In vivo distribution characteristics and anti-tumor effects of doxorubicin encapsulated in PEG-modified niosomes in solid tumor-bearing mice

Niosomes, non-ionic surfactant-based vesicles, are capable of encapsulating various drugs, and surface modifications by polyethylene glycol (PEG) are expected to facilitate the passive targeting of encapsulated drugs to solid tumors due to the longer blood circulation time. However, the niosomalization of drugs may also enhance the delivery of drugs to specific tissues at which free drugs do not normally accumulate. Therefore, in the present study, we prepared several doxorubicin (DOX)-encapsulated niosomes composed of different non-ionic surfactants, and examined their in vitro stability, in vivo biodisposition, and anti-tumor effects in solid tumor-bearing mice. In vitro DOX release from Brij 72 niosomes and Span 20 niosomes in the presence of serum was significantly suppressed by their PEGylation. Moreover, the PEGylation of Brij 72 niosomes and Span 20 niosomes markedly increased the plasma level of DOX encapsulated in each niosome after their intravenous injection into tumor-bearing mice. The liver, spleen, and heart distributions of DOX encapsulated in PEG Brij 72 niosomes and Span 20 niosomes were markedly lower and their tumor dispositions were markedly larger than each naked counterpart. These two DOX-encapsulated PEG niosomes exerted strong anti-tumor effect and prolonged the survival time of tumor-bearing mice. On the other hand, PEGylation did not significantly affect the in vitro stability, in vivo biodisposition, or anti-tumor effects of Tween 60 niosomes. These results demonstrate that the PEGylation of Brij 72 and Span 20 niosomes improved the biodisposition of encapsulated anti-cancer drugs, thereby increasing their therapeutic efficacies.