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1.
Drug Res (Stuttg) ; 74(6): 255-268, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38968949

ABSTRACT

This comprehensive review endeavors to illuminate the nuanced facets of linalool, a prominent monoterpene found abundantly in essential oils, constituting a massive portion of their composition. The biomedical relevance of linalool is a key focus, highlighting its therapeutic attributes observed through anti-nociceptive effects, anxiolytic properties, and behavioral modulation in individuals affected by dementia. These findings underscore the compound's potential application in biomedical applications. This review further explores contemporary formulations, delineating the adaptability of linalool in nano-emulsions, microemulsions, bio-capsules, and various topical formulations, including topical gels and lotions. This review covers published and granted patents between 2018-2024 and sheds light on the evolving landscape of linalool applications, revealing advancements in dermatological, anti-inflammatory, and antimicrobial domains.


Subject(s)
Acyclic Monoterpenes , Humans , Acyclic Monoterpenes/pharmacology , Acyclic Monoterpenes/therapeutic use , Acyclic Monoterpenes/chemistry , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Animals , Anti-Infective Agents/therapeutic use , Anti-Infective Agents/pharmacology , Anti-Anxiety Agents/therapeutic use , Anti-Anxiety Agents/pharmacology , Analgesics/therapeutic use , Analgesics/pharmacology , Patents as Topic , Emulsions , Oils, Volatile/therapeutic use , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Dermatologic Agents/therapeutic use , Dermatologic Agents/pharmacology , Dermatologic Agents/administration & dosage
2.
Int J Med Mushrooms ; 26(8): 27-40, 2024.
Article in English | MEDLINE | ID: mdl-38967209

ABSTRACT

Lingzhi or reishi mushroom, Ganoderma lucidum, is a medicinal mushroom quite widely developed as herbal medicine because it has acted as an anticancer, antitumor, antioxidant, and anti-inflammatory. The active mycochemical compounds of G. lucidum mushrooms, such as flavonoids and polysaccharides, can suppress the release of pro-inflammatory cytokines and prevent lipid peroxidation due to oxidative stress. Rheumatoid arthritis (RA) is an autoimmune disease where the exact cause is unknown, and RA prevalence continues to increase yearly. In patients with RA, joint damage and inflammation occur. This study aims to evaluate the effectiveness of G. lucidum nanogels as anti-arthritis, anti-inflammatory, and antioxidative. The research method was a true experiment using a control group and treatment group that randomly assigned, using 24 male Wistar rats (Rattus norvegicus) induced with complete Freund's adjuvant (CFA) 0.1 mL. The rats were divided into six groups; healthy control/HCt (did not receive the treatment), negative control/NCt (induced by CFA), and positive control/PCt (given 0.012 diclofenac sodium). TG1 (given 250 mg G. lucidum nanogels), TG2 (given 500 mg G. lucidum nanogels), TG3 (given 750 mg G. lucidum nanogels). IgG, eNOS, IL-1ß, COX-2, NOS, TNF-α, and IL-6 parameters were measured using ELISA, and the data obtained were analyzed by one-way ANOVA using SPSS (P < 0.05). The results showed that administering G. lucidum nanogels significantly reduced IgG, NOS, TNF-α, COX-2, IL-1ß, and IL-6 and increased eNOS levels. The anti-inflammatory and antioxidative activities in suppressing pro-inflammatory cytokines and increasing eNOS levels prove that the nanogel extract G. lucidum have the potential to be developed as anti-arthritis natural therapeutic.


Subject(s)
Anti-Inflammatory Agents , Antioxidants , Arthritis, Rheumatoid , Freund's Adjuvant , Rats, Wistar , Reishi , Animals , Male , Reishi/chemistry , Arthritis, Rheumatoid/drug therapy , Antioxidants/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Rats , Nanogels , Disease Models, Animal , Arthritis, Experimental/drug therapy , Arthritis, Experimental/chemically induced , Cytokines/metabolism , Polyethylene Glycols , Polyethyleneimine
4.
ACS Appl Mater Interfaces ; 16(26): 33081-33092, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38888094

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.


Subject(s)
Budesonide , Drug Carriers , Inflammatory Bowel Diseases , Nanoparticles , Silicon Dioxide , Budesonide/chemistry , Budesonide/administration & dosage , Budesonide/therapeutic use , Budesonide/pharmacokinetics , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Animals , Silicon Dioxide/chemistry , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/pathology , Drug Carriers/chemistry , Mice , Polymethacrylic Acids/chemistry , Drug Liberation , Humans , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Porosity , Hydrogen-Ion Concentration
5.
Int J Chron Obstruct Pulmon Dis ; 19: 1177-1196, 2024.
Article in English | MEDLINE | ID: mdl-38826697

ABSTRACT

Objective: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology. Research Methods: Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. Results: A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =-4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure. Conclusion: This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways.


