Impact of Fermentation on the Phytochemical Profile and Bioactivity Characteristics of Aqueous Matricaria recutita L. Root Extracts.

While the flowers of Matricaria recutita L., German chamomile, are widely used for medicinal and cosmetic purposes, little is known about its roots, which are used in complementary medicine for the preparation of aqueous fermented extracts for the treatment of cramps and anxiety. To broaden the understanding of the active principles involved, a model fermentation approach was developed and fermentates were compared to commercially manufactured tinctures. Coumarins and hydroxycinnamates were among the major secondary metabolites characterized using HPLC-MSn. After six months of fermentation and storage, low-molecular organic acids were detected by GC-MS. Fermentation contributed to the stabilization of antioxidant and radical scavenging activities, which were in a range of about 8-10 mg gallic acid equivalents/g dry weight and 20-24 mg trolox equivalents/g dry weight, determined by Folin-Ciocalteu and DPPH assays, respectively. In addition, antibacterial activities of the extracts against Gram-positive and -negative bacteria increased during the first week of fermentation. Fermentates were neither cytotoxic nor pro- or anti-inflammatory. Thus, fermentation of chamomile roots is a suitable method for the safe production of biofunctional aqueous chamomile root extracts that remain stable without the addition of synthetic preservatives.

Phytochemical Characterization of Chamomile (Matricaria recutita L.) Roots and Evaluation of Their Antioxidant and Antibacterial Potential.

Matricaria recutita L., German chamomile, is one of the most widely used medicinal plants, whose efficacy has been proven in numerous studies. However, its roots have attracted only little interest so far, since mainly above-ground plant parts are used for medicinal purposes. To broaden the knowledge of chamomile roots, a profound phytochemical characterization was performed along with a bioactivity screening of corresponding root extracts. While volatile constituents such as chamomillol and polyynes were detected using GC-MS, HPLC-MSn analyses revealed the occurrence of four coumarin glycosides, more than ten phenolic acid esters and five glyceroglycolipids. Furthermore, the antioxidant activity of the extracts was evaluated. Polar extracts revealed IC50 values ranging from 13 to 57 µg/mL in the DPPH radical scavenging assay, which is in the same range as reported for chamomile flower extracts. In addition, superoxide radical scavenging potential and mild antibacterial effects against S. aureus und B. subtilis were demonstrated. Moreover, to assess interspecies variation in chamomile roots, extracts of M. recutita were compared to those of M. discoidea DC. Interestingly, the latter revealed stronger antioxidant activity. The presented results aim at the valorization of chamomile roots, previously discarded as by-product of chamomile flower production, as a sustainable source of bioactive phytochemicals.

Amorphous and Co-Amorphous Olanzapine Stability in Formulations Intended for Wet Granulation and Pelletization.

The preparation of amorphous and co-amorphous systems (CAMs) effectively addresses the solubility and bioavailability issues of poorly water-soluble chemical entities. However, stress conditions imposed during common pharmaceutical processing (e.g., tableting) may cause the recrystallization of the systems, warranting close stability monitoring throughout production. This work aimed at assessing the water and heat stability of amorphous olanzapine (OLZ) and OLZ-CAMs when subject to wet granulation and pelletization. Starting materials and products were characterized using calorimetry, diffractometry and spectroscopy, and their performance behavior was evaluated by dissolution testing. The results indicated that amorphous OLZ was reconverted back to a crystalline state after exposure to water and heat; conversely, OLZ-CAMs stabilized with saccharin (SAC), a sulfonic acid, did not show any significant loss of the amorphous content, confirming the higher stability of OLZ in the CAM. Besides resistance under the processing conditions of the dosage forms considered, OLZ-CAMs presented a higher solubility and dissolution rate than the respective crystalline counterpart. Furthermore, in situ co-amorphization of OLZ and SAC during granule production with high fractions of water unveils the possibility of reducing production steps and associated costs.

Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being.

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review.

Supercritical Fluid Extraction with CO2 of Curcuma longa L. in Comparison to Conventional Solvent Extraction.

