Pub Date : 2021-08-31DOI: 10.15587/2519-4852.2021.239332
A. Kriukova, D. Lytkin, M. Marchenko, I. Vladymyrova
The aim of this work is to study of standardization parameters and pharmacological properties of Harpagophytum procumbens (H. procumbens) root dry extract. Materials and methods – obtaining of H. procumbens root dry extract was performed in accordance with developed scheme that is characterized by simplicity and cost-effectiveness of technology compared to analogous scheme. Study of standardization parameters of obtained extract was performed in accordance with the requirements of the monograph «Harpagophyti extractum siccum» of the State Pharmacopoeia of Ukraine 2.2., harmonized with the monograph «Harpagophyti extractum siccum» of the European Pharmacopoeia 9.5. Pharmacology study of analgesic and anti-inflammatory activities were conducted on the rat paw formalin-induced edema model. Results. Obtained H. procumbens root dry extract is a free flowing, non-hygroscopic, light brown powder with taste and odor that is specific to raw material of H. procumbens. Determined loss on drying was 3.2±0.18 %. Content of heavy metals in dry extract was not more than 0.01 % (100 ppm). Harpagoside was identified by TLC method. Chromatographic zones on the obtained chromatograms of the reference solution and test solutions are the same in intensity of a color, cross-over and sharpness of development. Based on the results of the research performed by HPLC method, it has been established that content of harpagoside in investigated H. procumbens root dry extract is 2.50±0.02 %. According to the results of pharmacological research it was found that investigated dry extract (the content of harpagoside is not less than 37.0 mg/kg) showed a higher activity compared to reference drug («Phong Te Thap»). Conclusions. A new method of obtaining dry extract of H. procumbens (3.5:1) was proposed. The developed green production technology is simple; it does not require special equipment and expensive solvents. A correspondence of quality parameters with the requirements of State Pharmacopoeia of Ukraine and European Pharmacopoeia: appearance, identification of harpagoside and fructose, loss of drying, content of heavy metals, assay of harpagoside (2.50±0.02 %) was set. Analgesic and anti-inflammatory activities of H. procumbens dry extract has been established
本研究的目的是研究原丘茴香根干提取物的标准化参数和药理性质。根据开发的方案进行了原藜根干提取物的材料和方法的获取,与类似方案相比,该方案具有简单和技术成本效益的特点。所得提取物的标准化参数研究按照乌克兰国家药典2.2的专著«Harpagophyti extract siccum»的要求进行。,与欧洲药典9.5版的专著«Harpagophyti extract siccum»相协调。对福尔马林致大鼠足跖水肿模型进行了镇痛和抗炎作用的药理学研究。结果。所获得的原藜根干提取物是一种自由流动、不吸湿的浅棕色粉末,具有原藜原料特有的味道和气味。干燥时的测定损失为3.2±0.18%。干提取物中重金属含量不超过0.01% (100 ppm)。采用薄层色谱法鉴别。在得到的参比溶液和测试溶液的色谱图上的色谱区在颜色强度、交叉度和显影清晰度方面是相同的。HPLC法测定结果表明,所研究的原杜仲根干提取物中哈巴苷的含量为2.50±0.02%。药理研究结果表明,所研究的干提取物(哈巴苷含量不低于37.0 mg/kg)比参比药(«Phong Te Thap»)具有更高的活性。结论。提出了一种提取原杜仲干提取物(3.5:1)的新方法。发达的绿色生产技术简单;它不需要特殊设备和昂贵的溶剂。设置符合乌克兰国家药典和欧洲药典要求的质量参数:外观、哈巴果苷和果糖的鉴别、干燥损失、重金属含量、哈巴果苷含量(2.50±0.02%)。已经证实了原丘茴香干提取物的镇痛和抗炎作用
{"title":"Development of Green Production Technology and Research of Harpagophytum Procumbens Root Dry Extract","authors":"A. Kriukova, D. Lytkin, M. Marchenko, I. Vladymyrova","doi":"10.15587/2519-4852.2021.239332","DOIUrl":"https://doi.org/10.15587/2519-4852.2021.239332","url":null,"abstract":"The aim of this work is to study of standardization parameters and pharmacological properties of Harpagophytum procumbens (H. procumbens) root dry extract. \u0000Materials and methods – obtaining of H. procumbens root dry extract was performed in accordance with developed scheme that is characterized by simplicity and cost-effectiveness of technology compared to analogous scheme. Study of standardization parameters of obtained extract was performed in accordance with the requirements of the monograph «Harpagophyti extractum siccum» of the State Pharmacopoeia of Ukraine 2.2., harmonized with the monograph «Harpagophyti extractum siccum» of the European Pharmacopoeia 9.5. Pharmacology study of analgesic and anti-inflammatory activities were conducted on the rat paw formalin-induced edema model. \u0000Results. Obtained H. procumbens root dry extract is a free flowing, non-hygroscopic, light brown powder with taste and odor that is specific to raw material of H. procumbens. Determined loss on drying was 3.2±0.18 %. Content of heavy metals in dry extract was not more than 0.01 % (100 ppm). Harpagoside was identified by TLC method. Chromatographic zones on the obtained chromatograms of the reference solution and test solutions are the same in intensity of a color, cross-over and sharpness of development. Based on the results of the research performed by HPLC method, it has been established that content of harpagoside in investigated H. procumbens root dry extract is 2.50±0.02 %. \u0000According to the results of pharmacological research it was found that investigated dry extract (the content of harpagoside is not less than 37.0 mg/kg) showed a higher activity compared to reference drug («Phong Te Thap»). \u0000Conclusions. A new method of obtaining dry extract of H. procumbens (3.5:1) was proposed. The developed green production technology is simple; it does not require special equipment and expensive solvents. A correspondence of quality parameters with the requirements of State Pharmacopoeia of Ukraine and European Pharmacopoeia: appearance, identification of harpagoside and fructose, loss of drying, content of heavy metals, assay of harpagoside (2.50±0.02 %) was set. Analgesic and anti-inflammatory activities of H. procumbens dry extract has been established","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125022147","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}
