Blood Plasma Concentrations Research Articles

MiRNA 511_5p is a potential biomarker for ocular toxoplasmosis.

Ocular toxoplasmosis (OT) is a frequent clinical manifestation due to infection by Toxoplasma gondii. It is characterized by an inflammatory process involving macrophages activated by pro-inflammatory cytokines. The expression of microRNAs takes place during the inflammatory process and, among them, miRNA 511 regulates the activation of macrophages. This study evaluated the expression of miRNA 511_5p in patients with OT and healthy controls. A total of 361 patients from the Hospital de Base of Fundação Faculdade de Medicina de São José do Rio Preto were enrolled and divided into four groups: G1-patients with active ocular lesions and reagent serology for T. gondii; G2-patients with scars and reagent serology for T. gondii; G3-patients without ocular lesions or scars and reagent serology for T. gondii; G4-patients without ocular lesions or scars and non-reagent serology for T. gondii. All patients underwent clinical and laboratory evaluation to confirm the diagnosis of OT. Serology tests, RNA extraction and cDNA synthesis were performed. The miRNA 511_5p levels were compared among the groups. The G1 group showed a high blood plasma concentration of miRNA 511_5p (mean 22.34) compared with the G2 (4.65), G3 (8.91) and G4 (3.52) groups (p<0.0001). These data suggest that miRNA 511_5p has significant potential as a biomarker for OT.

Independently tunable refractive index sensor based on metal-insulator-metal waveguide with key-shaped resonator and application in human blood plasma detection

In this paper, a metal-insulator-metal waveguide structure based on a key-shaped resonator is proposed. Firstly, the structure is simulated using the finite difference in time domain (FDTD) method, revealing the generation of three resonant peaks. And the theoretical results are then analyzed using multimode interference coupled mode theory (MICMT), demonstrating a high level of agreement with the simulation results. Then the parameters of the structure are adjusted, so that the resonant peaks can be tuned independently. Notably, the structure exhibits a maximum sensitivity of 1520 nm RIU−1 with a figure of merit (FOM*) of 195.89, highlighting its exceptional sensing capabilities. Additionally, an analysis of the asymmetric structure reveals the emergence of a new Fano resonance. Due to its outstanding sensing performance, the structure holds potential for applications blood plasma concentration testing. Feasibility is assessed in terms of blood plasma concentration detection, achiveing a maximum sensitivity of 3.07 nm l g−1. As a result, this structure offers promising opportunities in the field of on-chip optical integration and the biomedical field, among others.

Design of blood plasma concentrations sensor based on a one-dimensional photonic crystal

Abstract This study uses the transfer matrix method to calculate the transmittance spectrum of a one-dimensional photonic crystal (1D-PC). Herein, the crystal is composed of alternating layers of barium titanate ferroelectric and yttrium oxide dielectric. The spatial periodicity of the 1D-PC is broken by a cavity surrounded by thin layers of a critical high-temperature superconductor, which can be used to detect refractive index changes of plasma cells infiltrated into the cavity. The results reflect the existence of a maximum transmittance peak in the telecom region known as a localized mode within the photonic band gap. This study reveals that the localized mode shifts toward longer wavelengths as the operating temperature of the superconductor increases. Additionally, we calculate the sensitivity and quality factor of the localized mode, thereby finding that these quantities increase as the incidence angle increases. The proposed model works in cryogenic temperature environments and may be integrated into biosensor designs.

Benzylpenicillin concentrations in umbilical cord blood and plasma of premature neonates following intrapartum doses for group B streptococcal prophylaxis

Background and methodDutch obstetrics guideline suggest an initial maternal benzylpenicillin dose of 2,000,000 IU followed by 1,000,000 IU every 4 h for group-B-streptococci (GBS) prophylaxis. The objective of this study was to evaluate whether concentrations of benzylpenicillin reached concentrations above the minimal inhibitory concentrations (MIC) in umbilical cord blood (UCB) and neonatal plasma following the Dutch guideline.ResultsForty-six neonates were included. A total of 46 UCB samples and 18 neonatal plasma samples were available for analysis. Nineteen neonates had mothers that received intrapartum benzylpenicillin. Benzylpenicillin in UCB corresponded to concentrations in plasma drawn directly postpartum (R2 = 0.88, p < 0.01). A log-linear regression suggested that benzylpenicillin concentrations in neonates remained above the MIC threshold 0.125 mg/L up to 13.0 h after the last intrapartum dose.ConclusionsDutch intrapartum benzylpenicillin doses result in neonatal concentrations above the MIC of GBS.

