Particle and pharmaceutical composition comprising an insoluble camptothecin compound with double coreshell structure and method for manufacturing the same

A method for treating a subject with a cancer, comprising administering a therapeutically effective amount of a composition to the subject,

• wherein the composition comprises freeze-dried particles with particle size of less than 1 μm, said freeze-dried particles comprising
• (a) an inner core comprising
• (i) a hydrophobic camptothecin compound;
• and
• (ii) a hydrophilic camptothecin-based compound;
• and
• (b) an outer shell surrounding the inner core, said outer shell being formed of an amphiphilic block copolymer,
• wherein the amphiphilic block copolymer comprises a hydrophobic block and a hydrophilic block in a same chain;
• wherein the hydrophobic camptothecin compound is selected from the group consisting of 7-ethyl-10-hydroxycamptothecin (SN-38), camptothecin, 10-hydroxycamptothecin, a pharmaceutical acceptable salt thereof, and a combination thereof;
• wherein the hydrophilic camptothecin compound is selected from irinotecan, topotecan, belotecan, exatecan, lurtotecan, sinotecan, rubitecan, 9-nitrocamptothecin, 9-aminocamptothecin, gimatecan, BNP-1530, DB-67, BN-80915, BN-80927, a pharmaceutically acceptable salt thereof, a glucuronide metabolite thereof, and a glucuronide metabolite of the hydrophobic camptothecin compound, and a combination thereof;
• and
• wherein a proportion of the freeze-dried particles with a size more than 200 nm is 11.8% or less as measured by dynamic light scattering (DLS) method.