Pub Date : 2021-08-31DOI: 10.15587/2519-4852.2021.238329
O. Andryushayev, O. Ruban, Yuliia Maslii, Inna Rusak
The aim. To determine the intensified method of extraction of phenolic compounds from Acorus calamus leaves and optimal conditions for the process. Materials and methods. In order to develop the optimal intensified method of extraction samples were prepared in different conditions of raw materials-extractant ratio, temperature, time and multiplicity. As a raw materials spectrophotometrically pre-standardized Acorus calamus leaves were used. The extraction was carried out in a hermetically sealed ultrasonic extraction reactor PEX 1 (REUS, Contes, France). As the criteria of extraction efficiency were indicators of dry residue and total amount of flavonoids determined using methods described in State Pharmacopoeia of Ukraine. The amount of flavonoids was determined spectrophotometrically on a certified device Specord 200 (Analytik Jena, Germany). Results. According to our research results it was found that ultrasonic action and addition of surfactant significantly improves the efficiency of the extraction process. The optimal conditions for the process were determined. Experimentally proved that the rational raw material-extractant ratio is 1:15. Comparative study of the extraction process with different temperatures showed that the highest amount of extractives is achieved at temperature 70 °C and 45 min of duration. The optimal extraction multiplicity is 3. Conclusions. As a result of the study, the intensified extraction method for Acorus calamus leaves – re-maceration with ultrasound – was established. The conducted researches allowed to develop the method of extraction, expedient in the conditions of the modern pharmaceutical industry.
{"title":"Intensification of the Extraction Process of Phenolic Compounds from Acorus Calamus Leaves","authors":"O. Andryushayev, O. Ruban, Yuliia Maslii, Inna Rusak","doi":"10.15587/2519-4852.2021.238329","DOIUrl":"https://doi.org/10.15587/2519-4852.2021.238329","url":null,"abstract":"The aim. To determine the intensified method of extraction of phenolic compounds from Acorus calamus leaves and optimal conditions for the process. \u0000Materials and methods. In order to develop the optimal intensified method of extraction samples were prepared in different conditions of raw materials-extractant ratio, temperature, time and multiplicity. As a raw materials spectrophotometrically pre-standardized Acorus calamus leaves were used. The extraction was carried out in a hermetically sealed ultrasonic extraction reactor PEX 1 (REUS, Contes, France). As the criteria of extraction efficiency were indicators of dry residue and total amount of flavonoids determined using methods described in State Pharmacopoeia of Ukraine. The amount of flavonoids was determined spectrophotometrically on a certified device Specord 200 (Analytik Jena, Germany). \u0000Results. According to our research results it was found that ultrasonic action and addition of surfactant significantly improves the efficiency of the extraction process. The optimal conditions for the process were determined. Experimentally proved that the rational raw material-extractant ratio is 1:15. Comparative study of the extraction process with different temperatures showed that the highest amount of extractives is achieved at temperature 70 °C and 45 min of duration. The optimal extraction multiplicity is 3. \u0000Conclusions. As a result of the study, the intensified extraction method for Acorus calamus leaves – re-maceration with ultrasound – was established. The conducted researches allowed to develop the method of extraction, expedient in the conditions of the modern pharmaceutical industry.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134150141","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}
Pub Date : 2021-08-31DOI: 10.15587/2519-4852.2021.239279
L. Kucherenko, S. Shishkina, Elena Chonka