Curcuma longa L. is a traditional medicinal and spice plant containing a variety of lipophilic active substances with promising therapeutic properties. In this work, the solvent properties of supercritical carbon dioxide in a pressure and temperature range of 75-425 bar and 35-75 °C were investigated when Curcuma longa rhizomes were extracted. The three main curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, together with the three main constituents of the essential oil, i.e., ar-turmerone, α-turmerone, and ß-turmerone, were analyzed in the resulting extracts. For statistical evaluation, experiments were performed employing a full factorial design, in which flow rate, extraction time, and drug load were kept constant. Within the given conditions, the experimental design revealed an optimum yield of all aforementioned substances, when supercritical carbon dioxide extraction was performed at 425 bar and 75 °C. For comparison, solvent extracts using methanol and n-hexane were prepared and their main components were characterized using LC-MS. The stability of the extracts was monitored upon storage for 6 months at 22 and 40 °C under protection from light. The decomposition of individual compounds was mainly observed in the presence of residual water in the extracts.

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends.

The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those of tablets made with crystalline OLZ. The flowability of the amorphous and mostly of the co-amorphous OLZ powders decreased in comparison with the crystalline OLZ due to the higher cohesiveness of the former materials. The stability of the amorphous and co-amorphous OLZ prior to and after tableting was monitored by XRPD, FTIR, and NIR spectroscopies. Tablets presented long-lasting amorphous OLZ with enhanced water solubility, but the release rate of the drug decreased in comparison with tablets containing crystalline OLZ. In physical mixtures made of crystalline OLZ and SAC, an extent of amorphization of approximately 20% was accomplished through the application of compaction pressures and dwell times of 155 MPa and 5 min, respectively. The work highlighted the stability of amorphous and co-amorphous OLZ during tableting and the positive effect of compaction pressure on the formation of co-amorphous OLZ, providing an expedited amorphization technique, given that the process development-associated hurdles were overcome.

Influence of Oil Polarity and Cosurfactants on the Foamability of Mono- and Diacylphosphatidylcholine Stabilized Emulsions.

Foam formulations are safe and effective therapy options for the treatment of chronic skin conditions that require the application of a topical formulation to delicate skin areas, such as scalp psoriasis or seborrheic dermatitis. This study focused on the development of foamable emulsions based on aqueous phospholipid blends. The effects of cosurfactants (nonionic Lauryglucoside (LG); zwitterionic Lauramidopropyl betaine (LAPB)), as well as of oil phases of different polarities, namely paraffin oil (PO), medium-chain triglycerides (MCT) and castor oil (CO), were investigated. The foaming experiments showed that both the type of cosurfactant, as well as the type of oil phase, affects the quality of the resulting foam. Emulsions that were based on a combination of hydrogenated lysophosphatidylcholine (hLPC) and a non-hydrogenated phospholipid, as well as LG as a cosurfactant and MCT as an oil phase, yielded the most satisfactory results. Furthermore, profile analysis tensiometry (PAT), polarization microscopy and laser diffraction analysis were used to characterize the developed formulations. These experiments suggest that the employed phospholipids predominantly stabilize the emulsions, while the cosurfactants are mainly responsible for the formation and stabilization of the foams. However, it appears that both sets of excipients are needed in order to acquire stable emulsions with satisfactory foaming properties.

A comparison of emulsifiers for the formation of oil-in-water emulsions: stability of the emulsions within 9 h after production and MR signal properties.