Subject(s)
Drugs, Chinese Herbal , Network Pharmacology , Pulmonary Disease, Chronic Obstructive , Randomized Controlled Trials as Topic , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Treatment Outcome , Lung/drug effects , Lung/physiopathology , Anti-Inflammatory Agents/administration & dosage , Middle Aged , Male , Aged , Female , Injections
6.
Nutrients ; 16(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892648

ABSTRACT

Diabetic retinopathy (DR) is a major vision-threatening disease among the working-age population worldwide. Present therapeutic strategies such as intravitreal injection of anti-VEGF and laser photocoagulation mainly target proliferative DR. However, there is a need for early effective management in patients with early stage of DR before its progression into the more severe sight-threatening proliferative stage. Nutraceuticals, natural functional foods with few side effects, have been proposed to be beneficial in patients with DR. Over the decades, many studies, either in vitro or in vivo, have demonstrated the advantages of a number of nutraceuticals in DR with their antioxidative, anti-inflammatory, neuroprotective, or vasoprotective effects. However, only a few clinical trials have been conducted, and their outcomes varied. The low bioavailability and instability of many nutraceuticals have indeed hindered their utilization in clinical use. In this context, nanoparticle carriers have been developed to deliver nutraceuticals and to improve their bioavailability. Despite its preclinical nature, research of interventive nutraceuticals for DR may yield promising information in their clinical applications.


Subject(s)
Diabetic Retinopathy , Dietary Supplements , Diabetic Retinopathy/drug therapy , Humans , Antioxidants/administration & dosage , Biological Availability , Drug Delivery Systems , Animals , Anti-Inflammatory Agents/administration & dosage
7.
Clin Interv Aging ; 19: 981-991, 2024.
Article in English | MEDLINE | ID: mdl-38827237

ABSTRACT

Background: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury. Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery. Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China. Patients: 86 patients aged 60-75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio. Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 µg kg-1 for 10 min, followed by 0.5 µg kg-1 hr-1 for maintenance until the end of surgery. Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes. Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P<0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups. Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs. Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.


Subject(s)
Dexmedetomidine , Interleukin-6 , Postoperative Complications , Tumor Necrosis Factor-alpha , Humans , Dexmedetomidine/administration & dosage , Dexmedetomidine/pharmacology , Male , Female , Aged , Postoperative Complications/prevention & control , Middle Aged , Interleukin-6/blood , Tumor Necrosis Factor-alpha/blood , Inflammation/prevention & control , China , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Double-Blind Method , Biliary Tract Surgical Procedures/adverse effects , Acute Kidney Injury/prevention & control , Acute Kidney Injury/etiology
8.
Int J Nanomedicine ; 19: 5173-5191, 2024.
Article in English | MEDLINE | ID: mdl-38855733

ABSTRACT

Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.


Subject(s)
Acne Vulgaris , Anti-Bacterial Agents , Dicarboxylic Acids , Hair Follicle , Nanoparticles , Acne Vulgaris/drug therapy , Animals , Mice , Dicarboxylic Acids/chemistry , Dicarboxylic Acids/pharmacology , Hair Follicle/drug effects , RAW 264.7 Cells , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Particle Size , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Drug Delivery Systems/methods , Skin/drug effects , Skin/metabolism
9.
Sci Rep ; 14(1): 12800, 2024 06 04.
Article in English | MEDLINE | ID: mdl-38834591

ABSTRACT

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.


Subject(s)
Spinal Fusion , Tranexamic Acid , Humans , Tranexamic Acid/administration & dosage , Female , Male , Middle Aged , Spinal Fusion/methods , Spinal Fusion/adverse effects , Case-Control Studies , Aged , Lumbar Vertebrae/surgery , Administration, Intravenous , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Hemostatics/administration & dosage , Hemostatics/pharmacology , Adult , Blood Loss, Surgical/prevention & control , Antifibrinolytic Agents/administration & dosage , Antifibrinolytic Agents/therapeutic use
10.
Pharm Res ; 41(6): 1183-1199, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38849712

ABSTRACT

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.