Over the last decade, much attention has been paid to the prevention and treatment of chronic diseases of the oral mucosa. This is primarily due to the increase in the number of patients who seek dental care for diseases of the oral mucosa (DOM). Currently, due to the lack of special epidemiological studies, information on the pathology of the oral mucosa in the literature is almost non-existent. The etiology and pathogenesis have not been definitively elucidated. It is established that a significant role in the pathogenesis of chronic inflammatory processes belongs to the state of the microbiocenosis of the oral mucosa. One of the most striking examples of domestic drugs of the antioxidant group is thiotriazoline, developed by the staff of the NGO “Pharmatron”, as well as specialists of the Department of Pharmaceutical Chemistry of Zaporozhye State Medical University under the leadership of professor Mazur I. A. This drug has an antioxidant and membrane-stabilizing effect. The aim. The combined use of several drugs can be complicated by the formation of their supramolecular complexes. Therefore, before the introduction of several substances in it is necessary to model the possibility of intermolecular interactions between them. For this purpose, methods of quantum chemistry are used. Material and methods. We examined the structures and energy characteristics of the complexes, formed thiotriazoline and decamethoxin, also carried out analysis and established at what temperature the formation of a substance from two active components was possible. Results. As a result, the probability of the formation of intermolecular hydrogen bonds is reduced, which is very well seen in the trend of interactions between acid and morpholine. Conclusions. Quantum chemical study of a two-component system consisting of thiotriazoline and decamethoxine showed that the most energetically advantageous three-component complexes have a sufficiently low interaction energy of thiotriazoline and decamethoxine. In addition, the data that are provided in the analysis of the tree diagram suggest that in the technological process in the manufacture of dosage forms, it is advisable to use a temperature not higher than 115℃.
近十年来,口腔黏膜慢性疾病的防治受到了广泛的关注。这主要是由于因口腔黏膜疾病(DOM)而寻求牙科护理的患者人数增加。目前,由于缺乏专门的流行病学研究,文献中关于口腔黏膜病理的信息几乎为零。病因和发病机制尚未明确阐明。已经确定,在慢性炎症过程的发病机制中起重要作用的是口腔黏膜微生物病的状态。抗氧化类国产药物中最引人注目的例子之一是硫代三唑啉,它是由非政府组织“Pharmatron”的工作人员以及扎波罗热国立医科大学药物化学系的专家在Mazur I. a教授的领导下开发的,这种药物具有抗氧化和稳定膜的作用。的目标。几种药物的联合使用会因其超分子复合物的形成而变得复杂。因此,在引入几种物质之前,有必要对它们之间分子间相互作用的可能性进行建模。为此,使用了量子化学的方法。材料和方法。我们检查了配合物的结构和能量特征,形成了硫三唑啉和十甲氧胺,也进行了分析,并确定了在什么温度下,两种活性成分可能形成一种物质。结果。因此,分子间氢键形成的概率降低,这在酸与啉相互作用的趋势中可以很好地看到。结论。对硫代三唑啉和十甲基噻嗪双组分体系的量子化学研究表明,最具能量优势的三组分配合物具有足够低的硫代三唑啉和十甲基噻嗪的相互作用能。另外,从树形图分析中提供的数据可以看出,在剂型制造的工艺过程中,使用不高于115℃的温度为宜。
{"title":"Theoretical Study of the Possibility of Decamethoxin Complexes with Thiotriazolinе to Be Formed","authors":"L. Kucherenko, S. Shishkina, Elena Chonka","doi":"10.15587/2519-4852.2021.239279","DOIUrl":"https://doi.org/10.15587/2519-4852.2021.239279","url":null,"abstract":"Over the last decade, much attention has been paid to the prevention and treatment of chronic diseases of the oral mucosa. \u0000This is primarily due to the increase in the number of patients who seek dental care for diseases of the oral mucosa (DOM). \u0000Currently, due to the lack of special epidemiological studies, information on the pathology of the oral mucosa in the literature is almost non-existent. The etiology and pathogenesis have not been definitively elucidated. It is established that a significant role in the pathogenesis of chronic inflammatory processes belongs to the state of the microbiocenosis of the oral mucosa. \u0000One of the most striking examples of domestic drugs of the antioxidant group is thiotriazoline, developed by the staff of the NGO “Pharmatron”, as well as specialists of the Department of Pharmaceutical Chemistry of Zaporozhye State Medical University under the leadership of professor Mazur I. A. This drug has an antioxidant and membrane-stabilizing effect. \u0000The aim. The combined use of several drugs can be complicated by the formation of their supramolecular complexes. Therefore, before the introduction of several substances in it is necessary to model the possibility of intermolecular interactions between them. For this purpose, methods of quantum chemistry are used. \u0000Material and methods. We examined the structures and energy characteristics of the complexes, formed thiotriazoline and decamethoxin, also carried out analysis and established at what temperature the formation of a substance from two active components was possible. \u0000Results. As a result, the probability of the formation of intermolecular hydrogen bonds is reduced, which is very well seen in the trend of interactions between acid and morpholine. \u0000Conclusions. Quantum chemical study of a two-component system consisting of thiotriazoline and decamethoxine showed that the most energetically advantageous three-component complexes have a sufficiently low interaction energy of thiotriazoline and decamethoxine. In addition, the data that are provided in the analysis of the tree diagram suggest that in the technological process in the manufacture of dosage forms, it is advisable to use a temperature not higher than 115℃.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133639128","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}
Pub Date : 2021-07-11DOI: 10.38177/ajast.2021.5217
M. Santhiya, Lurthu Pushparaj
