Pharmaceutical nanotechnology最新文献

{"title":"A Review on Ocular Nanoformulation Based Formulations with Highlights on Pediatric Ocular Pharmacokinetics.","authors":"Ravinder Verma, Manisha Bhatia, Mithun Mojumder, Suraj Patel, Vivek Kumar Mishra, Pooja Mathur, Shailendra Bhatt, Jai Bharti Sharma","doi":"10.2174/0122117385307184240826041920","DOIUrl":"https://doi.org/10.2174/0122117385307184240826041920","url":null,"abstract":"<p><p>The potential use of nanoparticle-based formulations is being explored rapidly for drug delivery in ocular treatment. Despite having several advancements in the area of ocular therapy, the pharmacokinetics-based formulation development for pediatric ocular treatment is still not in proper focus. There are an inadequate number of degenerative ocular ailments with childhood onset. The purpose of this review is to focus on the pharmacokinetics studies of nanoparticle- based formulations for treating ocular diseases and problems associated with the ocular treatment of the pediatric population. Recent studies on pharmaceutical modeling of ocular formulations have also been discussed. Nanoparticle-based formulations were collected by conducting a literature survey on PubMed, Science Direct, and other portals. In this review, we have explored in detail the explanation behind the inequality among available ocular treatment regimens for youngsters as well as adults by specifically focusing on those diseases that can be distressing for children. Latest innovative developments and advancements in drug delivery systems and challenges in their usage particularly for young infant patients were also discussed. It can be concluded that the bioavailability of ocular formulations and their effect on ocular cells can be further enhanced manifolds by the development of nanoparticles-based formulations.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Preparation, Properties, and Applications of Solid Lipid Nanoparticles in Drug Delivery.","authors":"Ujjwal Kumar Biswas, Anindya Bose, Ankita Parmanik","doi":"10.2174/0122117385333634240911075833","DOIUrl":"https://doi.org/10.2174/0122117385333634240911075833","url":null,"abstract":"<p><p>Solid lipid nanoparticles (SLNs) are one of the extensively utilized nanocarriers in the pharmaceutical field due to their biocompatibility and biodegradability. These features of the carrier system have fuelled its use as the drug delivery system since the last three decades. This review presents different SLN preparation techniques, such as high shear homogenization, hot homogenization, cold homogenization, microemulsion-based technique, etc. The physicochemical nature of SLNs, comprising drug loading, drug release, particle size, zeta potential, stability, cytotoxicity, and cellular uptake, has been concisely discussed. The article also explains why SLNs are preferred to develop drug delivery systems in several pharmaceutical preparations. The key ingredients like lipid, surfactant/ stabilizer accompanied by co-surfactant, cryoprotectant, or charge modifiers used to fabricate SLNs are also briefly conferred. Here is an elaborate discussion of drugs that are used through various routes by the SLN carrier system and their outcome for utilization of this system. Regulatory aspects, patent aspects, and future prospects of SLN are also discussed here.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocurcumin-containing Spongy Membrane for Improving the Quality of Hard and Soft Tissues in the Extracted Tooth Area: A Double-Blind Split- Mouth Clinical Trial Study.","authors":"Sina Hessari, Farzin Ahmadpour, Javad Yazdani, Yasmin Golparvar Atashi, Solmaz Maleki Dizaj, Simin Sharifi","doi":"10.2174/0122117385311052240820114853","DOIUrl":"https://doi.org/10.2174/0122117385311052240820114853","url":null,"abstract":"<p><strong>Background: </strong>The assessment of the hard and soft tissue conditions is part of the overall dental treatments.</p><p><strong>Aim: </strong>In this study, we investigated nano curcumin-containing membranes to improve the quality of the hard and soft tissues in the extracted tooth area as a clinical trial study.</p><p><strong>Methods: </strong>After the patient was selected following the inclusion and exclusion criteria, the patients who had teeth extracted from both sides of the mouth (split mouth) on the side of the intervention received a membrane containing nanocurcumin, and on the control side, no material was placed in the socket. For data analysis, SPSS software version 24 was used. A significance threshold was deemed to be less than 0.05 in terms of probability.