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Franco PIR, do Carmo Neto JR, Braga YLL, de Lima Pedroso B, Martins JA, Rocha VL, Amaral AC, Martins DB, Ruiz KC, Pereira JX, Machado E Silva JR, Miguel MP. Melatonin-loaded lecithin and chitosan nanoparticles are cytotoxic to 4T1 breast cancer cells and safe in a BALB/c mouse model. Int J Biol Macromol 2025; 311:143401. [PMID: 40268017 DOI: 10.1016/j.ijbiomac.2025.143401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 04/14/2025] [Accepted: 04/19/2025] [Indexed: 04/25/2025]
Abstract
Melatonin is used as an adjuvant therapy in cancer treatment. However, its effectiveness is limited because of its low bioavailability. Polymeric nanoparticles (NPs) made of chitosan and lecithin have been developed to overcome this limitation and optimize localized drug delivery. These lecithin and chitosan-based NPs loaded with melatonin (NP-MEL) were evaluated for their cytotoxic potential in metastatic breast cancer cells and their safety profile in a murine model. Physicochemical characterization revealed efficient melatonin encapsulation (31 %), a positive zeta potential (48.6 mV), and controlled release at physiological pH. NP-MEL exhibited selective cytotoxicity in vitro, with a toxic concentration capable of killing 50 % of the cells (CC50) of 109.53 μg/mL for 4 T1 cancer cells and a significantly higher CC50 of 1460.59 μg/mL for normal VERO cells, resulting in a selectivity index of 13.33. In vivo experiments with BALB/c mice with tumor implantation treated with NP-MEL (2 mg/kg/day for 21 days) showed no significant changes in weight, clinical signs, or biochemical markers of liver and kidney function, except for changes in gamma-glutamyl transferase levels. Histopathological analyses confirmed the preservation of the liver and kidney architecture in the NP-MEL-treated group, in contrast to the moderate-to-severe kidney damage observed in animals treated with empty NPs. These findings highlight the low toxicity and therapeutic potential of NP-MEL as a controlled and targeted-release system for breast cancer treatment, indicating the need for further preclinical investigation.
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Affiliation(s)
- Pablo Igor Ribeiro Franco
- Instituto de Patologia Tropical e Saúde Pública, Laboratório de Histotécnica e Inovação, Centro Multiusuário de Pesquisa de Bioinsumos, Universidade Federal de Goiás, Goiânia, GO, Brazil.
| | - José Rodrigues do Carmo Neto
- Instituto de Patologia Tropical e Saúde Pública, Laboratório de Histotécnica e Inovação, Centro Multiusuário de Pesquisa de Bioinsumos, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Yarlla Loyane Lira Braga
- Instituto de Patologia Tropical e Saúde Pública, Laboratório de Histotécnica e Inovação, Centro Multiusuário de Pesquisa de Bioinsumos, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Bárbara de Lima Pedroso
- Instituto de Patologia Tropical e Saúde Pública, Laboratório de Histotécnica e Inovação, Centro Multiusuário de Pesquisa de Bioinsumos, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Juliana Assis Martins
- Laboratório de Nano & Biotecnologia, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Viviane Lopes Rocha
- Laboratório de Nano & Biotecnologia, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Andre Correa Amaral
- Laboratório de Nano & Biotecnologia, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Danieli Brolo Martins
- Programa de Pós-Graduação em Ciência Animal, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Katalina Cifuentes Ruiz
- Programa de Pós-Graduação em Ciência Animal, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Jonathas Xavier Pereira
- Instituto de Patologia Tropical e Saúde Pública, Laboratório de Histotécnica e Inovação, Centro Multiusuário de Pesquisa de Bioinsumos, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | - Juliana Reis Machado E Silva
- Departamento de Patologia, Genética e Evolução, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil
| | - Marina Pacheco Miguel
- Instituto de Patologia Tropical e Saúde Pública, Laboratório de Histotécnica e Inovação, Centro Multiusuário de Pesquisa de Bioinsumos, Universidade Federal de Goiás, Goiânia, GO, Brazil; Programa de Pós-Graduação em Ciência Animal, Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiânia, GO, Brazil.
