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- W4304607573 abstract "BT44 is a novel, second-generation glial cell line-derived neurotropic factor mimetic with improved biological activity and is a lead compound for the treatment of neurodegenerative disorders. Like many other small molecules, it suffers from intrinsic poor aqueous solubility, posing significant hurdles at various levels for its preclinical development and clinical translation. Herein, we report a poly(2-oxazoline)s (POx)-based BT44 micellar nanoformulation with an ultrahigh drug-loading capacity of 47 wt %. The BT44 nanoformulation was comprehensively characterized by 1H NMR spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), dynamic light scattering (DLS), and cryo-transmission/scanning electron microscopy (cryo-TEM/SEM). The DSC, XRD, and redispersion studies collectively confirmed that the BT44 formulation can be stored as a lyophilized powder and can be redispersed upon need. The DLS suggested that the redispersed formulation is suitable for parenteral administration (Dh ≈ 70 nm). The cryo-TEM measurements showed the presence of wormlike structures in both the plain polymer and the BT44 formulation. The BT44 formulation retained biological activity in immortalized cells and in cultured dopamine neurons. The micellar nanoformulation of BT44 exhibited improved absorption (after subcutaneous injection) and blood-brain barrier (BBB) penetration, and no acute toxic effects in mice were observed. In conclusion, herein, we have developed an ultrahigh BT44-loaded aqueous injectable nanoformulation, which can be used to pave the way for its preclinical and clinical development for the management of neurodegenerative disorders." @default.
- W4304607573 created "2022-10-12" @default.
- W4304607573 creator A5000929659 @default.
- W4304607573 creator A5006657051 @default.
- W4304607573 creator A5021184671 @default.
- W4304607573 creator A5025070309 @default.
- W4304607573 creator A5037126997 @default.
- W4304607573 creator A5039941233 @default.
- W4304607573 creator A5055031951 @default.
- W4304607573 creator A5077907142 @default.
- W4304607573 date "2022-10-11" @default.
- W4304607573 modified "2023-10-15" @default.
- W4304607573 title "Biological Activity <i>In Vitro</i>, Absorption, BBB Penetration, and Tolerability of Nanoformulation of BT44:RET Agonist with Disease-Modifying Potential for the Treatment of Neurodegeneration" @default.
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- W4304607573 doi "https://doi.org/10.1021/acs.biomac.2c00761" @default.