CD44 targeted-chondroitin sulfate nanoparticles: Fine-tuning hydrophobic groups to enhance in vitro pH-responsiveness and in vivo efficacy for advanced breast cancer treatment.

The design of tumor-targeting nanoparticles with precisely controlled physical-biological properties may improve the delivery of chemotherapeutic agents. This study introduces pH-sensitive chondroitin sulfate-cholesterol (ChS-Chol) nano-assemblies for targeted intracellular doxorubicin (Dox) delivery in breast cancer treatment. Various ChS-Chol copolymers were synthesized, yielding self-assembling nanostructures with adjustable lipophilic content. In an aqueous environment, the ChS-Chol conjugates could form self-assembled nanostructures with a narrower size variation and a high negative potential. Moreover, the carriers would rapidly disassemble and release Dox in response to acidic pH. The in vitro cytotoxicity assay exhibited concentration-related anti-proliferation activity with Dox-loaded nanoparticles against 4T1, MCF-7, and MDA-MB-231 breast cancer cells. The nanoparticles demonstrated enhanced early apoptosis induction, efficient cellular uptake, and improved prevention of tumor cell proliferation compared to free Dox. In vivo results showcased significant tumor growth inhibition, underscoring the potential of these nanoparticle-based drug delivery systems for breast cancer therapy. The study emphasizes tailored nanocarrier design, leveraging pH-responsiveness and precise hydrophobic tuning to achieve targeted and potent therapeutic effects in the fight against breast cancer.

Open, Observational, Single-Arm, Multicenter Study Assessing the Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine for Osteoarthritis Pain Reduction.

Osteoarthritis (OA) is an age-related degenerative joint disease with a great impact on patients' well-being and quality of life. This is an observational, open, single-arm multicenter study aimed to evaluate the effectiveness of a nutritional supplement in patients with knee and/or hip OA. A total of 186 patients were recruited from Spanish centers and received a supplement containing hydrolyzed collagen (3000 mg), chondroitin sulfate (800 mg), glucosamine sulfate (700 mg), turmeric extract (250 mg) and devil's claw (150 mg), once daily during 6 months. The primary outcome was the patients' self-perceived pain in the affected joints measured with a visual analogue scale (VAS). Secondary outcome was the patient's functioning, measured with the Lequesne Functional Index and the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Participants showed a significant reduction in self-perceived pain after 3 (mean reduction ± standard deviation, 1.99 ± 1.05) and 6 months (3.57 ± 1.39) of treatment (p < 0.0001 in both comparisons). Lequesne Functional Index score was significantly reduced at 3 months (3.86 ± 2.94) and at 6 months (6.73 ± 4.30) of treatment (p < 0.0001 in both comparisons). The WOMAC index was also significantly reduced after 3 (14.24 ± 10.04) and 6 months (26.43 ± 17.35) of treatment (p < 0.0001 in both comparisons). Significant reductions in WOMAC subdomains (p < 0.0001 in all comparisons) were observed. No severe adverse events were reported during the study. The main results arising from this study show that this nutritional supplementation can improve OA-related symptoms and physical function with a good safety profile in patients with hip and/or knee OA.

Distinct mechanisms underlying the therapeutic effects of low-molecular-weight heparin and chondroitin sulfate on Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder influenced by various factors, including age, genetics, and the environment. Current treatments provide symptomatic relief without impeding disease progression. Previous studies have demonstrated the therapeutic potential of exogenous heparin and chondroitin sulfate in PD. However, their therapeutic mechanisms and structure-activity relationships remain poorly understood. In this study, low-molecular-weight heparin (L-HP) and chondroitin sulfate (L-CS) exhibited favorable therapeutic effects in a mouse model of PD. Proteomics revealed that L-HP attenuated mitochondrial dysfunction through its antioxidant properties, whereas L-CS suppressed neuroinflammation by inhibiting platelet activation. Two glycosaminoglycan (GAG)-binding proteins, manganese superoxide dismutase (MnSOD2) and fibrinogen beta chain (FGB), were identified as potential targets of L-HP and L-CS, and we investigated their structure-activity relationships. The IdoA2S-GlcNS6S/GlcNAc6S unit in HP bound to SOD2, whereas the GlcA-GalNAc4S and GlcA-GalNAc4S6S units in CS preferred FGB. Furthermore, N-S and 2-O-S in L-HP, and 4-O-S, 6-O-S, and -COOH in L-CS contributed significantly to the binding process. These findings provide new insights and evidence for the development and use of glycosaminoglycan-based therapeutics for PD.

