PLGA microparticle formulations for tunable delivery of a nano-engineered filamentous bacteriophage-based vaccine: in vitro and in silico-supported approach

Rezvan Jamaledin; Rossella Sartorius; Concetta Di Natale; Valentina Onesto; Roberta Manco; Valentina Mollo; Raffaele Vecchione; Piergiuseppe De Berardinis; Paolo Antonio Netti

doi:10.1007/s40097-022-00519-9

PLGA microparticle formulations for tunable delivery of a nano-engineered filamentous bacteriophage-based vaccine: in vitro and in silico-supported approach

J Nanostructure Chem. 2023 Jan 11:1-16. doi: 10.1007/s40097-022-00519-9. Online ahead of print.

Authors

Affiliations

¹ Center for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, Italy.
² School of Engineering, Institute for Bioengineering, The University of Edinburgh, King's Buildings, Edinburgh, EH9 3JL, UK.
³ Institute of Biochemistry and Cell Biology (IBBC), CNR, 80131 Naples, Italy.
⁴ Interdisciplinary Research Centre On Biomaterials (CRIB), University of Naples Federico II, Naples, Italy.
⁵ Department of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, Naples, Italy.

Abstract

Bacteriophages have attracted great attention in the bioengineering field in diverse research areas from tissue engineering to therapeutic and clinical applications. Recombinant filamentous bacteriophage, carrying multiple copies of foreign peptides on protein capsid has been successfully used in the vaccine delivery setting, even if their plasma instability and degradation have limited their use on the pharmaceutical market. Encapsulation techniques in polymeric materials can be applied to preserve bacteriophage activity, extend its half-life, and finely regulate their release in the target environment. The main goal of this study was to provide tunable formulations of the bacteriophage encapsulated in polymeric microparticles (MPs). We used poly (lactic-co-glycolic-acid) as a biocompatible and biodegradable polymer with ammonium bicarbonate as a porogen to encapsulate bacteriophage expressing OVA (257-264) antigenic peptide. We demonstrate that nano-engineered fdOVA bacteriophages encapsulated in MPs preserve their structure and are immunologically active, inducing a strong immune response towards the delivered peptide. Moreover, MP encapsulation prolongs bacteriophage stability over time also at room temperature. Additionally, in this study, we show the ability of in silico-supported approach to predict and tune the release of bacteriophages. These results lay the framework for a versatile bacteriophage-based vaccine delivery system that could successfully generate robust immune responses in a sustained manner, to be used as a platform against cancer and new emerging diseases.

Graphical abstract: Synopsis: administration of recombinant bacteriophage-loaded PLGA microparticles for antigen delivery. PLGA microparticles release the bacteriophages, inducing activation of dendritic cells and enhancing antigen presentation and specific T cell response. Bacteriophage-encapsulated microneedles potentially can be administered into human body and generate robust immune responses.

Keywords: Controlled release; Immune responses; In silico; Nano-engineered bacteriophage; Phage display; Vaccination.

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