In this study, a novel dextrin-based micelle (OSAD-SH), dual-modified with octenyl succinic anhydride (OSA) and cysteamine, was developed to address the acid instability issues of micelle modified only by OSA and designed for curcumin delivery. Three amphiphilic OSAD-SH polymers with different free sulfhydryl content were first synthesized. The study demonstrated that OSAD-SH micelles exhibited strong self-assembly properties, appearing as spheres with diameters ranging from 92.41 to 194.20 nm. Blank micelles showed good dilution resistance, as well as stability against acid, thermal, and ionic strength. The curcumin encapsulated by the micelles was in an amorphous state. In vitro release experiment demonstrated that curcumin released from OSAD-SH micelles exhibited pH responsiveness. The Ritger-Peppas model effectively predicted the release behavior of curcumin, which followed a super case-II transport. The OSAD-SH micelle will be a promising nanocarrier for improving the physicochemical properties of curcumin in food fields.

The physiological and clinical importance of Glutathione and Cysteamine is emphasized by their participation in a range of conditions, such as diabetes, cancer, renal failure, Parkinson\'s disease, and hypothyroidism. This necessitates the requirement for accessible, expedited, and cost-efficient testing that can facilitate clinical diagnosis and treatment options. This article examines numerous techniques used to detect both glutathione and cysteamine. The discussed methods include electroanalytical techniques such as voltammetry and amperometry, which are examined for their sensitivity and ability to provide real-time analysis. Furthermore, this study investigates the accuracy of gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) in measuring the concentrations of glutathione and cysteamine. Additionally, the potential of new nanotechnology-based methods, such as plasmonic nanoparticles and quantum dots, to improve the sensitivity of detecting glutathione and cysteamine is emphasized.

Infectious diseases are a major threat to global health and cause millions of deaths every year, particularly in developing countries. The emergence of multidrug resistance challenges current antimicrobial treatments, inducing uncertainty in therapeutic protocols. New compounds are therefore necessary. A drug repurposing approach could play a critical role in developing new treatments used either alone or in combination with standard therapy regimens. Herein, we focused on cysteamine, an aminothiol endogenously synthesized by human cells during the degradation of coenzyme-A, which is a drug approved for the treatment of nephropathic cystinosis. Cysteamine influences many biological processes due to the presence of the highly reactive thiol group. This review provides an overview of cysteamine-mediated effects on different viruses, bacteria and parasites, with a particular focus on infections caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Mycobacterium tuberculosis, non-tuberculous mycobacteria (NTM), and Pseudomonas aeruginosa. Evidences for a potential use of cysteamine as a direct antimicrobial agent and/or a host-directed therapy, either alone or in combination with other antimicrobial drugs, are described.

There is a pressing need for novel pharmacological interventions and drug delivery innovations to attenuate the cigarette smoke-associated oxidative stress and lung disease. We report here on the attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and metabolomics of Wistar rats exposed to cigarette smoke for 28 days. The animals were treated for 15 days with plain cysteamine given orally or cysteamine as nanoemulsion given orally or via inhalation. The study design also included two control groups as follows: rats exposed to cigarette smoke but did not receive a treatment (diseased control group) and rats neither exposed to cigarette smoke nor a treatment (normal control group). The targeted metabolomics using Parallel Reaction Monitoring showed that in the diseased control group, ornithine, nicotinamide, xanthine, hypoxanthine, and caprolactam were increased compared with the normal control group. In addition, (±)8(9)-DiHET, which was initially downregulated in the diseased control group, exhibited a reversal of this trend with cysteamine nanoemulsion given via inhalation. The cysteamine nanoemulsion delivered by inhalation highlighted the importance of the route of drug administration for targeting the lungs. To the best of our knowledge, this is the first work to use ATR-FTIR and metabolomics in Wistar rat lung tissues, suggesting how cysteamine nanoemulsion can potentially reduce cigarette smoke-induced oxidative damage. The metabolites reported herein have potential implications for discovery of novel theranostics and, thus, to cultivate diagnostic and therapeutic innovation for early prevention and treatment of cigarette smoke-associated lung diseases.

BACKGROUND: Melasma is a chronic pigmentary disorder. In this study, an innovative cream combining cysteamine and tranexamic acid (TXA) was assessed.
OBJECTIVE: To evaluate the safety, efficacy, and patient satisfaction of a novel nano-formulated cysteamine and TXA combination cream in treating subjects with epidermal melasma.
METHODS:   Fifty (50) randomized subjects participated and received cysteamine and TXA combination cream. The cream was applied for 30 minutes daily for a 3-month duration. Treatment effectiveness, safety, patient satisfaction, and adherence were evaluated.
RESULTS: A continuous improvement in melasma was observed, with modified Melasma Area and Severity Index (mMASI) scores improving by 40%, 57%, and 63% at 30, 60, and 90 days, respectively. The primary endpoint of a decrease in mMASI scores was met, with 91% of participants experiencing melasma improvement. Patient Satisfaction and Patient Adherence scores indicated satisfaction. Convenience exhibited the strongest correlation with patient adherence.  Conclusion: Nano-formulated cysteamine and TXA combination cream showed significant efficacy in decreasing mMASI score while demonstrating a strong safety profile and patient satisfaction.  J Drugs Dermatol. 2024;23(7):529-537.     doi:10.36849/JDD.7765R1.

