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1.
PLoS One ; 17(2): e0263971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35171954

RESUMO

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.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Suplementos Nutricionais , Glucosamina/administração & dosagem , Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/dietoterapia , Animais , Cães , Método Duplo-Cego , Masculino , Resultado do Tratamento , Viscossuplementos/administração & dosagem
2.
Neuropharmacology ; 199: 108796, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34543632

RESUMO

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.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Sulfatos de Condroitina/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/imunologia , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/efeitos dos fármacos , Precursor de Proteína beta-Amiloide/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Sulfatos de Condroitina/administração & dosagem , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Peso Molecular , Doenças Neuroinflamatórias/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Presenilina-1/efeitos dos fármacos , Proteínas tau/efeitos dos fármacos
3.
Mar Drugs ; 19(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34436263

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Organismos Aquáticos , Sulfatos de Condroitina/farmacologia , Polissacarídeos/farmacologia , Administração Oral , Antineoplásicos/administração & dosagem , Sulfatos de Condroitina/administração & dosagem , Humanos , Polissacarídeos/administração & dosagem
4.
Int J Biol Macromol ; 184: 289-296, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119546

RESUMO

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.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , alfa-Amilases/antagonistas & inibidores , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Bovinos , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/enzimologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Concentração Inibidora 50 , Masculino , Camundongos , Tubarões , Especificidade da Espécie , Estreptozocina , Suínos , Resultado do Tratamento
5.
Carbohydr Polym ; 263: 117964, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33858569

RESUMO

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.


Assuntos
Sulfatos de Condroitina/química , Sulfatos de Condroitina/metabolismo , Colagenases/química , Colagenases/farmacologia , Cirrose Hepática/tratamento farmacológico , Nanopartículas/química , Silibina/química , Silibina/farmacologia , Animais , Cápsulas/química , Linhagem Celular , Sulfatos de Condroitina/administração & dosagem , Colagenases/administração & dosagem , Modelos Animais de Doenças , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/patologia , Camundongos , Nanopartículas/uso terapêutico , Silibina/administração & dosagem
6.
Drug Discov Today ; 26(5): 1185-1199, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33549530

RESUMO

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.


Assuntos
Sulfatos de Condroitina/metabolismo , Inflamação/patologia , Osteoartrite/patologia , Envelhecimento/fisiologia , Animais , Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/química , Humanos , Inflamação/terapia , Osteoartrite/terapia
7.
J Orthop Surg Res ; 16(1): 51, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33436038

RESUMO

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.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/farmacologia , Resinas Compostas , Implantes Dentários , Planejamento de Prótese Dentária , Mandíbula/inervação , Mandíbula/fisiologia , Células-Tronco Mesenquimais/fisiologia , Fator de Crescimento Neural/administração & dosagem , Fator de Crescimento Neural/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Cães , Masculino , Mandíbula/metabolismo , Fator de Crescimento Neural/metabolismo , Regeneração Nervosa/fisiologia , Osseointegração/fisiologia , Cicatrização
8.
ACS Appl Mater Interfaces ; 13(2): 2382-2398, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33406837

RESUMO

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.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Sulfatos de Condroitina/administração & dosagem , Portadores de Fármacos/química , Peptídeos/química , Queimadura Solar/prevenção & controle , Administração Tópica , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Linhagem Celular , Sulfatos de Condroitina/farmacocinética , Sulfatos de Condroitina/uso terapêutico , Portadores de Fármacos/metabolismo , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/metabolismo , Absorção Cutânea , Queimadura Solar/metabolismo , Queimadura Solar/patologia , Raios Ultravioleta/efeitos adversos
9.
Curr Eye Res ; 46(7): 919-929, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33289602

