UC Davis

7,8-Dihydroxyflavone (7,8-DHF) is a tyrosine receptor kinase B agonist that has been demonstrated to show therapeutic promise for treatment of several neuropsychiatric disorders, as well as injuries, of the central nervous system. Unfortunately, there is a gap in the delivery system for this drug as its pharmacokinetics could be improved upon by increasing its clearance time, while retaining the ability to affect neuronal cell types towards protection and proliferation. To this end, the loading of liposomes and extracellular vesicles with the small molecule has been posited as an effective delivery mechanism. As a hydrophobic drug, a scalable, efficient 7,8-DHF loading strategy that simultaneously produces homogenous particles for accurate therapeutic dosing is currently an unmet need. In service of this problem statement, we propose the optimization of the microfluidic-based NanoAssemblr Ignite LNP formulation platform first for the loading of a DOPC and cholesterol-based liposome, then incorporating within a hydrophobic drug and fluorophore labelled lipid. Results show the ability to effectively tune parameters to generate liposomes that encapsulates and retains the function of 7,8-DHF with a size of approximately 120 nm measured on NTA and a polydispersity index of 0.221 when measured through DLS. These liposomes also function better in a SY5Y neuroprotection assay than the free drug comparison when measuring cell count, area and an over 6-fold increase in neuron length between drug-loaded liposome and PBS control.