A universal stimuli-responsive biosensor for disease biomarkers through their cysteine residues: A proof of concept on carcinoembryonic antigen (CEA) biomarker

Carcinoembryonic antigen (CEA) is the gold standard biomarker for the clinical diagnosis of cancers diseases. Accurate, fast, and sensitive screening of CEA plays an important role in cancer disease detection and prognosis. This work reports the development of a new stimuli-responsive biosensor that determines the CEA blood plasma concentration within 10 min. Tert-butyl carbonate Naphthalene-flanked diketopyrroloprrole (mono-TBC-DPPN) fluorescent agent was synthesised, characterised and immobilised gold nanoparticles to develop the stimuli-responsive sensor. The target protein was purified from spiked plasma (from human blood), using an antibody-coated gold substrate. The purified CEA was then chemically modified to provide thiol groups (SH) that interact with the mono-TBC-DPPN on the surface of the stimuli-responsive biosensor to spontaneously displace it, thus leading to its fluorescence emission at 532 nm to a turn on. The new method and sensor was implemented to quantify CEA in spiked blood plasma down to 10 pg.mL−1 within 45 min (35 min for the protein purification and modification and 10 min for its quantification using the sensor)

Multiple Fano Resonances in a Metal–Insulator–Metal Waveguide for Nano-Sensing of Multiple Biological Parameters and Tunable Slow Light

A surface plasmonic waveguide made of metal–insulator–metal (MIM) capable of generating triple Fano resonances is proposed and numerically investigated for multi-biological parameter sensing as well as tunable slow light. The waveguide is made up of a bus waveguide with a silver baffle, a square split-ring cavity with a square center (SSRCSC), and a circular ring cavity with a square center (CRCSC). Based on the triple Fano resonances, human blood temperature and plasma concentration are measured simultaneously at different locations in the waveguide, and the maximum sensitivities were 0.25 nm/°C and 0.2 nm·L/g, respectively. Furthermore, the two biological parameters can be used to achieve tunable slow light, and it was found that the group delay responses to human blood temperature and plasma concentration all conformed to cubic functions. The MIM waveguide may have great applications in future nano-sensing of multiple biological parameters and information processing of optical chips or bio-optical chips.

Expression and localization of the neuropeptide phoenixin-14 and its receptor GRP173 in the canine reproductive organs and periovarian adipose tissue

Phoenixin-14 (PNX-14) is a regulatory neuropeptide encoded by the SMIM20 gene, which has been implicated in the reproductive cycle by modulating the hypothalamic-pituitary-gonadal (HPG) axis. Recently, we showed that PNX-14 is downregulated in bitches with cystic endometrial hyperplasia and pyometra. The objective of this study was to determine the expression of Smim20, PNX-14, and its putative receptor GRP173 in the canine ovary (both healthy and those with ovarian cysts), periovarian adipose tissue (PAT) and in the endometrium during the oestrous cycle. The expression was analysed by RT-qPCR and Western blot. In tissue sections, peptides were localised by immunofluorescent assays, and blood plasma concentrations of PNX-14 were detected by EIA. The results demonstrated increased levels of PNX in bitches in the anestrus groups compared to diestrus animals. The expression of GPR173 increased in PAT during the diestrus phase and endometrial tissue in late diestrus bitches. In the ovary, strong signals of PNX-14 and GPR173 were detected in the luteal and follicular cells. Furthermore, bitches with cystic ovaries were characterised by elevated circulating PNX levels and a significantly higher expression of PNX and GPR173 in gonadal tissues, when compared with healthy animals. Moreover, a positive correlation between PNX and progesterone in the blood of healthy bitches was noted, which changed to a negative correlation in females affected by cystic ovaries. These studies expand the knowledge regarding the expression and localization of the PNX/GRP173 system in canine reproductive organs during physiological and pathological conditions.