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Ribeiro RFN, Santos MR, Aquino M, de Almeida LP, Cavadas C, Silva MMC. The Therapeutic Potential of Melatonin and Its Novel Synthetic Analogs in Circadian Rhythm Sleep Disorders, Inflammation-Associated Pathologies, and Neurodegenerative Diseases. Med Res Rev 2025. [PMID: 40344229 DOI: 10.1002/med.22117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 02/27/2025] [Accepted: 04/24/2025] [Indexed: 05/11/2025]
Abstract
Melatonin, N-acetyl-5-methoxytryptamine, is a tryptophan-derived hormone mostly produced in the pineal gland, despite being synthesized locally at several tissues and organs. This production is rhythmically controlled by complex clock gene networks in the master pacemaker located in the suprachiasmatic nucleus of the hypothalamus. Melatonin is usually secreted only during the dark phase of the day and is essential to synchronize circadian rhythms and neuroendocrine physiological processes. Its main clinical use is associated with the treatment of jet lag and other circadian rhythm sleep disorders, with a growing number of other promising therapeutic applications due to the diverse physiological roles of melatonin. In this review, we explore melatonin and its receptors and provide an updated overview on research concerning the role of melatonin, either as an endogenous molecule or as a drug, in: sleep-wake cycle regulation; circadian rhythms; inflammatory processes that may compromise cardiovascular, respiratory, gastrointestinal, renal, and reproductive system functions; and neurodegenerative disorders such as Alzheimer's and Parkinson's disease. The most recent and promising research findings concerning melatonin synthetic analogs such as agomelatine and ramelteon are highlighted, pointing toward new compounds with promising pharmacological activity while emphasizing their structural differences and advantages when compared to melatonin.
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Affiliation(s)
- Rodrigo F N Ribeiro
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
- Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | | | - Maria Aquino
- Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - Luis Pereira de Almeida
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
- Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - Cláudia Cavadas
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
- Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - Maria Manuel C Silva
- Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
- Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal
- Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
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3
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Fayez E, Samir H, Youssef FS, Salama A, ElSayed MA. Administration of melatonin nanoparticles improves testicular blood flow, echotexture of testicular parenchyma, scrotal circumference, and levels of estradiol and nitric oxide in prepubertal ossimi rams under summer heat stress. Vet Res Commun 2024; 48:3953-3965. [PMID: 39441486 PMCID: PMC11538174 DOI: 10.1007/s11259-024-10563-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 09/29/2024] [Indexed: 10/25/2024]
Abstract
Environmental heat stress (HS) impairs reproductive efficiency in farm animals. This study investigated, for the first time, how the melatonin and melatonin nanoparticles treatment affected the testicular hemodynamics, testicular volume, echotexture [Pixel intensity (PIX) and integrated density (IND)], scrotal circumference, serum concentration of testosterone (T), estradiol (E2), nitric oxide (NO), and total antioxidant capacity (TAC) in prepubertal Ossimi ram lambs in hot climatic conditions. The lambs undergoing examination had a temperature humidity index (THI) of 87.05 ± 1.70, indicating severe HS condition. Fifteen prepubertal Ossimi ram lambs were exposed to a single s.c injection of either nano melatonin (nano melatonin group; 20 mg/ram; n = 5) or melatonin suspended in two ml of corn oil (melatonin group; 40 mg/ram; n = 5) or two ml of corn oil (control group; n = 5). Blood collection and ultrasonographic assessment of the testes and supratesticular arteries (STAs) were conducted immediately before treatment (W0) and once weekly for six successive weeks after nano melatonin and melatonin injection (W1-W6). Results revealed decreases (P < 0.05) in the Doppler indices (resistive index; RI and pulsatility index; PI) of the testicular arteries at most time points of the study in the nano melatonin and melatonin groups. PIX of testicular parenchyma was significantly increased (P ˂ 0.05) in the treated groups compared to the control one. IND of testicular parenchyma increased significantly in the nano melatonin group compared to the melatonin and control groups. Testicular volume and scrotal circumference significantly increased (P < 0.05) in nano melatonin and melatonin groups compared to the control one. T concentration did not significantly (P > 0.05) change in the treated groups compared to the control group. E2, NO, and TAC concentrations increased (P < 0.05) in the treated groups compared to the control one. In conclusion, this study extrapolated that administrations of melatonin or nano melatonin can ameliorate the effects of environmental HS in prepubertal Ossimi ram lambs with a more protective effect and lower dose of nano melatonin.
