Preparation and Evaluation of Irinotecan Poly(Lactic-co-Glycolic Acid) Nanoparticles for Enhanced Anti-tumor Therapy.

Irinotecan (IRT), the pro-drug of SN-38, has exhibited potent cytotoxicity against various tumors. In order to enhance the anti-tumor effect of IRT, we prepared IRT-loaded PLGA nanoparticles (IRT-PLGA-NPs) by emulsion-solvent evaporation method. Firstly, IRT-PLGA-NPs were characterized through drug loading (DL), entrapment efficiency (EE), particle size, zeta potential, transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). We next studied the in vitro release characteristics of IRT-PLGA-NPs. Finally, the pharmacokinetics and pharmacodynamics profiles of IRT-PLGA-NPs were investigated. The results revealed that IRT-PLGA-NPs were spherical with an average size of (169.97 ± 6.29) nm and its EE and DL were (52.22 ± 2.41)% and (4.75 ± 0.22)%, respectively. IRT-PLGA-NPs could continuously release drug for 14 days in vitro. In pharmacokinetics studies, for pro-drug IRT, the t1/2ß of IRT-PLGA-NPs was extended from 0.483 to 3.327 h compared with irinotecan solution (IRT-Sol), and for its active metabolite SN-38, the t1/2ß was extended from 1.889 to 4.811 h, which indicated that IRT-PLGA-NPs could prolong the retention times of both IRT and SN-38. The pharmacodynamics results revealed that the tumor doubling time, growth inhibition rate, and specific growth rate of IRT-PLGA-NPs were 2.13-, 1.30-, and 0.47-fold those of IRT-Sol, respectively, which demonstrated that IRT-PLGA-NPs could significantly inhibit the growth of tumor. In summary, IRT-PLGA-NPs, which exhibited excellent therapeutic effect against tumors, might be used as a potential carrier for tumor treatment in clinic.

Quantitative Assessment of Nanoparticle Biodistribution by Fluorescence Imaging, Revisited.

Fluorescence-based whole-body imaging is widely used in the evaluation of nanoparticles (NPs) in small animals, often combined with quantitative analysis to indicate their spatiotemporal distribution following systemic administration. An underlying assumption is that the fluorescence label represents NPs and the intensity increases with the amount of NPs and/or the labeling dyes accumulated in the region of interest. We prepare DiR-loaded poly(lactic- co-glycolic acid) (PLGA) NPs with different surface layers (polyethylene glycol with and without folate terminus) and compare the distribution of fluorescence signals in a mouse model of folate-receptor-expressing tumors by near-infrared fluorescence whole-body imaging. Unexpectedly, we observe that fluorescence distribution patterns differ far more dramatically with DiR loading than with the surface ligand, reaching opposite conclusions with the same type of NPs (tumor-specific delivery vs predominant liver accumulation). Analysis of DiR-loaded PLGA NPs reveals that fluorescence quenching, dequenching, and signal saturation, which occur with the increasing dye content and local NP concentration, are responsible for the conflicting interpretations. This study highlights the critical need for validating fluorescence labeling of NPs in the quantitative analysis of whole-body imaging. In light of our observation, we make suggestions for future whole-body fluorescence imaging in the in vivo evaluation of NP behaviors.