Safety and Toxicological Evaluation of Subunit Keyhole Limpet Hemocyanin-Loaded Lipid–PLGA Hybrid Nanoparticles (sKLH-hNPs) as a Nanocarrier for an Opioid Use Disorder Vaccine

International Journal of Toxicology · 2025-07-05 · 2 citations

A nanoparticle-based immunization strategy offers a promising treatment for opioid use disorder (OUD). This study tested the in vivo safety of subunit keyhole limpet hemocyanin-loaded lipid–PLGA hybrid nanoparticles (sKLH-hNPs) as a nanocarrier for OUD vaccine in adult male BALB/c mice by subcutaneous administration at an effective low dose (60 μg) and a dose 5-fold higher (300 μg), with cohorts of animals (n = 10/group, including controls) observed and evaluated for behavioral changes. At 3, 14, 28, and 56 days after dosing, mice (n = 3/dose) were sacrificed, and serum was collected for evaluation of electrolytes, minerals, proteins, liver function, renal function, and energy metabolism. Histological examination included all critical organs, gastrocnemius muscle, and skin from the site of injection. For behavioral evaluation, home cage, open field, and reflex observations were compared among the groups. Results demonstrated no statistical differences among the groups, with the exception of respirations observed in the home cage (O-RESP) on Day 3 ( P = 0.03). There was no evidence of any effect of the test product on energy (glucose, cholesterol, triglycerides) or mineral metabolism (phosphorus, calcium) and hepatic function (urea nitrogen, albumin, total bilirubin), and no indication that the test agent caused liver injury, cholestasis, muscle damage, or acid-base imbalance. Histological analysis in control and treated mice generally revealed no significant findings, although small areas of hemorrhage, lymphocyte infiltration, and thick areas in the subcutis were noted in a subset of samples from both control and treated animals. These experiments suggest that the nanoparticle-based product would be safe for vaccines treating OUD.

Hybrid-nanoparticle based oxycodone vaccines: impact of carrier proteins and adjuvants on their immunogenicity 2042

The Journal of Immunology · 2025-11-01

Abstract Description Opioid use disorder (OUD) is responsible for the loss of hundred of thousands of Americans lives each year. It has become one of the most profound public health crises facing the United States in the past decades. Despite its devastating effect, there are few available treatments outside of the overdose reversing drugs such as naloxone. New methods for OUD treatment are urgently needed. Here, we report the development of hybrid-nanoparticle based vaccines against oxycodone, one of the most used opioid analgesics. Different carrier proteins and adjuvants were formulated into different vaccines, and the immunogenicity studies revealed that the vaccine efficacy is highly dependent on the protein and adjuvants used. The nanovaccines showed superior immunogenicity and pharmacokinetic efficacy comparing to their conjugate vaccine counterpart. This study provides evidence that hybrid nanoparticle-based vaccines are superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD. Funding Sources National Institute on Drug Abuse (NIDA) award 5UG3DA048775 Topic Categories Vaccines and Immunotherapy (VAC)

Human blood markers of cholinergic neurotoxicity and neuropathy: A useful guide for laboratory applications

NeuroToxicology · 2024-01-13 · 4 citations

The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines

Biomaterials · 2024-08-18 · 7 citations

Effect of chlorpyrifos on VEGF gene expression

Chemico-Biological Interactions · 2023-05-30 · 9 citations

Effects of chlorpyrifos on transient receptor potential channels

Toxicology Letters · 2022 · 6 citations

• Chemistry
• Pharmacology
• Endocrinology

Perspective: Considerations for Prevention and Treatment of Dermal Exposure to Toxic Organophosphorus Compounds

Toxicology Current Research · 2021-10-04

The potential benefit of polyhydroxy fullerene nanomaterials in preventing and alleviating toxicities from cholinesterase-inhibiting organophosphorus toxicants is compared to other dermal protectants.

Formulation of Nanovaccines toward an Extended Immunity against Nicotine

ACS Applied Materials & Interfaces · 2021 · 10 citations

• Pharmacology
• Medicine
• Materials science

Nicotine vaccines have been investigated to assist with smoking cessation. Because smoking cessation is a long process, past nicotine vaccines required multiple injections to achieve long-term efficacy. It would be of great significance if extended efficacy can be achieved with fewer injections. Here, we report the assembly of lipid-polylactic acid (PLA) and lipid-poly(lactic-co-glycolic acid) (PLGA) hybrid nanoparticle (NP) based nicotine vaccines. Mice immunized with the lipid-PLGA vaccine produced higher titers of nicotine-specific antibodies than the lipid-PLA vaccine in short-term. However, the lipid-PLA vaccine was found to induce long-lasting antibodies. Three months after the immunization, only mice that received first two injections of the lipid-PLGA vaccine and a third injection of the lipid-PLA vaccine achieved a significantly lower brain nicotine concentration of 65.13 ± 20.59 ng/mg than 115.88 ± 37.62 ng/mg from the negative controls. The results indicate that not only the stability of the vaccines but also the combination of the vaccines impacted the long-term efficacy of the immunization. Lastly, both the body weight and the histopathology study suggest that the vaccines were safe to mice. These findings suggest that long-term immunity against nicotine can be realized by a rational administration of nanovaccines of different levels of stability.

Intracellular potassium depletion enhances apoptosis induced by staurosporine in cultured trigeminal satellite glial cells

Somatosensory & Motor Research · 2021-06-30 · 1 citations

Purpose Satellite glial cells (SGC) surrounding neurons in sensory ganglia can buffer extracellular potassium, regulating the excitability of injured neurons and possibly influencing a shift from acute to neuropathic pain. SGC apoptosis may be a key component in this process. This work evaluated induction or enhancement of apoptosis in cultured trigeminal SGC following changes in intracellular potassium [K]ic.Materials and methods We developed SGC primary cultures from rat trigeminal ganglia (TG). Purity of our cultures was confirmed using immunofluorescence and western blot analysis for the presence of the specific marker of SGC, glutamine synthetase (GS). SGC [K]ic was depleted using hypo-osmotic shock and 4 mM bumetanide plus 10 mM ouabain. [K]ic was measured using the K+ fluorescent indicator potassium benzofuran isophthalate (PBFI-AM).Results SGC tested positive for GS and hypo-osmotic shock induced a significant decrease in [K]ic at every evaluated time. Cells were then incubated for 5 h with either 2 mM staurosporine (STS) or 20 ng/ml of TNF-α and evaluated for early apoptosis and late apoptosis/necrosis by flow cytometry using annexin V and propidium iodide. A significant increase in early apoptosis, from 16 to 38%, was detected in SGC with depleted [K]ic after incubation with STS. In contrast, TNF-α did not increase early apoptosis in normal or [K]ic depleted SGC.Conclusion Hypo-osmotic shock induced a decrease in intracellular potassium in cultured trigeminal SGC and this enhanced apoptosis induced by STS that is associated with the mitochondrial pathway. These results suggest that K+ dysregulation may underlie apoptosis in trigeminal SGC.

Effects of polyhydroxyfullerenes on organophosphate-induced toxicity in mice

Toxicology · 2020-09-16 · 3 citations