Compositions comprising nanoparticles, method of making and uses thereof
Presented herein, in certain aspects, are cell-free therapeutic composition derived from human amniotic fluid (HAF) and uses thereof for the prevention and treatment of selected diseases and disorders.
1. A method of treating a disease or disorder in a subject, the method comprising:
administering to the subject having the disease or disorder a therapeutically effective amount of a composition comprising:
(a) a modified human amniotic fluid (HAF); and
(b) HAF-derived nanoparticles, the nanoparticles having a diameter of between 50 and 200 nm, and a concentration of the nanoparticles in the composition being at least 1×10 11 nanoparticles/ml.
2. The method of claim 1 , wherein the modified HAF is substantially free of cells, pathogens, vernix, lanugo, and macroparticles.
3. The method of claim 2 , wherein the disease or disorder is lung disease.
4. The method of claim 3 , wherein the lung disease is selected from the group consisting of acute respiratory distress syndrome, chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), pulmonary hypertension, COVID-19, acute respiratory distress syndrome (ARDS), and acute lung injury.
5. The method of claim 3 , wherein the lung disease is acute respiratory distress syndrome caused by COVID-19.
6. The method of claim 2 , wherein the nanoparticles have a diameter of between 100 and 200 nm.
7. The method of claim 2 , wherein the nanoparticles comprise membrane encapsulated extracellular vesicles.
8. The method of claim 2 , wherein the nanoparticles comprise exosomes.
9. The method of claim 2 , wherein the composition is made by a process comprising:
(a) obtaining a volume of HAF;
(b) centrifuging the volume of HAF at 500×g for 10 minutes (min) to obtain a first supernatant;
(c) centrifuging the first supernatant at 2000×g for 30 min to obtain a second supernatant; and
(d) filtering at least a portion of the second supernatant using a 0.22 uM filter.
10. The method of claim 9 , wherein the composition comprises saline.
11. The method of claim 9 , wherein the composition comprises a diluent.
12. The method of claim 2 , wherein the composition is made by a process comprising:
(a) obtaining a volume of HAF;
(b) centrifuging the volume of HAF at 500×g for 10 minutes (min) to obtain a first supernatant;
(c) centrifuging the first supernatant at 2000×g for 30 min to obtain a second supernatant;
(d) ultra-centrifuging a first portion of the second supernatant at 100,000×g for a minimum of 3 hours to obtain a pellet;
(e) isolating and resuspending the pellet in a volume of resuspension fluid to obtain a resuspended volume; and
(f) filtering at least a portion of the resuspended volume using a 0.22 uM filter.
13. The method of claim 12 , comprising filtering the second supernatant prior to ultracentrifugation.
14. The method of claim 12 , wherein the resuspension fluid comprises saline.
15. The method of claim 12 , wherein the resuspension fluid comprises a second portion of the second supernatant.
16. The method of claim 12 , wherein the composition comprises a diluent.
17. The method of claim 2 , wherein the concentration of the nanoparticles in the composition is at least 2×10 11 nanoparticles/ml.
18. The method of claim 2 , wherein the concentration of the nanoparticles in the composition is at least 4×10 11 nanoparticles/ml.
19. The method of claim 2 , wherein the nanoparticles comprise three or more surface-bound proteins selected from the group consisting of CD9, CD63, CD81, CD326 and CD133.
20. The method of claim 2 , wherein the nanoparticles comprise one, two, three, four, five, ten, twenty, twenty-five or thirty or more miRNAs selected from Table 1.
21. The method of claim 2 , wherein the nanoparticles comprise DNA polymerase beta, DNA polymerase lambda, telomerase reverse transcriptase and RAD50.
22. A method of treating a respiratory disorder in a subject, the method comprising:
administering to the subject having the respiratory disorder a therapeutically effective amount of a composition comprising:
(a) a modified human amniotic fluid (HAF); and
(b) HAF-derived nanoparticles, the nanoparticles having a diameter of between 50 and 200 nm, and a concentration of the nanoparticles in the composition being at least 1×10 11 nanoparticles/ml.
23. The method of claim 22 , wherein the concentration of the nanoparticles in the composition is at least 4×10 11 nanoparticles/ml.