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Affiliation(s)
- Eman Fayez
- Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Haney Samir
- Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
| | - Fady Sayed Youssef
- Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Ali Salama
- Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Mohamed Ai ElSayed
- Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
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Sundram S, Dhiman N, Malviya R, Awasthi R. Synthesis of Novel Acrylamide Graft Copolymer of Acacia nilotica Gum for the Stabilization of Melatonin Nanoparticles for Improved Therapeutic Effect: Optimization Using (3) 2 Factorial Design. Assay Drug Dev Technol 2024; 22:278-307. [PMID: 38962889 DOI: 10.1089/adt.2024.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2024] Open
Abstract
The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 32 factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker-Lonsdale drug release kinetics.
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Affiliation(s)
- Sonali Sundram
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, India
- Department of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Amity University, Noida, India
| | - Neerupma Dhiman
- Department of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Amity University, Noida, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, India
| | - Rajendra Awasthi
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun, India
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Cheaburu-Yilmaz CN, Atmaca K, Yilmaz O, Orhan H. Development, Characterization, and Evaluation of Potential Systemic Toxicity of a Novel Oral Melatonin Formulation. Pharmaceutics 2024; 16:871. [PMID: 39065568 PMCID: PMC11279405 DOI: 10.3390/pharmaceutics16070871] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/11/2024] [Accepted: 06/24/2024] [Indexed: 07/28/2024] Open
Abstract
The need to create safe materials for biomedical and pharmaceutical applications has become a significant driving force for the development of new systems. Therefore, a chitosan-coated copolymer of itaconic acid, acrylic acid, and N-vinyl caprolactam (IT-AA-NVC) was prepared by radical polymerization and subsequent coating via nanoprecipitation to give a system capable of sustained delivery of melatonin. Although melatonin brings undoubted benefits to the human body, aspects of the optimal dose, route, and time of administration for the obtaining of suitable treatment outcomes remain under discussion. The entrapment of melatonin in biocompatible polymeric systems can prevent its oxidation, decrease its toxicity, and provide an increased half-life, resulting in an enhanced pharmacokinetic profile with improved patient compliance. The structures of the biopolymer and conjugate were proven by FTIR, thermal properties were tested by DSC, and the morphologies were followed by SEM. The loading efficiency and in vitro release profile were studied by means of HPLC, and a delayed release profile with an initial burst was obtained. The potential systemic toxicity of the formulation was studied in vivo; a mild hepatotoxicity was observed following administration of the melatonin-loaded formulation to mice, both by histopathology and blood clinical biochemistry. Histopathology showed a mild nephrotoxicity as well; however, kidney clinical biochemistry did not support this.
