Pub Date : 2023-05-16DOI: 10.2174/1574885518666230516102626
S. Swain, Jayanti Panda, M. E. Bhanoji Rao
The present research describes the implementation of quality by-design principles for developing the mucoadhesive microcapsules of rabeprazole sodium for treating gastroesophageal reflux disease conditions. In addition, a holistic QbD-based product development strategy was implemented, where the target product profile was defined based on desired product quality of mucoadhesive microcapsules. Based on TPP, the critical quality attributes were identified. The identification of CMAs was carried out with the help of risk assessment and factor screening exercises, which indicated drug-polymer ratio (X1), temperature (X2), and stirring speed (X3) as the influential factors. The mucoadhesive microcapsules of rabeprazole sodium were prepared by a solvent evaporation method, and 33 Box-Behnken optimization design was used for the optimization of the selected factors, and mucoadhesive microcapsules formulations were evaluated for particle size (µm), drug entrapment efficiency (%), mucoadhesion (%), and in vitro drug release (Q18h) in percentage characteristics. Mathematical data analysis was performed to fit the two-factor interaction model, and optimized mucoadhesive microcapsules formulation was selected. The optimized mucoadhesive microcapsules indicated desired formulation characteristics with smaller particle size, good entrapment efficiency, better mucoadhesion, and sustained drug release characteristics. In a nutshell, the studies vouch for the successful development of mucoadhesive microcapsules for oral delivery of rabeprazole sodium which could be used to manage gastroesophageal reflux disease condition.
{"title":"Quality by design enabled formulation optimization of rabeprazole sodium mucoadhesive microcapsules for the treatment of gastroesophageal reflux disease","authors":"S. Swain, Jayanti Panda, M. E. Bhanoji Rao","doi":"10.2174/1574885518666230516102626","DOIUrl":"https://doi.org/10.2174/1574885518666230516102626","url":null,"abstract":"\u0000\u0000The present research describes the implementation of quality by-design principles for developing the mucoadhesive microcapsules of rabeprazole sodium for treating gastroesophageal reflux disease conditions.\u0000\u0000\u0000\u0000In addition, a holistic QbD-based product development strategy was implemented, where the target product profile was defined based on desired product quality of mucoadhesive microcapsules. Based on TPP, the critical quality attributes were identified. The identification of CMAs was carried out with the help of risk assessment and factor screening exercises, which indicated drug-polymer ratio (X1), temperature (X2), and stirring speed (X3) as the influential factors.\u0000\u0000\u0000\u0000The mucoadhesive microcapsules of rabeprazole sodium were prepared by a solvent evaporation method, and 33 Box-Behnken optimization design was used for the optimization of the selected factors, and mucoadhesive microcapsules formulations were evaluated for particle size (µm), drug entrapment efficiency (%), mucoadhesion (%), and in vitro drug release (Q18h) in percentage characteristics. Mathematical data analysis was performed to fit the two-factor interaction model, and optimized mucoadhesive microcapsules formulation was selected.\u0000\u0000\u0000\u0000The optimized mucoadhesive microcapsules indicated desired formulation characteristics with smaller particle size, good entrapment efficiency, better mucoadhesion, and sustained drug release characteristics.\u0000\u0000\u0000\u0000In a nutshell, the studies vouch for the successful development of mucoadhesive microcapsules for oral delivery of rabeprazole sodium which could be used to manage gastroesophageal reflux disease condition.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49594887","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 : 2023-05-16DOI: 10.2174/1574885518666230516150404
K. Pathak, M. Pathak, Riya Saikia, Urvashee Gogoi, R. Das, Pompi Patowary, Partha Pratim Kashyap, S. Bordoloi, J. Das, H. Sarma, M. Ahmad, Aparoop Das
Diabetic patients suffer from various comorbidities like cardiovascular diseases (CVDs), cancer, obesity, cognitive impairment, gout, leishmaniasis, etc. We aimed to review the pathological links between diabetes and its comorbidities and discuss the justification for using antidiabetic drugs in diabetes and associated comorbidities. Diabetic patients accompanied by comorbidities had to undergo a multidrug regimen apart from their common antidiabetic drugs, which affects their quality of life. There have been reports that some antidiabetic drugs ameliorate the comorbidities associated with diabetes. For instance, metformin is implicated in CVDs, cancer, as well as in cognitive impairment like Alzheimer's disease (AD); glyburide, a sulfonylurea, is found to be effective against leishmaniasis; and voglibose, an α- glucosidase inhibitor, is found to have suitable binding property against SARS-CoV-2 infection in diabetic patients. Targeting the comorbidities of diabetes with antidiabetic drugs may reduce the load of multidrug therapy in diabetic patients. The effectiveness of antidiabetic drugs against some diabetic comorbidities between the two pathophysiological conditions, i.e., diabetes and its comorbidities, may be due to certain bidirectional links like inflammation, oxidative stress, disruption in the metabolic milieu and obesity. There are published reports of the repurposing of antidiabetic drugs for specific diseases, however, compiled repurposed reports of antidiabetic drugs for a wide range of diseases are scarce. In this review, we attempt to justify the use of antidiabetic drugs in diabetes and associated comorbidities.
