Pub Date : 2022-02-12DOI: 10.24198/idjp.v3i3.38335
E. Amalia, I. Sopyan, Norisca Aliza Putriana, Sriwidodo Sriwidodo, A. Subarnas
Piperine is bioactive alkaloid extracted from white pepper (Piper albi Linn) with several beneficial pharmacological activities. It is also known to enhance the bioavailability of several limited solubilities of other compounds such as curcumin and resveratrol. Nevertheless, due to its poorly water-soluble character, piperine and extract of white pepper are less applied among other plant extracts. Therefore, our research focussed on the engineering of white pepper extract standardized to piperine in liposome solution and liposome powder for further preparation of various pharmaceutical dosage forms.Our research in preparation of extracted white pepper in liposome delivery system successfully prepared spheric liposome solution with 98.92%±1.17% and an average size of 398.7 nm. The liposome was also successfully prepared in dry powder form with sucrose as a carrier for liposome protection. The rehydration is successfully forming a spheric shape with a similar profile to the initial liposome solution. This research paves the way for scalable white pepper extract liposome preparation without the utilization of toxic organic solvent, to produce the commercial solvent-free product in the future.Keywords: Piperine, Piper albi Linn, liposome, extract, organic solvent-free, drug delivery system, spray dry
{"title":"Preparation of organic-solvent free liposome of Piper albi Linn extract in solution and powder form","authors":"E. Amalia, I. Sopyan, Norisca Aliza Putriana, Sriwidodo Sriwidodo, A. Subarnas","doi":"10.24198/idjp.v3i3.38335","DOIUrl":"https://doi.org/10.24198/idjp.v3i3.38335","url":null,"abstract":"Piperine is bioactive alkaloid extracted from white pepper (Piper albi Linn) with several beneficial pharmacological activities. It is also known to enhance the bioavailability of several limited solubilities of other compounds such as curcumin and resveratrol. Nevertheless, due to its poorly water-soluble character, piperine and extract of white pepper are less applied among other plant extracts. Therefore, our research focussed on the engineering of white pepper extract standardized to piperine in liposome solution and liposome powder for further preparation of various pharmaceutical dosage forms.Our research in preparation of extracted white pepper in liposome delivery system successfully prepared spheric liposome solution with 98.92%±1.17% and an average size of 398.7 nm. The liposome was also successfully prepared in dry powder form with sucrose as a carrier for liposome protection. The rehydration is successfully forming a spheric shape with a similar profile to the initial liposome solution. This research paves the way for scalable white pepper extract liposome preparation without the utilization of toxic organic solvent, to produce the commercial solvent-free product in the future.Keywords: Piperine, Piper albi Linn, liposome, extract, organic solvent-free, drug delivery system, spray dry ","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84660048","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 : 2022-01-28DOI: 10.24198/idjp.v3i3.36777
Y. D. Mardhiani, Deny Puriyani A, Lailatul Fadilah
Astaxanthin has antioxidant activity ten times greater than carotenoids such as -carotene and a hundred times higher than vitamin E. However, its utilization is still limited because its solubility in water is very low which results in low absorption by the skin, resulting in low bioavailability. In this case, to increase the potency of astaxanthin, this research was aimed at the formulation and characterization of astaxanthin nanoemulsions using polysorbate 80 and polyethyleneglycol 400 as a mixture of surfactants with a ratio of 7:1; 8:1 and 9:1 with the method of making a combination of low and high energy emulsification. The data obtained were analyzed using the Kruskal-Wallis test for data on the pH of the preparation and the efficiency of adsorption while the pH test during freeze-thaw stability was analyzed by the Wiloxon test. Based on the test results, it was found that the nanoemulsion preparation with the smix 9:1 formula is the most optimum formula among other formulas, which is to produce preparations with quite good characteristics organoleptically and give a light orange color appearance, clear, distinctive smell with a pH value that meets the SNI standard 16-164399-1996 with pH values ranging from 7.13 to 7.15 and based on the centrifugation test gave stable results and had particle size, polydispersity index and zeta potential values, respectively, 22.9 ± 9.4 nm, 0.435 and -21. ,4 mV and the value of entrapment efficiency ranges from 93.87% to 94.32%. However, the thermodynamic stability is not good enough. This is indicated by the instability of the preparation during the freeze-thaw test with the results of changes in color, transparency and changes in pH.Keywords: Nanoemulsion, Astaxanthin, Polyethyleneglycol 400, Polysorbate 80, Surfactants
