Complex Formulation Research Articles

Topical prebiotics/postbiotics and PRURISCORE validation in atopic dermatitis. International study of 396 patients

Aim: To investigate the efficacy and tolerability of a cream (Rilastil Xerolact PB) containing a mixture of prebiotics and postbiotics, and to validate the PRURISCORE itch scale in the management of atopic dermatitis.Methods: The study is based on 396 subjects of both sexes in three age groups (i.e., infants, children, adults) suffering from mild/moderate Atopic Dermatitis, recruited from 8 European countries and followed for 3 months.Results: The product demonstrated good efficacy combined with good/very good tolerability in all age groups. In particular, SCORAD, PRURISCORE and IGA scores decreased significantly over the course of the study. The PRURISCORE was preferred to VAS by the vast majority of patients.Conclusion: Even though the role of prebiotics and postbiotics was not formally demonstrated since these substances were part of a complex formulation, it can be reasonably stated that prebiotics and postbiotics have safety and standardization features that probiotics do not have. In addition they are authorized by regulatory authorities, whereas topical probiotics are not.

Low‐Temperature Plasma Sintering of Inkjet‐Printed Metal Salt Decomposition Inks on Flexible Substrates

Due to their complex formulation, conductive nanoparticle inks for inkjet printing are limited in terms of the types of metals and substrates that can be utilized. A new and simplified class of inks called metal salt decomposition (MSD) inks has the potential to introduce a multitude of metals, which can be printed directly onto a wide range of substrates. Here, the use of atmospheric oxygen plasma to develop polycrystalline Au and Pt films at processing temperatures near room temperature (≈33 °C) with excellent conductivities up to 105 S m−1 is demonstrated. The conformal nature of the ink allows metal films to be printed onto a broad range of temperature‐sensitive substrates including polymers, papers, and fabric. The Au ink is then used to build a simple light‐emitting diode circuit showing its flexibility, durability, and long‐term stability as deposited thin metal films. Additionally, such inks cost less than one‐third the price of similar nanoparticle inks highlighting their overall affordability and good stability.

Optimisation of an agar overlay assay for the assessment of the antimicrobial activity of topically applied semi-solid antiseptic products including honey-based formulations

The aim of this study was to optimise the so-called agar overlay assay to investigate the antimicrobial activity of some currently available topical antimicrobial products against a range of Gram positive and Gram negative bacteria. During the optimisation process, various assay parameters including base agar volume, overlay agar volume, overlay agar concentration, placement of products into wells or onto coverslip and inoculum concentration were taken into consideration. The optimised assay was found to be a convenient, suitable and effective platform for the assessment of the antimicrobial activity of commercial semi-solid over-the-counter (OTC) products (i.e. non-prescription medicines for topical application used commonly without supervision by a healthcare professional) containing a range of active pharmaceutical ingredients and to be potentially also applicable to complex natural product-based formulations (e.g. honey-based formulation, melaleuca oil-based formulation). The most auspicious aspect of the optimised method was its capability of determining the antimicrobial activity of intact products without further manipulation, unlike other tests that require products to be dissolved or dilute, thus compromising their integrity.

Evaluation of rheology and printability of 3D printing nutritious food with complex formulations

Understanding rheological properties and printability of complex food formulations is crucial for 3D printing. While nutritious formulations have been reported in the literature, these are still scarce when compared to the non-nutritious ones. These so-labeled nutritious formulations are achieved with few ingredients, leading to less challenging printability issues. The nutritious formulations presented here are reported for the first time and include up to 9 ingredients, including by-products (orange peel) and sustainable proteins (insect flour). This work aimed to evaluate and to correlate the printability and the rheological properties of nutritious complex food formulations. The concentration of pregelatinized corn starch (4–10% (w/w)) and printing temperature (27–47 °C) were varied. Rheological characterization of the studied food inks (i.e., amplitude sweep, shear-viscosity test, shear-recovery test, time-dependent shear test, temperature ramps, temperature sweep in the oscillatory mode) was performed. Printability was evaluated via a digital image analysis of the geometric features of the printed structures. An increment in the concentration of pregelatinized starch (from 4% to 10%) raised the yield stress and the storage modulus from 87.5 to 883.2 Pa and from 1004.9 to 2620.9 Pa, respectively. However, high values of rheological parameters did not correspond to an improved printability. For instance, the printability evaluation showed that formulations with 6% and 8% of pregelatinized starch were more suitable for printing than the one with 10%. Finally, initial mathematical correlations between rheology and printability were obtained and could be of benefit to potentialize complex food printing systems. The results presented showed that both, rheology, and printability analyzes, must be performed when printing complex formulations towards the development of personalized food items. More research in this regard is needed to develop new methodologies for the evaluation of 3D printing materials.