Analysis of association between vitamin D metabolite concentration in blood plasma and pancreatic cancer. Experience of one center

Introduction. An early detection of malignant neoplasms is of great practical importance for improvement of treatment results.&#x0D; Objective. To analyze the levels of dehydrocholecalciferol in patients with different forms of malignant neoplasms of the pancreas and chronic pancrestitis.&#x0D; Materials and methods. The cohort study enclosed the data from 160 patients, who were examined and treated in the Academician A.M. Granov Russian Scientific Center of Radiology and Surgical Technologies for the period from 2018 to 2022. The main group included 89 patients with morphologically confirmed diagnosis of the pancreatic cancer without metastases. The control group included 71 patient with the confirmed diagnosis of chronic pancreatitis. Vitamin D concentration was controlled prior to treatment.&#x0D; Results. The size of the tumor node with the location of pathological process in the head of the pancreas varied from 2.1 to 6.3 cm. In the subgroup of patients with tumor lesion of the head of the pancreas, decompression of biliary ducts due to mechanical jaundice was implemented in 43 (82.6 %) persons. When comparing the indicators of 25(ОН)D concentration, in 36 (69.2 %) patients of the main group, different degrees of fall of vitamin D concentration in blood plasma were found. Most often a pronounced deficit of vitamin D was diagnosed in patients with the tumor localized in the head of the pancreas (8 (15.9 % patients). Out of 37 patients with localization of the tumor node in the body/tail, 25 (67.5 %) persons demonstrated normal values of blood plasma vitamin D and 12 (13.4 %) different degrees of decrease in vitamin D concentration. A marked deficit of vitamin D was diagnosed in 2 (16.6 %) patients, deficit of vitamin D in 7 (58.3 %), insufficiency in 3 (25 %). In the control group, decrease in vitamin D level was determine in 12 (16.9 %) patients. An apparent deficit of vitamin D was diagnosed in 3 (4.2 %) patients, deficit of vitamin D in 4 (5.6 %), and insufficiency of vitamin D in 7 (9.8 %); normal values were registered in 57 (80.2 %) persons.&#x0D; Conclusions. Taking into account the obtained data regarding a reliable association between the deficit and insufficiency of vitamin D and the cancer of the head of the pancreas as well as literature data, it is worthwhile to use this indicator as a marker of early detection of pancreatic cancer in risk group patients.

High molar ratios of tumor necrosis factor α (TNF α) soluble receptors I and II to the TNF ligand in human plasma from male veterans with comorbid posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI)

Background and ObjectivesPosttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with chronic inflammation, as inferred from increased, but variable, peripheral levels of cytokines. We sought proof of concept for the notion that peripheral cytokine binding proteins and/or soluble receptors can confound measures of cytokines in those with a history of physical and psychological traumatic exposures. Efforts were focused on one of the major cytokines involved in inflammation, tumor necrosis factor-α (TNF- α). MethodsWe examined blood plasma concentrations of TNF-α, its soluble receptors (TNF-soluble receptors (sR) I and TNFsRII), and C-reactive protein (CRP-1) in a cohort of US Veterans. In a previous study, CRP-1 was shown to be reduced by probiotic anti-inflammatory treatment in this patient cohort. All participants (n = 22) were diagnosed with PTSD and had a history of mild TBI with persistent post-concussive symptoms. Exclusion criteria included medications directly targeting inflammation. ResultsMolar concentrations of soluble TNFsRI and II exceeded concentrations of the TNF-α ligand. TNFsRI, but not TNFsRII, was significantly associated with CRP-1 (Spearman Rho correlations = 0.518; p=.016 and 0.365; p = .104, respectively). ConclusionsTNF soluble receptors may bind to and sequester free TNF-α, suggesting that only measuring ligand concentrations may not provide a fully comprehensive view of inflammation, and potentially lead to inaccurate conclusions. TNFsRI concentration may provide a better estimate of inflammation than TNF-α for those with PTSD and post-acute mTBI with post-concussive symptoms, a hypothesis that invites further testing in larger studies.