{"title":"Astaxanthin Nanoemulsion Formulation and Evaluation","authors":"Y. D. Mardhiani, Deny Puriyani A, Lailatul Fadilah","doi":"10.24198/idjp.v3i3.36777","DOIUrl":"https://doi.org/10.24198/idjp.v3i3.36777","url":null,"abstract":"Astaxanthin has antioxidant activity ten times greater than carotenoids such as -carotene and a hundred times higher than vitamin E. However, its utilization is still limited because its solubility in water is very low which results in low absorption by the skin, resulting in low bioavailability. In this case, to increase the potency of astaxanthin, this research was aimed at the formulation and characterization of astaxanthin nanoemulsions using polysorbate 80 and polyethyleneglycol 400 as a mixture of surfactants with a ratio of 7:1; 8:1 and 9:1 with the method of making a combination of low and high energy emulsification. The data obtained were analyzed using the Kruskal-Wallis test for data on the pH of the preparation and the efficiency of adsorption while the pH test during freeze-thaw stability was analyzed by the Wiloxon test. Based on the test results, it was found that the nanoemulsion preparation with the smix 9:1 formula is the most optimum formula among other formulas, which is to produce preparations with quite good characteristics organoleptically and give a light orange color appearance, clear, distinctive smell with a pH value that meets the SNI standard 16-164399-1996 with pH values ranging from 7.13 to 7.15 and based on the centrifugation test gave stable results and had particle size, polydispersity index and zeta potential values, respectively, 22.9 ± 9.4 nm, 0.435 and -21. ,4 mV and the value of entrapment efficiency ranges from 93.87% to 94.32%. However, the thermodynamic stability is not good enough. This is indicated by the instability of the preparation during the freeze-thaw test with the results of changes in color, transparency and changes in pH.Keywords: Nanoemulsion, Astaxanthin, Polyethyleneglycol 400, Polysorbate 80, Surfactants ","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87517274","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 : 2022-01-28DOI: 10.24198/idjp.v3i3.36140
Yoga Windhu Wardhana, W. Budiati, Rizky Dwi Oktavia, Kalista Tritama Widyanti, I. S. Kurniawansyah, Yedi Herdiana
The development for ophthalmic delivery was purposed to achieve optimum drug loading for ocular therapeutic benefits. An adequate dose of the drug is needed to absorb in the conjunctival sac to take effect. In situ gel preparation was expected to provide these needs with the polymer aid that makes the droplets suddenly coagulate in the eye area to maintain the drug dose. The in situ gel dosage form is desired to overcome the poor bioavailability of conventional ciprofloxacin HCl eye drops on the market. Thus, this work was studied using two cellulose polymers such as hydroxyl propyl cellulose (HPC) and hydroxypropyl methylcellulose (HMPC) as a gelling forming agent. The effect of the in situ ophthalmic quality of the gel due to the two individual polymers separately and their combined use was investigated. The in situ gel quality includes the ability of gel-forming under the influence of varying temperature and stirring frequency difference (as a rheological study) was tested together with the drug release model model. Other ophthalmic preparation quality parameters such as clarity, pH measurement, drug content determination, sterility, and antibacterial activity have been evaluated. However, overall in situ gel formulation developed was of better quality compared to the conventional one. Consideration of the choice of cellulose derivative polymer type is seen to affect the quality of controlled release kinetics models.Keywords: Ophthalmic gel, Ciprofloxacin HCl, HPMC, HPC, Drug release kinetics