RESUMO

Purpose: To evaluate the efficacy of a preservative free sodium hyaluronate/chondroitin sulfate ophthalmic solution (SH/CS-PF) in patients with dry eye disease (DED).Methods: This was a randomized phase IV, multicentric, prospective, double-blind clinical trial. Intent-to-treat (ITT) and per-protocol (PP) analyses were performed. Patients were assigned to receive either SH/CS-PF, Systane® Ultra (PEG/PG) or Systane® Ultra PF (PEG/PG-PF) for 90 days. A total of 326 patients were included in the ITT, and 217 in the PP analysis. Efficacy endpoints were goblet cell density, Nelson's grades (conjunctival impression cytology), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), and Schirmer's test. Other parameters included were tolerability, measured by the ocular symptomatology; and safety, measured through corneal staining, intraocular pressure, visual acuity and adverse events.Results: In the ITT, there was a significant increase in mean goblet cell density in all treatments compared with their baseline (28.4% vs 21.4% and 30.8%), without difference between arms (p = .159). Eyes exposed to SH/CS-PF, PEG/PG and PEG/PG-PF showed Grade 0-I squamous metaplasia (85.5%, 87.9% and 93.2%, respectively). Similar improvements were observed for TBUT (1.24 ± 2.3s vs 1.27 ± 2.4s and 1.39 ± 2.3s) and OSDI scores at day 90 (-8.81 ± 8.6 vs -7.95 ± 9.2 and -8.78 ± 9.8), although no significant intergroup difference was found. Schirmer's test also presented improvement compared to baseline (1.38 ± 4.9 vs 1.50 ± 4.7 and 2.63 ± 5.9), with a significantly higher variation for PEG/PG-PF. There were no significant differences between treatments for any tolerability and safety parameter, nor between ITT and PP analyses for any outcome.Conclusions: The topical application of SH/CS-PF is as effective, safe and well tolerated as that of PEG/PG or PEG/PG-PF. The results suggest that SH/CS-PF may lead to normalization of clinical parameters and symptom alleviation in patients treated for DED.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Administração Oftálmica , Adulto , Idoso , Idoso de 80 Anos ou mais , Sulfatos de Condroitina/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Síndromes do Olho Seco/fisiopatologia , Feminino , Fluorofotometria , Humanos , Ácido Hialurônico/efeitos adversos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Conservantes Farmacêuticos , Estudos Prospectivos , Lágrimas/fisiologia , Resultado do Tratamento , Acuidade Visual/fisiologia , Adulto Jovem
10.
J Liposome Res ; 31(1): 30-44, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32064982

RESUMO

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.


Assuntos
Sulfatos de Condroitina/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Osteoartrite/tratamento farmacológico , Tapentadol/uso terapêutico , Administração Sublingual , Animais , Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/química , Portadores de Fármacos/química , Humanos , Masculino , Estrutura Molecular , Tamanho da Partícula , Ratos , Ratos Wistar , Tapentadol/administração & dosagem , Tapentadol/química
11.
Nat Rev Rheumatol ; 17(1): 59-66, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33116279

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Terapia por Exercício/métodos , Osteoartrite do Joelho/tratamento farmacológico , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/uso terapêutico , Consenso , Medicina Baseada em Evidências/métodos , Glucosamina/administração & dosagem , Glucosamina/uso terapêutico , Pessoal de Saúde/educação , Humanos , Injeções Intra-Articulares , Osteoartrite do Joelho/psicologia , Guias de Prática Clínica como Assunto , Qualidade de Vida , Redução de Peso/fisiologia
12.
Pediatr Res ; 89(6): 1373-1379, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32920604

RESUMO

Necrotizing enterocolitis (NEC) is a devastating condition affecting up to 5% of neonatal intensive care unit (NICU) admissions. Risk factors include preterm delivery, low birth weight, and antibiotic use. The pathogenesis is characterized by a combination of intestinal ischemia, necrosis of the bowel, reperfusion injury, and sepsis typically resulting in surgical resection of afflicted bowel. Targeted medical therapy remains elusive. Chondroitin sulfate (CS) holds the potential to prevent the onset of NEC through its anti-inflammatory properties and protective effect on the gut microbiome. The purpose of this review is to outline the many properties of CS to highlight its potential use in high-risk infants and attenuate the severity of NEC. The purpose of this review is to (1) discuss the interaction of CS with the infant microbiome, (2) review the anti-inflammatory properties of CS, and (3) postulate on the potential role of CS in preventing NEC. IMPACT: NEC is a costly medical burden in the United States. Breast milk is the best preventative measure for NEC, but not all infants in the NICU have access to breast milk. Novel therapies and diagnostic tools are needed for NEC. CS may be a potential therapy for NEC due to its potent anti-inflammatory properties. CS could be added to the formula in an attempt to mitigate breast milk disparities.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Enterocolite Necrosante/prevenção & controle , Microbioma Gastrointestinal , Leite Humano , Enterocolite Necrosante/microbiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Índice de Gravidade de Doença
13.
Thromb Haemost ; 121(1): 15-26, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32862408