Chondroitin Sulphate: An emerging therapeutic multidimensional proteoglycan in colon cancer.

Chondroitin sulfate (CS) is a sulfated glycosaminoglycan (GAG) that has captured massive attention in the field of drug delivery. As the colon is considered the preferred site for local and systemic delivery of bioactive agents for the treatment of various diseases, colon-targeted drug delivery rose to the surface of research. Amid several tactics to attain colon-targeted drug release, the exploitation of polymers degraded by colonic bacteria holds great promise. Chondroitin sulfate as a biodegradable, biocompatible mucopolysaccharide is known for its anti-inflammatory, anti-osteoarthritis, anti-atherosclerotic, anti-oxidant, and anti-coagulant effects. Besides these therapeutic functions, CS thrived to play a major role in nanocarriers as a matrix material, coat, and targeting ligand. This review focuses on the role of CS in nanocarriers as a matrix material or as a targeting moiety for colon cancer therapy, relating the present applications to future perspectives.

Effect of Oral Chondroitin Sulfate Supplementation on Acute Brain Injury in a Murine Necrotizing Enterocolitis Model.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating condition where inflammatory changes and necrosis in the gut results in activation of brain microglia and subsequent neurodevelopmental impairment. Chondroitin sulfate (CS) is a glycosaminoglycan in human breast milk that is absent in conventional formulas. We hypothesized that oral formula supplementation with CS during a murine model of experimental NEC would not only attenuate intestinal injury, but also brain injury. STUDY DESIGN: NEC was induced in mouse pups on postnatal days (PNDs) 5 to 8. Three conditions were studied: (1) breastfed controls, (2) NEC, and (3) NEC+enteral CS (formula+200 mg/kg/d of CS). Pups were euthanized on PND 9 or reunited with dams by the evening of PND 8. Intestinal segments were H&E stained, and immunohistochemistry was performed on brain tissue for Iba-1 to assess for microglial morphology and cortical changes. Neurodevelopmental assays were performed on mice reunited with foster dams on PND 9. Single-cell RNA-sequencing analysis was performed on human intestinal epithelial cells exposed to (1) nothing, (2) hydrogen peroxide (H 2 O 2 ) alone, or (3) H 2 O 2 + CS to look at the differential gene expression between groups. Groups were compared with ANOVA or Kruskal-Wallis tests as appropriate with p < 0.05 considered significant. RESULTS: Compared with NEC, mice treated with oral CS showed improved clinical outcomes, decreased intestinal injury, and attenuated microglial activation and deleterious cortical change. Mice with CS performed better on early neurodevelopmental assays when compared with NEC alone. Single-cell analysis of HIEC-6 cells demonstrated that CS treatment down regulated several inflammatory pathways including nuclear factor κB-suggesting an explanation for the improved Th17 intestinal cytokine profile. CONCLUSIONS: Oral CS supplementation improved both physiological, clinical, and developmental outcomes. These data suggest that CS is a safe compound for formula supplementation for the prevention of NEC.

Investigation of Drug-Interaction Potential for Arthritis Dietary Supplements: Chondroitin Sulfate, Glucosamine, and Methylsulfonylmethane.

Osteoarthritis is one of the leading conditions that promote the consumption of these dietary supplements. Chondroitin sulfate, glucosamine, and methylsulfonylmethane are among the prominent alternative treatments for osteoarthritis. In this study, these dietary supplements were incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes, and the formation of marker metabolites was measured to investigate their inhibitory potential on cytochrome P450 enzyme activities. The results revealed no significant inhibitory effects on seven CYPs, consistent with established related research data. Therefore, these substances are anticipated to have a low potential for cytochrome P450-mediated drug interactions with osteoarthritis medications that are likely to be co-administered. However, given the previous reports of interaction cases involving glucosamine, caution is advised regarding dietary supplement-drug interactions.

Comparative evaluation of cytotoxic and anti-metastatic function of microbial chondroitin sulfate and animal-originated commercial chondroitin sulfate in cancer cells.

