irinotecan sucrosofate

A liposomal dispersion formulated with the semisynthetic camptothecin analogue irinotecan, provided as the hydrochloride trihydrate form, which is encapsulated and entrapped within liposomes in a gelated or precipitated state as the irinotecan sucrose octasulfate (sucrosulfate) salt form, with potential antineoplastic activity. Upon administration of the liposomes containing irinotecan sucrosulfate, irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. During the S-phase, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery. Liposome encapsulation of this agent promotes efficient drug delivery into the cytosol from the endosome compartment of the cell, extends the circulation of irinotecan, and prolongs the duration of active therapy at the site of tumor to inhibit tumor growth.