{"title":"Therapeutic Repurposing of Antidiabetic Drugs in Diabetes-Associated\u0000Comorbidities","authors":"K. Pathak, M. Pathak, Riya Saikia, Urvashee Gogoi, R. Das, Pompi Patowary, Partha Pratim Kashyap, S. Bordoloi, J. Das, H. Sarma, M. Ahmad, Aparoop Das","doi":"10.2174/1574885518666230516150404","DOIUrl":"https://doi.org/10.2174/1574885518666230516150404","url":null,"abstract":"\u0000\u0000Diabetic patients suffer from various comorbidities like cardiovascular diseases\u0000(CVDs), cancer, obesity, cognitive impairment, gout, leishmaniasis, etc.\u0000\u0000\u0000\u0000We aimed to review the pathological links between diabetes and its comorbidities and discuss\u0000the justification for using antidiabetic drugs in diabetes and associated comorbidities.\u0000\u0000\u0000\u0000Diabetic patients accompanied by comorbidities had to undergo a multidrug regimen apart\u0000from their common antidiabetic drugs, which affects their quality of life. There have been reports that\u0000some antidiabetic drugs ameliorate the comorbidities associated with diabetes. For instance, metformin\u0000is implicated in CVDs, cancer, as well as in cognitive impairment like Alzheimer's disease (AD);\u0000glyburide, a sulfonylurea, is found to be effective against leishmaniasis; and voglibose, an α-\u0000glucosidase inhibitor, is found to have suitable binding property against SARS-CoV-2 infection in diabetic\u0000patients. Targeting the comorbidities of diabetes with antidiabetic drugs may reduce the load of\u0000multidrug therapy in diabetic patients.\u0000\u0000\u0000\u0000The effectiveness of antidiabetic drugs against some diabetic comorbidities between the two\u0000pathophysiological conditions, i.e., diabetes and its comorbidities, may be due to certain bidirectional\u0000links like inflammation, oxidative stress, disruption in the metabolic milieu and obesity. There are\u0000published reports of the repurposing of antidiabetic drugs for specific diseases, however, compiled repurposed\u0000reports of antidiabetic drugs for a wide range of diseases are scarce.\u0000\u0000\u0000\u0000In this review, we attempt to justify the use of antidiabetic drugs in diabetes and associated\u0000comorbidities.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42054811","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 : 2023-05-12DOI: 10.2174/1574885518666230512120450
M. Mohammadi, Ghazal Farhadifard, Rasool Haddadi, Khashayar Sanemar, Homa Farhadifard
Multiple sclerosis (MS) is a continuing demyelination inflammatory disease of the central nervous system (CNS). In this study, we investigated the effect of propolis on locomotor coordination and stress oxidative modifications in the demyelination model induced by cuprizone because of its antioxidant, neuroprotective, and anti-inflammatory properties. Mice were nourished with powdered chow, including 0.4%w/w cuprizone for one week and then 0.2%w/w cuprizone for four weeks, for MS induction. Mice were given propolis at various doses (100,150, and 200 mg/kg of body weight) during the last 4-weeks of treatment with cuprizone Based on our results, the number of falls decreased significantly in 150mg/kg and 200mg/kg propolis+cuprizone groups (p<0.001) but, no significant difference was reported between the 100mg/kg propolis+cuprizone group and the cuprizone group. The malondialdehyde level decreased significantly in 150mg/kg and 200 mg/kg propolis+cuprizone (p<0.01, p<0.001, respectively), although there was no significant difference in the 100 mg/kg propolis+cuprizone compared to cuprizone group. Glutathione levels increased significantly in 150mg/kg and 200mg/kg propolis+cuprizone groups (p<0.05, p<0.001, respectively) compared to the cuprizone group. There was no noteworthy difference in glutathione level at the 100mg/kg propolis+cuprizone concentration as compared to the cuprizone group. Propolis has the potential to be used as an adjunctive drug in multiple sclerosis treatment.
