Methods and compositions related to extracellular vesicles
Certain embodiments are directed to methods and compositions related to delivery of therapeutic agents via syncytiotrophoblast-derived extracellular vesicles (EVs).
1 . A full-term placental syncytiotrophoblast derived nanovesicle composition
manufactured by
(i) mechanically agitating human full-term placental intact villous tissue to generate agitated villous tissue (AVT) nanovesicles having an average diameter of 50 to 800 nm and comprising CD81, CD9, CD63, tumor susceptibility gene 101, programmed cell death 6-interacting protein (ALIX), P-gp, BCRP, and placental alkaline phosphatase (PLAP);
isolating said nanovesicles; and
(iii) encapsulating paclitaxel in the isolated AVT nanovesicles at greater than 40 weight percent of total nanovesicles to produce the nanovesicle composition.
2 . A method of delivering paclitaxel to a lung of a mammalian subject, the method comprising administering the AVT nanovesicle composition of claim 1 , wherein the administering comprises inhalation, parenteral, intravenous, intraarterial, subcutaneous, intratumoral, intramuscular, intraorbital, ophthalmic, intrahepatic, intracapsular, intraperitoneal, intranasal, aerosol, and/or suppository administration.
3 . The method of claim 2 , wherein the AVT nanovesicles further comprises a synthetic targeting agent comprising an antibody moiety, peptide or small molecule moiety derivatization.
4 . The method of claim 2 , wherein the AVT nanovesicles more preferentially localize to the subject's lungs compared to administering isolated dual-perfusion of placental lobule (DPPL) extracellular vesicles under the same conditions.