The role of the drying method on fish oil entrapment in a fish muscle protein ̶ κ-carrageenan ̶ fish protein hydrolysate wall matrix and the properties of colloidal dispersions

In an attempt to produce a dry functional ingredient from marine origin, salt-soluble fish muscle protein (MP), κ-carrageenan (C) and a fish protein hydrolysate (H) were used as wall material for fish oil (FO) microencapsulation, which was performed comparing two drying methods (spray-drying and heat-drying). Dry powders were initially obtained from MP and C separately and from the mixture of both (CMP), without and with addition of fish hydrolysate (MP-H, C–H, CMP-H). Finally, fish oil was entrapped in the most complex formulation (CMP-HFO). Composite powders with relatively low water solubility (≈50%) were obtained with both drying methods. The drying method strongly influenced the drying yield, as well as the rheological flow properties of the rehydrated dispersions. The mixture of fish muscle protein and/or fish hydrolysate with κ-carrageenan led to the formation of protein-polysaccharide interactions, deduced from the ζ potential, rheological properties, and submicron particle size analyses, which varied depending on the wall composition and drying method. Fish oil strongly interfered with such interactions, leading to highly heterogeneous microparticles and particle aggregates, which were much smaller when spray-dried than when heat-dried (D 4,3 = 8.13 ± 7.41 and 263.9 ± 15.08 μm, respectively). Fish oil remained highly entrapped by both methods (≥84%) and led to stable colloidal dispersions, the heat-dried sample presenting lower water resistance, noticeable higher viscosity and lower extent of lipid oxidation. Traces of residual heavy metals in the dry powders could be a limiting factor when using these marine-origin preparations as functional ingredients, depending on the quantities employed. • Stronger protein-carrageenan interactions in heat-dried samples. • Fish oil strongly interfered protein-carrageenan interactions in both dry powders. • Heat-dried CMP-HFO had lower water resistance and higher viscosity after dispersion. • Spray-drying induced higher lipid oxidation compared with heat-drying. • Trace amounts of heavy metals in both dry powders.

Advanced Dome cellulose/alginate/chitosan composite matrix design with gastric and intestinal co-targeting capacities

Dome matrix was designed with gastric and intestinal targeting capacities using melatonin and caffeine as model drugs, and alginate, chitosan and cellulose as composite materials. The melatonin, caffeine and intermediate hydroxypropylmethylcelluose-based dispersible modules were prepared through compaction. Caffeine piled module was capped at both ends with melatonin void modules via intermediate dispersible modules into Dome matrix. Dispersion of intermediate module detached melatonin module from Dome matrix and had it floated in stomach providing a more complete melatonin release due to favorable pH-pKa relationship of dissolution medium and drug. With reference to the caffeine module, the detachment of melatonin module facilitated its gastrointestinal transit as a reduced size matrix, with majority of caffeine delivered in colon. The dual site-targeted and -release Dome matrix is applicable as reference oral carrier for pharmaceutical, nutraceutical, functional food and veterinary medicine where a complex formulation and performancein vivoare required.