{"title":"Protective Effects of Propolis on Behavioral and Stress Oxidative Changes in\u0000Cuprizone-Induced Demyelination Model","authors":"M. Mohammadi, Ghazal Farhadifard, Rasool Haddadi, Khashayar Sanemar, Homa Farhadifard","doi":"10.2174/1574885518666230512120450","DOIUrl":"https://doi.org/10.2174/1574885518666230512120450","url":null,"abstract":"\u0000\u0000Multiple sclerosis (MS) is a continuing demyelination inflammatory disease of the central nervous system (CNS). In this study, we investigated the effect of propolis on locomotor coordination and stress oxidative modifications in the demyelination model induced by cuprizone because of its antioxidant, neuroprotective, and anti-inflammatory properties.\u0000\u0000\u0000\u0000Mice were nourished with powdered chow, including 0.4%w/w cuprizone for one week and then 0.2%w/w cuprizone for four weeks, for MS induction. Mice were given propolis at various doses (100,150, and 200 mg/kg of body weight) during the last 4-weeks of treatment with cuprizone\u0000\u0000\u0000\u0000Based on our results, the number of falls decreased significantly in 150mg/kg and 200mg/kg propolis+cuprizone groups (p<0.001) but, no significant difference was reported between the 100mg/kg propolis+cuprizone group and the cuprizone group. The malondialdehyde level decreased significantly in 150mg/kg and 200 mg/kg propolis+cuprizone (p<0.01, p<0.001, respectively), although there was no significant difference in the 100 mg/kg propolis+cuprizone compared to cuprizone group. Glutathione levels increased significantly in 150mg/kg and 200mg/kg propolis+cuprizone groups (p<0.05, p<0.001, respectively) compared to the cuprizone group. There was no noteworthy difference in glutathione level at the 100mg/kg propolis+cuprizone concentration as compared to the cuprizone group.\u0000\u0000\u0000\u0000Propolis has the potential to be used as an adjunctive drug in multiple sclerosis treatment.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43515176","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 : 2023-05-05DOI: 10.2174/1574885518666230505151446
R. Narang, T. Markandeywar, Dilpreet Singh
The nature of the wound typically dictates the available wound-healing therapies. On the other hand, inadequate care results in persistent wounds, fibrosis, tissue loss of function, and ultimately dismemberment. Suturing, unloading, irrigation, debridement, negative pressure therapies, growth factor supplementation, and grafting are examples of current medicines that all have limitations in terms of meeting the needs of full treatment. Natural or synthetic materials/polymers have been utilized to prepare smart thermosensitive hydrogels to facilitate quick and targeted action on wounds. These are intelligent hydrogel system that shows sol-gel transitions at physiological body temperature. Hydrogel provides a moist environment, scaffold-like structure, and localized delivery of drug/growth factor that speed up wound healing even if it eliminates side effects associated with systemic administration. In this article, we summarized the detailed mechanisms of wound healing, conventional strategies, and ongoing thorough research work in the field of thermosensitive hydrogels utilized for wound healing. Moreover, the clinical needs of this formulation, as evident from the commercially available systems are also described in the prior art.
{"title":"A Complete Sojorum On Thermosensitive Hydrogels For Wound Healing: Recent Developments And Ongoing Research","authors":"R. Narang, T. Markandeywar, Dilpreet Singh","doi":"10.2174/1574885518666230505151446","DOIUrl":"https://doi.org/10.2174/1574885518666230505151446","url":null,"abstract":"\u0000\u0000The nature of the wound typically dictates the available wound-healing therapies. On the other hand, inadequate care results in persistent wounds, fibrosis, tissue loss of function, and ultimately dismemberment. Suturing, unloading, irrigation, debridement, negative pressure therapies, growth factor supplementation, and grafting are examples of current medicines that all have limitations in terms of meeting the needs of full treatment. Natural or synthetic materials/polymers have been utilized to prepare smart thermosensitive hydrogels to facilitate quick and targeted action on wounds. These are intelligent hydrogel system that shows sol-gel transitions at physiological body temperature. Hydrogel provides a moist environment, scaffold-like structure, and localized delivery of drug/growth factor that speed up wound healing even if it eliminates side effects associated with systemic administration. In this article, we summarized the detailed mechanisms of wound healing, conventional strategies, and ongoing thorough research work in the field of thermosensitive hydrogels utilized for wound healing. Moreover, the clinical needs of this formulation, as evident from the commercially available systems are also described in the prior art.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47470585","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 : 2023-05-02DOI: 10.2174/1574885518666230502103159
Aparna D. Palshetkar, Aarti. U. Rasal, A. Murugan, N. Desai
