Challenges in SN38 drug delivery: current success and future directions.

INTRODUCTION: Clinical use of SN38 is limited by its poor aqueous solubility and hydrolysis of the lactone ring at pH > 6 to inactive carboxylate form. A variety of drug delivery systems have been developed to improve the solubility and stability of SN38, and reduce its toxicity. A few noteworthy formulations with some success in initial phases of clinical trials are reported. AREAS COVERED: This work aims to provide a comprehensive review on the various techniques and strategies employed (physical, chemical and biological methods) to improve physicochemical properties and to deliver the drug efficiently to the cancer cells. Physical methods such as nanoparticle encapsulation, cyclodextrin complexation; chemical methods such as prodrugs, polymer-, albumin- and immunoconjugates; and enzyme activated prodrug therapy are discussed. EXPERT OPINION: The challenges in SN38 drug delivery may be overcome by two ways: ensuring multiple layers of protection against degradation and slow but sustained release of therapeutically effective drug concentrations. It may also be achieved by preparing a polymer-drug conjugate and further encapsulating the conjugate in suitable carrier system; tumor-targeted SN38 delivery by using immunoconjugates, enzyme-activated prodrug therapy and antibody-directed nanoparticle delivery. However, selection of a suitable ligand for tumor targeting and use of safe and biocompatible nanoparticle systems play an important role in realizing this goal.