Heterogeneity in nanoparticles influences biodistribution and targeting

Aim: A large fraction of the administered dose of nanoparticles (NPs) localizes into nontarget tissue, which could be due to the heterogeneous population of NPs. Materials & methods: To investigate the impact of the above issue, we simultaneously tracked the biodistribution using optical imaging of two different sized poly(d,l-lactide co-glycolide) NPs, which also varied in their surface charge and texture, in a prostate tumor xenograft mouse model. Results: Although formulated using the same polymer and emulsifier concentration, small NPs were neutral (S-neutral-NPs), whereas large NPs were anionic (L-anionic-NPs). Simultaneous injection of these NPs, representing heterogeneity, shows significantly different biodistribution. S-neutral-NPs demonstrated longer circulation time than L-anionic-NPs (t(1/2) = 96 vs 13 min); accounted for 75% of total NPs accumulated in the tumor; and showed 13-fold greater tumor to liver signal intensity ratio than L-anionic-NPs. Conclusion: The data underscore the importance of formulating nanocarriers of specific properties to enhance their targeting efficacy. Original submitted 7 September 2012; Revised submitted 12 December 2012; Published online 26 June 2013