{"title":"Ophthalmic release of in situ gel Ciprofloxacin HCl based on combination of Hypromellose and HPC","authors":"Yoga Windhu Wardhana, W. Budiati, Rizky Dwi Oktavia, Kalista Tritama Widyanti, I. S. Kurniawansyah, Yedi Herdiana","doi":"10.24198/idjp.v3i3.36140","DOIUrl":"https://doi.org/10.24198/idjp.v3i3.36140","url":null,"abstract":"The development for ophthalmic delivery was purposed to achieve optimum drug loading for ocular therapeutic benefits. An adequate dose of the drug is needed to absorb in the conjunctival sac to take effect. In situ gel preparation was expected to provide these needs with the polymer aid that makes the droplets suddenly coagulate in the eye area to maintain the drug dose. The in situ gel dosage form is desired to overcome the poor bioavailability of conventional ciprofloxacin HCl eye drops on the market. Thus, this work was studied using two cellulose polymers such as hydroxyl propyl cellulose (HPC) and hydroxypropyl methylcellulose (HMPC) as a gelling forming agent. The effect of the in situ ophthalmic quality of the gel due to the two individual polymers separately and their combined use was investigated. The in situ gel quality includes the ability of gel-forming under the influence of varying temperature and stirring frequency difference (as a rheological study) was tested together with the drug release model model. Other ophthalmic preparation quality parameters such as clarity, pH measurement, drug content determination, sterility, and antibacterial activity have been evaluated. However, overall in situ gel formulation developed was of better quality compared to the conventional one. Consideration of the choice of cellulose derivative polymer type is seen to affect the quality of controlled release kinetics models.Keywords: Ophthalmic gel, Ciprofloxacin HCl, HPMC, HPC, Drug release kinetics ","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73080141","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 : 2022-01-28DOI: 10.24198/idjp.v3i3.37660
Yedi Herdiana, T. Rusdiana
The halal food market has grown worldwide, including the shift from food to other products, including halal pharmaceuticals (HPC). The growth followed by the abundance of literature has been on halal, especially pharmaceuticals. Muslim consumers need halal certification (HCT) on medicines to ensure that they do not consume or use products or services that are not halal. The government must guarantee to Muslim consumers that consumer goods or services circulating in the community are truly halal. The halal label itself will increase consumer confidence, expand the reach of the global halal food market, and increase the marketability of products in the market. Indonesia, which is predominantly Muslim, is considered a long extension in implementing HP until 2034. Different attitudes are shown by several countries with large non-Muslim majority populations but are very concerned about the implementation of HPC. The accelerated growth of knowledge of halalness, impact social media, will push the industry to implement HPC. In this review, we will discuss critical players in implementing HPC, including the ingredients that have been widely used but still doubt their halalness and what they are used for in the pharmaceutical industry. This knowledge is essential for industry and researchers to build safer alternative materials.Keywords: Halal, Indonesia, Muslim, Halal Pharmaceutical, Halal Certification.
{"title":"Indonesian Halal Pharmaceutical: Challenges And Market Opportunities","authors":"Yedi Herdiana, T. Rusdiana","doi":"10.24198/idjp.v3i3.37660","DOIUrl":"https://doi.org/10.24198/idjp.v3i3.37660","url":null,"abstract":"The halal food market has grown worldwide, including the shift from food to other products, including halal pharmaceuticals (HPC). The growth followed by the abundance of literature has been on halal, especially pharmaceuticals. Muslim consumers need halal certification (HCT) on medicines to ensure that they do not consume or use products or services that are not halal. The government must guarantee to Muslim consumers that consumer goods or services circulating in the community are truly halal. The halal label itself will increase consumer confidence, expand the reach of the global halal food market, and increase the marketability of products in the market. Indonesia, which is predominantly Muslim, is considered a long extension in implementing HP until 2034. Different attitudes are shown by several countries with large non-Muslim majority populations but are very concerned about the implementation of HPC. The accelerated growth of knowledge of halalness, impact social media, will push the industry to implement HPC. In this review, we will discuss critical players in implementing HPC, including the ingredients that have been widely used but still doubt their halalness and what they are used for in the pharmaceutical industry. This knowledge is essential for industry and researchers to build safer alternative materials.Keywords: Halal, Indonesia, Muslim, Halal Pharmaceutical, Halal Certification. ","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78870022","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 : 2022-01-28DOI: 10.24198/idjp.v3i3.37062