Cancer has the second-highest mortality rate worldwide after cardiovascular disease. In addition, breast and cervical cancer are two of the leading causes of cancer-related deaths among women. The tumor microenvironment, which consists of fibroblasts, immune cells, cells that form blood vessels, and proteins, is a therapeutic target for cancer therapy. As part of the cellular microenvironment, glycosaminoglycan chondroitin sulfate is associated with various aspects of tumor progression and metastasis depending on the sulfate pattern of chondroitin sulfate. This study evaluated the roles of Microbial Chondroitin Sulfate (CS) and Commercial CS in tumor growth and metastasis comparatively using MDA-MB-231 metastatic breast cancer cells, HeLa cervical cancer cells, and normal fibroblasts. In addition, the role of CS types in wound healing was also assessed comparatively.  Microbial CS was more cytotoxic in MDA-MB-231 cells than HeLa compared to Commercial CS. Although both CS reduced cell viability in normal cells, the selective index of Microbial CS in MDA-MB-213 cells was higher than its commercial counterpart. In addition, the role of CS types in wound healing was also assessed comparatively. Both types of CS decreased the cell migration in MDA-MB-231 cancer cells, but HeLa cells were more sensitive to Microbial CS than Commercial CS to heal the wound. The wound healing of NIH3T3 cells after Microbial CS was similarly high to the healing after Commercial CS. This preliminary study shows that microbial CS produced by biotechnological methods from a recombinant source created by our team can be an effective therapeutic agent in various types of cancer.

Recurrence after postoperative intravesical instillation therapy in Hunner type interstitial cystitis.

We performed a prospective, single-arm study comparing outcomes between transurethral ablation plus postoperative instillation of hyaluronic acid and chondroitin sulfate (HACS group) and transurethral ablation only in patients with Hunner type interstitial cystitis (historical control group). A total of 78 patients were enrolled, and 51 were included in the per-protocol analysis set. The 2-year recurrence rate was 47.1% (95% CI, 32.9-61.5) in the HACS group, which was significantly lower than that in the control group (86.2%; 95% CI, 74.6-93.9, P < 0.001). After instillation therapy, the hazard ratio for recurrence was 0.38 (95% CI, 0.23-0.65, P < 0.001). The HACS group had an increased recurrence-free survival with the median interval not being reached, while it was 11.4 months in the control group (95% CI, 8.8-13.8, P < 0.001). Regardless of the instillation treatment, there were significant improvements in all symptom questionnaire scores and pain compared to the baseline. However, in the instillation group, improvement was stable even after 12 months. In patients with Hunner type interstitial cystitis, intravesical instillation of hyaluronic acid and chondroitin sulfate after transurethral ablation significantly reduced the recurrence rate and maintained symptom improvement for more than 1 year.

Chondroitin sulfate supplementation improves clinical outcomes in a murine model of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) continues to be a devastating disease in preterm neonates and has a paucity of medical management options. Chondroitin sulfate (CS) is a naturally occurring glycosaminoglycan (GAG) in human breast milk (HM) and has been shown to reduce inflammation. We hypothesized that supplementation with CS in an experimental NEC model would alter microbial diversity, favorably alter the cytokine profile, and (like other sulfur compounds) improve outcomes in experimental NEC via the eNOS pathway. NEC was induced in 5-day-old pups. Six groups were studied (n = 9-15/group): (1) WT breastfed and (2) Formula fed controls, (3) WT NEC, (4) WT NEC + CS, (5) eNOS KO (knockout) NEC, and (6) eNOS KO NEC + CS. Pups were monitored for clinical sickness score and weights. On postnatal day 9, the pups were killed. Stool was collected from rectum and microbiome analysis was done with 16 s rRNA sequencing. Intestinal segments were examined histologically using a well-established injury scoring system and segments were homogenized and analyzed for cytokine profile. Data were analyzed using GraphPad Prism with p < 0.05 considered significant. CS supplementation in formula improved experimental NEC outcomes when compared to NEC alone. CS supplementation resulted in similar improvement in NEC in both the WT and eNOS KO mice. CS supplementation did not result in microbial changes when compared to NEC alone. Our data suggest that although CS supplementation improved outcomes in NEC, this protection is not conferred via the eNOS pathway or alteration of microbial diversity. CS therapy in NEC does improve the intestinal cytokine profile and further experiments will explore the mechanistic role of CS in altering immune pathways in this disease.