Superhydrophobic surface immobilisation by insoluble surfactant

The effects of insoluble surfactants, satisfying a Langmuir equation of state, on transverse Stokes flow over a superhydrophobic surface of unidirectional grooves with flat menisci are examined. The phenomenon of surface immobilisation, whereby surfactants cause part or all of the Cassie-state menisci to become effectively no-slip zones thereby degrading the slip properties of the surface, is of primary interest. The study employs a combined analytical and numerical approach allowing an exploration of surfactant effects over the full range of surface Péclet numbers, Marangoni numbers and surfactant loads. For small surface Péclet and Marangoni numbers, perturbation theory is used to gain basic insights into the physical mechanisms at work. That analysis also provides checks on a robust numerical scheme, built around a complex variable formulation of the problem, used to compute solutions across a wide range of non-dimensional parameter values. Two distinct mechanisms are found to be responsible for surface immobilisation. In the first, most commonly seen at higher surface Péclet numbers, a stagnant cap forms because swept surfactant immobilises a section of the meniscus before any portion of the meniscus reaches maximum packing. Such a cap exists even for a linear equation of state and grows in length with increasing Marangoni number. A second immobilisation mechanism is associated with the nonlinear equation of state: an immobilised region forms because the surfactant concentration reaches its maximum value near the downstream edge of the meniscus. Immobilisation of the latter form can occur at much lower surface Péclet numbers, even if the Marangoni number is small, as long as there is sufficient surfactant in the system. The study enhances understanding of how insoluble surfactants can degrade slip over superhydrophobic surfaces.

Modeling and demand-based control of responsive building envelope with integrated thermal mass and active thermal insulations

The static nature of current envelope design and operation is diametric to the mutable and transient forces and energies acting on our building stocks. Responsive building envelopes (or RBEs) have shown substantial energy saving potential for buildings by adaptively providing passive cooling/heating. In this research, an easy-to-implement yet flexible ‘demand-based’ control rule is proposed based on demand analysis to optimally control RBEs that integrate active insulation systems (AISs) and a sensible thermal energy storage (TES) layer. The controller developed herein calculates the desired thermal resistance for AIS layers and provides on-demand control of the heat flow into and out of the thermal mass to reduce AC load. It provides several benefits over the simple temperature-based controllers while does not require the complex formulation as needed for model predictive control. To quantify the thermal behavior and energy performance, a thermal network model is developed for RBEs to perform wholebuilding energy simulations of a residential thermal zone in six representative cities in the US. The results show apparent benefits of demand-based control strategy over traditional temperature-based control by offering higher energy savings and LPD reduction, especially in mild climate zones and during transitional seasons. Some design and implementation considerations for REBs with integrated AISs and TES are also discussed.

Formulation and Comparison of Glucomannan Metallocomplexes Made of Cobalt and Copper

The broad category of pharmaceutical science in which drugs are complex with metals like platinum, zinc iron, etc is defined as Metallopharmaceutics. The earliest work on Metallopharmaceutics is around 700 BC. In this work, Glucomannan, which is a plant-based drug, is used as a ligand to prepare anti-diabetic metal complexes of Cobalt and copper. Glucomannan is basically a polymer thought up of -(14)-linked D-mannose and D-glucose in a straight chain in a ratio of 8:5. Various pre-formulation studies were performed including swelling index and angle of repose for the pure drug only. The pre-formulation parameters inferred that the pure drug has fair flow properties with a swelling index of 81.8%. Formulations were analyzed spectrophotometrically using ATR-IR and UV-spectroscopy. In UV spectroscopy, it was analyzed that Glucomannan showed a distinct peak at 267 nm. Formulation of metal complexes was performed using the solvent-assisted method. The dissolution studies and release kinetics were performed for prepared Formulations (F1-F9). The Formulation F9 proved to be the best formulation following the Higuchi Diffusion plot with maximum linearity of 0.997. Thus, 500 mg Glucomannan + 1000 mg Cobalt (F9) had the sustained drug release throughout the dissolution period.

