An accelerated clearance was evoked in normal rats by the transfusion of serum from rats that had received PEGylated liposomes 5 days earlier, indicating that humoral serum factor(s) are also involved in causing the accelerated clearance.
These nanoformulations significantly prolonged DOX circulation time in the blood without the accelerated clearance observed after multiple injections.
In a perfused rat model, our laboratory showed markedly accelerated clearance in the setting of membrane injury due to Triton-X 100, a membrane detergent [12].
This could be caused either by in vivo binding competition with non-labelled RESCA1 conjugate, accelerated clearance or lower binding affinity of [Al18F]2.
Our laboratory in turn demonstrated accelerated clearance of the tracer following myocyte membrane injury due to Triton-X 100 in an isolated perfused rat heart model [12].
No significant increases in the number of Kupffer cells were detectable, although the liver most likely played an important role in the accelerated clearance.
Immunogenicity of therapeutic mAbs can cause hypersensitivity responses such as anaphylaxis and infusion reactions, and accelerated clearance of drug, resulting in decreased safety and efficacy (Chirmule et al., 2012).
For example, the A4B4 variant, (a prototype of Motavizumab, which is an in vitro affinity matured anti-RSV mAb derived from palivizumab), demonstrated broad tissue binding and accelerated clearance in vivo (Wu et al., 2007).
Tc-99m-teboroxime localizes primarily on the myocyte membrane in cultured myocytes [11] and demonstrates accelerated clearance following myocyte membrane injury due to treatment with Triton-X100 in isolated rat hearts [12].
Compared with mice inoculated with DNA (pCDNA-gD) or protein (rgD) only, mice inoculated with the combination of gD DNA and protein had enhanced ELISA antibody titers to DEV and had accelerated clearance of virus following challenge infection.
Systemic delivery of any viral or nonviral vector requires an appreciation of the adverse physiological barriers that exist in vivo and incorporation of well-designed vector components that limit non-specific uptake and accelerated clearance.
