Improvement of the pharmacokinetic characteristics of liposomal doxorubicin using CD47 biomimickry

Objectives In view of their biodegradability, biocompatibility, encapsulation efficiency and targeted release, as well as low toxicity, liposomes are being widely used in the context of drug delivery. However, the efficiency of such drug delivery systems might face limitations by macrophage-mediated clearance (CL), which reduces circulation half-life (T½). This problem can be resolved through surface functionalization via poly (ethylene glycol) (PEG) in the process of PEGylation. However, the use of PEG might have its own disadvantages. Accordingly, the main purpose of this study was to produce novel stealth nanoliposomes using CD47 mimicry peptide [namely self-peptide (SP)] as an alternative to PEG for minimizing macrophage-mediated CL and enhancing circulation T½. Methods At first, doxorubicin (Dox)-containing liposomes [i.e.liposomal Dox (LD)] were coated with different concentrations of SP (viz. SP-LD) (0.5%, 1% and 2%). In addition, PEG-functionalized LD (i.e. PLD) was fabricated as a standard control group. Then, various types of liposomal formulae were injected into a population of mice, assigned to six groups (four mice per group) for biodistribution. After sacrificing these animals in prespecified time points (namely 0.5, 6, 12, 24, 48, 72, 96 and 168 h), serum, liver, spleen, heart, kidney and lung samples were collected to estimate the encapsulated drug content in different groups through measuring intrinsic autofluorescence signal of Dox. Key findings The tissue distribution results in the liver, spleen, heart, kidney and lung samples indicated a significant difference between the SP-LD and the PLD groups. Furthermore, the examination of Dox content, 6 h after administration, showed a growth rate of 28% in Dox content in the SP group compared with the PLD one. Subsequently, these values were, respectively, 63% and 75% at 24 and 48 h. Conclusions The results of tissue distribution and serum kinetic analysis correspondingly revealed that the use of the SP could augment the circulation time of Dox in comparison with PEG, and it could additionally minimize the tissue accumulation of the drug, which is normally the cause of drug-induced toxicity. The use of the SP on nanoliposomes could prolong the circulation of T½ and diminish the tissue accumulation of LD. These findings are relevant for improving therapeutic efficacy and reducing the toxicity of liposomal drugs.