COVID-19 was deemed a global pandemic by the World Health Organization in February 2020. The prevalence of viral diseases worldwide has increased the importance of receiving immediate medical attention. There is currently no specific medication or vaccine under consideration to treat coronavirus infection. For reducing or preventing COVID-19 infections, a number of alternative therapies are anticipated, including the use of synthetic drugs, vaccines, interferon therapy etc. Due to the serious side effects of the utilized drug therapies, it is crucial to comprehend the pathogenesis of the coronavirus and explore safe and efficient treatment. Considering the contribution of plants and herbs in the management of viruses like HIV, Herpes Simplex, MERS-CoV, and influenza, they can be further utilised for COVID-19 treatment. According to reports, SARS-CoV2 infects host cells through Angiotensin-converting enzyme 2 receptors, causing pneumonia linked to COVID-19 as well as acute myocardial injury and long-term cardiovascular damage. A cure for SARS-CoV2 may lie in understanding the receptor, its targets, and the mechanism of viral replication. This review article highlights several plants that have the potential to inhibit ACE2, including Punica granatum, Citrus aurantium, Allium sativum, Piper longum, Curcuma longa, and Coriandrum sativum as well as their extracts and phytoconstituents, such as flavonoids, alkaloids, anthraquinone glycosides, phenolic acids, and others. This review will provide opportunities for researchers to explore the possibility of developing promising dosage forms that will increase the bioavailability and in vivo effectiveness of the lead candidates.
{"title":"Natural product-derived phytochemicals as potential inhibitors of angiotensin converting enzyme 2 (ACE2): promising drug candidates for COVID-19","authors":"Aparna D. Palshetkar, Aarti. U. Rasal, A. Murugan, N. Desai","doi":"10.2174/1574885518666230502103159","DOIUrl":"https://doi.org/10.2174/1574885518666230502103159","url":null,"abstract":"\u0000\u0000COVID-19 was deemed a global pandemic by the World Health Organization in February 2020. The prevalence of viral diseases worldwide has increased the importance of receiving immediate medical attention. There is currently no specific medication or vaccine under consideration to treat coronavirus infection. For reducing or preventing COVID-19 infections, a number of alternative therapies are anticipated, including the use of synthetic drugs, vaccines, interferon therapy etc. Due to the serious side effects of the utilized drug therapies, it is crucial to comprehend the pathogenesis of the coronavirus and explore safe and efficient treatment. \u0000Considering the contribution of plants and herbs in the management of viruses like HIV, Herpes Simplex, MERS-CoV, and influenza, they can be further utilised for COVID-19 treatment. According to reports, SARS-CoV2 infects host cells through Angiotensin-converting enzyme 2 receptors, causing pneumonia linked to COVID-19 as well as acute myocardial injury and long-term cardiovascular damage. A cure for SARS-CoV2 may lie in understanding the receptor, its targets, and the mechanism of viral replication. This review article highlights several plants that have the potential to inhibit ACE2, including Punica granatum, Citrus aurantium, Allium sativum, Piper longum, Curcuma longa, and Coriandrum sativum as well as their extracts and phytoconstituents, such as flavonoids, alkaloids, anthraquinone glycosides, phenolic acids, and others. This review will provide opportunities for researchers to explore the possibility of developing promising dosage forms that will increase the bioavailability and in vivo effectiveness of the lead candidates.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44106489","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 : 2023-04-28DOI: 10.2174/1574885518666230428153035
Kamal Uddin Zaidi, F. Shah, F. Khan
Multi-drug resistance of Pseudomonas aeruginosa comprises the most vital obstacles in the antibacterial fight worldwide. The innovation of novel and effective antibacterial and/or resistance modulators is crucial to variance the extent of resistance or to reverse multidrug resistance. This study aimed to determine the in vitro antibacterial activity of the F.carica against the Pseudomonas aeruginosa associated with nosocomial infection. We studied different extracts of F.carica in methanol, benzene and water with antibiotics and their synergistic effect against P. aeruginosa using minimum inhibitory concentration and fraction inhibitory concentration index. Our results revealed that the methanol extract of leaves possessed maximum phyto constituents and were active against P. aeruginosa. Methanol extracts of leaves alone and in combination with antibiotics showed a higher zone of inhibition and were synergistic (<0.5) compared to other extracts. Moreover, the combination of ofloxacin with all solvent extracts enhanced the synergistic antibacterial activity with respect to other antibiotics used. We explored the synergistic effects of F. carica methanol extracts alone and with antibiotics was the most potential against P. aeruginosa.
