Particle Yield Research Articles

PH/enzyme dual sensitive Gegenqinlian pellets coated with Bletilla striata polysaccharide membranes for the treatment of ulcerative colitis

Gegen Qinlian Decoction, derived from Zhang Zhongjing's Treatise on Typhoid Fever, has been widely used in the treatment of various common diseases, frequently-occurring diseases and difficult and complicated diseases, such as ulcerative colitis. In this study, Bletilla striata polysaccharide (BSP) was innovatively used as a film coating material to prepare Gegen Qinlian pellets with dual sensitivity of pH enzyme for the treatment of ulcerative colitis. BSP has the ability to repair the inflamed colon mucosa and can produce synergistic effects, while avoiding the adverse therapeutic effects caused by the early release of drugs from a single pH-sensitive pellets in the small intestine. The prepared pellets have a uniform particle size, good roundness, a particle size range from 0.8 mm to 1.0 mm, and a particle yield is 85.6 %. The results of in vitro release showed that ES-BSP pellets hardly released drugs in the pH range of 1.2–6.8. However, in the colon mimic fluid containing specific enzymes, the drug release was significantly accelerated, demonstrating the sensitivity of the pellets to pH enzymes. In vivo and ex vivo fluorescence imaging of small animals showed that Gegen Qinlian pellets with dual sensitivity of pH enzyme remained longer in the colon compared with pH-sensitive pellets. In vivo pharmacodynamics study showed that the Gegen Qinlian pellets with dual sensitivity of pH enzyme had a better therapeutic effect in the rat model of the ulcerative colon than the commercially available Gegenqinlian pellets in the control group.

Numerical Simulations of the Acceleration of Fast Protons and of the Excitation of Nuclear Reactions 11B(p, 3a) and 11B(p, n)C11 at the Intensities of Picosecond Laser Radiation in the Range 1018-1019 W/cm2

Results of numerical simulations for acceleration of proton beams at the irradiation of Al target by a superintense laser pulse are presented. There is a good agreement with the experimental data in a broad range of laser intensities from I = 1018 W/cm2 to I = 1019 W/cm2 at the fixed laser pulse duration. The obtained parameters of proton beams were used for calculation of the total yield of a particles and neutrons for the nuclear reactions 11B(p, 3a) and 11B(p, n)C11C at the collisions of proton beams with boron targets. It is shown that the number of a particles escaping boron target and arriving at track detectors is less than 5of the total amount of a particles, because the majority of these particles remain inside the target owing to ionization losses. The derived values of the yield ofparticles’ which arrive at detectors are in good agreement with the experimental data. We also calculate the total yield of neutrons in the reaction 11B(p, n)C11C. It is found that, at the intensity I = 1019 W/cm2 of the picosecond laser pulse, the yield is equal to Nn = 1.4 × 108 , this value is approximately of 3% of the total yield of a particles.

Lipid-based particle engineering via spray-drying for targeted delivery of antibiotics to the lung

Pulmonary delivery of antibiotics for the treatment of tuberculosis provides several benefits compared to conventional oral and parenteral administration. API-loaded particles delivered directly to alveolar macrophages, where Mycobacterium tuberculosis resides, can reduce the required dose and decrease the severe side effects of conventional treatment. In this work, lipid-microparticles loaded with rifampicin were engineered via spray-drying to be administered as a carrier-free dry powder for inhalation. Although, it is well-known that spray-drying of lipid-based excipients is strongly limited, a completely lipid-based formulation using diglycerol full ester of behenic acid was produced. The solid state of the lipid, providing high melting temperature, absence of polymorphism and monophasic crystallization, led to high yield of spray-dried particles (83%). Inhalable particles of mass median aerodynamic diameter of 2.36 µm, median geometric size of 2.05 µm, and negative surface (-50.03 mV) were engineered. Such attributes were defined for deep lung deposition and targeted delivery of antibiotics to alveolar macrophages. Superior aerodynamic performance as carrier-free DPI was associated to a high fine particle fraction of 79.5 %. No in vitro cytotoxic effects were found after exposing epithelial cell lines and alveolar macrophages. In vitro uptake of particles into alveolar macrophages indicated the efficiency of their targeted delivery. The use of highly processable and safe lipid-based excipients for particle engineering via spray-drying can extend the availability of materials for functionalized applications for pulmonary delivery.