Subject(s)
Administration, Cutaneous , Anti-Inflammatory Agents , Dexamethasone , Drug Delivery Systems , Edema , Iontophoresis , Needles , Skin Absorption , Skin , Animals , Iontophoresis/methods , Dexamethasone/administration & dosage , Dexamethasone/pharmacokinetics , Dexamethasone/analogs & derivatives , Rats , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Edema/drug therapy , Drug Delivery Systems/methods , Skin/metabolism , Skin/drug effects , Male , Drug Liberation , Inflammation/drug therapy , Rats, Sprague-Dawley
11.
Int J Mol Sci ; 25(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38892047

ABSTRACT

The emerging field of nanotechnology has paved the way for revolutionary advancements in drug delivery systems, with nanosystems emerging as a promising avenue for enhancing the therapeutic potential and the stability of various bioactive compounds. Among these, cannabidiol (CBD), the non-psychotropic compound of the Cannabis sativa plant, has gained attention for its therapeutic properties. Consequently, researchers have devoted significant efforts to unlock the full potential of CBD's clinical benefits, where various nanosystems and excipients have emerged to overcome challenges associated with its bioavailability, stability, and controlled release for its transdermal application. Therefore, this comprehensive review aims to explain CBD's role in managing acute inflammatory pain and offers an overview of the state of the art of existing delivery systems and excipients for CBD. To summarize this review, a summary of the cannabinoids and therapeutical targets of CBD will be discussed, followed by its conventional modes of administration. The transdermal route of administration and the current topical and transdermal delivery systems will also be reviewed. This review will conclude with an overview of in vivo techniques that allow the evaluation of the anti-inflammatory and analgesic potentials of these systems.


Subject(s)
Administration, Cutaneous , Cannabidiol , Drug Delivery Systems , Cannabidiol/administration & dosage , Cannabidiol/therapeutic use , Humans , Drug Delivery Systems/methods , Animals , Inflammation/drug therapy , Acute Pain/drug therapy , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Analgesics/administration & dosage , Analgesics/therapeutic use
12.
Ann Intern Med ; 177(6): JC62, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38830222

ABSTRACT

SOURCE CITATION: Heming N, Renault A, Kuperminc E, et al; APROCCHSS investigators and CRICS-TRIGGERSEP network. Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial. Lancet Respir Med. 2024;12:366-374. 38310918.


Subject(s)
Community-Acquired Infections , Drug Therapy, Combination , Fludrocortisone , Hydrocortisone , Shock, Septic , Shock, Septic/drug therapy , Shock, Septic/mortality , Humans , Hydrocortisone/therapeutic use , Hydrocortisone/administration & dosage , Fludrocortisone/therapeutic use , Community-Acquired Infections/drug therapy , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Pneumonia/drug therapy , Pneumonia/mortality , Male , Female
13.
Int J Mol Sci ; 25(11)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38892359

ABSTRACT

Transdermal drug delivery offers a promising alternative for administering medications like ibuprofen, known for its analgesic and anti-inflammatory properties, with reduced gastrointestinal side effects compared to oral administration. This study explored the potential synergistic effects of combining ibuprofen with lavender essential oil (LEO) in transdermal patches. The composition of LEO was analyzed, revealing predominant compounds such as linalyl acetate and linalool, which are known for their analgesic and anti-inflammatory properties. The physicochemical properties of the patches were investigated, indicating improved cohesion with the addition of LEO. Additionally, thermal stability assessments demonstrated enhanced stability with LEO incorporation with an increase in onset decomposition temperature from 49.0 to 67.9 °C. The antioxidant activity of patches containing LEO was significantly higher with a free radical scavenging ability of 79.13% RSA compared to 60% RSA in patches without LEO. Release and permeation studies showed that patches with LEO exhibited an increased permeation of ibuprofen through the skin with 74.40% of the drug released from LEO-containing patches compared to 36.29% from patches without LEO after 24 h. Moreover, the permeation rate was notably faster with LEO, indicating quicker therapeutic effects. The inclusion of LEO in transdermal patches containing ibuprofen holds promise for enhancing drug delivery efficiency and therapeutic effectiveness, offering a potential strategy for improved pain management with reduced side effects.


Subject(s)
Anti-Inflammatory Agents , Ibuprofen , Lavandula , Oils, Volatile , Plant Oils , Transdermal Patch , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/administration & dosage , Lavandula/chemistry , Plant Oils/chemistry , Plant Oils/pharmacology , Ibuprofen/chemistry , Ibuprofen/administration & dosage , Ibuprofen/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Administration, Cutaneous , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/administration & dosage , Drug Liberation , Acyclic Monoterpenes , Monoterpenes
14.
AAPS PharmSciTech ; 25(6): 144, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918282

ABSTRACT

The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity.


