Intraperitoneally-administered nanocarriers that release their therapeutic load based on the inflammatory environment of cancers

A method of treating a subject suffering from peritoneal cancer, the method comprising intraperitoneally administering to the subject a pharmaceutically effective amount of a nanocarrier composition, said nanocarrier composition comprising a plurality of porous silica nanoparticulates that:

• (a) are loaded with one or more pharmaceutically-active agents selected from the group consisting of doxorubicin, melphalan, bevacizumab, dactinomycin, cyclophosphamide, amifostine, etoposide, gemcitabine, altretamine, topotecan, cyclophosphamide, a taxane or a platinum based chemotherapeutic agent, and
• (b) that are encapsulated by and that support a lipid bilayer comprised of one or more compositions selected from the group consisting of a phospholipid, a phosphatidyl-choline, a phosphatidyl-serine, a phosphatidyl-diethanolamine, a phosphatidylinosite, a sphingolipid, and an ethoxylated sterol, and mixtures thereof to form a nanocarrier;
• wherein subsequent to administration, the nanocarrier's lipid bilayer is disrupted in vivo upon contact with a reactive oxygen species (ROS) selected from the group consisting of ozone (O3), hydrogen peroxide, hypochlorite ion, hydroxyl radical, superoxide anion (O2−), and peroxynitrite.

A pharmaceutical composition comprising:

• (a) an intraperitoneally-administered nanocarrier composition comprising a plurality of porous nanoparticulates that (1) are loaded with one or more pharmaceutically-active agents and (2) that are encapsulated by and that support a lipid bilayer which is disrupted in vivo upon contact with a reactive oxygen species;
• and
• (b) at least one pharmaceutically acceptable diluent or pharmaceutically-acceptable excipient.

-41. (canceled)