Injectable Bioadhesive Hydrogels Scavenging ROS and Restoring Mucosal Barrier for Enhanced Ulcerative Colitis Therapy.

Despite the progress in the therapy of ulcerative colitis (UC), long-lasting UC remission can hardly be achieved in the majority of UC patients. The key pathological characteristics of UC include an impaired mucosal barrier and local inflammatory infiltration. Thus, a two-pronged approach aiming at repairing damaged mucosal barrier and scavenging inflammatory mediators simultaneously might hold great potential for long-term remission of UC. A rectal formulation can directly offer preferential and effective drug delivery to inflamed colon. However, regular intestinal peristalsis and frequent diarrhea in UC might cause transient drug retention. Therefore, a bioadhesive hydrogel with strong interaction with intestinal mucosa might be preferable for rectal administration to prolong drug retention. Here, we designed a bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitin sulfate and polydopamine (CS-PDA). The presence of PDA would ensure the mucosa-adhesive behavior, and the addition of CS in the hydrogel network was expected to achieve the restoration of the intestinal epithelial barrier. To scavenge the key player (excessive reactive oxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potent ROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectal administration, the SF-loaded CS-PDA hydrogel could adhere to the colonic mucosa to allow prolonged drug retention. Subsequently, sustained SF release could be achieved to persistently scavenge ROS in inflammatory areas. Meanwhile, the presence of CS would promote the restoration of the mucosal barrier. Ultimately, scavenging ROS and restoring the mucosal barrier could be simultaneously achieved via this SF-loaded bioadhesive hydrogel scaffold. Our two-pronged approach might provide new insight for effective UC treatment.

Novel Key Ingredients in Urinary Tract Health-The Role of D-mannose, Chondroitin Sulphate, Hyaluronic Acid, and N-acetylcysteine in Urinary Tract Infections (Uroial PLUS®).

Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections.

Chondroitin Sulfate Improves Mechanical Properties of Gelatin Hydrogel for Cartilage Regeneration in Rats.

Cartilage injury is a common disease in daily life. Especially in aging populations, the incidence of osteoarthritis is increasing. However, due to the poor regeneration ability of cartilage, most cartilage injuries cannot be effectively repaired. Even cartilage tissue engineering still faces many problems such as complex composition and poor integration of scaffolds and host tissues. In this study, chondroitin sulfate, one of the main components of extracellular matrix (ECM), is chosen as the main natural component of the material, which can protect cartilage in a variety of ways. Moreover, the results show that the addition of chondroitin sulfate improves the mechanical properties of gelatin methacrylate (GelMA) hydrogel, making it able to effectively bear mechanical loads in vivo. Further, chondroitin sulfate is modified to obtain the oxidized chondroitin sulfate (OCS) containing aldehyde groups via sodium periodate. This special group improves the interface integration and adhesion ability of the hydrogel to host cartilage tissue through schiff base reactions. In summary, GelMA/OCS hydrogel is a promising candidate for cartilage regeneration with good biocompatibility, mechanical properties, tissue integration ability, and excellent cartilage repair ability.

Oral Delivery of Transformable Bilirubin Self-Assembled System for Targeted Therapy of Colitis.

Ulcerative colitis (UC) is a high incidence disease worldwide and clinically presents as relapsing and incurable inflammation of the colon. Bilirubin (BR), a natural antioxidant with significant anti-colitic effects, is utilized in preclinical studies as an intestinal disease therapy. Due to their water-insolubility, the design of BR-based agents usually involves complicated chemosynthetic processes, introducing various uncertainties in BR development. After screening numerous materials, it is identified that chondroitin sulfate can efficiently mediate the construction of BR self-assembled nanomedicine (BSNM) via intermolecular hydrogen bonds between dense sulfate and carboxyl of chondroitin sulfate and imino groups of BR. BSNM exhibits pH sensitivity and reactive oxygen species responsiveness, enabling targeted delivery to the colon. After oral administration, BSNM significantly inhibits colonic fibrosis and apoptosis of colon and goblet cells; it also reduces the expression of inflammatory cytokines. Moreover, BSNM maintains the normal level of zonula occludens-1 and occludin to sustain the integrity of intestinal barrier, regulates the macrophage polarization from M1 to M2 type, and promotes the ecological recovery of intestinal flora. Collectively, the work provides a colon-targeted and transformable BSNM that is simple to prepare and is useful as an efficient targeted UC therapy.