RESUMO

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.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/uso terapêutico , Fibrinolíticos/administração & dosagem , Fibrinolíticos/uso terapêutico , Trombose Venosa/tratamento farmacológico , Administração Oral , Animais , Células CACO-2 , Cápsulas , Sulfatos de Condroitina/efeitos adversos , Sulfatos de Condroitina/farmacocinética , Liberação Controlada de Fármacos , Fibrinolíticos/efeitos adversos , Fibrinolíticos/farmacocinética , Hemorragia/induzido quimicamente , Humanos , Absorção Intestinal , Masculino , Ratos Sprague-Dawley
14.
Kaohsiung J Med Sci ; 37(5): 411-418, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33340254

RESUMO

Promising cancer treatment requires the assistant of drug delivery systems (DDS) with the aim to increase the accumulation of drugs in tumor tissue. Herein, a hybrid DDS was successfully developed to integrate chondroitin sulfate (CS) and calcium carbonate (CC) in to one system. Anticancer drug adriamycin (Adr) was preloaded into CC nanoparticles to obtain Adr-loaded CC nanoparticles (CC/Adr). The resulted CS-CC/Adr nanoparticles as a biocompatible DDS was able to specifically target cancer cells to enhance the chemotherapy of lung cancer due to the surface modification of CS. Intracellular uptake as well as in vivo imaging results revealed the obtained CS-CC/Adr nanoparticles (size of ~100 nm) showed CS mediated tumor specific accumulation into A549 and LLC cells than unmodified CC/Adr, in which the CD44 receptor might be involved, which finally resulted in stronger anticancer capability than Adr or CC/Adr. As a result, CS-CC/Adr nanoparticles could be further extended to clinical administration in our future works.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Materiais Biocompatíveis , Carbonato de Cálcio/química , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Desenho de Fármacos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Hemólise , Humanos , Receptores de Hialuronatos/química , Técnicas In Vitro , Neoplasias Pulmonares/metabolismo , Masculino , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Nanomedicina/métodos , Nanopartículas/química , Transplante de Neoplasias
15.
Carbohydr Polym ; 251: 117103, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142641

RESUMO

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.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Glicosaminoglicanos/administração & dosagem , Receptores de Hialuronatos/imunologia , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/química , Ensaios Clínicos como Assunto , Doxorrubicina/administração & dosagem , Glicosaminoglicanos/química , Glicosaminoglicanos/imunologia , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/química , Terapia de Alvo Molecular , Nanopartículas/química , Neoplasias/patologia , Neoplasias/terapia , Inibidores da Topoisomerase II/administração & dosagem
16.
Reumatismo ; 72(3): 125-130, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213125

RESUMO

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1ß, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p<0.01), Lequesne (p=0.014) and VAS pain (p<0.01). On the contrary, no significant changes were found in the control group. The SF collected from the treated group showed a reduction of IL-8 (p=0.015), IL-6 and IL-10 levels, while no changes in cytokines were observed in the control group. This pilot study suggests that an oral administration of a preparation containing a combination of HA, CS and K can improve some clinical parameters and affect cytokine concentrations in SF in patients with knee OA.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Colágeno Tipo II/administração & dosagem , Ácido Hialurônico/administração & dosagem , Queratinas/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Líquido Sinovial/química , Administração Oral , Artrocentese , Combinação de Medicamentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Humanos , Interleucina-10/análise , Interleucina-1beta/análise , Interleucina-6/análise , Interleucina-8/análise , Pessoa de Meia-Idade , Projetos Piloto , Avaliação de Sintomas/métodos , Líquido Sinovial/efeitos dos fármacos
18.
Khirurgiia (Mosk) ; (7): 76-81, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32736467

RESUMO

OBJECTIVE: To evaluate symptom-modifying effects of a two-month parenteral therapy with chondroitin sulfate («Mucosat¼) in patients with knee and/or hip osteoarthritis (OA) in various combinations of adjuvant therapy. MATERIAL AND METHODS: There were 70 patients with primary and/or post-traumatic unilateral/bilateral knee and/or hip osteoarthritis (Kellgren-Lawrence grade I-II). Pain syndrome severity was assessed as ≥ 50 mm (100-mm VAS), total Leken's index - ≥ 5 points. The main group comprised 40 patients who received Mucosat for 60 days. NSAIDs were additionally prescribed in 9 (22.5%) of these patients. The control group included 30 patients with intra-articular injection of hyaluronic acid. All patients underwent clinical and functional examination (rating scales VAS, Leken's total index, WOMAC index, EQ-5D health questionnaire), laboratory diagnosis (IL-1, IL-6, TNF-α), X-ray examination, assessment of adverse events at 5 visits. RESULTS AND CONCLUSION: Administration of chondroitin sulfate is associated with reduced local pain syndrome and functional normalization of musculoskeletal system. Prolonged pain-free period with high safety profile due to reduced need for NSAIDs is an advantage of Mucosat therapy. Thus, this drug may be recommended for initial therapy. A combination of chondroitin sulfate with intra-articular injection of hyaluronic acid may be perspective for optimization of therapy and secondary prevention of exacerbations of OA. Further research is required.


