Microfluidics-generated PLA nanoparticles: impact of purification method on macrophage interactions, anti-inflammatory effects, biodistribution, and protein corona formation.

Polymeric nanoparticles (NPs) are traditionally formulated using batch methodologies that are poorly scalable and require time consuming, hands-on purification procedures. Here, we prepared poly(lactic acid) (PLA)-based polymeric NPs using a scalable microfluidics-based method and systematically investigated the impact of purification method (centrifugation tangential flow filtration (TFF)) to remove poly(vinyl alcohol) (PVA) on macrophage uptake, anti-inflammatory effects, biodistribution, and protein corona formation. TFF purification demonstrated significantly higher recovery of NPs compared to the centrifugation method, with little-to-no aggregation observed.

Lipid Nanoparticles from Walp Mitigate Sepsis through Multimodal Protein Corona Formation.

Background: Plant-derived nanoparticles (PDNP) are nano-sized particles isolated from various edible plants that contain bioactive components involved in regulating cellular immune responses against pathogenic intrusion and inflammation.

Purpose: This study describes a novel PDNP derived from Walp (maca) that efficiently captures pro-inflammatory cytokines and acute phase proteins in its protein corona to enhance survival in two representative lethal models of sepsis.

Methods: Lipid nanoparticles were isolated from maca (MDNP) and triacylglycerols and phytoceramides were identified as major constituents using lipidomics.

Multimodal nanoparticle-containing modified suberoylanilide hydroxamic acid polymer conjugates to mitigate immune dysfunction in severe inflammation.

Excessive immune activation and immunosuppression are opposing factors that contribute to the dysregulated innate and adaptive immune responses seen in severe inflammation and sepsis. Here, a novel analog of the histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA-OH), was incorporated into immunomodulatory poly(lactic acid)-based nanoparticles (iNP-SAHA) by employing a prodrug approach through the covalent modification of poly(lactic-co-glycolic acid) (PLGA) with SAHA-OH. iNP-SAHA formulation allowed for controlled incorporation and delivery of SAHA-OH from iNP-SAHA and treatment led to multimodal biological responses including significant reductions in proinflammatory cytokine secretions and gene expression, while increasing the survival of primary macrophages under lipopolysaccharide (LPS) challenge.

Cell and biomaterial delivery strategies to induce immune tolerance.

The prevalence of immune-mediated disorders, including autoimmune conditions and allergies, is steadily increasing. However, current therapeutic approaches are often non-specific and do not address the underlying pathogenic condition, often resulting in impaired immunity and a state of generalized immunosuppression. The emergence of technologies capable of selectively inhibiting aberrant immune activation in a targeted, antigen (Ag)-specific manner by exploiting the body's intrinsic tolerance pathways, all without inducing adverse side effects, holds significant promise to enhance patient outcomes.

Modified Suberoylanilide Hydroxamic Acid Reduced Drug-Associated Immune Cell Death and Organ Damage under Lipopolysaccharide Inflammatory Challenge.

Histone deacetylase inhibitors (HDACi) induce potent anti-inflammatory responses when used to treat inflammatory diseases. Suberoylanilide hydroxamic acid (SAHA), a pan-HDACi, decreases pro-inflammatory cytokine levels and attenuates cytokine storm in sepsis; however, its toxicity profile toward immune cells has limited its use as a sepsis therapeutic. Here, we developed a modification to SAHA by -hydroxymethylating the capping group to generate SAHA-OH.