Effects of hyaluronic acid and chondroitin sulfate on acute radiation proctitis in rats.

BACKGROUND: This study was designed to investigate the prophylactic and therapeutic effects of hyaluronic acid and chondroitin sulfate combination (HA/CS) on a model of acute radiation proctitis. METHODS: Rats were divided into five groups: SHAM; irradiation (IR) + saline (1 mL for 5th and 10th day); IR + HA/CS (1 mL for 5th and 10th day). A single fraction of 17.5 Gy was delivered to each rat. HA/CS was administered rectally each day after irradiation. Each rat was observed daily for signs of proctitis. Irradiated rats were euthanized on days 5 and 10. The mucosal changes were evaluated macroscopically and pathologically. RESULTS: According to the clinical findings, five rats in the irradiation + saline group showed grade 3-4 symptoms on the 10th day. No significant difference in the macroscopic finding scores on the 5th day was observed between the irradiation + saline and irradiation + HA/CS groups. In the pathological examination, radiation-induced mucosal damage was the most prominent finding 10 days after irradiation in saline-treated rats. On the 10th day, the irradiation + HA/CS group showed mild inflammation and slight crypt changes, which corresponded to grade 1-2 pathological findings. CONCLUSION: We think that HA/CS used in radiation cystitis can be beneficial for radiation proctitis.

Multifunctional chondroitin sulfate based hydrogels for promoting infected diabetic wounds healing by chemo-photothermal antibacterial and cytokine modulation.

Diabetic foot (DF) is difficult to heal due to the formation of drug-resistant bacterial biofilms and dysregulation of the wound microenvironment. To solve this problem, multifunctional hydrogels were prepared by in situ or spraying with 3-aminophenylboronic acid modified oxidized chondroitin sulfate (APBA-g-OCS), polyvinyl alcohol (PVA) and black phosphorus/bismuth oxide/ε-polylysine (BP/Bi2O3/ε-PL) as precursors for promoting infected diabetic wounds healing. The hydrogels display multiple stimulus responsiveness, strong adhesion and rapid self-healing ability owing to the dynamic borate ester bonds, hydrogen bonds and π-π conjugation cross-link points, remain synergistic chemo-photothermal antibacterial effect and anti-biofilm formation ability due to the doping of BP/ Bi2O3/ε-PL into the hydrogel by dynamic imine bonds crosslinking and possess anti-oxidation and inflammatory chemokine adsorption ability attributing to the presence of APBA-g-OCS. Most importantly, as a result of the above functions, the hydrogels can not only respond to the wound microenvironment to conduct combined PTT and chemotherapy for efficient anti-inflammation, but also improve the wound microenvironment by scavenging ROS and regulating the expression of cytokines, thus further accelerating collagen deposition, promoting granulation tissue formation and angiogenesis, finally promoting the healing of infected wounds in diabetic rats.

Efficient Therapy of Inflammatory Bowel Disease (IBD) with Highly Specific and Durable Targeted Ta2 C Modified with Chondroitin Sulfate (TACS).

Non-invasive localization of lesions and specific targeted therapy are still the main challenges for inflammatory bowel disease (IBD). Ta, as a medical metal element, has been widely used in the treatment of different diseases because of its excellent physicochemical properties but is still far from being explored in IBD. Here, Ta2 C modified with chondroitin sulfate (CS) (TACS) is evaluated as a highly targeted therapy nanomedicine for IBD. Specifically, TACS is modified with dual targeting CS functions due to IBD lesion-specific positive charges and high expression of CD44 receptors. Thanks to the acid stability, sensitive CT imaging function, and strong reactive oxygen species (ROS) elimination ability, oral TACS can accurately locate and delineate IBD lesions through non-invasive CT imaging, and specifically targeted treat IBD effectively because high levels of ROS are a central factor in the progression of IBD. As expected, TACS has much better imaging and therapeutic effects than clinical CT contrast agent and first-line drug 5-aminosalicylic acid, respectively. The mechanism of TACS treatment mainly involves protection of mitochondria, elimination of oxidative stress, inhibiting macrophage M1 polarization, protection of intestinal barrier, and restoration of intestinal flora balance. Collectively, this work provides unprecedented opportunities for oral nanomedicines to targeted therapy of IBD.

