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Variation in pH and osmolality (mOsm/kg) of the 5.5 mg/mL cysteamine formulation in Aquoral® on days 0, 3, 7, 15, 21, and 30: (a) pH; (b) osmolality.
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Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well...
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Background: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previ...
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... The commercialization of cysteamine treatment for nephropathic cystinosis in the 1990s has represented an enormous step forward in delaying the symptoms and an improvement of the quality of life of the patients (7). Cystine-depleting therapy [60] needs to be combined with cysteamine eye drops for the ocular manifestation of the disease [61,62]. When the initiation of the treatment is done at early age and the patient I. Ortea et al. ...
Cysteamine, an aminothiol, is the only available treatment for cystinosis, an incurable metabolic recessive disease characterized by detrimental symptoms at the renal, ocular, and muscular levels. Cystinosis is due to mutations in the CTNS gene encoding for the lysosomal symporter cystinosine. Cysteamine treatment only delays the symptoms, presents undesirable side effects and the patients depend on it for life. Thus, it is of paramount importance to find new complementary therapeutic targets for the disease, as well as to understand, at the molecular level, both the beneficial and detrimental effects of cysteamine. Here, we have used ZenoSWATH DIA proteomics and clustering analysis to unravel the differences between cystinotic and non-cystinotic skin fibroblasts, and to study the effect of increasing concentrations of cysteamine. Cystinotic cells present significant differences in proteins related to extracellular matrix structure and detoxification. Only a subset of those proteins is reversed by cysteamine in a dose-dependent manner, partially providing an explanation for its therapeutic benefits. Finally, cysteamine per se alters the levels of a group of lysosomal proteins that are not modulated in basal conditions. Our results will be helpful to understand the benefits, deficiencies, and detrimental effects of the cysteamine treatment.
... Hyaluronic acid (HA) as a vehicle has great advantages due to its viscosity, and mucoadhesive and biocompatible properties [24,25]. Bearing this in mind, a new compounded formulation of 0.55% cysteamine hydrochloride eye drops in HA packaged in innovative single-dose systems has been previously developed by our group [26]. Results showed that this formulation stored at 2-8 • C was stable for less than a week, while when stored at −20 • C, a stability of at least 30 days was reached. ...
... In addition, ocular biopermanence preclinical studies were conducted using positron emission tomography (PET), concluding that the ocular surface permanence offered by the HA is not affected by the reduction in viscosity derived from freezing process, where a half-life of 31.11 min for a HA formulation stored for 30 days at −20 • C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops [26]. ...
... Knowing its maximum period of stability would allow its translation into clinical practice, allowing the treatment to be dispensed for longer periods and reducing the number of visits to the hospital and the workload of HPD. The present study aimed to determine the previously developed cysteamine compounded formulation [26]: (1) the maximum stability period in terms of chemical, physical, and microbiological stability, as well as to evaluate packaging oxygen permeability and how it is affected by the freeze-thaw process; and, (2) the clinical ocular surface permanence in terms of tear stability and volume in healthy volunteers to confirm the previous preclinical results. ...
Background: Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in several tissues and organs causing, among others, severe eye symptoms. The high instability of cysteamine eye drops makes it difficult to develop formulations with an acceptable shelf life to be prepared in hospital pharmacy departments. Previously, a new compounded formulation of cysteamine eye drops in hyaluronic acid (HA) packaged in innovative single-dose systems was developed. Methods: Long-term stability at −20 °C of this formulation was studied considering the content of cysteamine, pH, osmolality, viscosity, and microbiological analysis. The oxygen permeability of single-dose containers was also studied and an ocular biopermanence study was conducted in healthy volunteers measuring lacrimal stability and volume parameters. Results: Data confirm that cysteamine concentration remained above 90% for 120 days, all parameters remaining within the accepted range for ophthalmic formulations. The permeability of the containers was reduced over time, while ocular biopermanence was maintained despite the freezing process and storage time. Conclusions: 0.55% cysteamine hydrochloride formulation in HA and packaged in single-dose containers preserved at −20 °C is stable for 120 days protected from light, presenting high potential for its translation into clinical practice when commercial presentations are not available.
... Finally, innovative solutions for ocular delivery based on hydrogels [149], nanocarriers [150] or polymeric micelles [151] will be of paramount importance for maximizing bench-to-bedside transition and to improve patient adherence to the new therapeutic drugs. ...
... Finally, innovative solutions for ocular delivery based on hydrogels [149], nanocarriers [150] or polymeric micelles [151] will be of paramount importance for maximizing bench-to-bedside transition and to improve patient adherence to the new therapeutic drugs. ...
Age-related macular degeneration (AMD) is a common ocular disease characterized by degeneration of the central area of the retina in the elderly population. Progression and response to treatment are influenced by genetic and non-genetic factors. Proteomics is a powerful tool to study, at the molecular level, the mechanisms underlying the progression of the disease, to identify new therapeutic targets and to establish biomarkers to monitor progression and treatment effectiveness. In this work, we systematically review the use of proteomics-based approaches for the study of the molecular mechanisms underlying the development of AMD, as well as the progression of the disease and on-treatment patient monitoring. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guidelines were followed. Proteomic approaches have identified key players in the onset of the disease, such as complement components and proteins involved in lipid metabolism and oxidative stress, but also in the progression to advanced stages, including factors related to extracellular matrix integrity and angiogenesis. Although anti-vascular endothelial growth factor (anti-VEGF)-based therapy has been crucial in the treatment of neovascular AMD, it is necessary to deepen our understanding of the underlying disease mechanisms to move forward to next-generation therapies for later-stage forms of this multifactorial disease.
... Finally, ocular deliveries innovative solutions based on hydrogels [149] nanocarriers [150] or polymeric micelles [151] will be of paramount importance for maximizing benchto-bedside transition and to improve patient adherence to the new therapeutical drugs. ...
Age-related macular degeneration (AMD) is a common ocular disease characterized by the de-generation of the central area of the retina in elderly population. Progression and response to treatment is influenced by genetic and non-genetic factors. Proteomics is a powerful tool to study, at the molecular level, the mechanisms underlaying the progression of the diseases, to identify new therapeutical targets and to establish biomarkers to monitor progression and treatment ef-fectiveness. In this work we pursue to systematically review the use of proteomic-based ap-proaches for the study of the molecular mechanisms underlying the development of AMD, as well as the progression of the disease and the on-treatment patient monitoring. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Proteomic approaches have identified key players on the onset of the disease, such as proteins involved in lipid metabolism and oxidative stress, but also in the progression to advanced stages, including factors related to extracellular matrix integrity and angiogenesis. Although an-ti-vascular endothelial growth factor (anti-VEGF)-based therapy has been crucial in the treatment of neovascular AMD it is necessary to get deeper into the underlying disease mechanisms to move forward to next-generation therapies of the later-stage forms of this multifactorial disease.
