Development of Extended Release SN-38 nanoparticles

SN-38 is the active metabolite of CPT-11 (Irinotecan), an anti-cancer drug against many malignancies including colorectal carcinoma [1-2]. The conversion of irinotecan to SN-38 is extremely variable and the genetic interindividual variability in the metabolism of SN-38 to form SN-38 glucoronide has been reported by Ohe et al., 1992 and Gupta et al. [3-4]. Additionally it has been shown that SN-38 is 100-1000 fold more active in vitro than its parent drug, CPT-11 [5], Nonetheless extreme hydrophobicity of SN-38 has prevented its clinical use [6]. One way of improving the solubility of SN-38 is to formulate the drug into nanoparticles. SN-38 nanoparticle can solve this problem, plus nanoparticle has lots of advantages including EPR effect. PLGA is biocompatible and biodegradable polymer that is extensively used to make nanoparticles [7].