Enzymatic preparation of chondroitin sulfate oligosaccharides and its alleviating effect on ovariectomy-induced osteoporosis in rats.

Postmenopausal osteoporosis is the most common type of osteoporosis. Chondroitin sulfate (CS) has been successfully employed as food supplement against osteoarthritis, while the therapeutic potential on postmenopausal osteoporosis is little explored. In this study, CS oligosaccharides (CSOs) were enzymatically prepared through the lysis of CS by a chondroitinase from Microbacterium sp. Strain. The alleviating effects of CS, CSOs and Caltrate D (a clinically used supplement) on ovariectomy (OVX) - induced rat's osteoporosis were comparatively investigated. Our data showed that the prepared CSOs was basically unsaturated CS disaccharide mixture of ∆Di4S (53.1%), ∆Di6S (27.7%) and ∆Di0S (17.7%). 12 weeks' intragastric administration of Caltrate D (250 mg/kg/d), CS or CSOs (500 mg/kg/d, 250 mg/kg/d, 125 mg/kg/d) could obviously regulate the disorder of serum indices, recover the mechanical strength and mineral content of bone, improve the cortical bones' density and the number and length of trabecular bones in OVX rats. Both CS and CSOs in 500 mg/kg/d and 250 mg/kg/d could restore more efficiently the serum indices, bone fracture deflection and femur Ca than Caltrate D. As compared with CS at the same dosage, CSOs exhibited a more significant alleviating effect. These findings suggested that there was great potential of CSOs as daily interventions for delaying the progression of postmenopausal osteoporosis.

[Retrospective Evaluation of the Use of a Dermal Substitute in Septorhinoplasty]. / Retrospektive Auswertung der Anwendung eines dermalen Ersatzmaterials bei der Indikation zur Septorhinoplastik.

BACKGROUND: At the present time, various methods exist for camouflaging the dorsum of the nose in septorhinoplasty. The subject of this paper is a retrospective descriptive evaluation of the surgical use of the bovine collagen/glycosaminoglycan matrix Integra Dermal Regeneration Template Single Layer Thin (IDRT-SL Thin) developed by Integra LifeSciences in septorhinoplasty procedures. METHODOLOGY: The focus of this work is to evaluate the postoperative tolerability, the safety, and the course of wound healing when IDRT-SL Thin is applied as a collagen sheet in septorhinoplasty. The evaluation was performed using an evaluation form that was developed for this paper. Patients included in the study were followed up for one year postoperatively; however, the postoperative observation period considered in the evaluation was 14 weeks. RESULTS: The analysis of the surgical results shows relatively homogeneous results for the criteria and time period we examined. No notable complications were observed within the patient cohort up to the 14th postoperative week. DISCUSSION: Despite the limiting factors within the study due to the lack of a control group undergoing other surgical treatment procedures and the small number of patient cases, the observation period of six and 14 weeks applied in this study is suitable to determine the suitability and tolerability in principle. The results presented in this study can therefore be understood as a possible starting point for further investigations on the use of IDRT-SL Thin in septorhinoplasty.

[Comparative analysis of the use of symptomatic slow acting drugs for osteoarthritis containing chondroitin sulfate or affecting its biosynthesis in patients with non-specific low back pain]. / Sravnitel'nyi analiz primeneniya simptomaticheskikh preparatov zamedlennogo deistviya, soderzhashchikh khondroitina sul'fat ili vliyayushchikh na ego biosintez, u patsientov s nespetsificheskoi bol'yu poyasnichno-kresttsovoi lokalizatsii.

