Polymer-supported lipid shells, onions, and flowers

Bershteyn, Anna; Chaparro, José; Yau, Richard G.; Kim, Mi-Kyung; Reinherz, Ellis L.; Moita, Luís F.; Irvine, Darrell J.

doi:10.1039/b804933e

Cited by 87 publications

(89 citation statements)

References 42 publications

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“…For adjuvant delivery, we prepared MPs (5.4 AE 0.5-μm diameter) and NPs (300 AE 21-nm diameter) with a biodegradable poly(DL-lactide-co-glycolide (PLGA) core and phospholipid surface coating (Fig. S2A), using an emulsion/solvent evaporation process we previously described (20). To confirm that dye-guided injection permitted accurate i.LN deposition of particles, we administered fluorescently labeled MPs to inguinal LNs of mice.…”

Section: Resultsmentioning

confidence: 99%

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In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles

Jewell

López

Irvine

2011

Proc. Natl. Acad. Sci. U.S.A.

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215

216

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Recent studies have demonstrated a simple, potentially universal strategy to enhance vaccine potency, via intralymph node (i.LN) injection. To date, intranodal immunization studies have focused on the delivery of unadjuvanted vaccines (e.g., naked DNA, peptide, or protein). We hypothesized that combining i.LN vaccination with controlled release biomaterials permitting sustained dosing of molecular adjuvants to the local tissue microenvironment would further enhance this promising vaccination strategy. To test this idea, we encapsulated the Toll-like receptor-3 ligand poly(inosinic:cytidylic acid) (polyIC) in biodegradable poly(lactide-co-glycolide) microparticles (MPs) designed to remain extracellular and release polyIC in the LN over several days. Intranodal injection of MPs increased persistence of polyIC in LNs compared to the same dose of soluble polyIC or polyIC formulated in nanoparticles, leading to increased accumulation of Toll-like receptor agonist in LNresident antigen presenting cells and more enduring dendritic cell activation. Intralymph node injection of ovalbumin mixed with polyIC-releasing MPs enhanced the humoral response and expanded ovalbumin-specific T cells to frequencies as high as 18% among all CD8 þ cells following a single injection (8.2-fold greater than the same vaccine given i.m.), a response that could not be matched by antigen mixed with polyIC-loaded nanoparticles or a 10-fold greater dose of soluble polyIC. Thus, i.LN immunization with slow release-formulated adjuvants may be a broadly applicable strategy to enhance therapeutic or prophylactic vaccines.C ompared to live attenuated pathogens, vaccines based on nonreplicating viral/bacterial vectors or subunit antigens offer enhanced safety but elicit weaker, less durable immune responses. Thus, enhancing the potency of these vector/subunit vaccines without sacrificing their excellent safety profile is a central focus of vaccine development. One strategy to enhance vaccine potency is to improve the delivery of antigen and adjuvant molecules to critical antigen presenting cells (APCs) in secondary lymphoid organs. In the "geographic" view of immunity, antigen which does not reach these sites for induction of primary immune responses is ignored by the immune system (1). Following traditional vaccine injection in peripheral tissues, soluble proteins or small particles (<50 nm) drain directly to lymph nodes (LNs), while cell-associated antigen or larger antigen particles access LNs by APC uptake and trafficking (2-4). Recently, intralymph node (i.LN) vaccination-injection of antigens/adjuvants directly into LNs-has shown great promise for vaccine delivery, improving the potency of DNA, RNA, peptide, protein, and dendritic cell-based vaccines (2). Studies have demonstrated as much as 10 6 -fold reductions in antigen dose (5, 6), 100-fold reductions in adjuvant dose (7), and enhanced protection with reduced side effects relative to traditional parenteral immunizations (2). Lymph node injection in humans is readily performed using ultraso...

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Section: Resultsmentioning

confidence: 99%

“…Lipid-coated PLGA MPs and NPs were synthesized by an emulsion/solvent evaporation process (20). Particle size and charge were measured by laser diffraction and electrophoretic mobility, respectively.…”

Section: Methodsmentioning

confidence: 99%

In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles

Jewell

López

Irvine

2011

Proc. Natl. Acad. Sci. U.S.A.

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215

216

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“…Glass microspheres coated with phospholipid layers evaluated the binding specificity of enzymes on cell surface (Obringer et al 1995) or quantified lipid-antibodies binding (Kiser et al, 1998). Recent work continues to investigate lipid-supporting particles based on minerals Nordlund et al 2009;Ahmed & Wunder, 2009;Xu et al, 2009;Oleson & Sahai, 2008;Pyiasena et al, 2008;Senarath-Yapa et al 2007;Moura & Carmona-Ribeiro, 2007;Parida et al, 2006), polymers Jha & Bose, 2009;Thevenot et al, 2008;Bershteyn et al 2008;Zuzzi et al, 2008;Troutier et al, 2005;Pereira et al, 2004), metals eg magnetoliposomes for biomedical applications or contrast agents in magnetic resonance imaging (Bulte & De Cuyper, 2003) or biological cells as templating cores to be dissolved to obtain capsules (Ge et al, 2003) or viruses for enhancing adenovirus tumor targeting in vivo (Singh et al, 2008). Polymer hollow capsules were produced by Möhwald and coworkers (Ge et al, 2003) from the polyelectrolyte layer-by-layer technique on biological cells.…”

Section: Bilayer Vesicle Particlesmentioning

confidence: 99%

Lipid-based Biomimetics in Drug and Vaccine Delivery

Carmona-Ribeiro¹

2010

Biomimetics Learning From Nature

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“…In this article biodegradable lipid-stabilized polymer particles (micro-and nanoscale) are synthesized using a modified double emulsion strategy 5,11 . Particle properties are characterized by laser diffraction and microscopy.…”

Section: Introductionmentioning

confidence: 99%

“…This paper presents a vaccination protocol that combines lipid-stabilized polymer particles and i.LN. delivery to generate controlled release vaccine depots 5,11 . A strong humoral response (i.e.…”

Section: Introductionmentioning

confidence: 99%

Intra-lymph Node Injection of Biodegradable Polymer Particles

Andorko

Tostanoski

Solano

et al. 2014

JoVE

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Generation of adaptive immune response relies on efficient drainage or trafficking of antigen to lymph nodes for processing and presentation of these foreign molecules to T and B lymphocytes. Lymph nodes have thus become critical targets for new vaccines and immunotherapies. A recent strategy for targeting these tissues is direct lymph node injection of soluble vaccine components, and clinical trials involving this technique have been promising. Several biomaterial strategies have also been investigated to improve lymph node targeting, for example, tuning particle size for optimal drainage of biomaterial vaccine particles. In this paper we present a new method that combines direct lymph node injection with biodegradable polymer particles that can be laden with antigen, adjuvant, or other vaccine components. In this method polymeric microparticles or nanoparticles are synthesized by a modified double emulsion protocol incorporating lipid stabilizers. Particle properties (e.g. size, cargo loading) are confirmed by laser diffraction and fluorescent microscopy, respectively. Mouse lymph nodes are then identified by peripheral injection of a nontoxic tracer dye that allows visualization of the target injection site and subsequent deposition of polymer particles in lymph nodes. This technique allows direct control over the doses and combinations of biomaterials and vaccine components delivered to lymph nodes and could be harnessed in the development of new biomaterial-based vaccines.

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Polymer-supported lipid shells, onions, and flowers

Cited by 87 publications

References 42 publications

In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles

In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles

Lipid-based Biomimetics in Drug and Vaccine Delivery

Intra-lymph Node Injection of Biodegradable Polymer Particles

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