide) (PLGA) to enhance the anticancer efficacy of 6-MP.

Methods: We prepared the 6-MPNs using a double-emulsion solvent evaporation method, characterizing them for the physicochemical properties.We then investigated the plasma, intestinal region and other igora vibrance 4-99 organs in Sprague Dawley (SD) rats for pharmacokinetics.Additionally, we evaluated its anticancer efficacy in vitro on the human T leukemia cell line Jurkat and in vivo on the ALL model mice.

Results: The 6-MPNs were spherical in shape with uniform particle size and high encapsulation efficiency.The in vitro release profile showed that 6-MPNs exhibited a burst release that a sustained release phase then followed.The apoptosis assay demonstrated that 6-MPNs could improve the in vitro cytotoxicity in Jurkat cells.

Pharmacokinetics profiles revealed that 6-MPNs had improved oral bioavailability.Tissue distribution experiments indicated that 6-MPNs increased the duodenum absorption of 6-MP, at the same time having a low accumulation of the toxic metabolites of 6-MP.The in vivo pharmacodynamics study revealed that 6-MPNs could prolong the survival time of the ALL model mice.

The prepared 6-MPNs, therefore, have superior properties in terms of anticancer efficacy against ALL with reduced systemic toxicity.Conclusion: Our nanomedicines provide a promising delivery strategy for 6-MP; they offer a simple preparation method and high significance for clinical translation.Keywords: 6-mercaptopurine, nanomedicines, Jurkat cells, acute lymphoblastic leukemia, ALL, bioavailability.