Nikita Lomis - Academia.edu (original) (raw)

Papers by Nikita Lomis

Pharmaceuticals, 2021

Congestive heart failure is a fatal cardiovascular disease resulting in tissue necrosis and loss ... more Congestive heart failure is a fatal cardiovascular disease resulting in tissue necrosis and loss of cardiac contractile function. Inotropic drugs such as milrinone are commonly used to improve the myocardial contractility and heart function. However, milrinone is associated with severe side effects and lower circulation time. In this article, a novel protein nanoparticle formulation for heart-targeted delivery of milrinone has been designed and tested. The formulation was prepared using albumin protein conjugated with the targeting ligand, angiotensin II peptide to form nanoparticles following the ethanol desolvation method. The formulation was characterized for size, charge, and morphology and tested in a rat model of congestive heart failure to study pharmacokinetics, biodistribution, and efficacy. The overall cardiac output parameters were evaluated comparing the formulation with the control non-targeted drug, milrinone lactate. This formulation exhibited improved pharmacokinetic...

Scientific Reports, 2018

Aging and chronic disease development are multifactorial processes involving the cumulative effec... more Aging and chronic disease development are multifactorial processes involving the cumulative effects of metabolic distress, inflammation, oxidative stress and mitochondrial dynamics. Recently, variations in the gut microbiota have been associated with age-related phenotypes and probiotics have shown promise in managing chronic disease progression. In this study, novel probiotic and synbiotic formulations are shown to combinatorially extend longevity in male Drosophila melanogaster through mechanisms of gut-brain-axis communication with implications in chronic disease management. Both the probiotic and synbiotic formulations rescued markers of metabolic stress by managing insulin resistance and energy regulatory pathways. Both formulations also ameliorated elevations in inflammation, oxidative stress and the loss of mitochondrial complex integrity. In almost all the measured pathways, the synbiotic formulation has a more robust impact than its individual components insinuating its com...

Molecular pharmaceutics, 2018

Cardiovascular diseases are the leading causes of mortality across the globe. Over the years, var... more Cardiovascular diseases are the leading causes of mortality across the globe. Over the years, various drug formulations and delivery methods have been tested for cardiac repair. Milrinone (MRN) is a widely known cardiac inotrope drug used for the treatment of congestive heart failure in patients, however, its efficacy is limited. This study is the first to report the design of a novel MRN-nanoformulation using human serum albumin nanoparticles (HSA-NPs). The HSA-NPs exhibit promising drug delivery characteristics, such as target specificity, nonimmunogenicity, biocompatibility, and enhanced bioavailability. This article describes a MRN-nanoformulation design for in vitro drug release, cellular uptake, biocompatibility, and other features. The MRN-nanoformulation was prepared by the ethanol desolvation technique and key parameters were optimized to obtain a desired particle size of 154.2 ± 5.8 nm, zeta potential of -29.5 ± 2.9 mV, and a drug encapsulation efficiency of 41.1 ± 1.7%. M...

The gut-brain-axis (GBA) describing the bidirectional communication between the gut microbiota an... more The gut-brain-axis (GBA) describing the bidirectional communication between the gut microbiota and brain was recently implicated in Alzheimer’s disease (AD). The current study describes a novel synbiotic containing three metabolically active probiotics and a novel polyphenol-rich prebiotic which has beneficial impacts on the onset and progression of AD. In a transgenic humanized Drosophila melanogaster model of AD, the synbiotic increased survivability and motility and rescued amyloid beta deposition and acetylcholinesterase activity. Such drastic effects were due to the synbiotic’s combinatorial action on GBA signaling pathways including metabolic stability, immune signaling, oxidative and mitochondrial stress possibly through pathways implicating PPARγ. Overall, this study shows that the therapeutic potential of GBA signaling is best harnessed in a synbiotic that simultaneously targets multiple risk factors of AD.

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial in... more Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificity, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lac...