P332 Evaluation of the efficacy of fumigation practices on the mycological flora in the Orthopedic Operation theatre environment of a tertiary care hospital

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesTo determine the pre and post-fumigation prevalence of fungi in the Orthopedic Operation Theatre of a tertiary care hospital and characterization of fungal isolates.MethodThis is a prospective environmental, analytical study conducted from July 2021 to January 2022. Pre- and post-fumigation samples were taken from Ultra and Modular OT of Orthopedic department every week by passive methods of air sampling using Gravity sedimentation method (1/1/1 scheme) on SDA and also by surface sampling using swabs. The fungal load of air was measured by calculating the number of CFU per cubic meter (CFU/m3) of air by Omeliansky formula. Fumigation of OT was done with a complex formulation of stabilized hydrogen peroxide 11% w/v with silver nitrate solution 0.01% (Baccishield®).All surface samples were inoculated on SDA with chloramphenicol and all plates were incubated at 22°C and 37°C. The isolates were identified by using standard mycological procedures. Statistical analysis was done using a T-test.ResultsOut of 19 surface sampling, fumigation was found to be 100% effective only on 3 occasions (15.79%) in Ultra OT and on 7 occasions (36.84%) in Modular OT. In air sampling ≥50% reduction was found in only 4 samplings (21.05%) in Ultra OT and 10 samplings (52.63%) in Modular OT. The counts were much more than the WHO OT permissible limits. A total of 16 species of fungi were isolated belonging to 11 genera.The most common isolate was Aspergillus niger, followed by sterile hyalohyphomycetes, A. flavus, Cladosporium spp., Curvularia spp., Bipolaris spicifera, A. fumigatus, etc. in both Ultra and Modular OT.Additionally, Exophiala spp. and Fonsecaea spp. were isolated in Ultra OT.The concentrations of fungi in Ultra OT before and after fumigation were in the range 22.11-58.97 CFU/m3 and 7.37-51.59 CFU/m3, respectively. Whereas, in Modular OT, the range was 14.74-36.86 CFU/m3 and 7.37-29.48 CFU/m3, respectively. Percentage reduction of fungi following fumigation with Baccishield varied from 0% to 75% both in Ultra OT and Modular OT. The statistically correlated P-value from pre- and post-fungal concentrations in Ultra and Modular OT were found to be .002 and .0002 respectively which was found significant by T-test, albeit ineffective as per standards.ConclusionIn corroboration with our findings, Baccishield has been reported to be less effective even by other researchers. Hence, this needs to be replaced by more effective fumigants. The ineffectiveness of fumigation in Ultra OT was most probably due to the lack of HEPA filters and not strictly following up of aseptic protocols. In Modular OT improper maintenance of ACs and lack of periodic cleaning up of HEPA filters may be contributing factors.Hence, implementing more stringent, frequent, and comprehensive disinfection and cleaning procedures, educating and motivating the health care personnel can help to improve the air quality of OTs that may aid in reducing post-operative infections.

ENCAPSULATION OF EXEMESTANE WITH β-CYCLODEXTRIN AND TERNARY AGENT: FORMULATION, EVALUATION AND ANTICANCER ACTIVITY

Objective: A potent aromatase inhibitor, Exemestane, is well known for its anticancer action in breast neoplasm. The vital problem of this medicament is its poor aqueous solubility, which hinders its dissolution in body fluids. Therefore, the present study targets to enhance the water solubility of Exemestane by means of its complexation with β-cyclodextrin and a suitable ternary agent. Methods: Inclusion complexes of Exemestane with β-cyclodextrin and ternary agent were prepared by kneading and lyophilization technique. Different hydrophilic polymers and organic acids were screened for their influential ability as a co-complex with a carrier; β-cyclodextrin. The validation of complex formation was carried out by various solid-state techniques. The geometry of Exemestane in the β-cyclodextrin cavity was picturized in docking studies. The in vitro anticancer activity of prepared inclusion complex formulations carried out using MCF-7 cell lines Results: Phase solubility analysis proved HPMC E5 as the best ternary agent for complexation of Exemestane with β-cyclodextrin as it improved the stability constant of the drug from 665.92 M-1 to 1238.38 M-1. The synthesized binary and ternary inclusion complexes exhibited 2.74 and 4.62 times enhanced solubilization of Exemestane. Likewise, the dissolution characteristics of Exemestane were improved, and drug release was increased by 1.18 and 1.42 times with binary and ternary freeze-dried formulations. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) study results presented the formation of binary and ternary complexes with significantly drooped crystallinity. Docking studies predicted encapsulation of rings A, B, and C of Exemestane in the cavity of β-cyclodextrin. In-line results were obtained in Fourier transform infrared (FTIR) studies. The cell growth inhibition of 62.78 % was achieved with a ternary complex of Exemestane which was far superior than the pure active moiety that showed mere 44.56 % of inhibition. Conclusion: Altogether, it can be concluded that the inclusion complex of Exemestane boosted its aqueous solubility, resulting in its increased dissolution and in vitro anticancer activity in a breast cancer MCF-7 cell line.