Quality by design – Spray drying of ciprofloxacin-quercetin fixed-dose combination intended for inhalation

Spray drying is a well-suited technique for producing fixed-dose drug combinations. There has been a growing interest in utilizing spray drying to engineer carrier-free inhalable drug particles. The aim of this study was to understand and optimise the spray drying process of a ciprofloxacin-quercetin fixed dose combination intended for pulmonary administration. A 24-1 fractional factorial design and multivariate data analysis was used to identify important process parameters and investigate correlations with particle characteristics. The independent variables were solute concentration along with the processing parameters: solution flow rate, atomizing air flow rate and inlet temperature. The dependent variables included particle size distribution, yield and residual moisture content (RMC). Correlations between dependent and independent variables were further investigated via principal component analysis. Overall, solution flow rate, atomizing air flow rate and inlet temperature were found to affect the particle size D(v,50) and D(v,90) while the solute concentration and the atomizing air flow rate mainly affected the span. The inlet temperature was the most important parameter affecting the RMC and the yield. The formulation with optimized independent variables had a D(v,50) and span values of 2.42 µm and 1.81 with excellent process yield >70% and low RMC i.e. 3.4%. The optimized formulation was further investigated for its in vitro aerosolization performance using next generation impactor (NGI); it exhibited high emitted dose (ED > 80%) and fine particle fractions (FPF > 70%) for both drugs.

The enzymatic modification of whey-proteins for spray drying encapsulation of Ginkgo-biloba extract

Ginkgo biloba extract (GBLE) contains many bioactives including flavonoids and terpene trilactones that play some pharmacological roles. These compounds are sensitive to operating conditions; so, encapsulation is a suitable approach to protect them. In this study, different carriers including maltodextrin (MD), and its combination with gum-Arabic (MD-GA), whey protein concentrate (MD-WPC), and whey-protein hydrolysate (MD-HWPC) were used to encapsulate GBLE. Powder production yield, physicochemical/functional characteristics, physical stability and flowability of particles were affected by the type and composition of carriers. FTIR results indicated the placement of phenolic compounds in the carrier matrix. The SEM images also showed the morphological changes of particles (especially the size, indentation and surface shrinkage) under the influence of various carriers. Microencapsulated powders formulated using MD-HWPC showed the highest values of TPC, DPPH, and ABTS and a lighter color which determined the suitability of this wall material (due to the improvement of surface activity and emulsifying properties of protein as a result of partial enzymatic hydrolysis) to protect the antioxidant properties of GBLE during spray-drying, improving the production yield and preserving physical and functional characteristics of the encapsulated powders.

Glutathione affinity chromatography for the scalable purification of an oncolytic virus immunotherapy from microcarrier cell culture.

Therapeutic viral vectors are an emerging technology with several clinical applications in gene therapy, vaccines, and immunotherapy. Increased demand has required the redevelopment of conventional, low-throughput cell culture and purification manufacturing methods such as static cell stacks and ultracentrifugation. In this work, scalable methods were investigated for the manufacture of an oncolytic virus immunotherapy application consisting of a prototype strain of coxsackievirus A21 (CVA21) produced in adherent MRC-5 cells. Cell culture was established in stirred-tank microcarrier bioreactors, and an efficient affinity chromatography method was developed for the purification of harvested CVA21 through binding of the viral capsids to an immobilized glutathione (GSH) ligand. Bioreactor temperature during infection was investigated to maximize titer, and a decrease in temperature from 37°C to 34°C yielded a two-three-fold increase in infectivity. After purification of the 34°C harvests, the GSH affinity chromatography elution not only maintained a >two-fold increase in infectivity and viral genomes but also increased the proportion of empty capsids compared to 37°C harvests. Using material generated from both infection temperature setpoints, chromatographic parameters and mobile phase compositions were studied at the laboratory scale to maximize infectious particle yields and cell culture impurity clearance. Empty capsids that co-eluted with full capsids from 34°C infection temperature harvests were poorly resolved across the conditions tested, but subsequent polishing anion exchange and cation exchange chromatography steps were developed to clear residual empty capsids and other impurities. Oncolytic CVA21 production was scaled-up 75-fold from the laboratory scale and demonstrated across seven batches in 250L single-use microcarrier bioreactors and purified with customized, prepacked, single-use 1.5L GSH affinity chromatography columns. The large-scale bioreactors controlled at 34°C during infection maintained a three-fold increase in productivity in the GSH elution, and excellent clearance of host cell and media impurities was observed across all batches. This study presents a robust method for the manufacture of an oncolytic virus immunotherapy application that may be implemented for the scalable production of other viruses and viral vectors which interact with glutathione.