OBJECTIVE: To provide a basis for the selection of suitable emulsifiers in oil-in-water emulsions used as tissue analogs for MRI experiments. Three different emulsifiers were investigated with regard to their ability to stabilize tissue-like oil-in-water emulsions. Furthermore, MR signal properties of the emulsifiers themselves and influences on relaxation times and ADC values of the aqueous phase were investigated. MATERIALS AND METHODS: Polysorbate 60, sodium dodecyl sulfate (SDS) and soy lecithin were used as emulsifiers. MR characteristics of emulsifiers were assessed in aqueous solutions and their function as a stabilizer was examined in oil-in-water emulsions of varying fat content (10, 20, 30, 40, 50%). Stability and homogeneity of the oil-in-water emulsions were evaluated with a delay of 3 h and 9 h after preparation using T1 mapping and visual control. Signal properties of the emulsifiers were investigated by 1H-MRS in aqueous emulsifier solutions. Relaxometry and diffusion weighted MRI (DWI) were performed to investigate the effect of various emulsifier concentrations on relaxation times (T1 and T2) and ADC values of aqueous solutions. RESULTS: Emulsions stabilized by polysorbate 60 or soy lecithin were stable and homogeneous across all tested fat fractions. In contrast, emulsions with SDS showed a significantly lower stability and homogeneity. Recorded T1 maps revealed marked creaming of oil droplets in almost all of the emulsions with SDS. The spectral analysis showed several additional signals for polysorbate and SDS. However, lecithin remained invisible in 1H-MRS. Relaxometry and DWI revealed different influences of the emulsifiers on water: Polysorbate and SDS showed only minor effects on relaxation times and ADC values of aqueous solutions, whereas lecithin showed a strong decrease in both relaxation times (r1,lecithin = 0.11 wt.%-1 s-1, r2,lecithin = 0.57 wt.%-1 s-1) and ADC value (Δ(ADC)lecithin = - 0.18 × 10-3 mm2/s⋅wt.%) with increasing concentration. CONCLUSION: Lecithin is suggested as the preferred emulsifier of oil-in-water emulsions in MRI as it shows a high stabilizing ability and remains invisible in MRI experiments. In addition, lecithin is suitable as an alternative means of adjusting relaxation times and ADC values of water.

Impact of Alkanediols on Stratum Corneum Lipids and Triamcinolone Acetonide Skin Penetration.

Alkanediols are widely used as multifunctional ingredients in dermal formulations. In addition to their preservative effect, considering their possible impact on drug penetration is also essential for their use. In the present study, the influence of 2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol on the skin penetration of triamcinolone acetonide from four different semisolid formulations was investigated. Furthermore, confocal Raman spectroscopy measurements were performed to examine the influence of the alkanediols on stratum corneum lipid content and order. Alkanediols were found to increase the penetration of triamcinolone acetonide. However, the extent depends strongly on the formulation used. In certain formulations, 1,2-pentanediol showed the highest effect, while in others the penetration-enhancing effect increased with the alkyl chain length of the alkanediol used. None of the tested alkanediols extracted lipids from the stratum corneum nor reduced its thickness. Notwithstanding the above, the longer-chained alkanediols cause the lipids to be converted to a more disordered state, which favors drug penetration. This behavior could not be detected for the shorter-chained alkanediols. Therefore, their penetration-enhancing effect is supposed to be related to an interaction with the hydrophilic regions of the stratum corneum.

The effect of alkanediols on the release of triamcinolone acetonide from semisolid dosage forms.

Alkanediols are frequently used as alternative antimicrobial preservatives for dermal formulations. However, these substances can also have an influence on the biopharmaceutical properties of the applied preparations. Therefore, the influence 2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol on the release of triamcinolone acetonide (TAA) from four different commonly used semi-solid vehicles was investigated. In addition, the solubility of TAA in aqueous alkanediol solutions was evaluated. It was observed that its solubility increases as a function of chain length of the alkanediol, with exception of 1,2-octanediol. This can be related to the corresponding solubility parameters. Despite alkanediols increase the aqueous solubility of TAA, polarization microscopic images revealed that a significant amount of the drug is present in the suspended state in all formulations. Therefore, TAA release was proportional to the square root of time, indicating Higuchi kinetic. Alkanediols modify the release of TAA depending on the used base. The addition of alkanediols to the hydrogel formulation result in a slightly augmented release rate of the drug with increasing chain length of the added alkanediol. In contrast, alkanediols having longer chain lengths diminish the TAA release rate from all tested creams. Consequently, TAA release revealed to be partially inequivalent upon the addition of alkanediols.

Preparation and Characterization of Electrospun Polylactic Acid (PLA) Fiber Loaded with Birch Bark Triterpene Extract for Wound Dressing.