Countless proteins contain signal patterns that act as entry point and guiding others protein to particular cell frameworks. Likewise, the mutation in the main chain protease of “spike” proteins seemed to be crucial in viral infection and recombination in COVID-19. A certain drug that binds to the sequence will further prevent coronavirus synchronization. To address this, we designed and characterized a new complex for COVID-19 inhibition that contains 1,10-phenantroline as a ligand and Dy(III) as more than just a metal. The absorption character in neat solvent, in the existence of 4.5 percent BSA, as well as the biological interplay of COVID-19 virus via molecular docking, has been carried out to determine the complex's efficacy in this pandemic situation. The complex's absorbance spectra shows intense peaks that correspond to intra ligand π - π*, n - π*, and charge transfer transitions. It also shows a red shift in peaks corresponding to LCT and MLCT transitions in 4.5 percent of BSA. The molecular docking analysis of the complex with the COVID-19 virus (PDB: 6LU7) reveals a strong polar interaction with various amino acids in the spike protein. The complex has awesome binding energies in the -8.8 kcal mol-1 range. As a result, they are legit contender compounds for the development of candidates against SARS-COV-2. We also evaluated the complex's basic energies, such as potential and steric energy, using Gaussian energy calculations.
{"title":"Insilico and Invitro Evaluation of Dy(III) Complex on Serum Albumin as well as Amino Acid Loops in M-Protease of SARS-Coronavirus-2","authors":"M. Santhiya, Lurthu Pushparaj","doi":"10.38177/ajast.2021.5217","DOIUrl":"https://doi.org/10.38177/ajast.2021.5217","url":null,"abstract":"Countless proteins contain signal patterns that act as entry point and guiding others protein to particular cell frameworks. Likewise, the mutation in the main chain protease of “spike” proteins seemed to be crucial in viral infection and recombination in COVID-19. A certain drug that binds to the sequence will further prevent coronavirus synchronization. To address this, we designed and characterized a new complex for COVID-19 inhibition that contains 1,10-phenantroline as a ligand and Dy(III) as more than just a metal. \u0000 \u0000The absorption character in neat solvent, in the existence of 4.5 percent BSA, as well as the biological interplay of COVID-19 virus via molecular docking, has been carried out to determine the complex's efficacy in this pandemic situation. The complex's absorbance spectra shows intense peaks that correspond to intra ligand π - π*, n - π*, and charge transfer transitions. It also shows a red shift in peaks corresponding to LCT and MLCT transitions in 4.5 percent of BSA. The molecular docking analysis of the complex with the COVID-19 virus (PDB: 6LU7) reveals a strong polar interaction with various amino acids in the spike protein. \u0000 \u0000The complex has awesome binding energies in the -8.8 kcal mol-1 range. As a result, they are legit contender compounds for the development of candidates against SARS-COV-2. We also evaluated the complex's basic energies, such as potential and steric energy, using Gaussian energy calculations.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"94 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117308952","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}
P. Hasibuan, Yuandani Yuandani, M. Tanjung, S. Gea, Khatarina Meldawati Pasaribu, M. Harahap, Yurika Almanda Perangin-Angin, Andre Prayoga, Junius Gian Ginting
Cellulose nanofibers (CNF), chitosan, and silver nanoparticles (AgNP) are widely used to enhance the active functions and antibacterial properties in wound dressing. This study was conducted to prepare CNF/AgNP/chitosan incorporation by straight incorporated method and its antimicrobial activity. CNF were isolated from oil palm empty fruit bunches (OPEFB) by pulping method and acid hydrolysis. AgNP were synthesized by green synthesis method. The wound dressing was produced by mixing 10% CNF solution in LiCl/DMAc and AgNP-chitosan in a glass plate with various variations of CNF/AgNP/chitosan, i.e. 100:0, 80:20, 60:40, and 50:50. UV-visible and TEM analyses were used to confirm the formation of AgNP and CNF in nanoscale. The results showed the particles with an absorption of 435 nm and spherical shapes. Based on the calculation by using imageJ analysis, the diameters of CNF were about 50 nm and lengths of several micrometers. FTIR was used to analyze the chemical bonding of AgNP/chitosan and the incorporated the AgNP/chitosan in CNF. From XRD analysis, the presence of AgNP did not affect the crystallinity of CNF. SEM images showed that the addition of AgNP resulted in the stretching of CNF pores on the pads. Thermal degradation of the film increased with the addition of AgNP/chitosan by up to 40%. Antimicrobial test and hemocompatibility test were shown that the formed film of CNF/AgNP/chitosan successfully inhibit bacterial growth and classified as non-hemolytic materials, thus can be further studied its potential as wound dressing.
