HPLC analysis and extraction method of SN-38 in brain tumor model after injected by polymeric drug delivery system

Abstract

SN-38 is a highly potent anticancer drug but its poor solubility in aqueous solvent and adverse side effects limit clinical applications. To overcome these limitations, SN-38-loaded-injectable drug delivery depots have been intratumorally administered in xenograft tumor model in nude mice. The extraction and high performance liquid chromatography (HPLC) were performed in order to determine the amount of SN-38 inside tumors. SN-38 was extracted from tumors using DMSO. HPLC analysis was validated and resulted in linearity over the concentration range from 0.03 to 150 µg/mL (r(2) ≥ 0.998). Lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were 0.308 µg/mL and 1.02 µg/mL, respectively. The extraction efficiency (% recovery) of SN-38 in porcine tissues was similar to that of tumors which provided more than 90% recovery in all concentrations. Moreover, the variability of precision and accuracy within and between-day were less than 15%. Therefore, this extraction and HPLC protocol was applied to determine the amount of SN-38 in tumors. Results show higher remaining amount of SN-38 in tumor from SN-38-loaded polymeric depots than that of SN-38 solution. These results reveal that SN-38-loaded polymeric depots can prevent the leakage of free-drug out of tumors and can sustain higher level of SN-38 inside tumor. Thus, the therapeutic efficacy can be elevated by SN-38-loaded polymeric depots.

Injectable SN-38-embedded Polymeric Microparticles Promote Antitumor Efficacy against Malignant Glioma in an Animal Model

“…Recent reports demonstrated that SN-38-loaded polymeric micelles or depots enhance and prolong the distribution of free SN-38 in vivo [35,38,39], and exert a potent antitumor effect against MG cells in vitro [38,40] and in animal models [19,35,41]. The effective release of SN-38 was reported to range from 14 h to 18 days [19,38,40,41]. In the present study, SN-38 was successfully loaded into PLGA microparticles [42] by using the electrospraying technique.…”

“…In an MG-bearing athymic/nude mice study, intratumoral administration of CPT-11 or SN-38 extended the average survival time of the MG-bearing animals from 22 days to 46 and 65 days, respectively [33]. Recent reports demonstrated that SN-38-loaded polymeric micelles or depots enhance and prolong the distribution of free SN-38 in vivo [35,38,39], and exert a potent antitumor effect against MG cells in vitro [38,40] and in animal models [19,35,41]. The effective release of SN-38 was reported to range from 14 h to 18 days [19,38,40,41].…”

Antibacterial and biocompatibility studies of triple antibiotics-impregnated external ventricular drainage: In vitro and in vivo evaluation

“…Briefly, serum was added with cold methanol then the mixture was centrifuged at 14,000 rpm, 10°C for 10 min. The supernatant was filtered and determined for drug concentration by HPLC [ 18 ].…”

Mechanism and optimization of supramolecular complexation‐enhanced fluorescence spectroscopy for the determination of SN‐38 in plasma and cells

“…[ 18,19 ] Nittayacharn et al . [ 20 ] validated HPLC method for the determination of SN‐38 inside tumours. The linear range was 0.03–150 μg·ml −1 , with lower limit of detection of 0.308 μg·ml −1 and lower limit of quantitation of 1.02 μg·ml −1 .…”