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Affiliation(s)
- Catalina N. Cheaburu-Yilmaz
- Biochemistry Division, Department of Chemistry, Faculty of Science, Dokuz Eylul University, 35390 Konak, Izmir, Türkiye
| | - Kemal Atmaca
- Pharmaceutical Toxicology Department, Faculty of Pharmacy, Ege University, 35040 Bornova, Izmir, Türkiye;
| | - Onur Yilmaz
- Leather Engineering Department, Faculty of Engineering, Ege University, 35100 Bornova, Izmir, Türkiye;
| | - Hilmi Orhan
- Pharmaceutical Toxicology Department, Faculty of Pharmacy, Ege University, 35040 Bornova, Izmir, Türkiye;
- İzmir Biomedicine and Genome Center (İBG-İzmir), Dokuz Eylul University Campus, 35340 Balcova, Izmir, Türkiye
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Farid A, Michael V, Safwat G. Melatonin loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles reduce inflammation, inhibit apoptosis and protect rat's liver from the hazardous effects of CCL4. Sci Rep 2023; 13:16424. [PMID: 37777583 PMCID: PMC10543381 DOI: 10.1038/s41598-023-43546-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 09/25/2023] [Indexed: 10/02/2023] Open
Abstract
Liver is an important organ that carries out major important functions including the detoxification of harmful chemicals. Numerous studies have lately focused on the impact of various substances, such as chemical pollutants and pharmaceutical drugs, on the liver. Melatonin (Mel) has been reported for the protection against liver injury. In order to enhance Mel therapeutic benefits and prevent any potential negative effects, Mel has to be delivered to the injured liver. Therefore, the goal of the current investigation was to create Mel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Mel-PLGA NPs) to alleviate carbon tetrachloride (CCL4)-induced liver damage in male Sprague Dawley rats. The prepared Mel-PLGA NPs were physically characterized to determine its size and charge. Moreover, Mel-PLGA NPs were examined, in vitro, to determine its antioxidant, anticoagulant, anti-inflammatory and cytotoxicity effects before being used in vivo. The effect of NPs on liver injury was evaluated through biochemical, immunological, histopathological examination and flow cytometry technique. Mel-PLGA NPs were smooth and spherical with no signs of aggregation and have in vitro antioxidant, anti-inflammatory and anticoagulant effects. NPs varied in size from 87 to 96 nm in transmission electron microscope images, while their hydrodynamic diameter was 41 nm and their zeta potential was -6 mV. Mel-PLGA NPs had encapsulation efficiency (EE%) and drug loading (DL%) of 59.9 and 12.5%, respectively. Treatment with Mel-PLGA NPs ameliorated all histopathological changes, in liver sections, that resulted from CCL4 administration; where, liver sections of treated groups were similar to those of healthy control GI. NPs administration were superior to free Mel and reversed the elevated levels of liver function enzymes, inflammatory cytokines and matrix metalloproteinases to their normal levels. Moreover, liver sections of groups treated with NPs showed negative immunostaining for nuclear factor-κB (NF-κB) and C-reactive protein indicating their anti-inflammatory behavior. Mel-PLGA NPs significantly protected liver from the toxicity of CCL4. The effective dose of NPs was 5 mg/kg indicating a reduction in the required Mel dose and its associated adverse effects.
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Affiliation(s)
- Alyaa Farid
- Biotechnology Department, Faculty of Science, Cairo University, Giza, Egypt.
| | - Valina Michael
- Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA), Giza, Egypt
| | - Gehan Safwat
- Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA), Giza, Egypt
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Lo YJ, Mishra VK, Lo HY, Dubey NK, Lo WC. Clinical Spectrum and Trajectory of Innovative Therapeutic Interventions for Insomnia: A Perspective. Aging Dis 2023; 14:1038-1069. [PMID: 37163444 PMCID: PMC10389812 DOI: 10.14336/ad.2022.1203] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 12/03/2022] [Indexed: 05/12/2023] Open
Abstract
Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.
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Affiliation(s)
| | | | | | - Navneet Kumar Dubey
- Victory Biotechnology Co., Ltd., Taipei 114757, Taiwan.
- ShiNeo Technology Co., Ltd., New Taipei City 24262, Taiwan.
| | - Wen-Cheng Lo
- Department of Surgery, Division of Neurosurgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Department of Neurosurgery, Taipei Medical University Hospital, Taipei 11031, Taiwan.
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan.