Study on Grinding Behavior Characteristics under Low-Speed Grinding Condition

In order to explore the crushing mechanism of minerals, this paper attempts to eliminate the throwing effect of media and study the grinding characteristics of minerals only under the action of abrasion force. In this paper, the method of removing the throwing state of media is to adjust the mill to a lower rotational speed, so that the grinding media are all in a cascading state. Three single-component pure minerals, quartz, pyrrhotite, and pyrite, commonly found in complex ores, were selected as research objects to study the grinding behavior characteristics of the three minerals only under the force of abrasion. The effects of mineral species, feed-particle sizes, grinding time, and other factors on the particle-size distribution and product-generation rate of grinding products are studied. The results show that from the particle-size distribution of grinding products, the yield of coarse particles is the highest, while the yield and t10 value of other fine particles are very low. The feed-particle size and the hardness of the mineral sample affect the grinding behavior. The product particle size is mainly 0.71 times the feed-particle size, and the other fine particle sizes generated are less than 0.5 times the feed-particle size.

Scattering and ion emission from insulator films

To determine the effect of the surface potential of dielectric samples on the yield of positive ions during ion irradiation, we studied the dependence of the current of secondary particles on the thickness of dielectric films. It is shown that the yield of positive secondary particles increases significantly with increasing thickness if the film charging potential does not exceed the breakdown value determined by the electrical strength of the film. An indirect confirmation of the film charging in these experiments is the time dependence of the current from the sample holder. An experimental evaluation of the apparatus effect caused by the emission of secondary electrons from a hemispherical collector has been carried out. Possible mechanisms of the observed phenomena are discussed.

Correlation of Cumulative Particle Production with Strange and Heavy-Flavor Particle Yields in the String Fusion Model

Correlation of Cumulative Particle Production with Strange and Heavy-Flavor Particle Yields in the String Fusion Model

Efficacy of Binary Ethylenimine in the Inactivation of Foot-and-Mouth Disease Virus for Vaccine Production in South Korea.

Foot-and-mouth disease (FMD) vaccines must be produced in a biosafety level 3 facility, so the FMD virus (FMDV) must be completely inactivated after amplification. The inactivation kinetics of FMDV during vaccine antigen production were assessed by evaluating whether the viral titer dropped below 10-7 TCID50/mL within 24 h of binary ethyleneimine (BEI) treatment. This study dealt with four FMD vaccine candidate strains for the efficacy of BEI treatment at different concentrations and temperatures to determine the optimal inactivation condition of each virus. Two domestic isolates, O/SKR/Boeun/2017 (O BE) and A/SKR/Yeoncheon/2017 (A YC), and two recombinant viruses, PAK/44/2008 (O PA-2) and A22/Iraq/24/64 (A22 IRQ), were investigated. The O BE and A22 IRQ required 2 mM BEI at 26 °C and 0.5 mM BEI at 37 °C for complete inactivation. The O PA-2 and A YC required 2 mM BEI at 26 °C and 1 mM BEI at 37 °C. Crucially, the yield of FMD virus particles (146S) in the viral infection supernatant was higher (>4.0 µg/mL) than those previously reported; additionally, there was little antigen loss, even after 24 h of treatment with 3 mM BEI. Overall, it is considered economical to produce FMD vaccines using these four kinds of viruses; therefore, these candidate strains will be prioritized for the manufacture of FMD vaccines in South Korea.

Particle Ratios in a Multicomponent Nonideal Hadron Resonance Gas

We have considered formation of a multicomponent nonideal hot and dense gas of hadronic resonances in the ultrarelativistic heavy ion collisions. In the statistical thermal model approach, the equation of state (EoS) of the noninteracting ideal hadron resonance gas (IHRG) does not incorporate either the attractive part or the short-range repulsive part of the baryonic interaction. On the other hand, in the nonideal hadron resonance gas (NIHRG) model, we can incorporate these interactions using the van der Waals (VDW) type approach. Studies have been made to see its effect on the critical parameters of the quark-hadron phase transition. However, it can also lead to modifications in the calculated relative particle yields. In this paper, we have attempted to understand the effect of such van der Waals-type interactions on the relative particle yields and also studied their dependences on the system’s thermal parameters, such as the temperature and baryon chemical potential μ B . We have also taken into account the decay contributions of the heavier resonances. These results on particle ratios are compared with the corresponding results obtained from the point-like, i.e., noninteracting IHRG model. It is found that the particle ratios get modified by incorporating the van der Waals-type interactions, especially in a baryon-rich system which is expected to be formed at lower RHIC energies, SPS energies, and in the forthcoming CBM experiments due to high degree of nuclear stopping in these experiments.

