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Nanoencapsulation of antioxidant peptides from Lupinus mutabilis in chitosan nanoparticles obtained by ionic gelling and spray freeze drying intended for colonic delivery

Arturo Intiquilla, Karim Jiménez-Aliaga, Amparo Iris Zavaleta, Alexander Gamboa, Nelson Caro, Mario Diaz, Martin Gotteland, Lilian Abugoch, Cristian Tapia

Abstract

Oxidative stress has long been associated with the pathogenesis of inflammatory bowel disease (IBD), and it has been suggested that the combined administration of antioxidants and anti-inflammatory agents may be helpful for its treatment. Biopeptides from plant proteins, such as soybean glycinin tripeptide VPY, effectively inhibit pro-inflammatory mediators in intestinal epithelial and immune cells, which are both involved in the pathogenesis of IBD. This study aimed to produce antioxidant biopeptides from proteins of Lupinus mutabilis seeds and then encapsulate them in chitosan nanoparticles (NPs) for colonic delivery. An antioxidant peptide fraction of less than three kDa (UF3) was obtained and added at different concentrations (0.1–0.4 mg/ml) in chitosan solutions. The NPs were prepared by gelation with tripolyphosphate (CTPP-UF3) or spray freeze-drying of the chitosan solution (SFDC-UF3). Sizes of 332 ± 13 and 465 ± 58 nm and maximum encapsulation efficiencies of 63.80 and 71.75%, respectively, were obtained. UF3 maintained its antioxidant capacity (>80%) and showed different release profiles in 1X PBS buffer at pH 7.4, depending on the encapsulation method. FT-IR showed hydrogen bonding and electrostatic interactions between the peptide and chitosan. Both nanosystems maintained cell viability greater than 70% in colonic cell lines HT-29. These results show that both methods are appropriate for the nanoencapsulation of UF3 and can be used to design nanoparticles for colonic delivery.

Keywords

Antioxidant, Peptidic fraction, Lupinus mutabilis, chitosan nanoparticles

Whey protein hydrolysates as prebiotic and protective agent regulate growth and survival of Lactobacillus rhamnosus CICC22152 during spray/freeze-drying, storage and gastrointestinal digestion

Hexiang Xie, Yang Liao, Meng Wai Woo, Hua Xiong, Qiang Zhao

Abstract

BACKGROUND
Probiotic products are receiving increasing attention because of their tremendous beneficial health effects. However, it is still a great challenge to preserve probiotic viability during processing, storage and gastrointestinal digestion. Encapsulation is a widely known technology for enhancing bacterial viability and product stability. Hence highly hydrolyzed whey protein hydrolysate (HWPH) and moderately hydrolyzed whey protein hydrolysate (MWPH) used as a one-step culture medium and wall material for Lactobacillus rhamnosus were investigated.

RESULTS
H/MWPH-substitutive medium for the growth of Lactobacillus rhamnosus presented double the biomass production compared to other media. The H/MWPH-substitutive medium in combination with freeze drying also led to the highest survival ratio (97.13 ± 9.16%) and cell viability (10.62 log CFU g⁻¹). The highest survival rate of spray-dried cells was 85.56 ± 7.4%. In addition, the cell viability of spray-dried Lactobacillus rhamnosus with MWPH as culture and dry medium was 0.79 log CFU g⁻¹ higher than that of HWPH. Images confirmed that spray-dried Lactobacillus rhamnosus in MWPH provided better protection and it showed greater sustained viability after gastrointestinal digestion.

CONCLUSION
Overall, WPH just as carrier provides better thermal protection and MWPH is a preferable two-in-one medium for probiotics. © 2022 Society of Chemical Industry.

Grain size analysis and characterization by Raman spectroscopy of a homogeneous sintered MOX fuel

Marion Le Guellec, Florent Lebreton, Laure Ramond, Philippe Martin, Abibatou Ndiaye, Thierry Gervais, Guillaume Bernard-Granger

Abstract

The grain size distribution of an U_0.89Pu_0.11O₂ MOX fuel, sintered from a freeze-granulated powder to 97% of the theoretical density at 1700 °C during 4 h, for an oxygen potential set to − 387 kJ/mol, was investigated. The sintered microstructure is constituted by 8.5 vol% of clusters of small grains, having an average grain size around 1.5 µm, dispersed in a polycristalline matrix made of larger grains having an average grain size around 7–8 µm. Characterizations by Raman micro-spectroscopy showed that the Pu/(U+Pu) content was not the same depending on the type of grain. The large grains constituting the sintered polycrystalline matrix have a Pu/(U+Pu) content in the range 9.0–11.0 mol%, which is close to the overall target. The small grains agglutinated in the form of clusters are however clearly depleted in Pu.