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Liang H, Yan Y, Sun W, Ma X, Su Z, Liu Z, Chen Y, Yu B. Preparation of Melatonin-Loaded Nanoparticles with Targeting and Sustained Release Function and Their Application in Osteoarthritis. Int J Mol Sci 2023; 24:ijms24108740. [PMID: 37240086 DOI: 10.3390/ijms24108740] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/07/2023] [Accepted: 05/12/2023] [Indexed: 05/28/2023] Open
Abstract
(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process of osteoarthritis (OA). Melatonin may be a new hope for the treatment of OA because of its antioxidant capacity. However, the mechanism of melatonin in the treatment of OA is still not completely clear, and the physiological characteristics of articular cartilage make melatonin unable to play a long-term role in OA. (2) The effects of melatonin on ROS and the innate immune response system in OA chondrocytes and the therapeutic effect in vivo were evaluated. Then, a melatonin-loaded nano-delivery system (MT@PLGA-COLBP) was prepared and characterized. Finally, the behavior of MT@PLGA-COLPB in cartilage and the therapeutic effect in OA mice were evaluated. (3) Melatonin can inhibit the activation of the innate immune system by inhibiting the TLR2/4-MyD88-NFκB signal pathway and scavenging ROS, thus improving cartilage matrix metabolism and delaying the progression of OA in vivo. MT@PLGA-COLBP can reach the interior of cartilage and complete the accumulation in OA knee joints. At the same time, it can reduce the number of intra-articular injections and improve the utilization rate of melatonin in vivo. (4) This work provides a new idea for the treatment of osteoarthritis, updates the mechanism of melatonin in the treatment of osteoarthritis, and highlights the application prospect of PLGA@MT-COLBP nanoparticles in preventing OA.
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Affiliation(s)
- Haifeng Liang
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Yiran Yan
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Wei Sun
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Xiaogang Ma
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Zhiwen Su
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Zhongxun Liu
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Yan Chen
- Ultrasound Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
| | - Bo Yu
- Orthopedic and Traumatology Department, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
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Shaik L, Boike S, Ramar K, Subramanian S, Surani S. COVID-19 and Sleep Disturbances: A Literature Review of Clinical Evidence. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:818. [PMID: 37241050 PMCID: PMC10221134 DOI: 10.3390/medicina59050818] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/05/2023] [Accepted: 04/10/2023] [Indexed: 05/28/2023]
Abstract
The need for adequate good quality sleep to optimally function is well known. Over years, various physical, psychological, biological, and social factors have been investigated to understand their impact on sleep. However, understanding the etiological processes that are involved in causing sleep disturbances (SD) as impacted by stressful phases such as pandemics has not been well studied. Many such etiological and management strategies have surfaced during the latest "coronavirus disease of 2019 (COVID-19) pandemic. The occurrence of these SD in the infected and uninfected individuals poses a need to investigate factors linked to such occurrence during this phase. Some of such factors include stressful practices such as social distancing, masking, vaccines, and medications availability, changes in routines, and lifestyles. As the status of infection improved, a collective term for all the prolonged effects of COVID-19 after the resolution of the primary infection called the post-COVID-19 syndrome (PCS) surfaced. Apart from impacting sleep during the infectious phase, the aftereffects of this virus left an even greater impact during the PCS. Various mechanisms have been hypothesized to be linked to such SD during the PCS, but the available data are inconclusive. Further, the varied patterns of incidence of these SDs differed by many factors, such as age, gender, and geographical location, making clinical management even more challenging. This review elucidates the impact of coronavirus 2 (SARS-CoV-2) (COVID) disease on sleep health during the various phases of the COVID-19 pandemic. We also investigate different causal relationships, management strategies, and knowledge gaps related to SD during the COVID-19 pandemic.