OBJECTIVE: Retrospective comparative analysis of the use of SYSADOA preparations containing chondroitin sulfate (Chondroguard, 2 ml, 25 amp., glycosaminoglycan-peptide complex, 1 ml 25 amp., bioactive concentrate of small marine fish, 2 ml, 10 amp.) in patients with chronic non-specific low back pain (LBP) of lumbar and sacral localization caused by spondylosis and osteochondrosis of the lumbar spine, at the stage of outpatient care. MATERIAL AND METHODS: Data of medical records of patients (n=120; men - 32, women - 88, age - 54.1±7.6 years, duration of disease exacerbation 4.0±1.7 months) with nonspecific LBP were systematized according to the inclusion/exclusion criteria. All patients were divided into 4 groups: Group 1 (n=30) received Chondroguard im., 2 ml every other day, the course of treatment was 25 injections, 25 days; Group 2 (n=30) received glycosaminoglycan-peptide complex on the 1st day - 0.3 ml, on the 2nd day - 0.5 ml, and then 3 times a week for 1 ml, course of treatment - 25 injections, 25 days; Group 3 (n=30) received bioactive concentrate of small marine fish, 2 ml im., every other day, the course of treatment was 10 injections; repeated courses of treatment - after 6 months; Group 4 (n=30) received Amelotex (meloxicam) at a dose of 15 mg once a day for 15 days. All patients of the first 3 groups received Amelotex at a dose of 15 mg with the possibility of reducing the dose to 7.5 mg or completely discontinuing the drug if necessary. Retrospectively, dynamic monitoring was performed in the medical records of outpatients after 50 days and 6 months from the start of therapy according to the following parameters: intensity of pain according to VAS, short form of the McGill pain questionnaire, vital signs of patients (Oswestry Disability Index, version 2.1a [Oswestry Disability Index], and Roland-Morris questionnaire), propensity to chronic pain syndrome according to the STarT Back Screening Tool questionnaire, the presence and severity of comorbid fibromyalgia according to the Fibromyalgia Rapid Screening Tool questionnaire, the level of pain catastrophization according to the Pain Catastrophizing Scale, the severity of comorbid anxiety and depression according to the Hospital Anxiety and Depression Scale, the severity comorbid insomnia (Insomnia Severity Index), quality of life according to the SF-36 scale, the effectiveness of drugs according to the patient on a 5-point scale, the need to take NSAIDs and analgesics, tolerability on a 4-point system. The safety of therapy was monitored using the WHO and Naranjo scales. RESULTS: In patients with nonspecific LBP, a greater degree of reduction in the intensity of the pain syndrome, a smaller number of exacerbations of the pain syndrome over 6 months of observation, an improvement in the functional status and life activity, a tendency to a decrease in the severity of anxiety and depression, sleep disturbances and comorbid fibromyalgia, limiting the risk of chronicity and catastrophization of pain, the presence of a structure-modifying effect on IVD and degenerative changes in the facet joints, a significant improvement in the physical and mental components of health, high satisfaction and safety of therapy, which included taking Chondroguard with meloxicam, with a decrease in the need to take the latter by the 50th day observation period compared to other regimens. The effects of Chondroguard and meloxicam turned out to be long-term and were recorded by the 6th month in the absence of Chondroguard, which indicated the preservation of the influence of highly purified cholesterol on the pathogenetic mechanisms of the formation of LBP. CONCLUSION: The study allows us to recommend the use of a parenteral form of cholesterol (Chondroguard, CJSC «PharmFirma «Sotex¼, Russia) for the treatment of nonspecific LBP with moderate or severe pain, chronic relapsing or persistent course, in combination with NSAIDs and their subsequent cancellation or administration on demand.

Chondroitin sulfate and L-Cysteine conjugate modified cationic nanostructured lipid carriers: Pre-corneal retention, permeability, and related studies for dry eye treatment.

In this study, a novel bioadhesive material, a conjugate of chondroitin sulfate and L-cysteine (CS-Cys), was synthesized and modified on the surface of the cationic nanostructured lipid carriers loaded dexamethasone to prepare a novel nano-lipid ocular delivery system (Dex-CS-Cys-cNLC). Through the permeation and retention studies of isolated cornea, it was demonstrated that Dex-CS-Cys-cNLC has better corneal permeation and retention ability and can better overcome the barrier effect of the ocular surface. In addition, the fluorescent probe (RhB) was used to replace the drug, and fluorescence imaging was used to investigate the ocular surface retention ability of the formulation, and the results showed that CS-Cys-cNLC has stronger retention ability and can effectively prolong the time of drug action in the ocular surface. Dex-CS-Cys-cNLC was not irritating to rabbit eye tissues and was a safe delivery system. The results of rabbit dry eye pharmacodynamic experiments also showed that Dex-CS-Cys-cNLC could effectively alleviate dry eye symptoms in rabbits, effectively repair corneal damage, and improve the stability of tear film. All these experimental results suggest that Dex-CS-Cys-cNLC is a promising drug delivery carrier for the treatment of anterior segment of the eye disease.