{"title":"Potential synergistic effect of F.carica against P. aeruginosa intended for the management of nosocomial infection","authors":"Kamal Uddin Zaidi, F. Shah, F. Khan","doi":"10.2174/1574885518666230428153035","DOIUrl":"https://doi.org/10.2174/1574885518666230428153035","url":null,"abstract":"\u0000\u0000Multi-drug resistance of Pseudomonas aeruginosa comprises the most vital obstacles in the antibacterial fight worldwide. The innovation of novel and effective antibacterial and/or resistance modulators is crucial to variance the extent of resistance or to reverse multidrug resistance.\u0000\u0000\u0000\u0000This study aimed to determine the in vitro antibacterial activity of the F.carica against the Pseudomonas aeruginosa associated with nosocomial infection.\u0000\u0000\u0000\u0000We studied different extracts of F.carica in methanol, benzene and water with antibiotics and their synergistic effect against P. aeruginosa using minimum inhibitory concentration and fraction inhibitory concentration index.\u0000\u0000\u0000\u0000Our results revealed that the methanol extract of leaves possessed maximum phyto constituents and were active against P. aeruginosa. Methanol extracts of leaves alone and in combination with antibiotics showed a higher zone of inhibition and were synergistic (<0.5) compared to other extracts. Moreover, the combination of ofloxacin with all solvent extracts enhanced the synergistic antibacterial activity with respect to other antibiotics used.\u0000\u0000\u0000\u0000We explored the synergistic effects of F. carica methanol extracts alone and with antibiotics was the most potential against P. aeruginosa.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42561124","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 : 2023-04-27DOI: 10.2174/1574885518666230427100702
Deepa S. Mandlik, S. Mandlik, Heena Choudhary
Alzheimer's disease (AD) is the most common neurodegenerative disease, accounting for 60–70% of dementia cases globally. Inflammation of the central nervous system (CNS) caused by microglia is a common characteristic of neurodegenerative illnesses such as Parkinson's disease and AD. Research has recently examined the relationship between neurodegenerative diseases and CNS microglia. Microglial cells comprise 10–15% of all CNS cells and are brain-resident myeloid cells mediating critical processes to support the CNS. Microglia have a variety of receptors that operate as molecular sensors, detecting exogenous and endogenous CNS injuries and triggering an immune response. Microglia serve as brain guardians by boosting phagocytic clearance and providing trophic support to enable tissue repair and maintain cerebral homeostasis, in addition to their traditional immune cell activity. At rest, microglia manage CNS homeostasis by phagocytic action, which removes pathogens and cell debris. Microglia cells that have been "resting" convert into active cells that create inflammatory mediators, protecting neurons and protecting against invading pathogens. Neuronal damage and neurodegenerative disorders are caused by excessive inflammation. Different microglial cells reply at different phases of the disease can lead to new therapy options and reduced inflammatory activity. This review focuses on the potential function of microglia, microglia subtypes, and M1/M2 phenotypic changes associated with neurodegenerative disorders. Microglial membrane receptors, the involvement of microglia in neuroinflammation, microglial targets in AD and the double role of microglia in AD pathogenesis are also discussed in this review.
{"title":"New Insights into Microglia as Therapeutic Targets in Alzheimer’s Disease","authors":"Deepa S. Mandlik, S. Mandlik, Heena Choudhary","doi":"10.2174/1574885518666230427100702","DOIUrl":"https://doi.org/10.2174/1574885518666230427100702","url":null,"abstract":"\u0000\u0000Alzheimer's disease (AD) is the most common neurodegenerative disease, accounting for\u000060–70% of dementia cases globally. Inflammation of the central nervous system (CNS) caused by microglia is a common characteristic of neurodegenerative illnesses such as Parkinson's disease and AD.\u0000Research has recently examined the relationship between neurodegenerative diseases and CNS microglia. Microglial cells comprise 10–15% of all CNS cells and are brain-resident myeloid cells mediating critical processes to support the CNS. Microglia have a variety of receptors that operate as molecular sensors, detecting exogenous and endogenous CNS injuries and triggering an immune response. Microglia serve as brain guardians by boosting phagocytic clearance and providing trophic\u0000support to enable tissue repair and maintain cerebral homeostasis, in addition to their traditional immune cell activity. At rest, microglia manage CNS homeostasis by phagocytic action, which removes\u0000pathogens and cell debris. Microglia cells that have been \"resting\" convert into active cells that create\u0000inflammatory mediators, protecting neurons and protecting against invading pathogens. Neuronal\u0000damage and neurodegenerative disorders are caused by excessive inflammation. Different microglial\u0000cells reply at different phases of the disease can lead to new therapy options and reduced inflammatory\u0000activity. This review focuses on the potential function of microglia, microglia subtypes, and M1/M2\u0000phenotypic changes associated with neurodegenerative disorders. Microglial membrane receptors, the\u0000involvement of microglia in neuroinflammation, microglial targets in AD and the double role of microglia in AD pathogenesis are also discussed in this review.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45294991","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 : 2023-04-26DOI: 10.2174/1574885518666230426152955
A. Thakkar, Purvika Mahajan