Optimizing the Parton Showers in PYTHIA8 for Xe–Xe collision at 5.44 TeV

We present the doubly differential invariant yield of primary charged particles [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text] in Xe–Xe collisions at [Formula: see text] = 5.44 TeV, as a function of [Formula: see text] in kinematic region of [Formula: see text] and for the pseudorapidity interval of [Formula: see text] by using PYTHIA8 tuned to different Parton Showers like Simple Showers (Time-Like, Space-Like), DIRE and VINCIA Showers. The predictions of hard and soft QCD processes of Parton Showers are then compared with the ALICE data at different centrality classes of 0–5%, 50–60% and 70–80%. The observed deviations are connected with the kinematics involved and are mostly due to the color coherence and soft gluon emission from parton pairs. As PYTHIA8 does not take into account the Cronin effect, thus the deviation at low [Formula: see text] is due to Cronin effect. The nuclear modification factor is constructed and it is observed that the signal is less than unity or suppression is seen which is coming from Parton Showers.

Single proton LET characterization with the Timepix detector and artificial intelligence for advanced proton therapy treatment planning

Objective. Protons have advantageous dose distributions and are increasingly used in cancer therapy. At the depth of the Bragg peak range, protons produce a mixed radiation field consisting of low- and high-linear energy transfer (LET) components, the latter of which is characterized by an increased ionization density on the microscopic scale associated with increased biological effectiveness. Prediction of the yield and LET of primary and secondary charged particles at a certain depth in the patient is performed by Monte Carlo simulations but is difficult to verify experimentally. Approach. Here, the results of measurements performed with Timepix detector in the mixed radiation field produced by a therapeutic proton beam in water are presented and compared to Monte Carlo simulations. The unique capability of the detector to perform high-resolution single particle tracking and identification enhanced by artificial intelligence allowed to resolve the particle type and measure the deposited energy of each particle comprising the mixed radiation field. Based on the collected data, biologically important physics parameters, the LET of single protons and dose-averaged LET, were computed. Main results. An accuracy over 95% was achieved for proton recognition with a developed neural network model. For recognized protons, the measured LET spectra generally agree with the results of Monte Carlo simulations. The mean difference between dose-averaged LET values obtained from measurements and simulations is 17%. We observed a broad spectrum of LET values ranging from a fraction of keV μm−1 to about 10 keV μm−1 for most of the measurements performed in the mixed radiation fields. Significance. It has been demonstrated that the introduced measurement method provides experimental data for validation of LETD or LET spectra in any treatment planning system. The simplicity and accessibility of the presented methodology make it easy to be translated into a clinical routine in any proton therapy facility.

Radiation-induced phenomena in thermally treated Kr matrices

The effect of thermal treatment on relaxation phenomena in Kr matrices irradiated with a low-energy electron beam has been studied. The experiments were carried out using measurements of the relaxation emissions of preirradiated Kr samples, which were unannealed and annealed before exposure to an electron beam. Three types of emissions were monitored in a correlated real-time manner: thermally stimulated luminescence, thermally stimulated exoelectron emission, and total yield of particles via pressure measurements. The energy levels of defects were estimated from the thermally stimulated luminescence data of the annealed sample. Two types of electron-hole traps created by electronic excitation were identified: close pairs and distant ones. Additional confirmation of the “excited state” mechanism of defect formation was obtained. Analysis of the correlation of yields and the effect of thermal treatment gave additional arguments in support of the crowdion model of anomalous low-temperature post-desorption from pre-irradiated Kr matrices.

Formulation of Polymeric Microparticles Using Eco-Friendly Extracted Crude Fucoidans from Edible Brown Seaweed Undaria pinnatifida.