{"title":"CNF/AgNP/chitosan Film With Antimicrobial and Antihemolytic Properties for Wound Healing","authors":"P. Hasibuan, Yuandani Yuandani, M. Tanjung, S. Gea, Khatarina Meldawati Pasaribu, M. Harahap, Yurika Almanda Perangin-Angin, Andre Prayoga, Junius Gian Ginting","doi":"10.2139/ssrn.3871593","DOIUrl":"https://doi.org/10.2139/ssrn.3871593","url":null,"abstract":"Cellulose nanofibers (CNF), chitosan, and silver nanoparticles (AgNP) are widely used to enhance the active functions and antibacterial properties in wound dressing. This study was conducted to prepare CNF/AgNP/chitosan incorporation by straight incorporated method and its antimicrobial activity. CNF were isolated from oil palm empty fruit bunches (OPEFB) by pulping method and acid hydrolysis. AgNP were synthesized by green synthesis method. The wound dressing was produced by mixing 10% CNF solution in LiCl/DMAc and AgNP-chitosan in a glass plate with various variations of CNF/AgNP/chitosan, i.e. 100:0, 80:20, 60:40, and 50:50. UV-visible and TEM analyses were used to confirm the formation of AgNP and CNF in nanoscale. The results showed the particles with an absorption of 435 nm and spherical shapes. Based on the calculation by using imageJ analysis, the diameters of CNF were about 50 nm and lengths of several micrometers. FTIR was used to analyze the chemical bonding of AgNP/chitosan and the incorporated the AgNP/chitosan in CNF. From XRD analysis, the presence of AgNP did not affect the crystallinity of CNF. SEM images showed that the addition of AgNP resulted in the stretching of CNF pores on the pads. Thermal degradation of the film increased with the addition of AgNP/chitosan by up to 40%. Antimicrobial test and hemocompatibility test were shown that the formed film of CNF/AgNP/chitosan successfully inhibit bacterial growth and classified as non-hemolytic materials, thus can be further studied its potential as wound dressing.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122089710","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}
Spinal cord injury (SCI) causes immune activation of resident microglia. Activated microglia have two different phenotypes, the pro-inflammatory classically activated (M1) phenotype and the anti-inflammatory alternatively activated (M2) phenotype. M1 phenotype microglia are the key factor in inflammation. The treatment of SCI remains a huge challenge due to the nontargeting and inefficiency of anti-inflammatory drugs through the blood-brain barrier (BBB). The purpose of this experiment was to design M2-type primary peritoneal macrophages exosomes (Exos) as a drug carrier for berberine (Ber), which can be efficiently targeted to deliver drugs to the injured spinal cord due to the natural advantage of Exos across the BBB. The Exos were loaded with Ber by an ultrasonic method. In vitro and in vivo experiments confirmed that the loaded sample (Exos-Ber) could decrease the M1 protein marker iNOS, elevate the M2 protein marker CD206 and reduce inflammatory and apoptotic cytokines (TNF-α, IL-1β, IL-6, Caspase 9, Caspase 8), which showed that Exos-Ber had a good anti-inflammatory and anti-apoptotic effect by inducing microglia from the M1 phenotype to M2 phenotype polarization. Moreover, the motor function of SCI mice was significantly improved after Exos-Ber treatment, indicating that Exos-Ber is a potential agent for SCI therapy.