N. Putriana, E. Mardawati, Y. W. Wardhana, N. Afifah, A. Wulandari, D. Wira, N. Masruchin
Free radicals are naturally produced from the body's metabolic processes, but the excessive amount of free radicals can interfere with human health because they cause oxidative stress. Therefore we need antioxidants that can protect against free radicals. Ficus lyrata W. is one of the antioxidant sources. This study aims to formulate instant granules from the Ethanol extract of Ficus lyrata W. using the wet granulation method. The formula is optimized using the Design Expert with the two-level factorial method. The optimized factors are xanthan gum 0,8-1,5% and PVP 0,5-5%. Granules are evaluated and analyzed using a Design Expert. The results obtained showed that Formula 4 with a combination of xanthan gum 0,8% and PVP 5% is the best formula, which the evaluation result is Loss On Drying (LOD) 3,28%, Flowability 16.043 ± 0.221 (g/s), Angle of Rest 21.77 ± 0.862, no precipitate for15 minutes, pH = 4.7, dispersed in 31 seconds and sedimentation time is 52.213 ± 1.7878 (minutes), the results of the antioxidant activity test of the ethanol extract of Ficus lyrata is 38,27 µg/ml, and instant granules is 145,02 µg/ml.Keywords: Antioxidant, Ficus lyrata W., Instant granules, Design expert
{"title":"Formulation and Evaluation of instant granules from Ketapang Badak fruit (Ficus lyrata Warb) using wet granulation method as an antioxidant supplement","authors":"N. Putriana, E. Mardawati, Y. W. Wardhana, N. Afifah, A. Wulandari, D. Wira, N. Masruchin","doi":"10.24198/idjp.v3i3.37062","DOIUrl":"https://doi.org/10.24198/idjp.v3i3.37062","url":null,"abstract":"Free radicals are naturally produced from the body's metabolic processes, but the excessive amount of free radicals can interfere with human health because they cause oxidative stress. Therefore we need antioxidants that can protect against free radicals. Ficus lyrata W. is one of the antioxidant sources. This study aims to formulate instant granules from the Ethanol extract of Ficus lyrata W. using the wet granulation method. The formula is optimized using the Design Expert with the two-level factorial method. The optimized factors are xanthan gum 0,8-1,5% and PVP 0,5-5%. Granules are evaluated and analyzed using a Design Expert. The results obtained showed that Formula 4 with a combination of xanthan gum 0,8% and PVP 5% is the best formula, which the evaluation result is Loss On Drying (LOD) 3,28%, Flowability 16.043 ± 0.221 (g/s), Angle of Rest 21.77 ± 0.862, no precipitate for15 minutes, pH = 4.7, dispersed in 31 seconds and sedimentation time is 52.213 ± 1.7878 (minutes), the results of the antioxidant activity test of the ethanol extract of Ficus lyrata is 38,27 µg/ml, and instant granules is 145,02 µg/ml.Keywords: Antioxidant, Ficus lyrata W., Instant granules, Design expert","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86782631","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 : 2021-11-03DOI: 10.24198/idjp.v3i2.34876
Irna Roniawati, N. Putriana, A. Putri, Yuniar Alfain Nur’aini
Saffron (Crocus sativus) is a plant that has been widely used in Asia, especially in the health sector. This can be related to other than that saffron is also known for its use as a cosmetic because Saffron has various kinds of pharmacological activities beneficial to human skin. Today's cosmetic users prefer cosmetics with herbal or natural ingredients, especially in Indonesia. This happens because it is considered that herbal cosmetics are safer and harmless in long-term use. Therefore, it is necessary to do related act ivities of saffron as a cosmetic ingredient. This is narrative research where the data is obtained from PubMed, Science Direct, and Google Scholar with keywords Saffron, Saffron for cosmetics, and others. There were eight references, with inclusion criteria being national and international journals and national websites published in 2011-2021, especially regarding the study of saffron activity as an ingredient for cosmetics. Then the data is analyzed narratively. It was found that