Assuntos
Sulfatos de Condroitina/uso terapêutico , Ácido Hialurônico/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Artralgia/tratamento farmacológico , Artralgia/etiologia , Sulfatos de Condroitina/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intra-Articulares , Osteoartrite do Quadril/complicações , Osteoartrite do Joelho/complicações , Substâncias Protetoras/administração & dosagem , Resultado do Tratamento
19.
Turk J Gastroenterol ; 31(6): 466-473, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32721918

RESUMO

BACKGROUND/AIMS: A novel medical device based on hyaluronic acid, chondroitin sulphate plus aluminum hydroxide (GERDOFF®, melt-in-mouth tablets) showed efficacy in reducing GER-related symptoms. This exploratory, open-label study evaluated symptomatic effects of a 14-day treatment with GERDOFF® in GERD patients. MATERIALS AND METHODS: GERD Impact Scale (GIS) questionnaire was filled at baseline visit, after 7 and 14 days of treatment; patients' Global Satisfaction was evaluated at the final visit. Primary endpoint was the reduction of heartburn episodes per week; secondary endpoints were GERD-related symptoms, patients' satisfaction, and safety. RESULTS: Forty patients were included, 22 were on stable therapy with proton pump inhibitor (PPI). Compared to baseline, the days with heartburn episodes and the GIS score progressively decreased during the first (p<0.0001) and the second week of treatment (p<0.0001). Heartburn episodes per week (p<0.0001) and the GIS score (p<0.0001) decreased in the first and the last 7 days of 14-day treatment and did not differ between patients on and off PPI. The treatment was safe and well-tolerated, and it was rated as very good (46.2%) or good (43.6%) on the satisfaction questionnaire. CONCLUSION: GERDOFF® could effectively treat GER symptoms in patients not responding to PPI or alginate-based formulation. ISRCTN_15143752.


Assuntos
Alginatos/administração & dosagem , Antiácidos/administração & dosagem , Sulfatos de Condroitina/administração & dosagem , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Feminino , Refluxo Gastroesofágico/complicações , Azia/tratamento farmacológico , Azia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Projetos Piloto , Vigilância de Produtos Comercializados , Inquéritos e Questionários , Comprimidos , Resultado do Tratamento
20.
Biomater Sci ; 8(12): 3454-3471, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32420550

RESUMO

The development of antimicrobial nanofibre dressings that can protect the injured tissues from commensal pathogens while promoting tissue regeneration finds enormous potential in plastic and reconstructive surgery practices. To achieve this goal, we investigated the effect of chondroitin sulphate on the morphology, mechanical properties, wettability and biocompatibility of polydopamine crosslinked electrospun gelatin nanofibres containing mineralized magnesium. To extend the durability of dressings, we prepared composite dressings containing polycaprolactone (PCL) and gelatin as blend or core-shell nanofibres. Nanofibre blends presented greater tensile strength and stretchability, while core-shell nanofibres displayed superior photoluminescent properties. In a porcine model of cutaneous burn injury, both the blend and core-shell nanofibre dressings displayed improved re-epithelialization, wound closure and clinical outcome in comparison to untreated burns. Histology of the biopsied tissues indicated smooth regeneration and collagen organization of the burns treated with core-shell nanostructures than untreated burns. This study compared the physico-chemical and biological properties of composite nanofibres that are capable of accelerating burn wound healing and possess antimicrobial properties, highlighting their potential as wound dressings and skin substitutes.


Assuntos
Antibacterianos/administração & dosagem , Bandagens , Sulfatos de Condroitina/administração & dosagem , Magnésio/administração & dosagem , Nanofibras/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Queimaduras/tratamento farmacológico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Gelatina/administração & dosagem , Gelatina/química , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Magnésio/química , Nanofibras/química , Poliésteres/administração & dosagem , Poliésteres/química , Suínos
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