The impact of birth weight, birth order, birth asphyxia, and colostrum intake per se on growth and immunity of the suckling piglets

Colostrum is the only source of passive immunity and the major source of nutrients and is crucial for thermoregulation of newborn piglets in their early life. However, the amount of colostrum obtained by each piglet [colostrum intake (CI)] differs considerably in large litters as born by contemporary hyperprolific sow lines. This experiment aimed to investigate the impact of the following individual characteristics of piglets; birth weight, birth order and neonatal asphyxia at birth on CI, and further to determine the relationship between the CI and the passive immunity transfer, and the growth performance of piglets prior to weaning. Twenty-four Danbred sows of the second-parity and their progeny (n = 460) were used. As main inputs in the prediction model to assess individual piglet CI were piglet birth weight, their weight gain, and the duration of colostrum suckling of the piglets. The asphyxia (state of oxygen deprivation) was assessed by measuring blood lactate concentration immediately after birth, and piglets sampled at d 3 of age for determination of blood plasma concentrations of immunoglobulins (Ig) G, A, and M. Piglets’ CI was negatively associated with asphyxia (P = 0.003), birth order (P = 0.005) and low birth weight have compromised the individual CI (P < 0.001). Average daily gain during the suckling period was greater among piglets with high CI (P = 0.001) and birth weight (P < 0.001). Body weight at weaning (d 24 of age) was positively associated with CI (P = 0.0004) and birth weight (P < 0.001). The probability of weaning was positively associated with CI and birth weight (P < 0.001) of the piglets. Concentrations of IgG (P = 0.02), IgA (P = 0.0007), and IgM (P = 0.04) in piglets’ plasma at d 3 of age were positively associated with CI, and were negatively associated with birth order (P < 0.001). The present study demonstrated that piglets’ individual characteristics at birth (birth weight, birth order, state of oxygen deprivation) have considerable effects on their CI. The knowledge gained from the results of this study gives a scientific base for development and implementation of more effective techniques in practice aimed to improve the piglets’ robustness during the suckling period.

Endothelin-1 production via placental (pro)renin receptor in a mouse model of preeclampsia

IntroductionPreeclampsia (PE) pathogenesis is explained by the two-stage disorder theory. However, mechanisms underlying hypertension and proteinuria in PE remain unclear. The role of (pro)renin receptor (PRR) in PE pathology has received special attention. We examined endothelin-1 (ET-1) production via placental PRR in a PE mouse model. MethodsAt 14.5 day-post-coitum (DPC), we performed a reduced uterine perfusion pressure (RUPP) operation, ligating the uterine arteriovenous vessels in female mice. We also infused these mice with a PRR inhibitor, decoy peptide in the handle region of prorenin (HRP) for mice (NH2-RIPLKKMPSV-COOH). At 18.5 DPC, blood, urine, and placenta were collected; fetus and placenta were weighed. We evaluated placental hypoxia using quantitative polymerase chain reaction (PCR), with hypoxia-inducible factor-1α (HIF-1α) as index. We also evaluated PRR, transforming growth factor-β1 (TGF-β1), and ET-1 expression in the placenta using quantitative PCR and western blotting. ET-1 concentration in blood plasma was assessed using enzyme-linked immunosorbent assay. ResultsBlood pressure and proteinuria significantly increased, and fetal and placental weights decreased in RUPP mice. HIF-1α, PRR, TGF-β1, and ET-1 expressions considerably increased in RUPP mice placentas. ET-1 concentration in RUPP mice blood plasma was markedly increased. PRR inhibitor suppressed these changes. DiscussionIn PE model mice that underwent RUPP treatment, placental hypoxia increased PRR and ET-1 expression suggesting a causative relationship between ET-1 and intracellular PRR signaling. RUPP treatment, when combined with HRP, reversed the effect of elevated ET-1 levels in the model. This study may help to elucidate the pathogenesis of PE considering PRR and ET-1.

Pluronic F-68 Montmorillonite As A Drug Delivery Vehicle For Extended Release Of Venlafaxine Hydrochloride.