Several bioactive compounds that hold a potential interest in the food industry as phenolic compounds, polysaccharides, proteins and vitamins, among others, are present in seaweeds. Green extraction technologies are the preferred way to obtain these compounds. Pressurized hot water extraction, from 160 to 220 °C, was tested to achieve high yields of these components from the edible brown seaweed, Undaria pinnatifida. The maximum fucoidan content was recovered at 160 °C, while the phloroglucinol content and antioxidant activity were maximum at 220 °C. The possibility of encapsulating these bioactive fractions using mannitol was assessed. The highest production yield of the polymeric particles was found using the 220 °C fraction (close to 75%). In order to formulate microparticles with bioactive potential, several ratios of liquid phases were assessed, 3:1, 1:1 and 1:3 (w:w), using the liquid fractions obtained at 160 °C and 220 °C. The yield production was always above 67%, being in the 1:3 ratio (160 °C:220 °C) and close to 75%. The rheological results indicated that the presence of microparticles enhanced the apparent viscosity of the aqueous dispersions with non-Newtonian profiles, achieving the highest viscosity for those formulated with microparticles from 160 °C:200 °C (3:1).

Constraining the {overline{textrm{K}}}{textrm{N}} coupled channel dynamics using femtoscopic correlations at the LHC

The interaction of textrm{K}^{-}with protons is characterised by the presence of several coupled channels, systems like {overline{textrm{K}}}^0n and uppi Sigma with a similar mass and the same quantum numbers as the textrm{K}^{-}p state. The strengths of these couplings to the textrm{K}^{-}p system are of crucial importance for the understanding of the nature of the Lambda (1405) resonance and of the attractive textrm{K}^{-}p strong interaction. In this article, we present measurements of the textrm{K}^{-}p correlation functions in relative momentum space obtained in pp collisions at sqrt{s}~=~13 Te, in p–Pb collisions at sqrt{s_{textrm{NN}}}~=~5.02 Te, and (semi)peripheral Pb–Pb collisions at sqrt{s_{textrm{NN}}}~=~5.02 Te. The emitting source size, composed of a core radius anchored to the textrm{K}^{+}p correlation and of a resonance halo specific to each particle pair, varies between 1 and 2 fm in these collision systems. The strength and the effects of the {overline{textrm{K}}}^0n and uppi Sigma inelastic channels on the measured textrm{K}^{-}p correlation function are investigated in the different colliding systems by comparing the data with state-of-the-art models of chiral potentials. A novel approach to determine the conversion weights omega , necessary to quantify the amount of produced inelastic channels in the correlation function, is presented. In this method, particle yields are estimated from thermal model predictions, and their kinematic distribution from blast-wave fits to measured data. The comparison of chiral potentials to the measured textrm{K}^{-}p interaction indicates that, while the uppi Sigma –textrm{K}^{-}p dynamics is well reproduced by the model, the coupling to the {overline{textrm{K}}}^0n channel in the model is currently underestimated.

Green synthesis of silver nanoparticles using hydroalcoholic root extract of Potentilla fulgens and evaluation of its cutaneous wound healing potential

The present study focuses on the green synthesis of silver nanoparticles (AgNPs) using hydro-alcoholic root extract of Potentilla fulgens and evaluation of its wound healing properties in the rat model. The dried roots of PF were refluxed in alcohol: water mixture (70:30) for 24 h and the extract were evaporated to dryness using a rotary evaporator. For the synthesis of AgNP-PF, different concentrations of the extract (1–5 mg) were allowed to react with different concentrations of silver nitrate (1–5 mM). The completion of the reaction was noted through color change from colorless to brown and this can be further confirmed using UV–visible spectroscopy. The optimized formulation was further characterized using DLS, TEM, EDX, FTIR, and XRD. The biosynthesized AgNP-PF were loaded into a topical carbopol gel and finally investigated for wound healing potential in experimental rats. Results revealed that the ratio of different concentrations of AgNO3 to plant extract significantly affected the particle size, shape, yield and stability of the AgNP-PF. A UV–visible absorption band of 410–440 nm indicated the synthesis of AgNP-PF. TEM data with a size range of 10–20 nm showed that the AgNP-PF were spherical in shape. FTIR revealed the presence of -OH group responsible for the reduction and stabilization, while XRD confirmed the crystallinity of the AgNP-PF. Topical AgNP-PF gel showed promising wound healing property with significant wound contraction in experimental rats. In conclusion, stable silver nanoparticles were successfully formulated by green synthesis and loaded efficiently for efficient wound healing.

