Title:Liposome Circulation Time is Prolonged by CD47 Coating
Volume: 27
Issue: 10
Author(s): Seyed Mohammad Gheibi Hayat, Mahmoud R. Jaafari, Mahdi Hatamipour, Peter E. Penson and Amirhossein Sahebkar*
Affiliation:
- Halal Research Center of IRI, FDA, Tehran,Iran
Keywords:
Liposome, CD47, kinetic, half-life, phagocytosis, macrophage.
Abstract:
Introduction: Bio-degradable nano-particles have many applications as drug delivery
vehicles because of their good bio-availability, controlled release, low toxicity and potential for encapsulation.
However, the most important obstacle to nanoparticulate drug delivery is elimination
by macrophages which reduces the residence time of nanoparticles in the blood. To overcome this
problem, the surface of the nanoparticle can be passivated by coating with Polyethylene glycol
(PEG). However, the use of PEG has its own disadvantages. CD47 receptor acts as a self marker
on the surface of many cells and inhibits phagocytosis. This study used a CD47 mimicry peptide as
a substitute for PEG to fabricate “stealth” nanoliposome with reduced macrophage clearance.
Methods: Doxorubibin was used as a model drug because of its inherent fluorescence. Doxorubicin-
containing liposomes were coated with different percentages of CD47 mimicry peptide (0.5%
and 1%). PEG-functionalized doxorubicin-containing liposomes, were used as a comparator. The
liposomal formulations were intravenously injected into mice. Serum was collected at pre-defined
time points and tissue samples were taken at 24 hours. Fluorescence was used to determine the concentration
doxorubicin in serum, heart, spleen, kidney, liver and lung tissues.
Results: Tissue biodistribution and serum kinetic studies indicated that compared with PEG, the
use of CD47 mimicry peptide increased the circulation time of doxorubicin in the circulation. Moreover,
unwanted accumulation of doxorubicin in the reticuloendothelial tissues (liver and spleen),
kidney and heart was significantly decreased by the CD47 mimicry peptide.
Conclusion: The use of a CD47 mimicry peptide on the surface of nanoliposomes improved the
residence time of liposomal doxorubicin in the circulation. The accumulation of drug in non-target
tissues was reduced, thereby potentially reducing toxicity.