Saffron (Crocus sativus) contains compounds that have a cosmetic activity such as safranal which can be used as a perfume, crocin as an antioxidant and as anti-dark spot, crocin, safranal, and crocetin as anti-UV, crocin, and crocetin as an anti-inflammatory and as coloring pigment in cosmetics, vitamin C, flavonoids and zinc as a face toner, kaempferol, crocin and crocetin as anti-wrinkle, zeaxanthin, lycopene, carotene, crocetin, picrocrocin, kaempferol, and crocin as anti-aging. Saffron (Crocus sativus) has various beneficial activities for the skin, so it can be used as an ingredient in making cosmetics.Keywords : Cosmetics, Herbal, Saffron, Herbal Cosmetics, Active Ingredient
{"title":"Review: Saffron’s Activity as an Active Ingredient in Cosmetics","authors":"Irna Roniawati, N. Putriana, A. Putri, Yuniar Alfain Nur’aini","doi":"10.24198/idjp.v3i2.34876","DOIUrl":"https://doi.org/10.24198/idjp.v3i2.34876","url":null,"abstract":"Saffron (Crocus sativus) is a plant that has been widely used in Asia, especially in the health sector. This can be related to other than that saffron is also known for its use as a cosmetic because Saffron has various kinds of pharmacological activities beneficial to human skin. Today's cosmetic users prefer cosmetics with herbal or natural ingredients, especially in Indonesia. This happens because it is considered that herbal cosmetics are safer and harmless in long-term use. Therefore, it is necessary to do related act ivities of saffron as a cosmetic ingredient. This is narrative research where the data is obtained from PubMed, Science Direct, and Google Scholar with keywords Saffron, Saffron for cosmetics, and others. There were eight references, with inclusion criteria being national and international journals and national websites published in 2011-2021, especially regarding the study of saffron activity as an ingredient for cosmetics. Then the data is analyzed narratively. It was found that Saffron (Crocus sativus) contains compounds that have a cosmetic activity such as safranal which can be used as a perfume, crocin as an antioxidant and as anti-dark spot, crocin, safranal, and crocetin as anti-UV, crocin, and crocetin as an anti-inflammatory and as coloring pigment in cosmetics, vitamin C, flavonoids and zinc as a face toner, kaempferol, crocin and crocetin as anti-wrinkle, zeaxanthin, lycopene, carotene, crocetin, picrocrocin, kaempferol, and crocin as anti-aging. Saffron (Crocus sativus) has various beneficial activities for the skin, so it can be used as an ingredient in making cosmetics.Keywords : Cosmetics, Herbal, Saffron, Herbal Cosmetics, Active Ingredient","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75552891","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 : 2021-11-03DOI: 10.24198/idjp.v3i2.35909
Yuta Takahashi, T. Araki, A. Nagamine, H. Yashima, Daisuke Nagano, K. Obayashi, Koujirou Yamamoto
Cigarette smoking is known to impact the promotion of carcinogenesis and tumor metastasis. On the other hand, some components in smoke were found to have health-promoting effects, and cancer suppressor effects of components in tobacco smoke have attracted attention. Although some studies showed the cancer suppressive effect of cigarette smoke extract (CSE) in vitro study, the effect of CSE administration on cancer is controversial. In this study, we investigated the effect of CSE-administration on tumor metastasis in a spontaneous tumor metastasis model using B16-BL6 cells, which is more clinical conditions. C57BL/6NCr mice were subcutaneously inoculated B16-BL6 cells into the footpad of the right rear leg. CSE was intraperitoneally administrated for 28 days from the day of inoculation. At 2 weeks after inoculation, the primary focus was excised. Subsequently, survival days of the mice were recorded to determine the effect of CSE-administration on spontaneous metastasis. The effect of CSE, α, β-unsaturated ketones, and aldehydes on B16-BL6 cell invasiveness were confirmed by matrigel invasion assay. Survival days of mice injected with 100% CSE was significantly shortened than that of control. B16-BL6 cell invasiveness was accelerated by the treatment with 0.1% CSE and 3 μM of crotonaldehyde. Intraperitoneal CSE-administration may progress spontaneous metastasis of B16-BL6 cells via enhancement of B16-BL6 cell invasiveness. As the cause, we found that crotonaldehyde contained in CSE may enhance the invasion ability of cancer cells. To clarify the cancer-suppressing effect of tobacco components, the effect of crotonaldehyde-removed CSE on tumor should be assessed in detail. Keywords: cigarette smoke extract (CSE), metastasis, crotonaldehyde (CA), B16-BL6 mouse melanoma cells, invasion