Due to the increased globalization of regulatory authorities, it has become important to enhance harmonization efforts in creating regulatory requirements, checking and determining GMP compliance, licensing production locations, recalling defective batches, and boosting information interchange. ICH and PIC/S are the international platforms that provide an appealing and stable framework for addressing such globalization concerns. A country having a membership of PIC/S or ICH gives an assurance of the quality, safety, and efficacy of their medical products exported across the globe. Joining such international platforms helps the Pharmaceutical Industries and Regulatory System of that country to improve quality standards. In the present study, the main objective is to gain knowledge regarding the procedures to obtain membership in international platforms such as ICH and PIC/S, and to know the changes/modifications that needs to be done at the institutional/organizational level before applying for the membership, also, to gain knowledge of the eligibility criteria for the application and to know the differences in regulatory guidance in GMP aspects of different regulatory authorities. By joining these international platforms, ICH and PIC/S, non-member countries will be able to tap into the potential for pharmaceutical exports, especially in the largest countries of the globe. After joining these international platforms, the semi or low-regulated nations’ pharmaceutical industries will be benefited greatly in terms of cost savings, export convenience, and most importantly, market access. Membership in ICH and PIC/S will be able to provide the semi or low-regulated Drug Regulatory Authority a global footprint and give foreign regulatory agencies confidence in semi or low-regulated regulatory agencies
{"title":"An overview and membership process of PIC/S and ICH and its requirement for Global Regulatory Harmonization of Drugs","authors":"A. Thakkar, Purvika Mahajan","doi":"10.2174/1574885518666230426152955","DOIUrl":"https://doi.org/10.2174/1574885518666230426152955","url":null,"abstract":"\u0000\u0000Due to the increased globalization of regulatory authorities, it has become important to enhance harmonization efforts in creating regulatory requirements, checking and determining GMP\u0000compliance, licensing production locations, recalling defective batches, and boosting information interchange. ICH and PIC/S are the international platforms that provide an appealing and stable framework for addressing such globalization concerns. A country having a membership of PIC/S or ICH\u0000gives an assurance of the quality, safety, and efficacy of their medical products exported across the\u0000globe. Joining such international platforms helps the Pharmaceutical Industries and Regulatory System\u0000of that country to improve quality standards. In the present study, the main objective is to gain\u0000knowledge regarding the procedures to obtain membership in international platforms such as ICH and\u0000PIC/S, and to know the changes/modifications that needs to be done at the institutional/organizational\u0000level before applying for the membership, also, to gain knowledge of the eligibility criteria for the application and to know the differences in regulatory guidance in GMP aspects of different regulatory\u0000authorities. By joining these international platforms, ICH and PIC/S, non-member countries will be\u0000able to tap into the potential for pharmaceutical exports, especially in the largest countries of the\u0000globe. After joining these international platforms, the semi or low-regulated nations’ pharmaceutical\u0000industries will be benefited greatly in terms of cost savings, export convenience, and most importantly, market access. Membership in ICH and PIC/S will be able to provide the semi or low-regulated\u0000Drug Regulatory Authority a global footprint and give foreign regulatory agencies confidence in semi\u0000or low-regulated regulatory agencies\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46822637","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}
Silymarin is extracted from the seeds of milk thistle (Silybum marianum), exhibits antioxidant properties, and is considered to treat numerous hepatic ailments like chronic liver disease, cirrhosis, and chemical degradation of liver cells and prevent hepatotoxicity from various drugs. The objective of the present study was to preclude the problem of poor dissolution of the relatively water-insoluble drug by formulating solid dispersions of the drug. Solid dispersions of silymarin were prepared by solvent evaporation method by using different polymers, i.e., PEG 6000 and poloxamer 407, in various ratios such as 1:2, 1:4 and 1:6. The compatibility of ingredients with the drug was tested by using Differential scanning calorimetry (DSC), X-Ray Diffractometry, and Fourier Transform-Infrared Spectroscopy (FT-IR). The scavenging activity of DPPH (2,2 diphenyl-1-picrylhydrazyl) radical was used to study the antioxidant activity, and an in vitro release study was conducted using phosphate buffer pH 6.8 as dissolution medium followed by the kinetic assessment to study the drug release mechanism. Solid dispersions with different polymers were successfully prepared by the solvent evaporation method. FTIR spectroscopy and DSC showed no chemical interaction between the drug and polymers. Powder XRD analyses of optimized solid dispersions showed a relative decrease in crystallinity compared to the pure drug. The dissolution profile of solid dispersions successfully exhibited 90.78% drug released, and the optimized batch was found to follow Higuchi drug release kinetics with an R2 value of 0.990. Furthermore, the optimized formulation F6 showed higher antioxidant activity compared to pure silymarin and ascorbic acid. The elevated bioavailability, as well as absorption, consistently regulates the specific therapeutic effect of the water-insoluble drug. The specific response of silymarin to various bodily functions upgrades various activities like anti-aging effects, anti-cancer, antihypertensive, etc. Solid dispersion of drugs with good aqueous solubility results in a decrease in dose frequency and enhanced specificity of the drug mechanism.
