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Updated: Nov 8, 2025
Assessing Whole-Body Lipid-Handling Capacity in Mice
Published on: November 24, 2020
Interrogating preclinical study of liposomes: The effect of mouse strain reexamined
Juan Guan1, Ercan Wu2, Pengpeng Jin3
1MOE Key Laboratory of Smart Drug Delivery, School of Pharmacy & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 201203, PR China; Department of Pharmacology, School of Basic Medical Sciences & Center of Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University, Shanghai 200032, PR China; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
Abstract:
Mice are arguably the most important tool in the preclinical evaluation of liposomes; however, the effects of inter-strain physiological variabilities on in vivo performance of liposomes have been seriously overlooked. The present study validated that plasma proteins (PPs) and the capability of mononuclear phagocyte system (MPS) (typically expressed by phagocytosis rate, K) were mice strain-dependent. Physiological variabilities in PPs and the phagocytosis rate jointly contributed to the inter-strain inconsistency of pharmacokinetic (PK) profiles of liposomes. For the PPs sensitive liposomes (such as plain PEGylated liposomes and folic acid functionalized PEGylated liposomes), inter-strain variabilities in PK profiles could be calibrated using the corrected phagocytic rate (KC = K×(c × Ig)/(alb×apo)), where c, Ig, alb and apo were respective the total content of complement proteins, immunoglobulins, albumin and apolipoproteins. While for the PPs insensitive liposomes (e.g., cRGD functionalized liposomes), phagocytic rate could be directly used to calibrate inter-strain difference of liposome PK profiles. Our data also warn that the reciprocal interaction between payloads and organisms would be much more complicated than that between liposomes and organisms, thus independent investigation should be conducted for each individual therapeutic agent.
Insights
Mouse strain differences significantly impact liposome performance by altering plasma proteins and phagocytosis rates. These physiological variations affect pharmacokinetic profiles, necessitating strain-specific calibration for accurate preclinical liposome evaluation.
Area of Science:
- Pharmacology
- Biomedical Engineering
- Preclinical Research
Background:
- Mice are crucial for preclinical liposome evaluation.
- Inter-strain physiological differences in mice are often overlooked.
- These variations impact in vivo liposome performance.
Purpose of the Study:
- To investigate how mouse strain variability affects liposome pharmacokinetics.
- To determine the role of plasma proteins and mononuclear phagocyte system activity.
- To develop methods for calibrating liposome performance across different mouse strains.
Main Methods:
- Validated plasma protein levels and mononuclear phagocyte system (MPS) phagocytosis rates (K) across different mouse strains.
- Analyzed the correlation between physiological variabilities and liposome pharmacokinetic (PK) profiles.
- Developed a corrected phagocytic rate (KC) formula for plasma protein-sensitive liposomes.
- Evaluated PK profiles of plasma protein-insensitive liposomes.
Main Results:
- Plasma proteins (PPs) and MPS phagocytosis rates (K) are significantly dependent on mouse strain.
- Variations in PPs and K jointly cause inconsistent liposome PK profiles between strains.
- A novel calibration method using KC = K×(c×Ig)/(alb×apo) was established for PPs-sensitive liposomes.
- Phagocytosis rate (K) alone can calibrate PK differences for PPs-insensitive liposomes.
- Payload-organism interactions are complex and require independent study.
Conclusions:
- Mouse strain differences in PPs and MPS activity are critical factors influencing liposome PK.
- The corrected phagocytic rate (KC) offers a viable approach to standardize liposome PK data across strains.
- Preclinical liposome studies must account for inter-strain physiological variabilities for accurate translation.
- Individual therapeutic agents require separate investigation due to complex payload-organism interactions.