Short half-life and low bioavailability of Venlafaxine hydrochloride (VF), an antidepressant drug, necessitates the frequent administration of VF tablets in a day in order to maintain adequate drug concentration in blood plasma. This generates the need for the development of formulations which could prolong the release of VF and reduce the multiple dosages. The present work explores the combination of Montmorillonite (Mt) with Pluronic F-68 (PF-68) (OrganoMT) for oral delivery of VF. The effect of various parameters including pH of aqueous drug solution, contact time and initial drug concentration on drug loading capacity of OrganoMT has been studied. The synthesized OrganoMT-VF complexes were characterized by various suitable techniques. XRD studies indicated that the VF molecules were intercalated within the OrganoMT layers. In vitro release behavior of VF from OrganoMT-VF complexes shows an extended-release pattern for a period of 30 h and reaches upto 70% and 60% compared to pure VF having complete release time of 5.5 h and 3.5 h in simulated gastric and intestinal fluid respectively. Various kinetic models were employed to elucidate the drug release mechanism where the best fitting was obtained with Korsmeyer Peppas model. The results suggest the possibility of designing an oral extended controlled release formulation for VF to minimize its administration frequency thereby increasing the effectiveness of drug. This improves patient compliance by reducing the dose from 4 times in 24 h to once in 24 h.

Real-time biosensor application of structurally chiral medium for detection and sensing of plasma in human blood

In this work, we theoretically investigated a unique and sensitive optical biosensor for detecting and sensing blood plasma using a structurally chiral medium. The proposed biosensor is a defective one-dimensional structure made from a structurally chiral material with point group symmetry where the defect layer is considered as a channel for the blood plasma. The transmission and reflection of the structure are investigated utilizing the transfer matrix method for the circularly polarized waves. It is shown that a defect mode is created in the middle of the circular Bragg photonic band gap for the right-handed circularly polarized waves and experiences a red shift by increasing the blood plasma concentration. Also, it is observed that the sensitivity of the sensor can be increased by increasing the thickness of the defect layer. In addition, we reveal that the increase of the tilt angle of the structurally chiral medium results in the decrease of photonic band gap width and causes to blue-shift of the defect mode. As a result, the performance of the sensor decreases by increasing the tilt angle. The proposed structure has an easy and efficient manufacturing process, high stability and cost-effectiveness and can provide real-time blood plasma biosensors.

Fabrication of an Enzyme Membrane for Creatinine Detection and Its Application to an Extended-Gate FET-Based Biosensor

An extended-gate field effect transistor (EGFET) based creatinine sensor using an enzyme-containing silk-fibroin membrane successfully fabricated. In this experiment, we used creatinine deiminase as a detection enzyme for serum creatinine, which is known as a marker of chronic kidney disease. The fabricated biosensor showed excellent potentiometric response to creatinine over a wide range from 0.007 - 0.4 mg/mL in phosphate buffer solution, which can enable to measure creatinine concentration in blood plasma.

Metal concentrations in cerebrospinal fluid, blood, serum, plasma, hair, and nails in amyotrophic lateral sclerosis: A systematic review and meta-analysis

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive muscle wasting, paralysis, and respiratory failure. Whereas approximately 10–15 % of ALS cases are familial, the etiology of the remaining, sporadic ALS cases remains largely unknown. Environmental exposures have been suggested as causative factors for decades, and previous studies have found elevated concentrations of metals in ALS patients. PurposeThis meta-analysis aims to assess metal concentrations in body fluids and tissues of ALS patients. MethodsWe searched the MEDLINE and EMBASE databases on December 7th, 2022 for cross-sectional, case-control, and cohort studies which measure metal concentrations in whole blood, blood plasma, blood serum, cerebrospinal fluid (CSF), urine, erythrocytes, nail, and hair samples of ALS patients. Meta-analysis was then performed when three or more articles existed for a comparison. FindingsTwenty-nine studies measuring 23 metals were included and 13 meta-analyses were performed from 4234 screened entries. The meta-analysis results showed elevated concentrations of lead and selenium. Lead, measured in whole blood in 6 studies, was significantly elevated by 2.88 µg/L (95 % CI: 0.83–4.93, p = 0.006) and lead, measured in CSF in 4 studies, was significantly elevated by 0.21 µg/L (95 % CI: 0.01 – 0.41, p = 0.04) in ALS patients when compared to controls. Selenium, measured in serum/plasma in 4 studies, was significantly elevated by 4.26 µg/L (95% CI: 0.73 – 7.79, p = 0.02) when compared to controls.Analyses of other metal concentrations showed no statistically significant difference between the groups. ConclusionLead has been discussed as a possible causative agent in ALS since 1850. Lead has been found in the spinal cord of ALS patients, and occupational exposure to lead is more common in ALS patients than in controls. Selenium in the form of neurotoxic selenite has been shown to geochemically correlate to ALS occurrence in Italy. Although no causal relationship can be established from the results of this meta-analysis, the findings suggest an involvement of lead and selenium in the pathophysiology of ALS. After a thorough meta-analysis of published studies on metal concentrations in ALS it can only be concluded that lead and selenium are elevated in ALS.