{"title":"Solubility Enhancement and Antioxidant Potential of Silymarin: A Poorly Water-Soluble Drug","authors":"Ashwani K. Dhingra, Deepshi Arora, Yugam Taneja, Kumar Guarve, Muskan Chauhan, Kajal Nagpal","doi":"10.2174/1574885518666230418114203","DOIUrl":"https://doi.org/10.2174/1574885518666230418114203","url":null,"abstract":"\u0000\u0000Silymarin is extracted from the seeds of milk thistle (Silybum marianum), exhibits antioxidant properties, and is considered to treat numerous hepatic ailments like chronic liver\u0000disease, cirrhosis, and chemical degradation of liver cells and prevent hepatotoxicity from various\u0000drugs.\u0000\u0000\u0000\u0000The objective of the present study was to preclude the problem of poor dissolution of the\u0000relatively water-insoluble drug by formulating solid dispersions of the drug.\u0000\u0000\u0000\u0000Solid dispersions of silymarin were prepared by solvent evaporation method by using different polymers, i.e., PEG 6000 and poloxamer 407, in various ratios such as 1:2, 1:4 and 1:6. The\u0000compatibility of ingredients with the drug was tested by using Differential scanning calorimetry\u0000(DSC), X-Ray Diffractometry, and Fourier Transform-Infrared Spectroscopy (FT-IR). The scavenging\u0000activity of DPPH (2,2 diphenyl-1-picrylhydrazyl) radical was used to study the antioxidant activity,\u0000and an in vitro release study was conducted using phosphate buffer pH 6.8 as dissolution medium followed by the kinetic assessment to study the drug release mechanism.\u0000\u0000\u0000\u0000Solid dispersions with different polymers were successfully prepared by the solvent evaporation method. FTIR spectroscopy and DSC showed no chemical interaction between the drug and\u0000polymers. Powder XRD analyses of optimized solid dispersions showed a relative decrease in\u0000crystallinity compared to the pure drug. The dissolution profile of solid dispersions successfully\u0000exhibited 90.78% drug released, and the optimized batch was found to follow Higuchi drug release\u0000kinetics with an R2 value of 0.990. Furthermore, the optimized formulation F6 showed higher\u0000antioxidant activity compared to pure silymarin and ascorbic acid.\u0000\u0000\u0000\u0000The elevated bioavailability, as well as absorption, consistently regulates the specific\u0000therapeutic effect of the water-insoluble drug. The specific response of silymarin to various bodily\u0000functions upgrades various activities like anti-aging effects, anti-cancer, antihypertensive, etc. Solid\u0000dispersion of drugs with good aqueous solubility results in a decrease in dose frequency and enhanced\u0000specificity of the drug mechanism.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49412167","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 : 2023-04-17DOI: 10.2174/1574885518666230417111247
S. Jalili, Mahdi Barazesh, Morteza Akhzari, Fouziyeh Faraji, Ebrahim Khorramdin
Non-alcoholic fatty liver disease (NAFLD) is currently the utmost common chronic liver disorder that happens through all age groups and is identified to occur in 14%-30% of the general population, demonstrating a critical and grossing clinical issue because of the growing incidence of obesity and overweight. From the histological aspect, it looks like alcoholic liver damage, but it happens in patients who avoid remarkable alcohol usage. NAFLD comprises a broad spectrum, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis (NASH), different levels of fibrosis, and cirrhosis. Patients with NASH are more susceptible to more rapid progression to cirrhosis and hepatocellular carcinoma. There is no single factor that drives proceeding from simple steatosis to NASH. However, a combination of multi parameters such as genetic background, gut microflora, intake of high fat/ fructose dietary contents or methionine/choline-deficient diet, and consequently accumulated hepatocellular lipids mainly including triglycerides and also other bio-analytes, such as free fatty acids, cholesterol, and phospholipids display a crucial role in disease promotion. NAFLD is related to overweight and insulin resistance (IR) and is regarded as the hepatic presentation of the metabolic syndrome, an amalgamation of medical statuses such as hyperlipidemia, hypertension, type 2 diabetes, and visceral obesity. Despite the increasing prevalence of this disease, which imposes a remarkable clinical burden, most affected patients remain undiagnosed in a timely manner, largely related to the asymptomatic entity of NAFLD patients and