NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Pilot study grant

Towards an in vitro system of predictive biomarkers of in vivo liposome efficacy

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At a glance

Completed
Award date
February 2014 - October 2014
Grant amount
£74,494
Principal investigator
Dr Andrew Devitt

Co-investigator(s)

Institute
Aston University

R

  • Replacement
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View the grant profile on GtR

Contents

Overview

Aims

This research aims to develop a ‘fingerprint’ for successful liposome formulations which avoids the use of animals in early screening of novel liposome antigen delivery/adjuvant systems.

Background

Adjuvants have an essential role in the adaptive immune response to vaccine antigens. Aluminium salt-based adjuvants are commonly used in human vaccines, however, they induce a weak cell mediated response and are not applicable to important intracellular infections such as tuberculosis, HIV and malaria.

Liposomes provide an attractive approach for vaccine design as they can both deliver antigen and exert adjuvant effects. However, the physicochemical composition of liposome formulations can profoundly affect adjuvant activity and consequent in vivo success of the formulation.  A major challenge is to predict which formulations will be efficacious and this is currently investigated in animals with around 50 rodents used per single adjuvant formulation.

Research details and methods

This research aims to develop a ‘fingerprint’ for successful liposome formulations based on in vitro assays which avoid the use of animals in the early screening of novel liposome antigen delivery/adjuvant systems.

A systems biology approach will be used to integrate results from a range of in vitro assays, to develop a predictive model of in vivo efficacy of liposome adjuvant formulations. The approach will use an existing panel of liposome formulations whose physicochemical properties and in vivo responses have already been characterised.

This panel will be screened in in vitro bioassays, assessing how liposomes attract, interact and stimulate the maturation of antigen-presenting cells (including macrophages and dendritic cells). The results of these in vitro assays will be correlated with in vivo responses to identify key markers of in vivo liposome efficacy.

Impacts

Publications

  1. Khadke S et al. (2019). Formulation and manufacturing of lymphatic targeting liposomes using microfluidics. Journal of Controlled Release 307:211-220. doi: 10.1016/j.jconrel.2019.06.002
  2. Nguyen DB et al. (2016). Characterization of Microvesicles Released from Human Red Blood Cells. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology 38(3):1085-99. doi: 10.1159/000443059
  3. Perrie Y et al. (2016). Designing liposomal adjuvants for the next generation of vaccines. Adv Drug Deliv Rev 99(Pt A): 85-96. doi: 10.1016/j.addr.2015.11.005
  4. Marshall LJ et al. (2015). Developing accurate models of the human airways. The Journal of pharmacy and pharmacology 67(3):464-72. doi: 10.1111/jphp.12340
  5. Kaur R et al. (2014). Effect of incorporating cholesterol into DDA:TDB liposomal adjuvants on bilayer properties, biodistribution, and immune responses. Mol Pharm 11(1):197-207. doi: 10.1021/mp400372j