{"title":"Berberine-Loaded M2 Macrophage-Derived Exosomes for Spinal Cord Injury Therapy","authors":"Zhanshan Gao, Chuanjie Zhang, Daoyong Li, Jiaquan Lin, X. Mei, Chao Wu","doi":"10.2139/ssrn.3734107","DOIUrl":"https://doi.org/10.2139/ssrn.3734107","url":null,"abstract":"Spinal cord injury (SCI) causes immune activation of resident microglia. Activated microglia have two different phenotypes, the pro-inflammatory classically activated (M1) phenotype and the anti-inflammatory alternatively activated (M2) phenotype. M1 phenotype microglia are the key factor in inflammation. The treatment of SCI remains a huge challenge due to the nontargeting and inefficiency of anti-inflammatory drugs through the blood-brain barrier (BBB). The purpose of this experiment was to design M2-type primary peritoneal macrophages exosomes (Exos) as a drug carrier for berberine (Ber), which can be efficiently targeted to deliver drugs to the injured spinal cord due to the natural advantage of Exos across the BBB. The Exos were loaded with Ber by an ultrasonic method. In vitro and in vivo experiments confirmed that the loaded sample (Exos-Ber) could decrease the M1 protein marker iNOS, elevate the M2 protein marker CD206 and reduce inflammatory and apoptotic cytokines (TNF-α, IL-1β, IL-6, Caspase 9, Caspase 8), which showed that Exos-Ber had a good anti-inflammatory and anti-apoptotic effect by inducing microglia from the M1 phenotype to M2 phenotype polarization. Moreover, the motor function of SCI mice was significantly improved after Exos-Ber treatment, indicating that Exos-Ber is a potential agent for SCI therapy.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131216952","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}
P. Lou, Shuyun Liu, Xuewen Xu, Cheng Pan, Yanrong Lu, Jingping Liu
Chronic wounds are still an intractable medical problem for both clinicians and researchers and cause a substantial social and medical burden. Current clinical approaches can only manage wounds but have limited capacity to promote the regeneration of chronic wounds. As a type of natural nanovesicle, extracellular vesicles (EVs) from multiple cell types (e.g., stem cells, immune cells, and skin cells) have been shown to participate in all stages of skin wound healing including inflammation, proliferation, and remodeling, and display beneficial roles in promoting wound repair. Moreover, EVs can be further re-engineered with genetic/chemical or scaffold material-based strategies for enhanced skin regeneration. In this review, we provide an overview of EV biology and discuss the current findings regarding the roles of EVs in chronic wound healing, particularly in immune regulation, cell proliferation and migration, angiogenesis, and extracellular matrix remodeling, as well as the therapeutic effects of EVs on chronic wounds by genetic modification, in combination with functionalized biomaterials, and as drug carriers. We also discuss the challenges and perspectives of translating EV-based therapies into clinical wound care in the future.
{"title":"Extracellular Vesicle-Based Therapeutics for the Regeneration of Chronic Wounds: Current Knowledge and Future Perspectives","authors":"P. Lou, Shuyun Liu, Xuewen Xu, Cheng Pan, Yanrong Lu, Jingping Liu","doi":"10.2139/ssrn.3681038","DOIUrl":"https://doi.org/10.2139/ssrn.3681038","url":null,"abstract":"Chronic wounds are still an intractable medical problem for both clinicians and researchers and cause a substantial social and medical burden. Current clinical approaches can only manage wounds but have limited capacity to promote the regeneration of chronic wounds. As a type of natural nanovesicle, extracellular vesicles (EVs) from multiple cell types (e.g., stem cells, immune cells, and skin cells) have been shown to participate in all stages of skin wound healing including inflammation, proliferation, and remodeling, and display beneficial roles in promoting wound repair. Moreover, EVs can be further re-engineered with genetic/chemical or scaffold material-based strategies for enhanced skin regeneration. In this review, we provide an overview of EV biology and discuss the current findings regarding the roles of EVs in chronic wound healing, particularly in immune regulation, cell proliferation and migration, angiogenesis, and extracellular matrix remodeling, as well as the therapeutic effects of EVs on chronic wounds by genetic modification, in combination with functionalized biomaterials, and as drug carriers. We also discuss the challenges and perspectives of translating EV-based therapies into clinical wound care in the future.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122481573","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}
Ya Xiao, Meng-Ran Xu, Na Lv, Chen Cheng, Pei Huang, Jiabin Li, Yi Hu, Ming Sun
The serious threat of drug-resistant bacterial pathogens has arisen through overuse of antibiotics. Photothermal therapy (PTT) has come to prominence as viable alternative strategy for antibacterial therapy. In this work, we report a NIR/pH dual stimuli-responsive antibacterial formulation based on zeolitic imidazolate frameworks-8 (ZIF-8) with strong antibacterial activity that combines photothermal heating with enhanced antibiotic delivery. ZIF-8 with polydopamine (PDA) surface modification was used to encapsulate the antibiotic vancomycin to construct a novel antimicrobial formulation (Van@ZIF-8@PDA). This treatment was tested against Gram-positive vancomycin-resistant Staphylococcus aureus Mu50. Results showed that the PDA coating improved ZIF-8 stability and dispersion, while also conferring a high photothermal conversion efficiency. Hyperthermia activated by near-infrared (NIR) light irradiation, in conjunction with pH-dependent nanoparticle degradation to release vancomycin, enabled tight control of drug delivery that functioned synergistically in the elimination of both planktonic bacteria prior to biofilm formation and established biofilms. We found that this combined formulation compromises cell structure while also degrading bacterial DNA. Moreover, further investigation showed that the Van@ZIF-8@PDA nanoparticles exhibit excellent biocompatibility, with low toxicity toward host organs and tissues, while also reducing the antibiotic concentration needed for effective bacterial control. Finally, we treated Mu50 in a mouse model of skin abscess and found that Van@ZIF-8@PDA was effective and safe in vivo. Cumulatively, this study shows that this NIR/pH dual stimuli-responsive nanoparticle-based formulation offers a promising potential strategy for clinical application against bacterial infection that circumvents antibiotic resistance.