the unavailability of accurate and efficient noninvasive diagnostic tests. However, liver biopsy is considered a gold standard for NAFLD diagnosis, but due to being expensive and invasiveness is inappropriate for periodic disease screening. Some noninvasive monitoring approaches have been established recently for NAFLD assessment. In addition to the problem of correct disease course prediction, no effective therapeutic modalities are approved for disease treatment. Imaging techniques can commonly validate the screening and discrimination of NAFLD; nevertheless, staging the disease needs a liver biopsy. The present therapeutic approaches depend on weight loss, sports activities, and dietary modifications, although different insulin-sensitizing drugs, antioxidants, and therapeutic agents seem hopeful. This review aims to focus on the current knowledge concerning epidemiology, pathogenesis, and different biochemical experiments and imaging modalities applied to diagnose the different grades of NAFLD and its management, as well as new data about pharmacological therapies for this disorder.
{"title":"Recent progresses on pathophysiology, diagnosis, therapeutic modalities, and management of Non-alcoholic fatty liver disorder","authors":"S. Jalili, Mahdi Barazesh, Morteza Akhzari, Fouziyeh Faraji, Ebrahim Khorramdin","doi":"10.2174/1574885518666230417111247","DOIUrl":"https://doi.org/10.2174/1574885518666230417111247","url":null,"abstract":"\u0000\u0000Non-alcoholic fatty liver disease (NAFLD) is currently the utmost common chronic liver\u0000disorder that happens through all age groups and is identified to occur in 14%-30% of the general\u0000population, demonstrating a critical and grossing clinical issue because of the growing incidence of\u0000obesity and overweight. From the histological aspect, it looks like alcoholic liver damage, but it happens in patients who avoid remarkable alcohol usage. NAFLD comprises a broad spectrum, ranging\u0000from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis (NASH), different\u0000levels of fibrosis, and cirrhosis. Patients with NASH are more susceptible to more rapid progression to\u0000cirrhosis and hepatocellular carcinoma. There is no single factor that drives proceeding from simple\u0000steatosis to NASH. However, a combination of multi parameters such as genetic background, gut microflora, intake of high fat/ fructose dietary contents or methionine/choline-deficient diet, and consequently accumulated hepatocellular lipids mainly including triglycerides and also other bio-analytes,\u0000such as free fatty acids, cholesterol, and phospholipids display a crucial role in disease promotion.\u0000NAFLD is related to overweight and insulin resistance (IR) and is regarded as the hepatic presentation\u0000of the metabolic syndrome, an amalgamation of medical statuses such as hyperlipidemia, hypertension, type 2 diabetes, and visceral obesity. Despite the increasing prevalence of this disease, which\u0000imposes a remarkable clinical burden, most affected patients remain undiagnosed in a timely manner,\u0000largely related to the asymptomatic entity of NAFLD patients and the unavailability of accurate and\u0000efficient noninvasive diagnostic tests. However, liver biopsy is considered a gold standard for NAFLD\u0000diagnosis, but due to being expensive and invasiveness is inappropriate for periodic disease screening.\u0000Some noninvasive monitoring approaches have been established recently for NAFLD assessment. In\u0000addition to the problem of correct disease course prediction, no effective therapeutic modalities are\u0000approved for disease treatment. Imaging techniques can commonly validate the screening and discrimination of NAFLD; nevertheless, staging the disease needs a liver biopsy. The present therapeutic approaches depend on weight loss, sports activities, and dietary modifications, although different insulin-sensitizing drugs, antioxidants, and therapeutic agents seem hopeful. This review aims to focus on\u0000the current knowledge concerning epidemiology, pathogenesis, and different biochemical experiments\u0000and imaging modalities applied to diagnose the different grades of NAFLD and its management, as\u0000well as new data about pharmacological therapies for this disorder.\u0000","PeriodicalId":11004,"journal":{"name":"Current Drug Therapy","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43778281","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}
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