Metal ratios as possible biomarkers for amyotrophic lateral sclerosis

Background and ObjectivesAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown aetiology. Metals have been suspected to contribute to ALS pathogenesis since mid-19th century, yet studies on measured metal concentrations in ALS patients have often yielded conflicting results, with large individual variation in measured values. Calculating metal concentration ratios can unveil possible synergistic effects of neurotoxic metals in ALS pathogenesis. The aim of this study was to investigate if ratios of different metal concentrations in cerebrospinal fluid (CSF) and blood plasma, respectively, differ between ALS patients and healthy controls. MethodsCerebrospinal fluid and blood plasma were collected from 17 ALS patients and 10 controls. Samples were analysed for 22 metals by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), and all possible 231 metal ratios calculated in each body fluid. ResultsFifty-three metal ratios were significantly elevated in ALS cases as compared to controls (p < 0.05); five in blood plasma, and 48 in CSF. The finding of fewer elevated ratios in blood plasma may indicate specific transport of metals into the central nervous system. The elevated metal ratios in CSF include Cd/Se (p = 0.031), and 16 ratios with magnesium, such as Mn/Mg (p = 0.005) and Al/Mg (p = 0.014). ConclusionMetal ratios may be used as biomarkers in ALS diagnosis and as guidelines for preventive measures.

Onset timing and duration of augmented renal clearance in a mixed intensive care unit

BackgroundAugmented renal clearance (ARC) is associated with lower blood plasma concentrations of renally excreted drugs; however, its time course is unknown. The current study aimed to determine the onset timing/duration of ARC, its risk factors, and its association with clinical outcomes by continuous monitoring of urinary creatinine clearance (CrCl) in critically ill patients.MethodsData were retrospectively obtained from the medical records of 2592 critically ill patients admitted to the intensive care unit (ICU) from January 2019 to June 2022 at a tertiary emergency hospital. Among these, patients with continuously measured urinary CrCl were selected and observed over time. We evaluated the onset timing and duration of ARC by plotting Kaplan–Meier curves. Furthermore, by multivariate analyses, factors associated with the onset and persistence of ARC were analyzed, and the association between the ARC time course and clinical outcomes was evaluated.ResultsThe prevalence of ARC was 33.4% (245/734). ARC onset was within 3 days of admission in approximately half of the cases, and within 1 week in most of the other cases. In contrast, the persistence duration of ARC varied widely (median, 5 days), and lasted for more than a month in some cases. Multivariate analysis identified younger age, male sex, lower serum creatinine at admission, admission with central nervous system disease, no medical history, use of mechanically assisted ventilation, and vasopressor use as onset factors for ARC. Furthermore, factors associated with ARC persistence such as younger age and higher urinary CrCl on ARC day 1 were detected. The onset of ARC was significantly associated with reduced mortality, but persistent of ARC was significantly associated with fewer ICU-free days.ConclusionsDespite the early onset of ARC, its duration varied widely and ARC persisted longer in younger patients with higher urinary CrCl. Since the duration of ARC was associated with fewer ICU-free days, it may be necessary to consider a long-term increased-dose regimen of renally excreted drugs beginning early in patients who are predicted to have a persistent ARC.

Investigating Generation of Antibodies against the Lipid Nanoparticle Vector Following COVID-19 Vaccination with an mRNA Vaccine.