Comparative study of size exclusion chromatography for isolation of small extracellular vesicle from cell-conditioned media, plasma, urine, and saliva

Introduction: Extracellular vesicles (EVs) are secreted from all types of cells and are involved in the trafficking of proteins, metabolites, and genetic material from cell to cell. According to their biogenesis and physical properties, EVs are often classified as small EVs (including exosomes) or large EVs, and large oncosomes. A variety of methods are used for isolated EVs; however, they have several limitations, including vesicle deformation, reduced particle yield, and co-isolate protein contaminants. Here we present an optimized fast and low-cost methodology to isolate small EVs (30–150 nm) from biological fluids comparing two SEC stationary phases, G200/120 and G200/140 columns.Methods: The optimization parameters considered were a) the selection of the stationary phase, b) the eluate volume per fraction, and c) the selection of the enriched 30–150 nm EVs-fractions. The efficiency and separation profile of each UF/SEC fraction was evaluated by Nanoparticle tracking analysis (NTA), flow cytometry, total protein quantification, and Western blot.Results: Both columns can isolate predominantly small EVs with low protein contaminants from plasma, urine, saliva, and HEK293-derived EV from collection medium. Column G200/ 40 offers a more homogeneous enrichment of vesicles between 30 and 150 nm than G200/120 [76.1 ± 4.4% with an average size of 85.9 ± 3.6 nm (Mode: 72.8 nm)] in the EV collection medium. The enrichment, estimated as the vesicle-to-protein ratio, was 1.3 × 1010 particles/mg protein for G200/40, obtaining a more significant EVs enrichment compared to G200/120. The optimized method delivers 0.8 ml of an EVs-enriched-outcome, taking only 30 min per sample. Using plasma, the enrichment of small EVs from the optimized method was 70.5 ± 0.18%, with an average size of 119.4 ± 6.9 nm (Mode: 120.3 nm), and the enrichment of the vesicle isolation was 4.8 × 1011 particles/mg protein. The average size of urine and saliva -EVs samples was 147.5 ± 3.4 and 111.9 ± 2.5 nm, respectively. All the small EVs isolated from the samples exhibit the characteristic cup-shaped morphology observed by Transmission electron microscopy (TEM).Discussion: This study suggests that the combination of methods is a robust, fast, and improved strategy for isolating small EVs.

Towards dry fractionation of soybean meal into protein and dietary fiber concentrates

Tribo-electrostatic separation of hexane-defatted soybean flour was studied to produce protein- and fiber-rich fractions. The separation was carried out under laminar and turbulent airflow rates and plate voltages ranging from ±1 to ±6.5 kV. The combination of laminar airflow rate and high plate voltage resulted in the highest yield of protein and fiber particles with modest enrichment levels. Accordingly, the soybean flour was enriched in protein from 55.3 to 58.4% and fiber from 15.4 to 19.6%, accounting for 44.4 and 16.8% protein and fiber separation efficiencies, respectively. The distribution of protein and fiber along the negatively charged electrode showed no significant difference in terms of enrichment level. Still, more protein and fiber particles accumulated at the bottom of the electrode, according to the yield results. At 7 LPM and ±6.5 kV, a direct relationship was found between protein content and the average particle size of the fractions. In contrast, a reverse relationship was found for the fiber content. • Soybean meal flour was fractionated via dry tribo-electrostatic separation. • The impact of voltage and flow rate on protein and fiber enrichment was investigated. • Laminar airflow and high voltage resulted in modest protein and fiber enrichments. • Protein and particle size of the fractions were directly correlated at laminar flow. • The protein and fiber were uniformly enriched along the negative electrode.

Influence of Radiation Environment Variability on Cumulative Heavy-Ion-Induced Leakage Current in SiC Power Devices

Silicon carbide power devices may exhibit step increases in leakage current when exposed to heavy ions while biased in the off state. Estimating the magnitude of this phenomenon over time in the variable solar energetic particle environment represents a challenge, as the probability of occurrence and step sizes are widely variable. The Prediction of Solar particle Yields for Characterizing Integrating Circuits code is used to generate potential environmental flux spectra. Using an existing method, leakage current increases during broad-beam irradiation are characterized by frequency and magnitude. In this paper, these characterizations are applied to various environmental flux spectra to generate a range of cumulative leakage current increases. This process is repeated to produce distributions of leakage current increases that account for environmental variability and step size variability. Comparing the results for various operating voltages, mission durations, and shielding, it is shown that shielding thickness and operating voltage have a significant influence on the potential cumulative leakage current increase.