Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38.
SN38 (7-ethyl-10-hydroxy camptothecin) is a prominent and efficacious anticancer agent. It is poorly soluble in both water and pharmaceutically approved solvents; therefore, the direct formulation of SN38 in solution form is limited. Currently, the water soluble prodrug of SN38, irinotecan (CPT-11), is formulated as a low pH solution and is approved for chemotherapy. However, CPT-11, along with most other water-soluble prodrugs shows unpredictable inter-patient conversion to SN38 in vivo, instability in the physiological environment and variable dose-related toxicities. More recently, macromolecular prodrugs (i.e. EZN-2208, IMMU-130) and nanomedicine formulations (i.e. nanoemulsions, polymeric micelles, lipid nanocapsule/nanoparticle, and liposomes) of SN38 have been investigated for improved delivery to cancer cells and tissues. Specifically, these carriers can take advantage of the EPR effect to direct drug preferentially to tumour tissues, thereby substantially improving efficacy and minimising side effects. Furthermore, oral delivery has been shown to be possible in preclinical results using nanomedicine formulations (i.e. dendrimers, lipid nanocapsules, polymeric micelles). This review summarizes the recent advances for the delivery of SN38 with a focus on macromolecular prodrugs and nanomedicines.
Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA, Australia.
Vaskor
V
Bala
Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA, Australia.
Shasha
S
Rao
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC, Australia.
Ben J
BJ
Boyd
Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA, Australia. Electronic address: clive.prestidge@unisa.edu.au.
Clive A
CA
Prestidge
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D000077146:Irinotecan; D050997:Nanomedicine / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D000077146:Irinotecan; D002166:Camptothecin
7-Ethyl-10-hydroxy camptothecin; Macromolecule; Polymer drug conjugate; Targeted delivery