{"title":"Dual Stimuli-Responsive MOF-Based Nanosystem for Synergistic Photothermal/Pharmacological Antibacterial Therapy","authors":"Ya Xiao, Meng-Ran Xu, Na Lv, Chen Cheng, Pei Huang, Jiabin Li, Yi Hu, Ming Sun","doi":"10.2139/ssrn.3692009","DOIUrl":"https://doi.org/10.2139/ssrn.3692009","url":null,"abstract":"The serious threat of drug-resistant bacterial pathogens has arisen through overuse of antibiotics. Photothermal therapy (PTT) has come to prominence as viable alternative strategy for antibacterial therapy. In this work, we report a NIR/pH dual stimuli-responsive antibacterial formulation based on zeolitic imidazolate frameworks-8 (ZIF-8) with strong antibacterial activity that combines photothermal heating with enhanced antibiotic delivery. ZIF-8 with polydopamine (PDA) surface modification was used to encapsulate the antibiotic vancomycin to construct a novel antimicrobial formulation (Van@ZIF-8@PDA). This treatment was tested against Gram-positive vancomycin-resistant Staphylococcus aureus Mu50. Results showed that the PDA coating improved ZIF-8 stability and dispersion, while also conferring a high photothermal conversion efficiency. Hyperthermia activated by near-infrared (NIR) light irradiation, in conjunction with pH-dependent nanoparticle degradation to release vancomycin, enabled tight control of drug delivery that functioned synergistically in the elimination of both planktonic bacteria prior to biofilm formation and established biofilms. We found that this combined formulation compromises cell structure while also degrading bacterial DNA. Moreover, further investigation showed that the Van@ZIF-8@PDA nanoparticles exhibit excellent biocompatibility, with low toxicity toward host organs and tissues, while also reducing the antibiotic concentration needed for effective bacterial control. Finally, we treated Mu50 in a mouse model of skin abscess and found that Van@ZIF-8@PDA was effective and safe in vivo. Cumulatively, this study shows that this NIR/pH dual stimuli-responsive nanoparticle-based formulation offers a promising potential strategy for clinical application against bacterial infection that circumvents antibiotic resistance.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"656 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122958580","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}
Aaron J. Clasky, Jeffrey Watchorn, Paul Z. Chen, F. Gu
Recent advances in biomaterials integrate metal nanoparticles with hydrogels to generate composite materials that exhibit new or improved properties. By precisely controlling the composition, arrangement and interactions of their constituents, these hybrid materials facilitate biomedical applications through myriad approaches. In this work we seek to highlight three popular frameworks for designing metal nanoparticle-hydrogel hybrid materials for biomedical applications. In the first approach, the properties of metal nanoparticles are incorporated into a hydrogel matrix such that the composite is selectively responsive to stimuli such as light and magnetic flux, enabling precisely activated therapeutics and self-healing biomaterials. The second approach mediates the dynamic reorganization of metal nanoparticles based on environment-directed changes in hydrogel structure, leading to chemosensing, microbial and viral detection, and drug-delivery capabilities. In the third approach, the hydrogel matrix spatially arranges metal nanoparticles to produce metamaterials or passively enhance nanoparticle properties to generate improved substrates for biomedical applications including tissue engineering and wound healing. This article reviews the construction, properties and biomedical applications of metal nanoparticle-hydrogel composites, with a focus on how they help to prevent, diagnose and treat diseases. Discussion includes how the composites lead to new or improved properties, how current biomedical research leverages these properties and the emerging directions in this growing field.