Keywords

Microstructure, Grain size, Raman spectroscopy, MOX

Spray-freeze-dried lyospheres: Solid content and the impact on flowability and mechanical stability

Annika Rautenberg, Alf Lamprecht

Abstract

Handling low-density pharmaceutical products, such as lyophilisates, presents a challenge. Spray-freeze-dried (SFD) particles, overcoming many of these challenges, were analysed regarding flowability, mechanical stability, product properties (morphology, particle size) and physicochemical properties of the spraying solution (density, viscosity, freezing point, glass transition). Mannitol-polyvinylpyrrolidone 25 (PVP 25) solutions in concentrations ranging from 2.5 to 20% (w/w) were spray-freeze-dried with three different nozzle-diameters (25, 50, 100 μm). Results show it is not only possible to spray SFD solutions with various physicochemical properties (viscosity ≤3.07 ± 0.04 mPa·s, freezing point depravation ≤1.867 ± 0.058 °C) to produce a free-flowable powder but also the possibility to regulate median particle size via nozzle diameter and solid content of the solution (147–458 μm). All formulations containing at least 0.1 g/ml solid content exhibit a flowability comparable to commercially available excipients products with ten times higher densities, a good or passable flowability (angle of repose ≤40°) and no significant decrease in median particle size after mechanical stability testing (p ≥ 0.05), which can both be attributed to their high average sphericity (> 0.90). This shows that SFD is a suitable method to produce freeze-dried flowable products that maintain their mechanical stability.

Keywords

Spray-freeze-drying, Lyospheres, Low-density powder

Characterization by electron probe microanalysis, Raman spectroscopy and transmission electron microscopy of a MOX fuel sintered from a freeze-granulated powder

Julie Simeon, Florent Lebreton, Laure Ramond, Philippe Martin, Doris Drouan, Catherine Sabathier, Guillaume Bernard-Granger

Abstract

The microstructure of a 98.7 % dense U_0.856Pu_0.144O_1.993 sintered sample (average grain size around 1.5 µm) has been characterized by electron probe microanalysis, Raman spectroscopy and transmission electron microscopy. Raman spectroscopy gives results comparable to electron probe microanalysis in terms of studying the spatial distribution of plutonium in a homogeneous sintered MOX fuel. The use of transmission electron microscopy allows additional characterizations of great interest for investigating the chemical homogeneity of sintered MOX fuels. At the scale of the elementary grains constituting the sintered polycrystal, a variation in the Pu/(U+Pu) content has been observed which can change typically from 0 to about 40 at% over a short distance (from 100 to 150 nm). Thereby, the thorough characterization of the microstructure of MOX fuels by transmission electron microscopy is a critical step to understand their genesis and to apprehend their dissolution properties with a view to their reprocessing.

Keywords

Microstructure, EPMA, Raman spectroscopy, TEM, Oxides, MOX

Selectivity of Ru-rich Ru-Ti-O oxide surfaces in parallel oxygen and chlorine evolution reactions

Kateřina Minhová Macounová, Rebecca Katharina Pittkowski, Roman Nebel, Andrea Zitolo, Petr Krtil

Abstract

The electrocatalytic behaviour of single-phase Ru_1-xTi_xO₂ materials was studied to outline general trends controlling the selectivity of oxide-based anodes in parallel oxygen evolution and chlorine evolution reactions. Materials with x ranging between 0 and 0.2 were prepared by spray freeze freeze drying approach. Prepared materials show a non-homogeneous distribution of Ti in the structure with dominant clustering of the Ti along the (001) direction. For materials with x higher than 0.1 the dominant linear clustering of Ti along the z-axis changes, including Ti clustering also along (111) direction. Prepared materials are active in both oxygen evolution and chlorine evolution reactions. The Ti has a pronounced effect on the selectivity of the prepared materials. Ti presence affects the selectivity of the prepared materials in a complex manner. Materials featuring a low Ti content (x∼0.05) retain a preference for oxygen evolution reaction even in presence of chlorides and are more selective for oxygen evolution than pure RuO₂. The selectivity towards chlorine evolution increases with increasing Ti content and, apparently, also with clustering of Ti along the (111) direction. The selectivity towards chlorine evolution may be related to the tendency of the prepared catalysts to evolve the oxygen via lattice oxygen evolution reaction (LOER) reflecting the ability of the catalyst surface to form active sites under operando conditions.