Drug-loaded electrospun fibers have attracted increasing attention as a promising wound dressing material due to their capability of preventing from infections and inflammation and maintaining an appropriate environment for wound healing. In this study, polylactic acid (PLA), which is widely used in wound management, was chosen as electrospinnable polymer. A triterpene extract (TE) from the outer bark of birch known for its anti-inflammatory, antiviral, antibacterial, and wound healing effects was chosen to produce TE-loaded PLA electrospun fibers for wound dressing. A binary solvent system of dichloromethane (DCM) and dimethyl sulfoxide (DMSO) was employed, and the ratio of the solvents was optimized for preparing smooth and uniform fibers. The morphology of TE-loaded PLA electrospun fibers was investigated by scanning electron microscopy (SEM). The entrapment of TE in PLA fibers was confirmed by confocal laser scanning microscopy (CLSM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to analyze the solid state of TE in PLA fibers. The release behavior of TE was assayed by a shaking flask method for a period of 96 h. The results revealed that TE-loaded electrospun PLA microfibers could be reliably prepared and are promising future candidates in wound therapy.

Assessing a Mass-Based Method for the Preparation of Low-Dosed Paediatric Capsules with Baclofen and Spironolactone.

Despite the steadily improving medical care situation in pediatrics, some drugs are still not available in a suitable dose or dosage form and thus need to be prepared extemporaneously. Capsules can be easily compounded at the hospital and public pharmacies, offering an alternative to liquid formulations. This study aims at testing a mass-based approach for the extemporaneous preparation of low-dose pediatric capsules and investigating systematically the API loss during this procedure. A total of 54 capsule batches were prepared with baclofen and spironolactone as pediatric-relevant drugs. The hard capsules were prepared using three different bulking agents consisting of either mannitol, lactose-monohydrate and microcrystalline cellulose mixed with 0.5% colloidal silica. Capsules were tested according to Ph. Eur. method "2.9.40 Content Uniformity" as well as for occurring powder loss and mass uniformity. The results reveal that the mass-based approach, in general, allows the preparation of low-dose pediatric capsules of appropriate quality. However, absolute quality is highly dependent on the homogeneity of the powder mixture and the use of defined parameters for capsule preparation.

Supercritical Fluid Technology for the Development of 3D Printed Controlled Drug Release Dosage Forms.

Supercritical CO2 loading of preformed 3D printed drug carriers with active pharmaceutical ingredients (APIs) shows great potential in the development of oral dosage forms for future personalized medicine. We designed 3D printed scaffold like drug carriers with varying pore sizes made from polylactic acid (PLA) using a fused deposition modelling (FDM) 3D printer. The 3D printed drug carriers were then loaded with Ibuprofen as a model drug, employing the controlled particle deposition (CPD) process from supercritical CO2. Carriers with varying pore sizes (0.027-0.125 mm) were constructed and loaded with Ibuprofen to yield drug-loaded carriers with a total amount of 0.83-2.67 mg API (0.32-1.41% w/w). Dissolution studies of the carriers show a significantly decreasing dissolution rate with decreasing pore sizes with a mean dissolution time (MDT) of 8.7 min for the largest pore size and 128.2 min for the smallest pore size. The API dissolution mechanism from the carriers was determined to be Fickian diffusion from the non-soluble, non-swelling carriers. Using 3D printing in combination with the CPD process, we were able to develop dosage forms with individually tailored controlled drug release. The dissolution rate of our dosage forms can be easily adjusted to the individual needs by modifying the pore sizes of the 3D printed carriers.

Investigations on Alkanediols as Alternative Preservatives in a Nonionic Hydrophilic Cream.

Alkanediols are often used as alternative antimicrobial preservatives for dermal formulations, e.g., hydrophilic creams. These substances show an antimicrobial effect due to their amphiphilic structure. At the same time, their amphiphilic behavior enables various interactions with the cream base itself. Therefore, the effect of four different alkanediols, namely 1,2-pentanediol, 2-methyl-2,4-pentanediol (hexylene glycol), 1,2-hexanediol, and 1,2-octanediol on the physical stability of a nonionic hydrophilic cream was investigated. Further, the incorporation of the alkanediols into lamellar structures of the cream was evaluated using differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) measurements. The interaction with the mixed crystals of the cream was found to increase with raising alkyl chain length of the added alkanediol. As a result, consistency and stability of the cream are slightly impaired. A test for efficacy of antimicrobial preservation according to the European Pharmacopoeia (Ph.Eur.) revealed that the antimicrobial activity is directly linked to the length of the alkyl chain of the alkanediols. 2-Methyl-2,4-pentanediol differs from both findings. This compound has non-vicinal hydroxy groups which result in a reduced amphiphilicity compared to the others. Consequently, it has a smaller impact on the colloidal structure of the cream and shows a comparatively low antimicrobial activity.