{"title":"Effect of nicotine- and tar-removed cigarette smoke extract on cancer metastasis","authors":"Yuta Takahashi, T. Araki, A. Nagamine, H. Yashima, Daisuke Nagano, K. Obayashi, Koujirou Yamamoto","doi":"10.24198/idjp.v3i2.35909","DOIUrl":"https://doi.org/10.24198/idjp.v3i2.35909","url":null,"abstract":"Cigarette smoking is known to impact the promotion of carcinogenesis and tumor metastasis. On the other hand, some components in smoke were found to have health-promoting effects, and cancer suppressor effects of components in tobacco smoke have attracted attention. Although some studies showed the cancer suppressive effect of cigarette smoke extract (CSE) in vitro study, the effect of CSE administration on cancer is controversial. In this study, we investigated the effect of CSE-administration on tumor metastasis in a spontaneous tumor metastasis model using B16-BL6 cells, which is more clinical conditions. C57BL/6NCr mice were subcutaneously inoculated B16-BL6 cells into the footpad of the right rear leg. CSE was intraperitoneally administrated for 28 days from the day of inoculation. At 2 weeks after inoculation, the primary focus was excised. Subsequently, survival days of the mice were recorded to determine the effect of CSE-administration on spontaneous metastasis. The effect of CSE, α, β-unsaturated ketones, and aldehydes on B16-BL6 cell invasiveness were confirmed by matrigel invasion assay. Survival days of mice injected with 100% CSE was significantly shortened than that of control. B16-BL6 cell invasiveness was accelerated by the treatment with 0.1% CSE and 3 μM of crotonaldehyde. Intraperitoneal CSE-administration may progress spontaneous metastasis of B16-BL6 cells via enhancement of B16-BL6 cell invasiveness. As the cause, we found that crotonaldehyde contained in CSE may enhance the invasion ability of cancer cells. To clarify the cancer-suppressing effect of tobacco components, the effect of crotonaldehyde-removed CSE on tumor should be assessed in detail. Keywords: cigarette smoke extract (CSE), metastasis, crotonaldehyde (CA), B16-BL6 mouse melanoma cells, invasion ","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78809186","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 : 2021-11-03DOI: 10.24198/idjp.v3i2.35849
Abd. Kakhar Umar, J. H. Zothantluanga
Quercetin derivatives are known to have significant anticancer activity. The activity is strongly influenced by the type and position of the substituent group. By studying the structural pattern of quercetin and its impact on their binding affinity, the development of quercetin-based drugs can be optimized. The study aimed to determine the impact of 3D structure, type, and position of quercetin moiety on its activity against ROS-modulating enzymes that play a role in the induction and growth of ROS-induced cancer. The 23 natural quercetin derivatives were docked to 7 ROS-modulating enzymes using Autodock Vina to determine their binding affinity and interaction. The interaction stability was further studied through molecular dynamics simulation using the CABS Flex 2.0 server. Determination of crucial amino acid targets of the quercetin group was determined using DockFlin. Finally, the toxicity of each test ligand was determined using the pkCSM server. The highest binding affinity for SOD and NOX was produced by quercetin 3'-glucoside with the binding energy of -10.2 and -12.8 kcal/mol. Quercetin 3,4'-diglucoside had the highest binding affinity for CAT and GR at -11.5 and -10.5 kcal/mol, respectively. Routine produced the highest binding affinity at LOX (-10.9). Quercetin 3-O-xyloside and quercetin 3-O-rhamnoside-7-O-glucoside had the highest binding affinity in XO with a value of -10.4 kcal/mol. The glucose and prenyl groups are beneficial for quercetin in interacting with all ROS-modulating enzymes except XO. In contrast, the methoxy group negatively affects all interactions of quercetin with receptors. The perfect fit between the binding pocket and the 3D structure of the ligand greatly benefits the ligand in accessing more amino acids in the binding pocket. Their interaction stability and toxicity show that quercetin 3'-glucoside, quercetin 3,4'-diglucoside, and rutin are potent oxidative stress modulators in treating ROS-induced cancer.
