Poly(lactic acid)-based particulate systems are promising tools for immune modulation.
Poly(lactic acid) (PLA) is one of the most successful and versatile polymers explored for controlled delivery of bioactive molecules. Its attractive properties of biodegradability and biocompatibility in vivo have contributed in a meaningful way to the approval of different products by the FDA and EMA for a wide range of biomedical and pharmaceutical applications, in the past two decades. This polymer has been widely used for the preparation of particles as delivery systems of several therapeutic molecules, including vaccines. These PLA vaccine carriers have shown to induce a sustained and targeted release of different bacterial, viral and tumor-associated antigens and adjuvants in vivo, triggering distinct immune responses. The present review intends to highlight and discuss the major advantages of PLA as a promising polymer for the development of potent vaccine delivery systems against pathogens and cancer. It aims to provide a critical discussion based on preclinical data to better understand the major effect of PLA-based carrier properties on their interaction with immune cells and thus their role in the modulation of host immunity.



During the last decades, vaccination has had a great impact on global health with the control of many severe diseases. Polymeric nanosystems have emerged as promising strategies to stabilize vaccine antigens, promoting their controlled release to phagocytic cells, thus avoiding the need for multiple administrations. One of the most promising polymers are the aliphatic polyesters, which include the poly(lactic acid). This is a highly versatile biodegradable and biocompatible polymer. Products containing this polymer have already been approved for all food and some biomedical applications. Despite all favorable characteristics presented above, PLA has been less intensively discussed than other polymers, such as its copolymer PLGA, including regarding its application in vaccination and particularly in tumor immunotherapy. The present review discusses the major advantages of poly(lactic acid) for the development of potent vaccine delivery systems, providing a critical view on the main properties that determine their effect on the modulation of immune cells.
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Université Catholique de Louvain, 1200 Brussels, Belgium; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Carina
C
Peres
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Ana I
AI
Matos
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies, UCL School of Pharmacy, London, UK.
João
J
Conniot
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies, UCL School of Pharmacy, London, UK.
Vanessa
V
Sainz
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Eva
E
Zupančič
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal; Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Université Catholique de Louvain, 1200 Brussels, Belgium.
Joana M
JM
Silva
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
Luís
L
Graça
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
Rogério
R
Sá Gaspar
Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Université Catholique de Louvain, 1200 Brussels, Belgium.
Véronique
V
Préat
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. Electronic address: hflorindo@ff.ulisboa.pt.
Helena F
HF
Florindo
D000818:Animals; D006801:Humans; D007109:Immunity / Q000187:drug effects; D056747:Immunomodulation / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D011091:Polyesters / Q000494:pharmacology*; D014612:Vaccines / Q000008:administration & dosage
D011091:Polyesters; D014612:Vaccines; C033616:poly(lactide)
Adjuvant; Immune modulation; Microparticles; Nanoparticles; Poly(lactic acid); Vaccine