Metal nanoclusters (NCs) as a new kind of luminophore have acquired sufficient interest, but their widespread application is restricted on account of their relatively low electrochemiluminescence (ECL) efficiency. Then, aqueous metal NCs with high ECL efficiency were strongly anticipated, especially for the ultrasensitive analysis of biomarkers. Herein, a near-infrared (NIR) ECL biosensing strategy for the test of neuron-specific enolase (NSE) was proposed by utilizing N-acetyl-l-cysteine (NAC)- and cysteamine (Cys)-stabilized gold NCs (NAC/Cys-AuNCs) as ECL emitters with the NIR ECL emission around 860 nm and a metal-organic framework/palladium nanocubes (ZIF-67/PdNCs) hybrid as the coreaction accelerator through their admirable electrocatalytic activity. The NIR emission would reduce photochemical injury to the samples and even realize nondestructive analysis with highly strong susceptibility and suitability. Furthermore, the utilization of ZIF-67/PdNCs could improve the ECL response of NAC/Cys-AuNCs by facilitating the oxidation of the coreactant triethylamine (TEA), leading to the production of a larger quantity of reducing intermediate radical TEA•+. Consequently, NAC/Cys-AuNCs with ZIF-67/PdNCs displayed 2.7 fold enhanced ECL emission compared with the single NAC/Cys-AuNCs using TEA as the coreactant. In addition, HWRGWVC (HWR), a heptapeptide, was introduced to immobilize antibodies for the specially binding Fc fragment of the antibodies, which improved the binding efficiency and sensitivity. As a result, a \"signal-on\" immunosensor for NSE analysis was obtained with an extensive linear range of 0.1 to 5 ng/mL and a low limit of detection (0.033 fg/mL) (S/N = 3). This study provides a wonderful method for the development of an efficient nondestructive immunoassay.

The disrupted oxidative redox homeostasis plays a critical role in the progress of ulcerative colitis (UC). Herein, hydrogel-forming viscous liquid (HSD) composed of cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) has been designed for UC. When the viscous HSD liquid was infused into colitis colon, SOD would convert the pathological superoxide (O2·-) to hydrogen peroxides (H2O2), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H2O2, enhancing its adhesion toward colitis colon. H2O2-treated HSD presented the higher storage modulus and stronger adhesion force toward porcine colon than the untreated HSD. Besides, H2O2-treated HSD presented the slower erosion profile in the colitis-mimicking medium (pH 3-5), while its rapid degradation was displayed in physiologic condition (pH7.4). The combination of pH-resistant erosion and ROS-responsive adhesion for HSD rendered it with the specifical retention on the inflamed colonic mucosa of DSS-induced colitis mice. Rectally administrating HSD could effectively hinder the body weight loss, reduce the disease activity index and improve the colonic shorting of DSS-induced colitis mice. Moreover, the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were substantially decreased, the colonic epitheliums were well rearranged and the tight junction proteins were greatly recovered after HSD treatment. Besides, HSD also modulated the gut flora, markedly augmenting the abundance of Firmicutes, Barnesiella and Lachnospiraceae. Moreover, HSD treatment could regulate oxidative redox homeostasis via activating Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH). Collectively, HSD might be a promising therapy for UC treatments. STATEMENT OF SIGNIFICANCE: Herein, a hydrogel-forming viscous liquid (HSD) was designed by cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) for UC treatments. When the viscous HSD liquid was infused into a colitis colon, SOD would convert the pathological superoxide to hydrogen peroxides (H2O2), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H2O2, enhancing its adhesion to the colitis colon. The colonic epitheliums of DSS-induced colitis mice were well rearranged and the tight junction proteins (Zonula-1 and Claudin-5) were greatly recovered after the HSD treatment. Moreover, the HSD treatment could regulate oxidative redox homeostasis via activating the Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH).

Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine\'s inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment.

Cystinosis is a lysosomal storage disorder usually presenting with renal disease in infancy. As soon as the diagnosis is made, cysteamine (a cystine-depleting medication), is started, significantly improving life expectancy. We describe a young woman taking lifelong cysteamine for nephropathic cystinosis, who became acutely encephalopathic with a spastic tetraparesis secondary to cysteamine toxicity, which was potentially worsened by copper deficiency. On replacing copper and reducing the dose of cysteamine, she made a full neurological recovery. We discuss the case, and review cystinosis and what is known about cysteamine toxicity.

Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)\'s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5-26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50-3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60-36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects.