RESUMEN
The objective of the present study was to assess the effect of intra-articular Hyaluronic acid (HA) and Chondroitin sulfate (CS) supplementation (Hialurom® Hondro (HH)) on pain symptoms and joint mobility. In total, 60 mg/mL sodium hyaluronate and 90 mg/mL CS were administered to 21 patients (17 females and 4 males) respecting the in-force requirements, excluding patients with some specific comorbidities. In addition to the clinical study (where the pain intensity (severity) and joint mobility were assessed), rheological characterization was conducted evaluating the following parameters: elastic modulus (G'), loss modulus (Gâ³) oscillatory frequency (fc) at 0.5 Hz and 2.5 Hz, crossover frequency (fc), relaxation time (λ) where it was noticed that the addition of chondroitin sulfate (CS) to sodium hyaluronate (SH) significantly enhances and improves the viscoelastic properties, particularly at higher shear frequencies. A significant decrease in pain intensity felt by the subjects was found, from 7.48 (according to Wong-Baker scale)-pain close to 8 (the patient is unable to perform most activities), to more reduced values of 5.86-at 6 weeks after injection, 4.81-at 3 months after injection, and 5.24-at 6 months after injection, improvements in symptoms was fast and durable. Data related to the evolution of joint mobility show that at 6 weeks after injection, the mobility of joints increased by 17.8% and at 6 months by 35.61%. No serious adverse events were reported with undesired effects so that they would impose additional measures. Better resistance to enzymatic degradation and free radicals could be expected from the synergic combination of sodium hyaluronate and chondroitin sodium sulfate, this having a special importance for the patients, granting them the ability to perform more ample movements and reducing dependency on attendants, thus increasing quality of life.
Asunto(s)
Sulfatos de Condroitina , Ácido Hialurónico , Osteoartritis de la Rodilla , Viscosuplementación , Humanos , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/uso terapéutico , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/uso terapéutico , Femenino , Masculino , Osteoartritis de la Rodilla/tratamiento farmacológico , Persona de Mediana Edad , Viscosuplementación/métodos , Anciano , Dolor/tratamiento farmacológico , Rango del Movimiento Articular/efectos de los fármacos , Viscosuplementos/administración & dosificación , Viscosuplementos/uso terapéutico , Reología , Inyecciones Intraarticulares , Dimensión del DolorRESUMEN
BACKGROUND: Intravesical instillation of hyaluronic acid (HA) has been associated with reduced sexual dysfunction in participants with recurrent urinary tract infections (rUTIs), but the efficacy of an oral treatment has never been investigated. AIM: To investigate the efficacy of an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C in improving sexual and urinary symptoms in a cohort of reproductive-age participants with rUTI. METHODS: In a monocentric randomized crossover pilot trial, participants with rUTI who were referred to our institute between March 2022 and April 2023 were randomized 1:1 in 2 groups: intervention vs control. All participants had an oral preparation of cranberry, D-mannose, propolis extract, turmeric, and Boswellia twice a day for 3 months. The intervention group also included an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C once a day for 3 months. Crossover of treatment occurred at 3 months for an additional 3 months. At baseline and 3 and 6 months, participants were evaluated clinically and with the International Prostate Symptom Score (IPSS) and Female Sexual Function Index (FSFI). Descriptive statistics and logistic regression models tested the impact of the intervention on urinary and sexual symptoms at each follow-up assessment. OUTCOMES: Improvement in sexual and urinary symptoms as measured by the FSFI and IPSS. RESULTS: Overall, 27 (54%) participants had an FSFI score <26.5 at enrollment. At 3 months, FSFI scores were higher in the intervention group vs control (P < .001), but IPSS scores were lower (P = .03). After crossover of treatment, FSFI and IPSS scores remained stable in the intervention group. However, after crossover, the control group showed a significant improvement in IPSS and FSFI scores (all P < .01) vs the 3-month assessment. At last follow-up, urinary and sexual symptoms were comparable between groups. In logistic regression analyses, the intervention group was associated with early improvement in sexual symptoms (odds ratio, 3.9; P = .04) and urinary symptoms (odds ratio, 5.1; P = .01) after accounting for clinical confounders. CLINICAL IMPLICATIONS: Combination treatment with HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C is effective if started immediately or even after a few months from symptoms in participants with rUTI. STRENGTHS AND LIMITATIONS: The main limitation is the lack of long-term follow-up. CONCLUSION: The oral formulation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C could be an effective therapy against urinary and sexual distress in participants with rUTI (NCT06268483; ClinicalTrials.gov).
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Acetilglucosamina , Ácido Ascórbico , Sulfatos de Condroitina , Estudios Cruzados , Ácido Hialurónico , Infecciones Urinarias , Humanos , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/uso terapéutico , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/uso terapéutico , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/uso terapéutico , Femenino , Masculino , Adulto , Infecciones Urinarias/tratamiento farmacológico , Acetilglucosamina/administración & dosificación , Acetilglucosamina/uso terapéutico , Administración Oral , Proyectos Piloto , Disfunciones Sexuales Fisiológicas/tratamiento farmacológico , Persona de Mediana Edad , Recurrencia , Própolis/administración & dosificación , Própolis/uso terapéutico , Manosa/administración & dosificación , Manosa/uso terapéuticoRESUMEN
Objective.Severe traumatic brain injury (sTBI) induced neuronal loss and brain atrophy contribute significantly to long-term disabilities. Brain extracellular matrix (ECM) associated chondroitin sulfate (CS) glycosaminoglycans promote neural stem cell (NSC) maintenance, and CS hydrogel implants have demonstrated the ability to enhance neuroprotection, in preclinical sTBI studies. However, the ability of neuritogenic chimeric peptide (CP) functionalized CS hydrogels in promoting functional recovery, after controlled cortical impact (CCI) and suction ablation (SA) induced sTBI, has not been previously demonstrated. We hypothesized that neuritogenic (CS)CP hydrogels will promote neuritogenesis of human NSCs, and accelerate brain tissue repair and functional recovery in sTBI rats.Approach.We synthesized chondroitin 4-Osulfate (CS-A)CP, and 4,6-O-sulfate (CS-E)CP hydrogels, using strain promoted azide-alkyne cycloaddition (SPAAC), to promote cell adhesion and neuritogenesis of human NSCs,in vitro; and assessed the ability of (CS-A)CP hydrogels in promoting tissue and functional repair, in a novel CCI-SA sTBI model,in vivo. Main results.Results indicated that (CS-E)CP hydrogels significantly enhanced human NSC aggregation and migration via focal adhesion kinase complexes, when compared to NSCs in (CS-A)CP hydrogels,in vitro. In contrast, NSCs encapsulated in (CS-A)CP hydrogels differentiated into neurons bearing longer neurites and showed greater spontaneous activity, when compared to those in (CS-E)CP hydrogels. The intracavitary implantation of (CS-A)CP hydrogels, acutely after CCI-SA-sTBI, prevented neuronal and axonal loss, as determined by immunohistochemical analyses. (CS-A)CP hydrogel implanted animals also demonstrated the significantly accelerated recovery of 'reach-to-grasp' function when compared to sTBI controls, over a period of 5-weeks.Significance.These findings demonstrate the neuritogenic and neuroprotective attributes of (CS)CP 'click' hydrogels, and open new avenues for the development of multifunctional glycomaterials that are functionalized with biorthogonal handles for sTBI repair.
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Lesiones Traumáticas del Encéfalo , Hidrogeles , Células-Madre Neurales , Neuritas , Ratas Sprague-Dawley , Recuperación de la Función , Hidrogeles/administración & dosificación , Animales , Ratas , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Humanos , Células-Madre Neurales/efectos de los fármacos , Neuritas/efectos de los fármacos , Neuritas/fisiología , Masculino , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/farmacología , Glicosaminoglicanos/administración & dosificación , Células Cultivadas , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiologíaRESUMEN
BACKGROUND: To compare retention times of various ophthalmic viscosurgical devices (OVDs) and soft-shell combinations. METHODS: Experimental study. Eighteen rabbit eyes were divided into six groups of three eyes, based on OVDs tested. A: Endocoat, B: HealonPro, C: Viscoat, D: Provisc, E: Endocoat and HealonPro and F: Viscoat and Provisc. OVDs were stained with 10% fluorescein dye before being injected into the anterior chamber. Phacoemulsification, using fixed parameters, was performed. If OVD persisted after 60 s, a standardised irrigation and aspiration technique replaced phacoemulsification. The time until central and complete clearance of the OVD were video-recorded and measured. RESULTS: Mean central retention times (CRT) were found to be: HealonPro-5.33 ± 2.56 s, Provisc-3.33 ± 1.11 s, Endocoat-75.0 ± 3.26 s, Viscoat-62.33 ± 5.19 s, combining HealonPro with Endocoat-22.67 ± 4.75 s and Provisc with Viscoat-11.0 ± 0.82 s. The mean total retention time (TRT) was: Endocoat-80.0 ± 8.17 s, Viscoat-81.67 ± 2.09 s, HealonPro with Endocoat-81.33 ± 3.35 s, and Provisc with Viscoat-71.0 ± 2.94 s. For HealonPro and Provisc, CRT and TRT remained identical across all trials. CONCLUSIONS: Retention times varied, with cohesive OVDs exhibiting shorter durations than dispersive OVDs. Among dispersive OVDs, TRTs were comparable; however, Endocoat displayed an extended CRT. In soft shell trials, the combination of HealonPro and Endocoat exhibited prolonged CRT and TRT, suggesting enhanced corneal protection.
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Combinación de Medicamentos , Ácido Hialurónico , Facoemulsificación , Viscosuplementos , Animales , Conejos , Viscosuplementos/administración & dosificación , Ácido Hialurónico/administración & dosificación , Factores de Tiempo , Sulfatos de Condroitina/administración & dosificación , Modelos AnimalesRESUMEN
We have previously developed an in vitro instrument, termed subcutaneous injection site simulator (SCISSOR), that can be used to monitor release properties of an active pharmaceutical ingredient (API) and formulation components of a medicine designed for SC injection. Initial studies to validate the SCISSOR instrument applications used a simple hyaluronic acid (HA) hydrogel to monitor early release events. We now report a type of cross-linked HA that can, when combined with HA, provide a hydrogel (HA-XR) with optical clarity and rheological properties that remain stable for at least 6 days. Incorporation of 0.05-0.1 mg/mL of collagens isolated from human fibroblasts (Col F), bovine type I collagen (Col I), chicken collagen type II (Col II), or chondroitin sulphate (CS) produced HA or HA-XR hydrogel formats with optical clarity and rheological properties comparable to HA or HA-XR alone. HA + Col F hydrogel had a much greater effect on release rates of 70 kDa compared to 4 kDa dextran, while Col F incorporated into the HA-XR hydrogel accentuated differences in release rates of prandial and basal forms of insulin as well as decreased the release rate of denosumab. A hydrogel format of HA + Col I was used to examine the complex events for bevacizumab release under conditions where a target ligand (vascular endothelial growth factor) can interact with extracellular matrix (ECM). Together, these data have demonstrated the feasibility of using a cross-linked HA format to examine API release over multiple days and incorporation of specific ECM elements to prepare more biomimetic hydrogels that allow for tractable examination of their potential impact of API release.
Asunto(s)
Ácido Hialurónico , Hidrogeles , Inyecciones Subcutáneas , Ácido Hialurónico/química , Hidrogeles/química , Humanos , Animales , Interacciones Farmacológicas/fisiología , Bovinos , Reología , Sulfatos de Condroitina/química , Sulfatos de Condroitina/administración & dosificación , Insulina/administración & dosificación , Insulina/química , Bevacizumab/administración & dosificación , Bevacizumab/química , Colágeno/químicaRESUMEN
AIM: This study was aimed to assess the efficacy and safety of two oral Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOAs)-Glucosamine Sulfate, Chondroitin Sulfate, and their combination regimen in the management of knee osteoarthritis (KOA). METHODS: This systematic review was conducted according to PRISMA 2020 guidelines. A detailed literature search was performed from 03/1994 to 31/12/2022 using various electronic databases including PubMed, Embase, Cochrane Library, and Google Scholar, using the search terms-Glucosamine sulfate (GS), Chondroitin sulfate (CS), Knee osteoarthritis, Joint pain, Joint disease, and Joint structure, for literature concerning glucosamine, chondroitin, and their combination in knee osteoarthritis treatment. Cochrane Collaboration's Risk assessment tool (version 5.4.1) was used for assessing the risk of bias and the quality of the literature. The data was extracted from the included studies and subjected to statistical analysis to determine the beneficial effect of Glucosamine Sulfate, Chondroitin Sulfate, and their combination. RESULTS: Twenty-five randomized controlled trials (RCTs) were included in this systematic review. In short, exclusively 9 RCTs for GS, 13 RCTs for CS, and 3 RCTs for the combination of GS and CS. All these studies had their treatment groups compared with placebo. In the meta-analysis, CS showed a significant reduction in pain intensity, and improved physical function compared to the placebo; GS showed a significant reduction in tibiofemoral joint space narrowing. While the combination of GS and CS showed neither a reduction in pain intensity, nor any improvement in the physical function. However, the combination exhibited a non-significant reduction in joint space narrowing. In the safety evaluation, both CS and GS have shown good safety profile and were well tolerated. CONCLUSION: This meta-analysis revealed that the CS (with decreased pain intensity and improvement in the physical function), and GS (with significant reduction in the joint space narrowing) have significant therapeutic benefits. However, their combination did not significantly improve the symptoms or modify the disease. This may be due to the limited trials that are available on the combination of the sulfate forms of the intervention. Hence, there is a scope for conducting multicentric randomised controlled trials to evaluate and conclude the therapeutic role of CS and GS combination in the management of KOA.
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Sulfatos de Condroitina , Quimioterapia Combinada , Glucosamina , Osteoartritis de la Rodilla , Ensayos Clínicos Controlados Aleatorios como Asunto , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/efectos adversos , Sulfatos de Condroitina/uso terapéutico , Humanos , Osteoartritis de la Rodilla/tratamiento farmacológico , Glucosamina/uso terapéutico , Glucosamina/administración & dosificación , Glucosamina/farmacología , Resultado del TratamientoRESUMEN
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer for which effective therapies are lacking. Targeted remodeling of the immunosuppressive tumor microenvironment (TME) and activation of the body's immune system to fight tumors with well-designed nanoparticles have emerged as pivotal breakthroughs in tumor treatment. To simultaneously remodel the immunosuppressive TME and trigger immune responses, we designed two potential therapeutic nanodelivery systems to inhibit TNBC. First, the bromodomain-containing protein 4 (BRD4) inhibitor JQ1 and the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) were coloaded into chondroitin sulfate (CS) to obtain CS@JQ1/CXB nanoparticles (NPs). Then, the biomimetic nanosystem MM@P3 was prepared by coating branched polymer poly(ß-amino ester) self-assembled NPs with melittin embedded macrophage membranes (MM). Both in vitro and in vivo, the CS@JQ1/CXB and MM@P3 NPs showed excellent immune activation efficiencies. Combination treatment exhibited synergistic cytotoxicity, antimigration ability, and apoptosis-inducing and immune activation effects on TNBC cells and effectively suppressed tumor growth and metastasis in TNBC tumor-bearing mice by activating the tumor immune response and inhibiting angiogenesis. In summary, this study offers a novel combinatorial immunotherapeutic strategy for the clinical TNBC treatment.
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Azepinas , Celecoxib , Triazoles , Neoplasias de la Mama Triple Negativas , Microambiente Tumoral , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral/efectos de los fármacos , Animales , Femenino , Ratones , Humanos , Celecoxib/administración & dosificación , Línea Celular Tumoral , Sulfatos de Condroitina/química , Sulfatos de Condroitina/administración & dosificación , Nanopartículas/química , Nanopartículas/administración & dosificación , Meliteno/administración & dosificación , Meliteno/química , Apoptosis/efectos de los fármacos , Sistema de Administración de Fármacos con Nanopartículas/química , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Polímeros/química , Ratones Desnudos , Sistemas de Liberación de Medicamentos/métodosRESUMEN
AIM: To evaluate the efficacy of Artneo (AN) in comparison with a combination of glucosamine hydrochloride and chondroitin sulfate (GC) in patients with osteoarthritis (OA) of the knee joint (KJ). MATERIALS AND METHODS: 70 patients with stages I-III of primary knee OA were randomized into 2 groups. Participants in the 1st (n=35) took AN 1 caps/day, in the 2nd (n=35) GC according to the standard regimen. After 7, 30, 90, 180 days, the Lequesne index (severity of OA), pain when moving according to VAS, WOMAC score were assessed, after 1, 3, 6 months - quality of life SF-36 and morning stiffness, after 6 months - MRI with T2 mapping, laboratory safety indicators. RESULTS: Over the course of 6 months of use, an improvement in the WOMAC index and a decrease in pain were observed without intergroup differences, and a greater decrease in stiffness in the AN group. After 3 months, the severity of OA decreased from moderate to mild in the AN group and was significantly lower compared to the GC group; quality of life (physical component of SF-36) was higher in the AN group. After 6 months, there was an improvement in cartilage ultrastructure (T2 relaxation time) in both groups and a more pronounced reduction of the synovitis area (MRI) in the AN group (2.95 and 1.37 times in the AN and GC group, respectively). There were no clinically significant adverse reactions observed in both groups. CONCLUSION: The use of AN in patients with stage I-III primary knee OA was not inferior in efficacy to the combination of GC. Further studies with greater statistical power (sample size) and follow-up period are warranted including in real clinical practice.
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Sulfatos de Condroitina , Glucosamina , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/tratamiento farmacológico , Masculino , Femenino , Glucosamina/administración & dosificación , Glucosamina/farmacología , Persona de Mediana Edad , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/farmacología , Resultado del Tratamiento , Dimetilsulfóxido/administración & dosificación , Dimetilsulfóxido/farmacología , Triterpenos/administración & dosificación , Triterpenos/farmacología , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Anciano , Colágeno Tipo II/administración & dosificación , Calidad de Vida , Índice de Severidad de la Enfermedad , Dimensión del Dolor , Quimioterapia Combinada , Sulfonas/administración & dosificación , Sulfonas/farmacologíaRESUMEN
This study is a randomized, placebo-controlled, double-blinded trial performed to investigate the effects of a dietary supplement containing a mixture of Boswellia serrata Roxb., chlorophyll, green tea extract, glucosamine, chondroitin sulfate, hyaluronic acid, and further in the manuscript: non-hydrolised type II collagen in dogs with osteoarthritis (OA). A total of 40 dogs were enrolled in the study, they were randomly divided in control (CTR) and treatment (TRT) groups. The TRT group received the dietary supplement for 60 days. The CTR group received a placebo for the same number of days. All the subjects had veterinary evaluations during the trial and owners were requested to fill in questionnaires on chronic pain using the Helsinki Chronic Pain Index. The product was easy to administer and no side effects were reported. Combining results from veterinarian and owner evaluations, the tested product proved to be significantly beneficial in alleviating pain and in reducing the clinical signs in dogs with OA.
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Sulfatos de Condroitina/administración & dosificación , Suplementos Dietéticos , Glucosamina/administración & dosificación , Ácido Hialurónico/administración & dosificación , Osteoartritis de la Rodilla/dietoterapia , Animales , Perros , Método Doble Ciego , Masculino , Resultado del Tratamiento , Viscosuplementos/administración & dosificaciónRESUMEN
Our previous study found that low molecular weight chondroitin sulfate (LMWCS) had neuroprotective effects against the toxicity of amyloid-ß (Aß) peptides both in vitro and in vivo, and we speculated that the effects might be related with its anti-oxidative activities. In this study, the anti-Alzheimer's disease (AD) activity of LMWCS was further studied in 5XFAD transgenic mice. After 4-month gavage, the levels of Aß1-42 level, amyloid precursor protein (APP) and presenilin 1 (PS1) were significantly decreased in the brains of 5XFAD mice, indicating the alteration of APP metabolism by LMWCS. Besides, LMWCS inhibited the secretions of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6. Furthermore, the suppression of neuroinflammation by LMWCS was supported by the decreased expressions of glial fibrillary acidic protein (GFAP) and toll-like receptor 2 (TLR2) in the brains. LMWCS also reduced the production of reactive oxygen species (ROS) and the level of phospho-tau (Ser404) in the brains. Nevertheless, the changes in the behavior tests were moderate. In conclusion, LMWCS administration ameliorated APP metabolism, neuroinflammation, ROS production and tau protein abnormality in the brains of 5XFAD mice, displaying the potential to improve the pathological changes of AD mouse brain. LMWCS could be considered as a promising anti-AD drug candidate, nonetheless, the therapy regimen need to be optimized to improve its pharmacotherapy efficacy.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Sulfatos de Condroitina/farmacología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Fármacos Neuroprotectores/farmacología , Enfermedad de Alzheimer/inmunología , Péptidos beta-Amiloides/efectos de los fármacos , Precursor de Proteína beta-Amiloide/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Sulfatos de Condroitina/administración & dosificación , Citocinas/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Peso Molecular , Enfermedades Neuroinflamatorias/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Presenilina-1/efectos de los fármacos , Proteínas tau/efectos de los fármacosRESUMEN
Marine organisms are a source of active biomolecules with immense therapeutic and nutraceutical potential. Sulfated fucose-rich polysaccharides are present in large quantities in these organisms with important pharmacological effects in several biological systems. These polysaccharides include sulfated fucan (as fucoidan) and fucosylated chondroitin sulfate. The development of these polysaccharides as new drugs involves several important steps, among them, demonstration of the effectiveness of these compounds after oral administration. The oral route is the more practical, comfortable and preferred by patients for long-term treatments. In the past 20 years, reports of various pharmacological effects of these polysaccharides orally administered in several animal experimental models and some trials in humans have sparked the possibility for the development of drugs based on sulfated polysaccharides and/or the use of these marine organisms as functional food. This review focuses on the main pharmacological effects of sulfated fucose-rich polysaccharides, with an emphasis on the antidislipidemic, immunomodulatory, antitumor, hypoglycemic and hemostatic effects.
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Antineoplásicos/farmacología , Organismos Acuáticos , Sulfatos de Condroitina/farmacología , Polisacáridos/farmacología , Administración Oral , Antineoplásicos/administración & dosificación , Sulfatos de Condroitina/administración & dosificación , Humanos , Polisacáridos/administración & dosificaciónRESUMEN
Inhibiting the activity of the intestinal enzyme α-amylase that catalyzes the degradation of starch into glucose can control blood glucose and provide an essential way for the treatment of Type-II diabetes mellitus (T2DM). Here, we compared the structural information of chondroitin sulfate (CS) from different origins and the effects on activity of α-amylase and blood glucose have been investigated. The inhibitory effects of shark and porcine CSs against α-amylase activity is obvious with IC50 values of 11.97 and 14.42 mg/ml, respectively, but the bovine CS almost no effect. From the data of fluorescence spectroscopic analyses, CSs from shark and pig quench Try fluorescence intensity of the enzyme, whereas bovine CS induces an increase. In vivo, oral administration of shark and porcine CSs efficiently suppresses postprandial blood glucose levels in normal and diabetic mice. Our study found that CSs from different sources showed different biological functions even if both molecular weight and disaccharide subunit composition are almost the same, and demonstrated that the CSs from shark and pig as α-amylase inhibitors could be regarded as a novel functional food ingredient in T2DM management.
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Sulfatos de Condroitina/administración & dosificación , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , alfa-Amilasas/antagonistas & inhibidores , Administración Oral , Animales , Glucemia/efectos de los fármacos , Bovinos , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/enzimología , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Concentración 50 Inhibidora , Masculino , Ratones , Tiburones , Especificidad de la Especie , Estreptozocina , Porcinos , Resultado del TratamientoRESUMEN
Components of the extracellular matrix (ECM) are overexpressed in fibrotic liver. Collagen is the main component of the liver fibrosis stroma. Here we demonstrate that chondroitin sulfate coated multilayered 50-nm nanoparticles encapsulating collagenase and silibinin (COL + SLB-MLPs) break down the dense collagen stroma, while silibinin inhibits activated hepatic stellate cells. The nanoparticles were taken up to a much greater extent by hepatic stellate cells than by normal hepatocytes, and they down-regulated production of type I collagen. In addition, chondroitin sulfate protected the collagenase from premature deactivation. COL + SLB-MLPs were delivered to the cirrhotic liver, and the collagenase and silibinin synergistically inhibited fibrosis in mice. Immunofluorescence staining of liver tissues revealed that CD44, mediated by chondroitin sulfate, delivered the nanoparticles to hepatic stellate cells. This strategy holds promise for degrading extracellular stroma and thereby facilitating drug penetration into fibrotic liver and related diseases such as liver cirrhosis and liver cancer.
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Sulfatos de Condroitina/química , Sulfatos de Condroitina/metabolismo , Colagenasas/química , Colagenasas/farmacología , Cirrosis Hepática/tratamiento farmacológico , Nanopartículas/química , Silibina/química , Silibina/farmacología , Animales , Cápsulas/química , Línea Celular , Sulfatos de Condroitina/administración & dosificación , Colagenasas/administración & dosificación , Modelos Animales de Enfermedad , Células Estrelladas Hepáticas/efectos de los fármacos , Humanos , Receptores de Hialuranos/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/patología , Ratones , Nanopartículas/uso terapéutico , Silibina/administración & dosificaciónRESUMEN
Chondroitin sulfate (CS) belongs to a class of molecules called glycosaminoglycans (GAGs). These are long, linear chains of polysaccharides comprising alternating amino sugars and hexuronic acid. Similar to other GAGs, CS is important in a multitude of biological activities. Alteration of CS levels has been implicated in several pathological conditions, including osteoarthritis (OA) and other inflammatory diseases, as well as physiological conditions, such as aging. Therefore, devising replenishment strategies for this molecule is an important area of research. In this review, we discuss the nature of CS, its function in different organs, and its implications in health and disease. We also describe different methods for the exogenous administration of CS.
Asunto(s)
Sulfatos de Condroitina/metabolismo , Inflamación/patología , Osteoartritis/patología , Envejecimiento/fisiología , Animales , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/química , Humanos , Inflamación/terapia , Osteoartritis/terapiaRESUMEN
BACKGROUND: Osseointegration is the premise of the chewing function of dental implant. Nerve growth factor (NGF), as a neurotrophic factor, can induce bone healing. However, the influence of NGF-chondroitin sulfate (CS)/hydroxyapatite (HA)-coating composite implant on the osseointegration and innervations is still not entirely clear. MATERIALS AND METHODS: NGF-CS/HA-coating composite implants were prepared using the modified biomimetic method. The characteristics of NGF-CS/HA-coating implants were determined using a scanning electron microscope. After NGF-CS/HA-coating implants were placed in the mandible of Beagle dogs, the early osseointegration and innervation in peri-implant tissues were assessed through X-ray, Micro-CT, maximal pull-out force, double fluorescence staining, toluidine blue staining, DiI neural tracer, immunohistochemistry, and RT-qPCR assays. RESULTS: NGF-CS/HA-coating composite implants were made successfully, which presented porous mesh structures with the main components (Ti and HA). Besides, we revealed that implantation of NGF-CS/HA-coating implants significantly changed the morphology of bone tissues and elevated maximum output, MAR, BIC, and nerve fiber in the mandible of Beagle dogs. Moreover, we proved that the implantation of NGF-CS/HA-coating implants also markedly upregulated the levels of NGF, osteogenesis differentiation, and neurogenic differentiation-related genes in the mandible of Beagle dogs. CONCLUSION: Implantation of NGF-CS/HA-coating composite implants has significant induction effects on the early osseointegration and nerve regeneration of peri-implant tissues in the mandible of Beagle dogs.
Asunto(s)
Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/farmacología , Resinas Compuestas , Implantes Dentales , Diseño de Prótesis Dental , Mandíbula/inervación , Mandíbula/fisiología , Células Madre Mesenquimatosas/fisiología , Factor de Crecimiento Nervioso/administración & dosificación , Factor de Crecimiento Nervioso/farmacología , Regeneración Nerviosa/efectos de los fármacos , Oseointegración/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Perros , Masculino , Mandíbula/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Regeneración Nerviosa/fisiología , Oseointegración/fisiología , Cicatrización de HeridasRESUMEN
In this article, we describe a method of delivery of chondroitin sulfate to skin as nanoparticles and demonstrate its anti-inflammatory and antioxidant role using UV irradiation as a model condition. These nanoparticles, formed through electrostatic interactions of chondroitin sulfate with a skin-penetrating peptide, were found to be homogenous with positive surface charges and stable at physiological and acidic pH under certain conditions. They were able to enter into the human keratinocyte cell line (HaCaT), artificial skin membrane (mimicking the human skin), and mouse skin tissue unlike free chondroitin sulfate. The preapplication of nanoparticles also exhibited reduced levels of oxidative stress, cyclobutane pyrimidine dimer formation, TNF-α, and so on in UV-B-irradiated HaCaT cells. In an acute UV-B irradiation mouse model, their topical application resulted in reduced epidermal thickness and sunburn cells, unlike in the case of free chondroitin sulfate. Thus, a completely noninvasive method was used to deliver a bio-macromolecule into the skin without using injections or abrasive procedures.
Asunto(s)
Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Sulfatos de Condroitina/administración & dosificación , Portadores de Fármacos/química , Péptidos/química , Quemadura Solar/prevención & control , Administración Tópica , Animales , Antiinflamatorios/farmacocinética , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacocinética , Antioxidantes/uso terapéutico , Línea Celular , Sulfatos de Condroitina/farmacocinética , Sulfatos de Condroitina/uso terapéutico , Portadores de Fármacos/metabolismo , Femenino , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/patología , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Nanopartículas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Péptidos/metabolismo , Absorción Cutánea , Quemadura Solar/metabolismo , Quemadura Solar/patología , Rayos Ultravioleta/efectos adversosRESUMEN
Recent treatment approaches of osteoarthritis (OA) face a number of obstacles due to the progressive multitude of pain generators, nociceptive mechanisms, first pass mechanism, less efficacy and compromised safety. The present study was aimed to bring a novel approach for the effective management of OA, by developing sublingual targeted nanovesicles (NVs) bearing tapentadol HCl (TAP), surface modified with chondroitin sulfate (CS). Optimized nontargeted nanovesicle formulation (MB-NV) was developed by an ultrasound method, characterized as spherical in shape, nanometric in size (around 150 nm) with narrow size distribution (polydispersity index <0.5), and good entrapment efficiency (around 50%). MB-NV conjugated with CS which was confirmed by IR and 1H NMR spectroscopy. C-MB-NV showed improved pharmacokinetics parameters i.e. increased t1/2 (9.7 h), AUC (159.725 µg/mL*h), and MRT (14.99 h) of TAP than nontargeted formulation and plain drug soln. C-MB-NV in in vitro release studies proved sustained drug release pattern for more than 24 h following Higuchi model kinetics with Fickian diffusion (n ≤ 0.5).Targeted nanovesicles exhibited an improved bioavailability and enhanced analgesic activity in a disease-induced Wistar rat model which indicated the superior targeting potential of C-MB-NV exploiting CD44 receptors as mediators, overexpressed at the affected joints in the OA model. It could be a propitious approach to accustomed therapies for methodical and efficient management in advanced OA therapy.
Asunto(s)
Sulfatos de Condroitina/uso terapéutico , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Osteoartritis/tratamiento farmacológico , Tapentadol/uso terapéutico , Administración Sublingual , Animales , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/química , Portadores de Fármacos/química , Humanos , Masculino , Estructura Molecular , Tamaño de la Partícula , Ratas , Ratas Wistar , Tapentadol/administración & dosificación , Tapentadol/químicaRESUMEN
The polysaccharide-based biomaterials hyaluronic acid (HA) and chondroitin sulfate (CS) have aroused great interest for use in drug delivery systems for tumor therapy, as they have outstanding biocompatibility and great targeting ability for cluster determinant 44 (CD44). In addition, modified HA and CS can self-assemble into micelles or micellar nanoparticles (NPs) for targeted drug delivery. This review discusses the formation of HA- and CS-based NPs, and various types of CS-based NPs including CS-drug conjugates, CS-polymer NPs, CS-small molecule NPs, polyelectrolyte nanocomplexes (PECs), CS-metal NPs, and nanogels. We then focus on the applications of HA- and CS-based NPs in tumor chemotherapy, gene therapy, photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and immunotherapy. Finally, this review is expected to provide guidelines for the development of various HA- and CS-based NPs used in multiple cancer therapies.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Glicosaminoglicanos/administración & dosificación , Receptores de Hialuranos/inmunología , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Animales , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/química , Ensayos Clínicos como Asunto , Doxorrubicina/administración & dosificación , Glicosaminoglicanos/química , Glicosaminoglicanos/inmunología , Humanos , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/química , Terapia Molecular Dirigida , Nanopartículas/química , Neoplasias/patología , Neoplasias/terapia , Inhibidores de Topoisomerasa II/administración & dosificaciónRESUMEN
Knee osteoarthritis (OA) is a heterogeneous disease associated with substantial effects on quality of life, and its clinical management is difficult. Among the several available guidelines for the management of knee OA, those from OARSI and ESCEO were updated in 2019. Here, we examine the similarities and differences between these two guidelines and provide a narrative to help guide health-care providers through the complexities of non-surgical management of knee OA. OARSI and ESCEO both recommend education, structured exercise and weight loss as core treatments, topical NSAIDs as first-line treatments and oral NSAIDs and intra-articular injections for persistent pain. Low-dose, short-term acetaminophen, pharmaceutical grade glucosamine and chondroitin sulfate are recommended by ESCEO whereas OARSI strongly recommends against their use (including all glucosamine and chondroitin formulations). Despite this difference, the two guidelines are consistent in the majority of their recommendations and provide useful treatment recommendations for individuals with OA and health-care providers.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Terapia por Ejercicio/métodos , Osteoartritis de la Rodilla/tratamiento farmacológico , Administración Tópica , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/uso terapéutico , Sulfatos de Condroitina/administración & dosificación , Sulfatos de Condroitina/uso terapéutico , Consenso , Medicina Basada en la Evidencia/métodos , Glucosamina/administración & dosificación , Glucosamina/uso terapéutico , Personal de Salud/educación , Humanos , Inyecciones Intraarticulares , Osteoartritis de la Rodilla/psicología , Guías de Práctica Clínica como Asunto , Calidad de Vida , Pérdida de Peso/fisiologíaRESUMEN
Fucosylated chondroitin sulfate (FCS) polysaccharide isolated from sea cucumber has potent anticoagulant activity. Based on its resistance to the enzymes present in vertebrates, it may serve as an anticoagulant and shows antithrombotic effects when delivered through gastro-resistant (GR) tablets. However, due to the multiple plasma targets of FCS polysaccharide in the coagulation pathway, bleeding can occur after its oral administration. In the current study, we used FCS oligomers, in particular a mixture of oligosaccharides having 6 to 18 saccharide units, as the active ingredient in GR microcapsules for oral anticoagulation. In a Caco-2 model, the FCS oligomers showed higher absorption than native FCS polysaccharides. Oral administration of FCS oligomer-GR microcapsules provided a dose-dependent, prolonged anticoagulant effect with a selective inhibition of the intrinsic coagulation pathway when compared with subcutaneous administration of FCS oligomers or oral administration of unformulated FCS oligomers or native FCS-GR microspheres. Continued oral administration of FCS oligomer-GR microcapsules did not result in the accumulation of oligosaccharides in the plasma. Venous thrombosis animal models demonstrated that FCS oligomers delivered via GR microcapsules produced a potent antithrombotic effect dependent on their anticoagulant properties in the plasma, while oral administration of unformulated FCS oligomers at the same dose exhibited a weaker antithrombotic effect than the formulated version. Oral administration of FCS oligomer-GR microcapsules resulted in no bleeding, while oral administration of native FCS-GR microcapsules resulted in bleeding (p < 0.05). Our present results suggest that a FCS oligomer-GR microcapsule formulation represents an effective and safe oral anticoagulant for potential clinical applications.