{"title":"From Prevention to Diagnosis and Treatment: Biomedical Applications of Metal Nanoparticle-Hydrogel Composites","authors":"Aaron J. Clasky, Jeffrey Watchorn, Paul Z. Chen, F. Gu","doi":"10.2139/ssrn.3697765","DOIUrl":"https://doi.org/10.2139/ssrn.3697765","url":null,"abstract":"Recent advances in biomaterials integrate metal nanoparticles with hydrogels to generate composite materials that exhibit new or improved properties. By precisely controlling the composition, arrangement and interactions of their constituents, these hybrid materials facilitate biomedical applications through myriad approaches. In this work we seek to highlight three popular frameworks for designing metal nanoparticle-hydrogel hybrid materials for biomedical applications. In the first approach, the properties of metal nanoparticles are incorporated into a hydrogel matrix such that the composite is selectively responsive to stimuli such as light and magnetic flux, enabling precisely activated therapeutics and self-healing biomaterials. The second approach mediates the dynamic reorganization of metal nanoparticles based on environment-directed changes in hydrogel structure, leading to chemosensing, microbial and viral detection, and drug-delivery capabilities. In the third approach, the hydrogel matrix spatially arranges metal nanoparticles to produce metamaterials or passively enhance nanoparticle properties to generate improved substrates for biomedical applications including tissue engineering and wound healing. This article reviews the construction, properties and biomedical applications of metal nanoparticle-hydrogel composites, with a focus on how they help to prevent, diagnose and treat diseases. Discussion includes how the composites lead to new or improved properties, how current biomedical research leverages these properties and the emerging directions in this growing field.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124691161","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}
S. Mao, Weicai Yan, Hui-wen Peng, Chi-Shuo Chen, Ying-Chieh Chen
Since the degree of severity and geometry of wounds vary, it is necessary to prepare an anti-adhesive hydrogel that possesses dynamically controllable material properties, exhibits biodegradability, and possesses drug-releasing properties. Injectable, sprayable, oxygen peroxide (H2O2)-sensitive and photo-cross-linkable hydrogels that permit in situ dynamic and spatial control of their physicochemical properties were synthesized for the prevention of postoperative adhesion. Albumin is the most abundant protein in blood serum and serves as a carrier for a number of molecules that exhibit poor water solubility. It is therefore a suitable biomaterial for the fabrication of hydrogels since it presents a low risk of life-threatening complications and does not require immunosuppressive therapy for preventing graft rejection. As micromolar concentrations of endogenous H2O2 are produced after tissue damage, aqueous pre-polymer solutions that exhibit solution-to-gel transition behaviors in response to H2O2 were developed. These solutions form a thin layer of hydrogel that fully covers the wound site and acts as a barrier. The physicochemical properties of this hydrogel can then be spatially post-adjusted via transdermal exposure to light to release drugs, depending on what is required for the particular injury. A significant reduction in postoperative peritoneal adhesion was observed in an animal model involving severe sidewall and bowel abrasions. This study demonstrated that the fabricated dually cross-linked, albumin-based hydrogels have great potential in such applications because they showed a low immune response, easy handling, full wound coverage, and tunable biodegradability. Precise spatial and controllable drug-release profiles may also be achieved via in situ transdermal post-tuning of the biomaterials, depending on the injury.
{"title":"Injectable and Sprayable Albumin/Serum Hydrogels that Demonstrate the Complete Coverage of a Wound and Possess Dynamically and Spatially Controllable Material Properties for the Prevention of Post-Operative Adhesion","authors":"S. Mao, Weicai Yan, Hui-wen Peng, Chi-Shuo Chen, Ying-Chieh Chen","doi":"10.2139/ssrn.3518166","DOIUrl":"https://doi.org/10.2139/ssrn.3518166","url":null,"abstract":"Since the degree of severity and geometry of wounds vary, it is necessary to prepare an anti-adhesive hydrogel that possesses dynamically controllable material properties, exhibits biodegradability, and possesses drug-releasing properties. Injectable, sprayable, oxygen peroxide (H2O2)-sensitive and photo-cross-linkable hydrogels that permit in situ dynamic and spatial control of their physicochemical properties were synthesized for the prevention of postoperative adhesion. Albumin is the most abundant protein in blood serum and serves as a carrier for a number of molecules that exhibit poor water solubility. It is therefore a suitable biomaterial for the fabrication of hydrogels since it presents a low risk of life-threatening complications and does not require immunosuppressive therapy for preventing graft rejection. As micromolar concentrations of endogenous H2O2 are produced after tissue damage, aqueous pre-polymer solutions that exhibit solution-to-gel transition behaviors in response to H2O2 were developed. These solutions form a thin layer of hydrogel that fully covers the wound site and acts as a barrier. The physicochemical properties of this hydrogel can then be spatially post-adjusted via transdermal exposure to light to release drugs, depending on what is required for the particular injury. A significant reduction in postoperative peritoneal adhesion was observed in an animal model involving severe sidewall and bowel abrasions. This study demonstrated that the fabricated dually cross-linked, albumin-based hydrogels have great potential in such applications because they showed a low immune response, easy handling, full wound coverage, and tunable biodegradability. Precise spatial and controllable drug-release profiles may also be achieved via in situ transdermal post-tuning of the biomaterials, depending on the injury.","PeriodicalId":390608,"journal":{"name":"MatSciRN: Drug Delivery (Topic)","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124057871","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}