</p><p><strong>Results: </strong>Two months after tooth extraction, during implant placement, the average gingival thickness on the \"intervention side,\" was 3.1±0.34 mm, while the average gingival thickness on the \"control side\" was 2.6±0.42 mm. Then, the membrane could improve the quality of soft tissue (P< 0.0001). As another outcome, the application of this membrane did not significantly affect bone repair in these patients compared to the control group (P = 0.72). However, the histology data revealed that the newly generated bone of the intervention group was seen close to the membrane, demonstrating the osteoconductive ability of the membrane.</p><p><strong>Conclusion: </strong>Based on the obtained results, the newly developed membrane can be used to improve the quality of hard and soft tissues in the extracted tooth area. Nonetheless, more efforts in nanocurcumin dosage adjustment are needed for hard tissue regeneration in future studies.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid Crystalline Lipid Nanoparticles: Emerging Trends and Applications in Skin Cancer.","authors":"Kamya Varshney, Rupa Mazumder, Anjna Rani, Pratibha Pandey, Malakapogu Ravindra Babu","doi":"10.2174/0122117385312450240816055942","DOIUrl":"https://doi.org/10.2174/0122117385312450240816055942","url":null,"abstract":"<p><p>Liquid crystalline lipid nanoparticles (LCNPs) represent a type of membrane-based nano-carriers formed through the self-assembly of lyotropic lipids. These lipids, such as unsaturated monoglycerides, phospholipids, and co-lipids, create liquid crystals or vesicles with an aqueous core enclosed by a natural or synthetic phospholipid bilayer upon exposure to an aqueous medium. Liquid crystalline lipid nanoparticles (LCNPs), akin to liposomes, have garnered significant attention as nanocarriers suitable for a diverse range of hydrophobic and hydrophilic molecules. Their notable structural advantage lies in a mono-channel network organization and the presence of multiple compartments, resulting in heightened encapsulation efficiency for various substances. Cubosomes, spongosomes, hexosomes, and multicompartment nanoparticles are examples of lipid nanocarriers with interior liquid crystalline structures that have recently gained a lot of interest as effective drug delivery systems. Additionally, LCNPs facilitate the sustained release of encapsulated compounds, including therapeutic macromolecules. This review delves into the structure of liquid crystalline lipid nanoparticles, explores preparation techniques, and outlines their applications in the context of skin cancer.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation Strategy and An Overview of Nano-Structured Lipid Carrier-Based Topical Gel as a Novel Drug Delivery System.","authors":"Ujjwal Kumar Biswas, Anindya Bose","doi":"10.2174/0122117385325593240820044758","DOIUrl":"https://doi.org/10.2174/0122117385325593240820044758","url":null,"abstract":"<p><p>Nano-Structured Lipid Carriers (NLCs) are improved Solid Lipid Nanoparticles (SLNs) that recover the permanency and capacity of drug payload. There are 3 different types of NLCs which have been anticipated. The aforementioned Lipid Nano Particles (LNPs) possess possible tenders in drug delivery systems, cosmeceuticals, clinical research and many others. Here, we highlight the structure, ingredients, different manufacturing techniques and analysis of NLCs which are rudiments in formulating a unique drug delivery system. These types of formulations are therapeutically advantageous like skin hydration, occlusion and improved bioavailability as well as skin targeting. In this article, we have also discussed the features, and novelty of NLCs, different advantages as promising assistance in topical drug delivery systems, shortcomings and utilisations of LNPs by concentrating on NLCs.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Graphene@C3N4-Cu Beads Nanocomposites and their Antimicrobial Efficacy Against Drug-Resistant Bacteria and Fungi.","authors":"Mohd Sajjad Ahmad Khan","doi":"10.2174/0122117385318008240816043647","DOIUrl":"https://doi.org/10.2174/0122117385318008240816043647","url":null,"abstract":"<p><strong>Background: </strong>Increased intake of drugs worldwide and the subsequent advent of resistance to existing antibiotics have globally threatened health organizations. To combat the problem of these drug-resistant infections, as an alternative approach, graphene (GN)-related nanomaterials have attracted significant interest because of their effective anti-microbial potential. The present study shows the synthesis and characterization of nanocomposite of GN with carbon nitride viz. g- C3N4, g-C3N4-Cu, and GN@g-C3N4-Cu. Further, we investigated the anti-microbial potential of these nanocomposites against strains of Gram-negative and Gram-positive bacteria, viz., a multidrug- resistant strain of Pseudomonas aeruginosa (MDRPA), a methicillin-resistant strain of Staphylococcus aureus ATCC33593 (MRSA), and an azole-sensitive fungal strain (Candida albicans ATCC14053).