Effect of multivitamin drug on intractable dry eye symptoms.

Dry eye is a disorder of tear film and ocular surface characterized by ocular discomforts. It is associated with multiple causes and sometimes intractable. We investigated the effect of oral multivitamin supplementation (MVG) on dry eyes. Tear break-up time (TBUT), fluorescein ocular surface staining score, and tear secretion Schirmer test were measured in dry eye patients refractory to conventional topical treatment. The ocular surface disease index (OSDI), visual analog pain score (VAS), and modified standardized patient evaluation of eye dryness questionnaire were analyzed. In total, 42 eyes of 42 patients were included. TBUT increased at 1 and 3 months compared to baseline (p < 0.05). OSDI decreased at 1 and 3 months compared to baseline (p < 0.05). VAS score, impact on life, and frequency of total symptoms decreased at 3 months compared to baseline (p < 0.05). Oral administration of MVG, a vitamin complex formulation, was effective in stabilizing tear stability and alleviating symptoms in patients with intractable dry eye. Thus, it may be a viable treatment option for intractable dry eye.

Effects of xanthan gum and sodium alginate on gelatinization and gels structure of debranched pea starch by pullulanase

This study evaluated the impacts of xanthan gum (XG), sodium alginate (SA), and XG-SA complex formulations on the pasting, rheology, structural properties, amylose content, and in vitro digestibility of debranched pea starch (DBPS) treated with pullulanase. The amylose content of DBPS increased from 34.24% to 49.35%. The resistant starch (RS) increased from 35.12% to 38.90%. Further, the addition of polysaccharides increased the viscosity of DBPS, and the fluidity of the DBPS gels was enhanced. The amylose content and relative crystallinity (RC) of the XG-added samples decreased. In contrast, the RC of SA and XG-SA samples increased from 38.34% to 40.97%–40.48% and 47.64%, respectively. Additionally, XG, SA, and XG-SA increased the RS content, and the highest RS content (52.65%) was noted for 1% SA. This study provides a theoretical basis and new insights about DBPS and polysaccharide applications in food and materials. • Xanthan gum (XG), sodium alginate (SA) and XG-SA increased the viscosity of DBPS. • XG and SA enhanced the gel fluidity and water holding capacity of DBPS. • The resistant starch content increased in the presence of XG and SA. • XG and SA improved the gelation properties of DBPS in different ways.

Safety and Efficiency in Robotics: The Control Barrier Functions Approach

This article aims at presenting an introductory overview of the theoretical framework of control barrier functions (CBFs) and of their application to the design of safety-related controllers for robotic systems. The article starts by describing the basic concepts of CBFs and how they can be used to build optimization problems embedding CBF-based constraints, whose solutions correspond to the control input enforcing the desired safety properties into the behavior of the controlled system. Simple examples, understandable for readers with a basic background in control theory and accompanied with source code for their simulation, are used to highlight the appealing features of the CBF-based approach. Then, more complex formulations applicable to robotic manipulators are introduced, recalling recent literature results allowing users to implement a robust design methodology. Finally, it is shown that CBFs are suitable for the implementation of safe human–robot collaboration in a realistic industrial scenario by means of the experimental validation in an industrial setup for collaborative robotics.