Keywords

Ru-Ti-O oxides, oxygen evolution, chlorine evolution, selectivity, local structure

Effects of drying methods on physical properties and morphology of trehalose/mannitol mixtures

Daniel Tristan Osanlóo, Jonas Fransson, Björn Bergenståhl, Anna Millqvist-Fureby

Abstract

Solid-state properties of dried protein formulations are important for stability and functionality of the product. This study investigates how different drying technologies (freeze-drying with and without annealing, spray drying and spray-freeze drying) affect the structure and solid-state properties of a set of matrix formulations composed of trehalose (glass former) and mannitol (scaffolding agent) in five ratios. The dried materials were characterized using differential scanning calorimetry, thermogravimetric analysis, x-ray diffraction and scanning electron microscopy. The morphology of the dried matrix is determined by the drying technology and the composition. In all mixtures, mannitol partially dissolved in the amorphous trehalose, resulting in reduced glass transition temperature. At least 50% mannitol is required to achieve a scaffolding effect through crystallized mannitol. At 25% mannitol poor structural stability is obtained regardless of drying technology. Despite the vast differences in drying kinetics, all drying technologies resulted in similar amorphous content in the dried material.

Keywords

Freeze-drying, spray-freeze drying, spray drying, scaffolding, morphology, solid-state

Micro-fluidic Spray Freeze Dried Ciprofloxacin Hydrochloride-Embedded Dry Powder for Inhalation

Yingjie Chen, Shen Yan, Shengyu Zhang, Quanyi Yin, Xiao Dong Chen, Winston Duo Wu

Abstract

Active pharmaceutical ingredient (API)-embedded dry powder for inhalation (AeDPI) is highly desirable for pulmonary delivery of high-dose drug. Herein, a series of spray freeze-dried (SFD) ciprofloxacin hydrochloride (CH)-embedded dry powders were fabricated via a self-designed micro-fluidic spray freeze tower (MFSFT) capable of tuning freezing temperature of cooling air as the refrigerant medium. The effects of total solid content (TSC), mass ratio of CH to L-leucine (Leu) as the aerosol dispersion enhancer, and the freezing temperature on particle morphology, size, density, moisture content, crystal properties, flowability, and aerodynamic performance were investigated. It was found that the Leu content and freezing temperature had considerable influence on the fine particle fraction (FPF) of the SFD microparticles. The optimal formulation (CH/Leu = 7:3, TSC = 2%w/w) prepared at – 40°C exhibited remarkable effective drug deposition (~ 33.38%), good aerodynamic performance (~ 47.69% FPF), and excellent storage stability with ultralow hygroscopicity (~ 1.93%). This work demonstrated the promising feasibility of using the MFSFT instead of conventional liquid nitrogen assisted method in the research and development of high-dose AeDPI.

Keywords

Active pharmaceutical ingredient-embedded dry powder for inhalation (AeDPI), Spray freeze drying, Adjustable freezing temperature, Porous and brittle microparticle, High fine particle fraction

Solid state of inhalable high dose powders

Bishal Raj Adhikari, Keith C. Gordon, Shyamal C. Das

Abstract

High dose inhaled powders have received increased attention for treating lung infections. These powders can be prepared using techniques such as spray drying, spray-freeze drying, crystallization, and milling. The selected preparation technique is known to influence the solid state of the powders, which in turn can potentially modulate aerosolization and aerosolization stability. This review focuses on how and to what extent the change in solid state of high dose powders can influence aerosolization. It also discusses the commonly used solid state characterization techniques and the application of potential strategies to improve the physical and chemical stability of the amorphous powders for high dose delivery.

Keywords

Aerosolization, Amorphous, Antibiotic, Chemical stability, Co-amorphous, Crystalline, Dry powder inhaler, Lung infection, Pulmonary drug delivery

Effect of spray freeze drying on the structural modification and rehydration characteristics of micellar casein powders

Jinbo Ren, Minjie Liao, Lingjun Ma, Fang Chen, Xiaojun Liao, Xiaosong Hu, Song Miao, John Fitzpatrick, Junfu Ji

Abstract

Micellar casein (MC) is usually spray-dried into powder form for transportation and storage. However, the micellar structure maintained by colloidal calcium phosphate (CCP) and hydrophobic forces leads to poor rehydration ability of MC powders, which limits its potential applications. Here, spray freeze drying (SFD) with controlled droplet size was used to produce MC powders. Their effects on the structure of MC and the subsequent rehydration characteristics including wetting, dispersion and dissolution were investigated. The results showed SFD powders obtained from smaller droplet size caused more than 50% of serum Ca²⁺ and PO₄³⁻ to release from the micellar structure. These powder particles exhibited extremely high porosity (92%) and spherical morphology, which thus greatly shortened their wetting time. Furthermore, the smallest droplets during SFD were believed to produce the MC powders with the quickest dispersion and best solubility, as over 80% of the solids could be completely dissolved in just 15 min.

Keywords

Micellar casein (MC), Spray freeze drying (SFD), Droplet size, Rehydration behaviors, Colloidal calcium phosphate (CCP)