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Affiliation(s)
- Likhita Shaik
- Department of Family Medicine, Hennepin Healthcare, Minneapolis, MN 55415, USA
| | - Sydney Boike
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA
| | | | | | - Salim Surani
- Department of Pulmonary, Critical Care and Sleep Medicine, Texas A&M University, College Station, TX 77843, USA
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Păncescu FM, Rikabi AAKK, Oprea OC, Grosu AR, Nechifor AC, Grosu VA, Tanczos SK, Dumitru F, Nechifor G, Bungău SG. Chitosan-sEPDM and Melatonin-Chitosan-sEPDM Composite Membranes for Melatonin Transport and Release. MEMBRANES 2023; 13:282. [PMID: 36984671 PMCID: PMC10057635 DOI: 10.3390/membranes13030282] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 02/25/2023] [Indexed: 06/18/2023]
Abstract
Melatonin is the hormone that focuses the attention of the researchers in the medical, pharmaceutical, materials, and membranes fields due to its multiple biomedical implications. The variety of techniques and methods for the controlled release of melatonin is linked to the multitude of applications, among which sports medicine occupies a special place. This paper presents the preparation and characterization of composite membranes based on chitosan (Chi) and sulfonated ethylene-propylene-diene terpolymer (sEPDM). The membranes were obtained by controlled vacuum evaporation from an 8% sEPDM solution in toluene (w/w), in which chitosan was dispersed in an ultrasonic field (sEPDM:Chi = 1:1, w/w). For the comparative evaluation of the membranes' performances, a melatonin-chitosan-sulfonated ethylene-propylene-diene terpolymer (Mel:Chi:sEPDM = 0.5:0.5:1.0, w/w/w) test membrane was made. The prepared membranes were morphologically and structurally characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), energy-dispersive spectroscopy analysis (EDAX), thermal analysis (TG, DSC), thermal analysis coupled with chromatography and infrared analysis, and contact angle measurements, but also from the point of view of performance in the process of transport and release of melatonin in dedicated environments (aqueous solutions with controlled pH and salinity). The prepared membranes can release melatonin in amounts between 0.4 mg/cm2·per day (sEPDM), 1.6 mg/ cm2·per day (Chi/sEPDM), and 1.25 mg/cm2·per day (Mel/Chi/SEPDM).
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Affiliation(s)
- Florentina Mihaela Păncescu
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Abbas Abdul Kadhim Klaif Rikabi
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
- Al–Mussaib Technical College, Al–Furat Al–Awsat Technical University (ATU), Babylon–Najaf Street, Kufa 54003, Iraq
| | - Ovidiu Cristian Oprea
- Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Alexandra Raluca Grosu
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Aurelia Cristina Nechifor
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Vlad-Alexandru Grosu
- Department of Electronic Technology and Reliability, Faculty of Electronics, Telecommunications and Information Technology, University Politehnica of Bucharest, 061071 Bucharest, Romania
| | - Szidonia-Katalin Tanczos
- Department of Bioengineering, University Sapientia of Miercurea-Ciuc, 500104 Miercurea-Ciuc, Romania
| | - Florina Dumitru
- Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Gheorghe Nechifor
- Analytical Chemistry and Environmental Engineering Department, University Politehnica of Bucharest, 011061 Bucharest, Romania
| | - Simona Gabriela Bungău
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
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11
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Wang L, Wang C, Choi WS. Use of Melatonin in Cancer Treatment: Where Are We? Int J Mol Sci 2022; 23:ijms23073779. [PMID: 35409137 PMCID: PMC8998229 DOI: 10.3390/ijms23073779] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/22/2022] [Accepted: 03/28/2022] [Indexed: 02/05/2023] Open
Abstract
Cancer represents a large group of diseases accounting for nearly 10 million deaths each year. Various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, and immunotherapy, have been applied for cancer treatment. However, the outcomes remain largely unsatisfying. Melatonin, as an endogenous hormone, is associated with the circadian rhythm moderation. Many physiological functions of melatonin besides sleep–wake cycle control have been identified, such as antioxidant, immunomodulation, and anti-inflammation. In recent years, an increasing number of studies have described the anticancer effects of melatonin. This has drawn our attention to the potential usage of melatonin for cancer treatment in the clinical setting, although huge obstacles still exist before its wide clinical administration is accepted. The exact mechanisms behind its anticancer effects remain unclear, and the specific characters impede its in vivo investigation. In this review, we will summarize the latest advances in melatonin studies, including its chemical properties, the possible mechanisms for its anticancer effects, and the ongoing clinical trials. Importantly, challenges for the clinical application of melatonin will be discussed, accompanied with our perspectives on its future development. Finally, obstacles and perspectives of using melatonin for cancer treatment will be proposed. The present article will provide a comprehensive foundation for applying melatonin as a preventive and therapeutic agent for cancer treatment.
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Affiliation(s)
- Leilei Wang
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China;
| | - Chuan Wang
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China;
| | - Wing Shan Choi
- Division of Oral and Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China;
- Correspondence: ; Tel.: +852-28590266
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