Despite the success of mRNA-based vaccines against infectious diseases (including COVID-19), safety concerns have been raised relating to the lipid nanoparticles (LNPs) used to deliver the mRNA cargo. Antibodies against the polyethylene glycol (PEG) coating on these non-viral vectors are present in the general population and can in some instances induce allergic reactions. Furthermore, treatment with PEGylated therapeutics may increase the plasma concentration of such anti-PEG antibodies. The widespread use of PEGylated nanoparticles for mRNA vaccines concerns researchers and clinicians about a potential rise in future cases of allergic reactions against mRNA vaccines and cross-reactions with other PEGylated therapeutics. To determine if vaccination with Comirnaty increased the plasma concentration of antibodies against LNPs, we investigated the blood plasma concentration of anti-LNP antibodies in healthy individuals before and after vaccination with the mRNA-based COVID-19 vaccine Comirnaty (BNT162b2). Blood samples were acquired from 21 healthy adults before vaccination, 3-4 weeks after the first vaccination dose but before the second dose, and 2-6 months after the second (booster) dose. The blood plasma concentration of antibodies recognizing the LNPs was analyzed using a microscopy-based assay capable of measuring antibody-binding to individual authentic LNPs. No significant increase in anti-LNP antibodies was observed after two doses of Comirnaty. The LNPs used for intramuscular delivery of mRNA in the vaccine against COVID-19, Comirnaty, do, therefore, not seem to induce the generation of anti-vector antibodies.

Super disintegrating oromucosal nanofiber patch of zolmitriptan for rapid delivery and efficient brain targeting

Oromucosal administration of zolmitriptan using electrospun nanofiber can potentially result in blood plasma concentrations analogous to intravenous kinetics and targeting the brain due to anatomical features of the delivery site. Herein, we report the optimization of zolmitriptan and polyvinylpyrrolidone nanofibers using a Quality by Design approach. Fourier transform infrared spectroscopy, and Thermogravimetric analysis ruled out any physical and/or chemical interaction between the drug and excipient. Diffraction studies revealed a sharp decrease in the crystalline index of pure zolmitriptan from 85.75% to 8.35%. Likely, calorimetry studies show a sharp decline in the enthalpy of fusion from 126.4 J/g before electrospinning to 67.24 J/g post electrospinning, demonstrating amorphization of the drug. The disintegration of nanofiber occurs within less than a second, and about 82% of the medicament was released in 60 s in an in vitro test, compared to 67% from the Zomig Rapimelt® tablet. Rapid drug flux of 22.07 and 22.62 μg/cm2/h occurred when nanofiber patches were applied to buccal and soft palate mucosa in an ex vivo permeability test. Biocompatibility studies established that the nanofiber patches were neither toxic nor irritating to the oral epithelium. Groups of rabbits received the zolmitriptan solution intravenously and orally, or optimized nanofibers were applied to the buccal and soft palate mucosa. Pharmacokinetic analysis in blood plasma indicated similar kinetics of oromucosal patches and intravenous administration. More importantly, concentrations achieved in the hindbrain after administration of the patch over the soft palatal mucosa produce significantly higher concentrations than buccal or IV administration (>2-folds). The drug targeting these brain regions likely resulted from rapid dissolution, enhanced permeation, amorphization, and specialized drug transport via a trigeminal nose base-pons-medullary axis.

Enzyme-Triggered l-α/d-Peptide Hydrogels as a Long-Acting Injectable Platform for Systemic Delivery of HIV/AIDS Drugs.

Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organization. Patient adherence to complicated dosage regimens remains a key barrier. There is a need for convenient long-acting formulations that deliver drugs over sustained periods. This paper presents an alternative platform, an injectable in situ forming hydrogel implant to deliver a model antiretroviral drug (zidovudine [AZT]) over 28 days. The formulation is a self-assembling ultrashort d or l-α peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), covalently conjugated to zidovudine via an ester linkage. Rheological analysis demonstrates phosphatase enzyme instructed self-assembly, with hydrogels forming within minutes. Small angle neutron scattering data suggest hydrogels form narrow radius (≈2nm), large length fibers closely fitting the flexible cylinder elliptical model. d-Peptides are particularly promising for long-acting delivery, displaying protease resistance for 28 days. Drug release, via hydrolysis of the ester linkage, progress under physiological conditions (37°C, pH 7.4, H2 O). Subcutaneous administration of Napffk(AZT)Y[p]G-OH in Sprague Dawley rats demonstrate zidovudine blood plasma concentrations within the half maximal inhibitory concentration (IC50 ) range (30-130ng mL-1 ) for 35 days. This work is a proof-of-concept for the development of a long-acting combined injectable in situ forming peptide hydrogel implant. These products are imperative given their potential impact on society.