Subject(s)
Chitosan , Dexamethasone , Drug Delivery Systems , Drug Liberation , Gels , Micelles , Poloxamer , Dexamethasone/administration & dosage , Dexamethasone/chemistry , Chitosan/chemistry , Gels/chemistry , Drug Delivery Systems/methods , Poloxamer/chemistry , Surface-Active Agents/chemistry , Chemistry, Pharmaceutical/methods , Hydrogels/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemistry , Nanoparticles/chemistry , Drug Carriers/chemistry , Rheology/methods , Oral Ulcer/drug therapy , Administration, Oral , Lipids/chemistry , Oleic Acid/chemistry
15.
AAPS PharmSciTech ; 25(6): 145, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918292

ABSTRACT

The objective of the current research was to develop abietic acid (AA)-loaded hybrid polymeric nanoparticles (HNPs) for anti-inflammatory and antioxidant activity after oral administration. AAHNPs were developed by microinjection technique and optimized by 3-factor 3-level Box-Behnken design. The AAHNPs were evaluated for morphology, FTIR, X-ray diffraction, in-vitro release, ex-vivo permeation, in-vitro antioxidant, and in-vivo anti-inflammatory activity. The optimized AAHNPs (AAHNPsopt) displayed 384.5 ± 6.36nm of PS, 0.376 of PDI, 23.0 mV of ZP, and 80.01 ± 1.89% of EE. FTIR and X-ray diffraction study results revealed that AA was encapsulated into a HNPs matrix. The AAHNPsopt showed significant (P < 0.05) high and sustained release of AA (86.72 ± 4.92%) than pure AA (29.87 ± 3.11%) in 24h. AAHNPsopt showed an initial fast release of AA (20.12 ± 3.07% in 2h), which succeeded in reaching the therapeutic concentration. The AAHNPsopt showed 2.49-fold higher ex-vivo gut permeation flux than pure AA due to the presence of lipid and surfactant. The AAHNPsopt exhibited significantly (P < 0.05, P < 0.01, P < 0.001) higher antioxidant activity as compared to pure AA at each concentration. AAHNPsopt formulation displayed a significantly (P < 0.05) higher anti-inflammatory effect (21.51 ± 2.23% swelling) as compared to pure AA (46.51 ± 1.74% swelling). From the in-vitro and in-vivo finding, it was concluded that HNPs might be a suitable carrier for the improvement of the therapeutic efficacy of the drug.


Subject(s)
Abietanes , Anti-Inflammatory Agents , Antioxidants , Drug Carriers , Lipids , Nanoparticles , Polymers , Nanoparticles/chemistry , Animals , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Rats , Polymers/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Lipids/chemistry , Drug Carriers/chemistry , Abietanes/pharmacology , Abietanes/administration & dosage , Abietanes/chemistry , X-Ray Diffraction/methods , Drug Liberation , Administration, Oral , Male , Particle Size , Rats, Wistar , Chemistry, Pharmaceutical/methods
16.
Life Sci ; 351: 122841, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38897349

ABSTRACT

AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.


Subject(s)
Anti-Inflammatory Agents , Cardiac Surgical Procedures , Selenium , Humans , Male , Female , Aged , Cardiac Surgical Procedures/methods , Selenium/administration & dosage , Selenium/pharmacology , Double-Blind Method , Middle Aged , Prospective Studies , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Recovery of Function/drug effects , Dietary Supplements , Antioxidants/administration & dosage , Antioxidants/pharmacology , Oxidative Stress/drug effects
17.
Int J Pharm ; 659: 124250, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38777304

ABSTRACT

The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.


Subject(s)
Anti-Inflammatory Agents , Blood Glucose , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Insulin , Polysaccharides , Animals , Polysaccharides/administration & dosage , Polysaccharides/chemistry , Blood Glucose/drug effects , Blood Glucose/analysis , Administration, Oral , Insulin/administration & dosage , Insulin/pharmacokinetics , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , Mice , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/pharmacokinetics , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Male , Vitamin B 12/administration & dosage , Nanoparticles/administration & dosage , Drug Liberation , Drug Carriers/chemistry , Humans
18.
Clin Exp Dent Res ; 10(3): e886, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38798063