槲皮素衍生物具有显著的抗癌活性。取代基的类型和位置对活性有很大影响。通过研究槲皮素的结构模式及其对其结合亲和力的影响，可以优化槲皮素类药物的开发。本研究旨在确定槲皮素片段的三维结构、类型和位置对其抗ros调节酶活性的影响，这些酶在ros诱导癌症的诱导和生长中起作用。利用Autodock Vina将23种天然槲皮素衍生物与7种ros调节酶对接，测定它们的结合亲和力和相互作用。利用CABS Flex 2.0服务器进行分子动力学模拟，进一步研究其相互作用稳定性。用DockFlin测定槲皮素组的关键氨基酸靶点。最后，使用pkCSM服务器确定每个测试配体的毒性。槲皮素3′-葡萄糖苷对SOD和NOX的结合能力最强，结合能分别为-10.2和-12.8 kcal/mol。槲皮素3,4′-二葡萄糖苷对CAT和GR的结合亲和力最高，分别为-11.5和-10.5 kcal/mol。常规蛋白在LOX位点的结合亲和力最高(-10.9)。槲皮素3- o -木糖苷和槲皮素3- o -鼠李糖苷-7- o -葡萄糖苷在XO中的结合亲和力最高，为-10.4 kcal/mol。葡萄糖和戊烯基有利于槲皮素与除XO外的所有ros调节酶相互作用。相反，甲氧基对槲皮素与受体的所有相互作用都有负面影响。结合袋与配体三维结构的完美契合，极大地有利于配体在结合袋中获取更多的氨基酸。槲皮素3′-葡萄糖苷、槲皮素3,4′-二葡萄糖苷和芦丁的相互作用、稳定性和毒性表明，槲皮素3′-葡萄糖苷和芦丁是有效的氧化应激调节剂，可治疗ros诱导的癌症。
{"title":"Structure-Based Virtual Screening and Molecular Dynamics of Quercetin and Its Natural Derivatives as Potent Oxidative Stress Modulators in ROS-induced Cancer","authors":"Abd. Kakhar Umar, J. H. Zothantluanga","doi":"10.24198/idjp.v3i2.35849","DOIUrl":"https://doi.org/10.24198/idjp.v3i2.35849","url":null,"abstract":"Quercetin derivatives are known to have significant anticancer activity. The activity is strongly influenced by the type and position of the substituent group. By studying the structural pattern of quercetin and its impact on their binding affinity, the development of quercetin-based drugs can be optimized. The study aimed to determine the impact of 3D structure, type, and position of quercetin moiety on its activity against ROS-modulating enzymes that play a role in the induction and growth of ROS-induced cancer. The 23 natural quercetin derivatives were docked to 7 ROS-modulating enzymes using Autodock Vina to determine their binding affinity and interaction. The interaction stability was further studied through molecular dynamics simulation using the CABS Flex 2.0 server. Determination of crucial amino acid targets of the quercetin group was determined using DockFlin. Finally, the toxicity of each test ligand was determined using the pkCSM server. The highest binding affinity for SOD and NOX was produced by quercetin 3'-glucoside with the binding energy of -10.2 and -12.8 kcal/mol. Quercetin 3,4'-diglucoside had the highest binding affinity for CAT and GR at -11.5 and -10.5 kcal/mol, respectively. Routine produced the highest binding affinity at LOX (-10.9). Quercetin 3-O-xyloside and quercetin 3-O-rhamnoside-7-O-glucoside had the highest binding affinity in XO with a value of -10.4 kcal/mol. The glucose and prenyl groups are beneficial for quercetin in interacting with all ROS-modulating enzymes except XO. In contrast, the methoxy group negatively affects all interactions of quercetin with receptors. The perfect fit between the binding pocket and the 3D structure of the ligand greatly benefits the ligand in accessing more amino acids in the binding pocket. Their interaction stability and toxicity show that quercetin 3'-glucoside, quercetin 3,4'-diglucoside, and rutin are potent oxidative stress modulators in treating ROS-induced cancer.","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77557862","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 : 2021-08-03DOI: 10.24198/idjp.v3i2.37368
Yuya Ishikawa, T. Araki, Miki Sato, H. Yashima, Daisuke Nagano, K. Yamamoto
We developed a simple method for quantifying sunitinib N-oxide (SNO) in human serum using a supported liquid extraction (SLE) method and liquid chromatography/tandem mass spectrometry (LC-MS/MS) to assess the impact of SNO on adverse drug reactions (ADRs) caused by sunitinib. SNO was extracted using an SLE method and analyzed using an Xevo-TQ (Waters) LC-MS/MS system. SNO and voriconazole (internal standard; ISTD) were detected in ESI positive mode, with transitions at 415.4/326.3 for SNO and 350.1/281.1 for voriconazole. The retention times of SNO and voriconazole were 2.25 and 2.67 min, respectively, and good calibration curve was obtained from 0.1–5.0 ng/mL for SNO. The regression equation (weight = 1/x2) describing the calibration curve in human serum was y = 2.81 × 10-9 x2 + 0.000253 x – 0.00202 (R2 = 0.990), where y is the peak area ratio of SNO against the ISTD and x is the nominal concentration of SNO. The intra- and inter-assay accuracy varied between -2.4 and 15.6% and all data except the limit of quantification (LOQ) were within ±10%. The precision varied between 6.7–15.4% and all data except LOQ were under 15%. The mean recovery ratio of SNO was 90.3 ± 4.9%, and the mean matrix factor was 0.96 ± 0.031. This is the first report of a method to quantify SNO in blood. This method will help in elucidating the effects of SNO in humans, contribute to the elucidation of the ADRs expression factors associated with sunitinib, and aid in optimizing treatment with sunitinib.