3,4,5-Trimethoxychalcones Tubulin Inhibitors with a Stable Colchicine Binding Site as Potential Anticancer Agents

The development of microtubule perturbing drugs is one of the most promising anticancer therapeutic methods. Unfortunately, limitation such as drug resistance, adverse side effects, complex formulations and synthesis, and limited bioavailability of these microtubule perturbing drugs has aroused the search for a new molecule of the tubulin system. Different substituents of chalcone were designed, synthesized, and determined for inhibition of tubulin assembly and toxicity in human cancer cell lines based on conventional colchicine site ligands and a computer model of the colchicine binding site on tubulin. A molecular docking study indicated that the chalcone scaffold could fit the colchicine site on tubulin in a similar orientation to the natural product. The 3,4,5-trimethoxyphenyl ring, which occupies the same sub-cavity as the equivalent molecule in colchicine, appeared to benefit the ligand of α,β-tubulin interaction. Several 3,4,5-trimethoxychalcone compounds demonstrated improved cytotoxicity against MCF-7 cells and inhibited tubulin assembly in vitro as potently as colchicine. The most active chalcone 1 with the IC50 of 6.18 ± 0.69 μM prevented the proliferation of human cell lines at micromolar concentrations, causing microtubule destabilization and mitotic arrest in humans inhibiting breast cancer cells.

The Ogden and the extended tube model as backbone in describing electroactive polymers: advancements in modelling nonlinear behaviour and fracture.

Hyperelastic constitutive relations form the basis of advanced models for novel materials. Such elastic deformation potentials are the backbone for complex material formulations at elastic and inelastic deformations, especially when embedded into powerful frameworks like generalized standard materials, as well as multiphysical and multiscale formulations. With the focus on electroactive polymers, the article at hand demonstrates the derivation of a variational, rate-dependent electromechanical model for quasi-incompressible polymers and the derivation of an electromechanical model for regularized fracture mechanics by means of the phase-field method. Starting at the prominent Ogden and the extended tube model, some developments from the last decades are revisited and presented via the principle of virtual power, for instance, the established mixed element formulation, nonlinear viscoelasticity and electromechanical coupling. An electromechanically fully coupled representative crack element is used to derive a novel phase-field model for fracture. A key property of the proposed model is the ability to describe the electrical free-space behaviour inside the crack gap, which is demonstrated by adopting three common crack-face conditions. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'.

Translating the Manufacture of Immunotherapeutic PLGA Nanoparticles from Lab to Industrial Scale: Process Transfer and In Vitro Testing.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug delivery systems are known to offer a plethora of potential therapeutic benefits. However, challenges related to large-scale manufacturing, such as the difficulty of reproducing complex formulations and high manufacturing costs, hinder their clinical and commercial development. In this context, a reliable manufacturing technique suitable for the scale-up production of nanoformulations without altering efficacy and safety profiles is highly needed. In this paper, we develop an inline sonication process and adapt it to the industrial scale production of immunomodulating PLGA nanovaccines developed using a batch sonication method at the laboratory scale. The investigated formulations contain three distinct synthetic peptides derived from the carcinogenic antigen New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) together with an invariant natural killer T-cell (iNKT) activator, threitolceramide-6 (IMM60). Process parameters were optimized to obtain polymeric nanovaccine formulations with a mean diameter of 150 ± 50 nm and a polydispersity index <0.2. Formulation characteristics, including encapsulation efficiencies, release profiles and in vitro functional and toxicological profiles, are assessed and statistically compared for each formulation. Overall, scale-up formulations obtained by inline sonication method could replicate the colloidal and functional properties of the nanovaccines developed using batch sonication at the laboratory scale. Both types of formulations induced specific T-cell and iNKT cell responses in vitro without any toxicity, highlighting the suitability of the inline sonication method for the continuous scale-up of nanomedicine formulations in terms of efficacy and safety.