</p><p><strong>Methods: </strong>The morphological characterization of GN@g-C3N4-Cu nanocomposite was executed by scanning electron microscopy, whereas the elemental analysis and their distribution were studied by energy-dispersive X-ray spectroscopy and elemental mapping methods. Furthermore, the anti-microbial and antibiofilm efficacies of g-C3N4, g-C3N4-Cu, and GN@g-C3N4-Cu nanocomposites were evaluated by disc diffusion, two-fold serial micro broth dilution, and 96 well microtiter plate methods.</p><p><strong>Results: </strong>The ternary g-C3N4-Cu@GN, apart from the structures of g-C3N4-Cu, showed big sheets of GN. The observance of C, N, O, and Cu in the elemental analysis, as well as their uniform distribution in the mapping, indicated the successful fabrication of g-C3N4-Cu@GN. GN@g-C3N4-Cu followed by g-C3N4-Cu and (g-C3N4) exhibited significantly higher antimicrobial activity (zone of inhibition from 14.33 to 49.33 mm) against both the drug-resistant bacterial strains and azole-sensitive C. albicans. MICs of nanocomposites ranged from 32 -256 μg/ml against the tested strains. Whereas all three nanocomposites at sub-MICs (0.25 A- and 0.5 A- MICs) showed concentration- dependent inhibition of biofilm formation in MDRPA, MRSA, and C. albicans by allowing 11.35% to 32.59% biofilm formation.</p><p><strong>Conclusion: </strong>Our study highlights the enhanced efficiency of GN@g-C3N4-Cu nanocomposites as potential anti-microbial and antibiofilm agents to overcome the challenges of multi-drug-resistant bacteria and azole-sensitive fungi. Such kind of nanocomposites could be used to prevent nosocomial infections if coated on medical devices and food manufacturing instruments.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced Nanotechnological Approaches for Effective Delivery of Rutin: An Updated Review.","authors":"Keshav Bansal, Hemant Bhati, Vanshita Singh, Uday Pratap","doi":"10.2174/0122117385308249240723111115","DOIUrl":"https://doi.org/10.2174/0122117385308249240723111115","url":null,"abstract":"<p><p>Polyphenols are a group of naturally occurring compounds that have intriguing biological activities. Among these compounds is rutin, a polyphenolic flavanol found in many plants, including passion flowers, buckwheat seed, fruits and fruit rinds, and citrus fruits (such as orange, grapefruit, lemon, and lime). Various studies have demonstrated rutin to possess antibacterial, antifungal, antiallergic, anti-inflammatory, anti-diabetic, anti-adipogenic, anti-carcinogenic, anti-apoptotic, anti-osteoporotic, radioprotective, gastroprotective, neuroprotective, and nephroprotective activities. Despite its benefits, rutin's therapeutic applicability is severely limited due to its low water solubility, sensitivity to oxidation, and dissolving rate. However, these problems can be overcome by employing an efficient delivery approach. An extensive number of nanocarriers can be developed for medicinal use if pre-clinical as well as human-clinical studies are completed. The current review presents an overview of effective rutin nano-formulations for targeted therapy in various health disorders. This review article discusses the clinical evidence, current status, as well as future opportunities of rutin nanocarriers for increasing rutin's bioactivity for possible medicinal uses.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Synthesis of Silver Nanoparticles from Syzygium cumini (L.) Skeels Seed Extract and their Potential Medicinal Applications.","authors":"Apsara Kavital, Murigendra B Hiremath, Ritesh Vernekar, Pradeep S Goudar","doi":"10.2174/0122117385316957240710045706","DOIUrl":"https://doi.org/10.2174/0122117385316957240710045706","url":null,"abstract":"<p><strong>Aim: </strong>Nanotechnology is considered as one of the fastest-developing areas in the biomedicine field. Hence, the green synthesis of silver nanoparticles from Syzygium cumini seed extract was carried out in this study.</p><p><strong>Methodology: </strong>The synthesized nanoparticles were characterized by UV-Vis spectroscopy, FTIR (Fourier transform infrared), FE-SEM (Field Emission scanning electron microscopic), AFM (Atomic Force Microscope), XRD (X-ray diffraction), and EDX (Energy dispersive X-Ray). Their antioxidant and anti-inflammatory activity were evaluated by DPPH (2,2-diphenyl-1- picrylhydrazyl), PM (Phosphomolybdenum) assay, and albumin denaturation assay. Further, the antibacterial activity of the nanoparticles was studied against Gram-positive and Gram-negative bacteria using the agar well diffusion method. In addition, the antidiabetic activity of nanoparticles was studied by α-amylase and α-glucosidase inhibition assays.