Orbit

PURPOSE The overall goal was to restore a normal and synchronous blink in unilateral lagophthalmo... more PURPOSE The overall goal was to restore a normal and synchronous blink in unilateral lagophthalmos. We describe the biocompatibility profiling of a novel ferromagnetic implant used for electromagnetic eyelid force generation. METHODS A non-contact blink detection system and an electromagnetic stimulation system were designed and tested. A modified Lester-Burch speculum equipped with strain gauge technology was used in blinking force measurement. Samarium-cobalt magnets were prototyped and coated with parylene-C. Biocompatibility testing was performed using NIH/3T3 mouse fibroblast cells with MTT colorimetric assay cytotoxic quantification. OUTCOME MEASURES Cellular viability and interleukin concentrations. RESULTS Our system was capable of detecting 95.5 ± 3.6% of blinks in various lighting conditions. Using our force measuring device, the difference between non-paralyzed and paralyzed orbicularis oculi (OO) for normal and forceful blinking closure was 40.4 g and 101.9 g, respectively. A 16.6 × 5.0 × 1.5 mm curved shaped samarium cobalt eyelid implant was successfully developed and showed a reproducible blink at 100 ms with full corneal coverage with external eyelid taping. Compared to gold weights, parylene-C coated samarium cobalt implants showed not only excellent cell viability (82.0 ± 4.9% vs. 88.4 ± 0.9%, respectively, p > .05), but also below detection threshold for pro-inflammatory marker concentrations (interleukin-6 < 2 pg/mL and interleukin-10 < 3 pg/mL). CONCLUSIONS We demonstrated excellent in-vitro biocompatibility of our parylene-C coated samarium cobalt implants. We believe that our novel approach can improve the quality-of-life of affected individuals and provides new understanding of blinking biomechanics.

Artificial Cells, Nanomedicine, and Biotechnology, Apr 12, 2018

Journal of Functional Foods

Abstract Imbalances in the gut microbiota are directly associated with the pathogenesis of diabet... more Abstract Imbalances in the gut microbiota are directly associated with the pathogenesis of diabetes and obesity. The current study investigates how the combination of three probiotics Lactobacillus plantarum NCIMB 8826, L. fermentum NCIMB 5221 and Bifidobacteria longum subsp. infantis NCIMB 702255 with a novel polyphenol-rich prebiotic Triphala has combinatorial benefits on the symptoms and underlying mechanisms of diet-induced diabetes and obesity. Drosophila melanogaster fed either a high-fat (HFD) or high-sugar diet (HSD) were pretreated with individual or combined probiotic and/or prebiotic therapy. The individual probiotics elicited some beneficial effects on the physiological markers of diabetes and obesity including reductions in total weight, glucose and triglyceride levels with Lp8826 having a higher efficacy against HSD and Bi702255 against HFD stresses; however, a combinatorial effect was observed with the probiotic and synbiotic formulations. Further, the synbiotic formulation consistently rescued variations in insulin resistance and lipogenesis outlining the synbiotic’s potential for treating metabolic disorders.

The gut microbiota is essential to health and has recently become a target for live bacterial cel... more The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastroin-testinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecul...

Canadian Journal of Cardiology

The user has requested enhancement of the downloaded file. All in-text references underlined in b... more The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately.

J. Mater. Chem. B, 2015

Host body response to a foreign medical device plays a critical role in defining its fate post im... more Host body response to a foreign medical device plays a critical role in defining its fate post implantation.

Human serum albumin nanoparticles (HSA-NPs) are widely-used drug delivery systems with applicatio... more Human serum albumin nanoparticles (HSA-NPs) are widely-used drug delivery systems with applications in various diseases, like cancer. For intravenous administration of HSA-NPs, the particle size, surface charge, drug loading and in vitro release kinetics are important parameters for consideration. This study focuses on the development of stable HSA-NPs containing the anti-cancer drug paclitaxel (PTX) via the emulsion-solvent evaporation method using a high-pressure homogenizer. The key parameters for the preparation of PTX-HSA-NPs are: the starting concentrations of HSA, PTX and the organic solvent, including the homogenization pressure and its number cycles, were optimized. Results indicate a size of 143.4 ˘ 0.7 nm and 170.2 ˘ 1.4 nm with a surface charge of´5.6 ˘ 0.8 mV and´17.4 ˘ 0.5 mV for HSA-NPs and PTX-HSA-NPs (0.5 mg/mL of PTX), respectively. The yield of the PTX-HSA-NPs was ~93% with an encapsulation efficiency of ~82%. To investigate the safety and effectiveness of the PTX...