Analysis and Modeling of Sunscreen Ingredients’ Behavior in an Aquatic Environment

Sunscreens have become a product based on increasingly complex formulations that include, among many ingredients, a mixture of UV filters to provide optimal sun ultraviolet radiation protection. A significant group of scientific works deals with the impact of UV filters in aquatic media. However, the knowledge of the mechanism and kinetics of the compound’s direct release, fate, and its transformation and interaction with living organisms is necessary to assess its environmental occurrence and behavior and to predict potential and real impacts on the aquatic environment. This review outlines the existing analysis and modeling of the release and behavior of sunscreen’s ingredients in the marine environment, including aquatic organisms. The physical-chemical properties, photodegradation, and release kinetics of particles and chemicals into the water are studied by hydrodynamic and kinetic models. Direct photolysis of chemicals is modeled as pseudo-first-order kinetics, while the indirect pathway by the reaction of sunscreen with reactive oxygen species is described as second-order kinetics. The interaction of UV filters with marine biota is studied mainly by toxicokinetic models, which predict their bio-accumulation in the organisms’ tissues. These models consider the chemicals’ uptake and excretion, as well as their transfer between different internal animal organs, as a first-order kinetic process. The studies analyzed in the present work represent a driver of change for the beauty and personal care industry, in order to seek new ecological alternatives through the application of R&amp;D tactics.

Ultra-/Small Angle X-ray Scattering (USAXS/SAXS) and Static Light Scattering (SLS) Modeling as a Tool to Determine Structural Changes and Effect on Growth in S. epidermidis.

Usually, to characterize bacterial cells' susceptibility to antimicrobials, basic microbiology techniques such as serial dilutions or disk assays are used. In this work, we present an approach focused on combining static light scattering (SLS) and ultra-/small angle X-ray scattering (USAXS/SAXS). This approach was used to support microbiology techniques, with the aim of understanding the structural changes caused to bacteria when they are exposed to different stresses like pH, oxidation, and surfactants. Using USAXS/SAXS and SLS data, we developed a detailed multiscale model for a Gram-positive bacterium, S. epidermidis, and we extracted information regarding changes in the overall size and cell thickness induced by different stresses (i.e., pH and hydrogen peroxide). Increasing the concentration of hydrogen peroxide leads to a progressive reduction in cell wall thickness. Moreover, the concomitant use of pH and hydrogen peroxide provides evidence for a synergy in inhibiting the S. epidermidis growth. These promising results will be used as a starting base to further investigate more complex formulations and improve/refine the data modeling of bacteria in the small angle scattering regime.

A Novel Berberine–Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats

Developing a new drug delivery system is one of the useful approaches to overcome the limited use of berberine (BBR) to enhance its absorption and bioavailability. We prepared a novel berberine–glycyrrhizic acid (BBR–GL) complex formulation to increase the plasma concentration and bioavailability of BBR by improving BBR solubility and lowering the absorption barrier. The complex formulation with BBR and GL in the ratio 1:1 was developed through the self-assembly process and evaluated in vitro. Compared with BBR and BBR/GL physical mixture, the BBR–GL complex showed different characteristics by SEM, DSC, FT-IR, and PXRD measurement. In pharmacokinetic evaluation, the BBR–GL complex significantly increased the plasma concentration of BBR and the major metabolite berberrubine (BBB), with the AUC of BBR elevated to 4.43-folds, while the complex was safe as BBR. Furthermore, doxorubicin (DOX) was used to induce cardiotoxicity. Hematological study, histopathological examinations, electrocardiography (ECG), cardiac secretion measurement, and biochemical index analysis proved that the model of doxorubicin-induced cardiotoxicity (DIC) was conducted successfully. With the AUC of BBR increasing in the BBR–GL complex and the absorbed complex itself, the BBR–GL complex enhanced prevention effect to DIC and exhibited a significant prevention effect to attenuate heart damage. Our findings demonstrated that a novel BBR-loaded BBR–GL complex formulation could increase BBR plasma concentration. Improvement of BBR bioavailability by the BBR–GL complex could coordinate with GL to attenuate DIC. Concerning the safety of the drug delivery system at present, the BBR–GL complex could be a potential therapeutic formulation for the prevention of cardiac damage in the clinical application of doxorubicin.