Synthesis of immunomodulatory biomimetic lipid polymer hybrid nanoparticles and application of zebrafish larvae in immunomodulation screening
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Date
2025
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Publisher
Elsevier B.V.
Abstract
Since the antibiotic golden era of the mid-20th century, there have been limited antibiotics approved, while antibiotic resistance continues to escalate disproportionately, outpacing the rate of novel antibiotic discovery. This imbalance poses a serious global health concern, with an estimated annual death toll of 10 million due to antibiotic resistance by 2050. There is a growing interest in immunotherapy as an alternative approach to conventional antibiotics due to its ability to target and stimulate immune system, leveraging its innate ability to self-eradicate pathogens. This study synthesized lipid polymer hybrid nanoparticles (LPHNPs) conjugated with two immunomodulatory agents, namely, curdlan and mycolic acid (MA), as a potential immunotherapy for bacterial infections. LPHNPs were synthesized using lecithin and polycaprolactone (PCL) at a 15 % lipid-to-polymer (w/w) ratio. Additionally, PCL-curdlan copolymer, comprising 15 % w/w curdlan, was successfully synthesized and used to conjugate the LPHNPs with various curdlan concentrations. Furthermore, The LPHNPs were conjugated with varying MA concentrations, with or without curdlan. In-vivo assessment of the immunomodulatory effect of the LPHNPs was conducted using a larval zebrafish model assessing behaviour and immunofluorescence, as indicators of immune stimulation. The data suggests that curdlan exhibits a more complex immunoregulatory role as demonstrated by the countered stimulated behavioural effect while inflammation remained heightened. This work also provides new insights that zebrafish larvae are a valuable screening tool in the development of nanoparticle immunotherapies.
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Keywords
Biomimetic nanoparticles, Curdlan, Immunotherapy and infectious diseases, Lipid-polymer hybrid nanoparticles, Mycolic acid
Citation
Irabin, A.F., Ollewagen, T., Smith, C., Ahmed, R., Reineke, J., Reijnders, R., Sampson, S.L., du Plessis, N. and Dube, A., 2025. Synthesis of immunomodulatory biomimetic lipid polymer hybrid nanoparticles and application of zebrafish larvae in immunomodulation screening. European Journal of Pharmaceutical Sciences, 207, p.107037.