Effects of size and targeting ligand on biodistribution of liposome nanoparticles in tumor mice

Objectives The size of liposome and route of administration plays an important role in their transport into the blood stream, followed by accumulation in various tissues/organs as delivery vector for therapeutic purpose. The objective of this study is to investigate the effect of size and targeting antibody on the biodistribution of liposomes administered by i.p. and/or i.v. in mice.

Methods Liposomes were prepared at varying size ranging from 100 nm to 400 nm, radiolabeled with 111In through DTPA conjugated on the lipid, and tested their biodistribution after intra-peritonial (i.p.) injection into mice.

Results It was observed that i.p. administered liposomes of size ~100 nm showed highest uptake into the blood stream (~36 % ID/g as early as 6 h), comparable to that obtained by i.v injection. The i.p. administered liposomes of size ~ 200 nm and ~300 nm were also able to traverse into the blood stream but with limited ease compared to the liposomes of size of ~100 nm. Also, as the size of the liposome increased their comparative liver, spleen and lung uptake increased. It was observed i.p administered liposomes of size ~ 400 nm showed negligible uptake into blood stream indicating that the cut-off limit was reached. The targeting antibody also increased the 10-30% of the retention of liposomes, regardless of the size, in the peritoneal space with tumor target by i.p. injection.

Conclusions Immunoliposomes of size ~100 nm may be ideal for i.p/i.v. administration for achieving high plasma concentration and subsequent tumor targeting using tumor vasculature whereas immunoliposomes of larger size >300-400 nm) may be ideal for i.p. administration and retention of the liposomes in the peritoneal cavity for targeting tumors located in the peritoneal cavity and surrounding areas.

Research Support This work was supported by NIH/NCI R01CA135358 and CCSG P30 CA44579.