Influence of PVA Molecular Weight and Concentration on Electrospinnability of Birch Bark Extract-Loaded Nanofibrous Scaffolds Intended for Enhanced Wound Healing.

Triterpenes from the outer bark of birch (TE) are known for various pharmacological effects including enhanced wound healing. Apart from an already authorized oleogel, electrospun nanofiber mats containing these triterpenes in a polyvinyl alcohol (PVA) matrix appear to be an advantageous application form. The effects of PVA molecular weight and concentration on the fiber morphology have been investigated. Three different molecular weights of PVA ranging from 67 to 186 kDa were used. The concentration of PVA was varied from 5 to 20 wt%. Polymer solutions were blended with colloidal dispersions of birch bark extract at a weight ratio of 60:40 (wt.%). The estimated viscosity of polymer solutions was directly linked to their concentration and molecular weight. In addition, both pure and blended solutions showed viscoelastic properties with a dominant viscous response in the bulk. Fiber morphology was confirmed using scanning electron microscopy (SEM). Both polymer concentration and molecular weight were found to be significant factors affecting the diameter of the fibers. Fiber diameter increased with a higher molecular weight and polymer concentration as more uniform fibers were obtained using PVA of higher molecular weight (146-186 kDa). In vitro drug release and ex vivo permeation studies indicated a faster drug release of betulin from electrospun scaffolds with lower PVA molecular weight. Our research suggests that the fabricated TE-loaded PVA electrospun dressings represent potential delivery systems of TE for wound care applications.

Erratum: Mwiiri, F.K.; et al. Electrospun Bioactive Wound Dressing Containing Colloidal Dispersions of Birch Bark Dry Extract. Pharmaceutics 2020, 12, 770.

The authors wish to make the following correction to this paper [...].

Development of probiotic orodispersible tablets using mucoadhesive polymers for buccal mucoadhesion.

OBJECTIVE: Probiotic bacteria, such as different lactobacilli strains, have successfully been used to treat gingivitis and periodontitis or caries. By formulating probiotics as orodispersible tablet (ODT), the benefits of this dosage form could be utilized. Without any further measures, the probiotic bacteria will be eliminated too fast from the intended site of action, the oral mucosa. The use of mucoadhesive granules, composed of mucoadhesive polymer and probiotics, is a promising strategy to prolong the contact time between lactobacilli and oral mucosa without delaying disintegration. METHODS: Three common mucoadhesive polymers, anionic Carbopol 971P NF, nonionic Metolose 65SH50 and cationic chitosan were included into tablets either by direct compression (DC) or after granulation with the probiotics. Disintegration, mucoadhesion of the tablets, and storage stability of the probiotics were characterized. RESULTS: By incorporating a sufficient amount of polymer superior probiotic mucoadhesion could be achieved. All formulations based on granulated probiotics and mucoadhesive polymer fulfilled the Food and Drug Administration (FDA) acceptance level for disintegration of orodispersible tablets. These formulations exhibited excellent storage stability under refrigerated conditions over 30 months. Interestingly, ODTs including Carbopol 971P NF still proved superior mucoadhesion after long-term storage, whereas the mucoadhesive effect of Metolose 65SH50 and chitosan declined markedly. CONCLUSIONS: The results of this study suggest that Carbopol 971P NF was the most appropriate polymer for a probiotic mucoadhesive ODT.

Optimized Birch Bark Extract-Loaded Colloidal Dispersion Using Hydrogenated Phospholipids as Stabilizer.

This study investigated the formulation and processing of aqueous colloidal dispersions containing a birch bark dry extract (TE) as the active substance and hydrogenated phospholipids (Phospholipon 90H) as stabilizer, which can be used in the preparation of electrospun wound dressings. Colloidal dispersions manufactured using a two-stage homogenization process had a bimodal particle size distribution, which was most significantly (p < 0.0001) affected by the phospholipid content. The size of the single particles decreased from an average particle size of about 4 µm to a particle size of approximately 400 nm. Dynamic interfacial tension studies performed using a profile analysis tensiometer (PAT) showed that the phospholipids strongly declined the interfacial tension, whereas a further decrease was observed when phospholipids were combined with birch bark extract. Interfacial viscoelasticity properties analyzed using the oscillating drop technique resulted in an increase of both interfacial elasticity and viscosity values. These results indicated that the phospholipids are preferentially located at the lipophilic/water interface and a stable film is formed. Furthermore, the results point to a synergistic interaction between phospholipids and TE. Confocal Raman microscopy (CRM) suggested that the TE is predominantly located in the oil phase and the phospholipids at the interface.

