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Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in children. 6-Mercaptopurine (6-MP) is a core chemotherapeutic drug for ALL, but its clinical application is limited by poor solubility, low biological availability, and significant side effects. To address these limitations and to investigate the impact of developmental differences between children and adults on drug absorption, this study developed 6-MP-loaded poly (lactic-co-glycolic acid) nanoparticles (6-MPNs) using a double emulsion-solvent evaporation method. We comprehensively applied high-performance liquid chromatography-mass spectrometry (HPLC-MS) and label-free quantitative proteomics, along with GO functional annotation via eggnog-mapper (v2.0) and protein-protein interaction analysis using STRING (v10.5), to systematically evaluate the pharmacokinetics, intestinal distribution, and duodenal protein expression differences of 6-MPNs in animal models of different ages. All animal studies were approved by the Animal Ethics Committee of Capital Medical University (Approval No.: AEEI-2020-072) and conducted in accordance with relevant guidelines. The results showed that 6-MPNs significantly improved the biological availability of 6-MP. Rats at 4 weeks of age group exhibited higher AUClast (area under curve from time zero to time of last measurable concentration) and Cmax (maximum concentration), faster intestinal absorption, more rapid propulsion, and higher transport efficiency from the intestinal epithelium to the portal vein compared to the rats at 16 weeks of age group. Proteomic analysis revealed that the rats at 16 weeks of age group had significantly lower expression of proteins related to fat digestion and transport, pancreatic secretion, membrane lipid metabolism, brush border recruitment, and microvillus adhesion. These findings suggest that the higher biological availability of 6-MPNs in younger animals may result from longer relative intestinal length, higher intestinal wall transport efficiency and more dynamic barrier construction.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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