</p><p><strong>Results: </strong>The surface plasmon resonance at 430 nm confirmed the formation of silver nanoparticles. They were stable and spherical in shape, with sizes ranging from 30 to 90 nm. The DPPH inhibition % of silver nanoparticles varied from 7.91±0.39% to 68.35±0.76%. The % inhibition of albumin denaturation was comparable to the diclofenac. Further, the results of antibacterial activity revealed that the zone of inhibition for all the test bacteria varied from 14.33±0.58 to 25.33±0.58 mm, where B. cereus was more susceptible. In addition, the % inhibition of α-amylase and α-glucosidase varied from 19.91±0.15% to 61.43±0.31% and 15.26±0.11% to 55.38±0.20%, respectively.</p><p><strong>Conclusion: </strong>This study is the first attempt of utilizing the silver nanoparticles synthesized from S. cumini seed extract for antidiabetic activity. The study suggests that these nanoparticles could be well utilized in pharmaceutical industries as an efficient antioxidant, anti-inflammatory, antibacterial, and antidiabetic drug.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composite with Silver Nanoparticles and Oregano Essential Oil-Loaded Nanoparticles Intended for Wound Healing.","authors":"Laura Hernández-Rizo, Angélica Villanueva-Martínez, Enrique Salas-Téllez, Brígida Del Carmen Camacho-Enríquez, María Gabriela Vargas-Martínez, Adriana Ganem-Rondero","doi":"10.2174/0122117385315666240708060501","DOIUrl":"https://doi.org/10.2174/0122117385315666240708060501","url":null,"abstract":"<p><strong>Purpose: </strong>Since wounds are a primary source of infection, it is desirable to have a wound dressing that prevents infectious processes during the tissue regeneration phase. In this regard, silver nanoparticles, oregano essential oil, and chitosan have been utilized due to their antimicrobial activity. This work focused on the preparation of a composite containing these three components, intended to provide protection for wounds, especially by exerting antimicrobial effects.</p><p><strong>Methods: </strong>A composite based on chitosan nanoparticles loaded with oregano essential oil (OEO) and silver nanoparticles was fabricated through the casting-solvent evaporation method. The films were prepared from a suspension of chitosan nanoparticles. The nanoparticles were characterized by size and entrapment efficiency. The surface of the films was observed by SEM, and the mechanical resistance, occlusive capacity, and antimicrobial activity against S. aureus, E. coli, and P. aeruginosa were evaluated. The release of OEO from the films was studied using Franz-type cells.</p><p><strong>Results: </strong>A composite was successfully prepared from a dispersion of OEO-loaded chitosan nanoparticles (147.8 nm, PDI = 0.35; entrapment efficiency = 80.9 %; loading capacity = 38 %) and silver nanoparticles (19.6 nm, PDI = 0.4). A film could be formed that made the composite by pouring the chitosan nanoparticle dispersion directly into molds. The composite presented advantageous characteristics, such as being semi-occlusive (occlusion factor ~ 40 % and reduction in TEWL of 18 %), allowing the sustained release of OEO (about 0.2 mgCm-2 h-1 during 8 h), and having antimicrobial activity for the three strains evaluated.</p><p><strong>Conclusion: </strong>The prepared composite can be considered a potential candidate for dressing materials intended to prevent and treat wound infections.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytosomes Nanocarrier with Insight Towards the Future in Cancer Therapy: A Mini-Review.","authors":"Innocent Sutnga, Akash Sharma, Raja Chakraborty","doi":"10.2174/0122117385304559240626101716","DOIUrl":"https://doi.org/10.2174/0122117385304559240626101716","url":null,"abstract":"<p><p>Cancer is classified as having one of the highest mortality rates on a global scale, presenting a significant challenge in its treatment, especially when conventional chemotherapy methodologies are used. Conversely, there is a growing interest in utilizing herbal medicine as an alternative to the treatment of cancer because of its lack of adverse effects compared to contemporary medical strategies. The incorporation of nanotechnology into therapy has attracted attention owing to its efficacy in the treatment of various illnesses. Phytosomes play a crucial role in the treatment of cancer by enhancing the characteristics of drugs and nanostructures within carriers to enable targeted drug delivery. The establishment of chemical bonds between phospholipid molecules and bioactive compounds from plants ensures the stability of phytosomes, thus establishing them as an innovative mechanism for drug delivery systems that transport plant-derived constituents to specific areas. This mini-overview discusses the potential phytosome complexes, uses, drawbacks, patents, challenges, and prospects of phytosomes in cancer treatment. Thus, numerous phytosomal formulations incorporating plant-derived components have exhibited promising anticancer properties, with several formulations currently undergoing clinical trials.</p>","PeriodicalId":19774,"journal":{"name":"Pharmaceutical nanotechnology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}