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  • An orally bioavailable nanoparticle-based formulation composed of sub-micron particles of the macrolide antibiotic rapamycin incorporated into a pH-sensitive poly(methyl methacrylate) polymer, with potential immunomodulating and antineoplastic activities. Upon oral administration of the encapsulated rapamycin, the nanoparticle specifically delivers rapamycin at the tumor site. Rapamycin binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate a complex that binds to and inhibits the activation of the serine/threonine kinase mammalian target of rapamycin (mTOR), a key regulatory kinase. This may suppress mTORC1 activity. In addition, inhibition of mTOR may modulate central memory CD8 T cells, CD3+/CD56+ natural killer (NK) cells and CD8 T-cell responses. This may kill tumor cells. Compared to the administration of rapamycin alone, this formulation improves oral bioavailability of rapamycin with more consistent rapamycin levels, thereby allowing for administration of lower rapamycin dosage, which improves and minimizes rapamycin\'s toxicity. Upregulated in some tumors, mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility, and survival that is located downstream of the PI3K/Akt signaling pathway.
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