Red blood cells for drug delivery
It is an object of the present invention a method to introduce compounds inside red blood cells comprising: —providing red blood cells from a subject; —providing one or more compounds to be encapsulated in said red blood cells; —providing a loading device comprising a microporous matrix; —feeding said loading device with a suspension comprising said red blood cells and said one or more compounds; —collecting the red blood cells exiting from said loading device, which are encapsulated red blood cells; characterized in that: —said red blood cells and said one or more compound are in suspension at a pH of between 6.8 and 7.8, preferably of between 7.35 and 7.45; —the pores in said microporous matrix have a minimum size of at least 3 times the size of a red blood cell, that is a minimum size of at least 20 μm; —the pores in said microporous matrix have an average size of between 30 and 500 μm, or of between 40 and 400 μm, or of between 50 and 350 μm, or of between 100 and 250 μm; —said porous matrix has a length L of at least 1 mm and a width W and a height H such that it comprises at least one unit cell, said unit cell being equal to the microporous matrix volume that, repeated by rototranslation through the vectors that generate the matrix, fills the whole matrix itself; wherein said loading device is fed with said suspension in such a way to obtain an average fluid speed of between 10 −4 and 10 m/s. Further objects of the present invention are a microporous matrix, a loading device comprising the same, a fluidic circuit and a machine for implementing said method and red blood cells encapsulated with at least one compound according to said method.
1. A method to introduce compounds inside red blood cells, the method comprising:
providing red blood cells from a subject;
providing one or more compounds to be encapsulated in the red blood cells;
providing a loading device comprising a microporous matrix;
feeding the loading device with a suspension comprising the red blood cells and the one or more compounds; and
collecting the red blood cells exiting from the loading device, which are encapsulated red blood cells;
wherein:
the red blood cells and the one or more compound are in suspension at a pH of between 6.8 and 7.8;
the pores in the microporous matrix have a minimum size of at least 3 times the size of a red blood cell, that is a minimum size of at least 20 μm;
the pores in the microporous matrix have an average size of between 30 and 500 μm;
the porous matrix has a length L of at least 1 mm and a width W and a height H such that it comprises at least one unit cell, the unit cell being equal to the microporous matrix volume that, repeated by rototranslation through the vectors that generate the matrix, fills the whole matrix itself, and
wherein the loading device is fed with the suspension in such a way to obtain an average fluid speed of between 10 −4 and 10 m/s.
2. The method according to claim 1 , wherein the pores in the microporous matrix have an average size of between 40 and 400 μm.
3. The method according to claim 1 , wherein the pores in the microporous matrix have an average size of between 50 and 350 μm.
4. The method according to claim 1 , wherein the pores in the microporous matrix have an average size of between 100 and 250 μm.
5. The method according to claim 1 , wherein the loading device further comprises at least one duct having a length parallel to a main direction of the flow of the suspension in the channel and a section, described by dimensions w ×h, transversal to the flow itself, wherein the section has dimensions such that a smaller dimension between w and h of the section is greater than 20 μm.
6. The method according to claim 1 , wherein the red blood cells are suspended in PBS, or the red blood cells are suspended in whole blood and a hematocrit of the suspension is of between 1 and 50%.
7. The method according to claim 6 , wherein the red blood cells are suspended in albumin supplemented PBS.
8. Red blood cells encapsulated with at least one compound according to the method of claim 1 .
9. Encapsulated red blood cells according to claim 8 for use in the treatment of diseases.