ABSTRACT

OBJECTIVE: This study evaluates the efficacy of a novel mucoadhesive patch containing Nigella sativa 10% extract compared to triamcinolone 0.1% in alleviating symptoms and reducing lesion severity in patients with erosive-atrophic oral lichen planus. METHODS AND MATERIALS: A pilot study comprising two groups, each with 10 patients, was conducted. The intervention group received mucoadhesive patches containing N. sativa 10% extract, while the control group received triamcinolone acetonide 0.1% patches. Pain and burning intensity, measured through visual analog scale, and lesion severity based on the Thongprasom scale were assessed weekly for 4 weeks. Descriptive records were kept for side effects and patient satisfaction. RESULTS: Pain and burning intensity decreased in both groups throughout the sessions, with the N. sativa group showing a greater reduction than the triamcinolone group. The reduction in burning intensity within each group was significant (p < .001), and there was a significant difference between groups only in the second session (p = .045). The overall difference between groups was not significant (p > .05). Lesion severity also decreased significantly in both groups (p < .001), with a significant difference between groups observed in the third session (p = .043) and overall throughout the study (p = .006). CONCLUSION: The use of N. sativa extract in mucoadhesive patches was as effective as corticosteroids in reducing pain, burning, and lesion severity in patients with oral lichen planus, with N. sativa showing superior results in some sessions. Notably, no significant complications were observed with N. sativa use, making it a promising treatment option for lichen planus.


Subject(s)
Lichen Planus, Oral , Nigella sativa , Plant Extracts , Adult , Aged , Female , Humans , Male , Middle Aged , Anti-Inflammatory Agents/administration & dosage , Lichen Planus, Oral/drug therapy , Nigella sativa/chemistry , Pain Measurement , Phytotherapy/methods , Pilot Projects , Plant Extracts/administration & dosage , Treatment Outcome , Triamcinolone/administration & dosage , Triamcinolone/therapeutic use , Triamcinolone Acetonide/administration & dosage , Triamcinolone Acetonide/therapeutic use
19.
Article in English | MEDLINE | ID: mdl-38809185

ABSTRACT

OBJECTIVE: To determine the effect of a single intraoperative dose of dexamethasone on the risk of postoperative reflux (POR) in horses undergoing small intestinal surgery and to investigate its association with incisional complications and short-term survival. DESIGN: Retrospective cohort study over an 11-year period (2008-2019). SETTING: UK-based private referral center. ANIMALS: Two hundred and forty client-owned horses >6 months of age undergoing exploratory laparotomy for treatment of a small intestinal lesion. INTERVENTIONS: Ninety-seven horses received a single intraoperative dose of dexamethasone (0.1 mg/kg, IV). MEASUREMENTS AND MAIN RESULTS: Of 97 horses that received dexamethasone, 52 (53.6%) required small intestinal resection. Of 143 horses that did not receive dexamethasone, small intestinal resection was performed in 78 (54.5%). A total of 70 horses (29%) developed POR. There was no difference in the risk of POR between horses that received dexamethasone (25/97; 26%) and those that did not (45/143; 31%, P = 0.34). Risk factors associated with the development of POR included small intestinal resection (odds ratio [OR]: 4.55, 95% confidence interval [CI]: 2.27-9.11, P < 0.001), a PCV >40% 24 hours postoperatively (OR: 4.11, 95% CI: 2-8.45, P < 0.001), and a WBC count >10 × 109/L on admission (OR: 3.29, 95% CI: 1.47-7.41, P = 0.004). Dexamethasone was not associated with the odds of POR. Horses undergoing repeat laparotomy had a higher risk of incisional infection (OR: 8.07, 95% CI: 1.98-32.81, P = 0.004). Dexamethasone administration was not associated with incisional infection. The development of POR was negatively associated with short-term survival (OR: 0.07, 95% CI: 0.03-0.17, P ≤ 0.001). Dexamethasone administration was not retained in the final multivariable model for survival. CONCLUSIONS: Intraoperative dexamethasone was not associated with the development of POR in this study population, nor did it have an effect on postoperative survival or incisional infection in horses undergoing surgical management of small intestinal disease.


Subject(s)
Dexamethasone , Horse Diseases , Intestine, Small , Laparotomy , Postoperative Complications , Animals , Horses , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Retrospective Studies , Horse Diseases/surgery , Female , Male , Laparotomy/veterinary , Laparotomy/adverse effects , Intestine, Small/surgery , Postoperative Complications/veterinary , Cohort Studies , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Intestinal Diseases/veterinary , Intestinal Diseases/surgery
20.
J Agric Food Chem ; 72(23): 13054-13068, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38809142

ABSTRACT

Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.


Subject(s)
Colitis, Ulcerative , Flavones , Inflammasomes , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Oxidative Stress , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Mice , Oxidative Stress/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Inflammasomes/immunology , Inflammasomes/metabolism , Inflammasomes/drug effects , Flavones/administration & dosage , Flavones/chemistry , Flavones/pharmacology , RAW 264.7 Cells , Humans , Male , Saccharomyces cerevisiae/chemistry , Capsules/chemistry , Macrophages/drug effects , Macrophages/immunology , Polyphenols/chemistry , Polyphenols/administration & dosage , Polyphenols/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology
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