Electrospun Bioactive Wound Dressing Containing Colloidal Dispersions of Birch Bark Dry Extract.

Novel birch bark dry extract (TE)-loaded polyvinyl alcohol (PVA) fiber mats intended for wound therapy were developed through an electrospinning process. Colloidal dispersions containing TE as the active substance were prepared by the high-pressure homogenization (HPH) technique using hydrogenated phospholipids as stabilizer. Subsequently, the colloidal dispersions were blended with aqueous PVA solutions in the ratio of 60:40 (wt.%) and electrospun to form the nanofiber mats. Fiber morphology examined using scanning electron microscopy (SEM) indicated that fibers were uniform and achieved diameters in the size range of 300-1586 nm. Confocal Raman spectral imaging gave good evidence that triterpenes were encapsulated within the electrospun mats. In vitro drug release and ex vivo permeation studies indicated that the electrospun nanofibers showed a sustained release of betulin, the main component of birch bark dry extract, making the examined dressings highly applicable for several wound care applications. Ex vivo wound healing studies proved that electrospun fiber mats containing TE accelerated wound healing significantly more than TE oleogel, which was comparable to an authorized product that consists of TE and sunflower oil and has proved to enhance wound healing. Therefore, our results conclude that the developed TE-PVA-based dressings show promising potential for wound therapy, an area where effective remedy is needed.

Lactate Production Precedes Inflammatory Cell Recruitment in Arthritic Ankles: an Imaging Study.

PURPOSE: Inflammation is involved in many disease processes. However, accurate imaging tools permitting diagnosis and characterization of inflammation are still missing. As inflamed tissues exhibit a high rate of glycolysis, pyruvate metabolism may offer a unique approach to follow the inflammatory response and disease progression. Therefore, the aim of the study was to follow metabolic changes and recruitment of inflammatory cells after onset of inflammation in arthritic ankles using hyperpolarized 1-13C-pyruvate magnetic resonance spectroscopy (MRS) and 19F magnetic resonance imaging (MRI), respectively. PROCEDURE: Experimental rheumatoid arthritis (RA) was induced by intraperitoneal injection of glucose-6-phosphate-isomerase-specific antibodies (GPI) containing serum. To monitor pyruvate metabolism, the transformation of hyperpolarized 1-13C-pyruvate into hyperpolarized 1-13C-lactate was followed using MRS. To track phagocytic immune cell homing, we intravenously injected a perfluorocarbon emulsion 48 h before imaging. The animals were scanned at days 1, 3, or 6 after GPI-serum injection to examine the different stages of arthritic inflammation. Finally, to confirm the pyruvate metabolic activity and the link to inflammatory cell recruitment, we conducted hematoxylin-eosin histopathology and monocarboxylase transporter (MCT-1) immune histochemistry (IHC) of inflamed ankles. RESULTS: Hyperpolarized 1-13C-pyruvate MRS revealed a high rate of lactate production immediately at day 1 after GPI-serum transfer, which remained elevated during the progression of the disease, while 19F-MRI exhibited a gradual recruitment of phagocytic immune cells in arthritic ankles, which correlated well with the course of ankle swelling. Histopathology and IHC revealed that MCT-1 was expressed in regions with inflammatory cell recruitment, confirming the metabolic shift identified in arthritic ankles. CONCLUSIONS: Our study demonstrated the presence of a very early metabolic shift in arthritic joints independent of phagocytic immune cell recruitment. Thus, hyperpolarized 1-13C-pyruvate represents a promising tracer to monitor acute arthritic joint inflammation, even with minor ankle swelling. Furthermore, translated to the clinics, these methods add a detailed characterization of disease status and could substantially support patient stratification and therapy monitoring.