{"title":"Development of a quantitative method for sunitinib N-oxide","authors":"Yuya Ishikawa, T. Araki, Miki Sato, H. Yashima, Daisuke Nagano, K. Yamamoto","doi":"10.24198/idjp.v3i2.37368","DOIUrl":"https://doi.org/10.24198/idjp.v3i2.37368","url":null,"abstract":"We developed a simple method for quantifying sunitinib N-oxide (SNO) in human serum using a supported liquid extraction (SLE) method and liquid chromatography/tandem mass spectrometry (LC-MS/MS) to assess the impact of SNO on adverse drug reactions (ADRs) caused by sunitinib. SNO was extracted using an SLE method and analyzed using an Xevo-TQ (Waters) LC-MS/MS system. SNO and voriconazole (internal standard; ISTD) were detected in ESI positive mode, with transitions at 415.4/326.3 for SNO and 350.1/281.1 for voriconazole. The retention times of SNO and voriconazole were 2.25 and 2.67 min, respectively, and good calibration curve was obtained from 0.1–5.0 ng/mL for SNO. The regression equation (weight = 1/x2) describing the calibration curve in human serum was y = 2.81 × 10-9 x2 + 0.000253 x – 0.00202 (R2 = 0.990), where y is the peak area ratio of SNO against the ISTD and x is the nominal concentration of SNO. The intra- and inter-assay accuracy varied between -2.4 and 15.6% and all data except the limit of quantification (LOQ) were within ±10%. The precision varied between 6.7–15.4% and all data except LOQ were under 15%. The mean recovery ratio of SNO was 90.3 ± 4.9%, and the mean matrix factor was 0.96 ± 0.031. This is the first report of a method to quantify SNO in blood. This method will help in elucidating the effects of SNO in humans, contribute to the elucidation of the ADRs expression factors associated with sunitinib, and aid in optimizing treatment with sunitinib.","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79669708","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 : 2021-08-03DOI: 10.24198/idjp.v3i2.35312
Yoga Windhu Wardhana, Risanteni Riskasari, Fikri Alatas
Phase transition between drugs with polymorphisms needs attention due to unconscious changes in quality. Valsartan (VAL) is a drug model with polymorphic events to be studied here. Two polymorphic forms were obtained from recrystallization with various organic solvents such as acetonitrile and n-butyl acetate. With untreated materials (from the market) were used as a comparison in this study. The phase transition of each polymorph was studied through grinding and humidity variations (RH 75% and 98%) treatment. The polymorph characterization was observed by microscope light polarization (PLM), Fourier Transform Infrared (FTIR), and Powdered X-ray Diffractometer (PXRD). The transition among polymorphic VAL was monitored by PXRD. There were significant differences in morphology, IR spectra, and diffractograms pattern. Found that the untreated VAL was amorphous, whereas the others were in high crystallinity. The polymorph form from n-butyl acetate was a metastable one that transformed easier into stable crystalline (from acetonitrile) than another polymorph.Keywords : Valsartan, Phase transition, Polymorphism, Recrystallization
{"title":"Phase Transitions Among of Valsartan Polymorphs due to Grinding and Humidity Variations","authors":"Yoga Windhu Wardhana, Risanteni Riskasari, Fikri Alatas","doi":"10.24198/idjp.v3i2.35312","DOIUrl":"https://doi.org/10.24198/idjp.v3i2.35312","url":null,"abstract":"Phase transition between drugs with polymorphisms needs attention due to unconscious changes in quality. Valsartan (VAL) is a drug model with polymorphic events to be studied here. Two polymorphic forms were obtained from recrystallization with various organic solvents such as acetonitrile and n-butyl acetate. With untreated materials (from the market) were used as a comparison in this study. The phase transition of each polymorph was studied through grinding and humidity variations (RH 75% and 98%) treatment. The polymorph characterization was observed by microscope light polarization (PLM), Fourier Transform Infrared (FTIR), and Powdered X-ray Diffractometer (PXRD). The transition among polymorphic VAL was monitored by PXRD. There were significant differences in morphology, IR spectra, and diffractograms pattern. Found that the untreated VAL was amorphous, whereas the others were in high crystallinity. The polymorph form from n-butyl acetate was a metastable one that transformed easier into stable crystalline (from acetonitrile) than another polymorph.Keywords : Valsartan, Phase transition, Polymorphism, Recrystallization ","PeriodicalId":13455,"journal":{"name":"Indonesian Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80011115","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：