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

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.

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“…Similarly, microencapsulated BPs in poly (lactic-co-glycolic acid) were developed using a double emulsification approach by Jamaledin, R. et al, 2023. A sustained release was observed with bacteriophage-loaded MPs formulations, with a rapid initial release followed by a slower release over time [ 25 ].…”

Lipid- and Polymer-Based Nanocarrier Platforms for Cancer Vaccine Delivery

“…The encapsulation process prolonged the bacteriophage's stability and maintained its immunological activity, inducing a strong immune response in marrowderived DCs in vitro. 96 In addition to immunogenic peptides and proteins, PNPs have been employed for the delivery of immunoadjuvants. TLR 7 agonist (R837) was loaded in PNPs designed to synergize immunotherapy with photodynamic therapy.…”

“…Using PLGA as a biocompatible copolymer, a bacteriophage expressing the antigenic peptide OVA 257–264 was encapsulated into PLGA microparticles. The encapsulation process prolonged the bacteriophage’s stability and maintained its immunological activity, inducing a strong immune response in bone marrow-derived DCs in vitro …”

Polymer Microspheres and Their Application in Cancer Diagnosis and Treatment

“…Zaman et al conducted a study evaluating the effectiveness of microneedle-embedded particulate-based whole-cell lysate vaccines for treating breast cancer in a mouse tumor model [ 99 ]. Another study focused on fine-tuning microneedles to predict the release of phages by optimizing the components of microneedle patches for intradermal delivery [ 100 ]. Photothermal therapy has shown promise in inducing long-term immune memory and promoting memory T-cell differentiation, similar to in situ vaccines.…”