Pub Date : 2023-07-24DOI: 10.35516/jjps.v16i2.1491
N. Idkaidek
Physiologically-based pharmacokinetic (PBPK) modeling is a strong mathematical tool that integrates body physiology, drug physicochemical properties and pharmacokinetics to predict detailed drug profiles in different parts of the body. PBPK modeling can also be used to predict the effects of drug-drug interactions and diseases on drug pharmacokinetics. The use of special modules enables the extrapolation to different routes and also different species. PBPK steps for successful modeling will be discussed with examples using GastroPlus program. Such in-silico work can minimize the number and risks of in vivo clinical studies done on healthy subjects or on patients.
{"title":"Development of Successful Physiologically-Based Pharmacokinetic (PBPK) Models","authors":"N. Idkaidek","doi":"10.35516/jjps.v16i2.1491","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1491","url":null,"abstract":"Physiologically-based pharmacokinetic (PBPK) modeling is a strong mathematical tool that integrates body physiology, drug physicochemical properties and pharmacokinetics to predict detailed drug profiles in different parts of the body. PBPK modeling can also be used to predict the effects of drug-drug interactions and diseases on drug pharmacokinetics. The use of special modules enables the extrapolation to different routes and also different species. PBPK steps for successful modeling will be discussed with examples using GastroPlus program. Such in-silico work can minimize the number and risks of in vivo clinical studies done on healthy subjects or on patients.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46029345","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1482
Y. Sari
Electronic cigarettes (e-cigs) use has been dramatically increased recently, especially among youths. In this study, we evaluated the effect of one- and three-months continuous exposure to e-cig vapor (JUUL pods), containing high nicotine concentration, on the expression of glutamate receptors and transporters and mainly the associated neuroinflammatory markers in drug reward brain regions such as nucleus accumbens (NAc) core (NAc-core), NAc shell (NAc-shell) and hippocampus (HIP) in female C57BL/6 mice. We revealed that three months’ exposure to mint or mango flavored-JUUL (containing 5% nicotine, 59 mg/ml) induced upregulation in metabotropic glutamate receptor 1 (mGluR1) and postsynaptic density protein 95 (phosphorylated and total PSD95) expression, and downregulation of mGluR5 and glutamate transporter 1 (GLT-1) in the NAc-shell. Three months’ exposure to JUUL induced upregulation of mGluR5 and GLT-1 expression in the HIPP. We further revealed that mice exposed to JUUL Mango and JUUL Mint for one month had significantly increased TNF-α expression in the NAc-core and NAc-shell, with elevation in IL-1β as well. NAc-shell also showed significantly increased levels of IL-6 and HMGB-1 for both flavors. There were significantly increased levels of TNF-α in the NAc-core and NAc-shell for both Mint- and Mango-exposed JUUL mice for three months. NAc-shell also showed significantly increased levels of IL-1β, IL-6, HMGB-1, and RAGE after three months of JULL exposure, while the hippocampus showed significantly decreased levels of HMGB-1 for both flavors. These findings demonstrated that exposure to e-cig vapor containing high nicotine concentrations induced differential effects on glutamatergic system as well as induction of proinflammatory markers in the brain.
{"title":"Chronic Inhalation of Pod-based e-cigarette Aerosols on Inflammatory Biomarkers in the Central Nervous and Peripheral Systems","authors":"Y. Sari","doi":"10.35516/jjps.v16i2.1482","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1482","url":null,"abstract":"Electronic cigarettes (e-cigs) use has been dramatically increased recently, especially among youths. In this study, we evaluated the effect of one- and three-months continuous exposure to e-cig vapor (JUUL pods), containing high nicotine concentration, on the expression of glutamate receptors and transporters and mainly the associated neuroinflammatory markers in drug reward brain regions such as nucleus accumbens (NAc) core (NAc-core), NAc shell (NAc-shell) and hippocampus (HIP) in female C57BL/6 mice. We revealed that three months’ exposure to mint or mango flavored-JUUL (containing 5% nicotine, 59 mg/ml) induced upregulation in metabotropic glutamate receptor 1 (mGluR1) and postsynaptic density protein 95 (phosphorylated and total PSD95) expression, and downregulation of mGluR5 and glutamate transporter 1 (GLT-1) in the NAc-shell. Three months’ exposure to JUUL induced upregulation of mGluR5 and GLT-1 expression in the HIPP. We further revealed that mice exposed to JUUL Mango and JUUL Mint for one month had significantly increased TNF-α expression in the NAc-core and NAc-shell, with elevation in IL-1β as well. NAc-shell also showed significantly increased levels of IL-6 and HMGB-1 for both flavors. There were significantly increased levels of TNF-α in the NAc-core and NAc-shell for both Mint- and Mango-exposed JUUL mice for three months. NAc-shell also showed significantly increased levels of IL-1β, IL-6, HMGB-1, and RAGE after three months of JULL exposure, while the hippocampus showed significantly decreased levels of HMGB-1 for both flavors. These findings demonstrated that exposure to e-cig vapor containing high nicotine concentrations induced differential effects on glutamatergic system as well as induction of proinflammatory markers in the brain.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48145190","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1496
R. Shawahna, A. Zyoud, Aseel Haj-Yahia, Raheek Taya
Purpose: Recently, different international regulatory agencies and task forces have encouraged the pharmaceutical industry to develop child-friendly oral dosage forms. The biopharmaceutical classification system (BCS) has emerged as a tool that facilitates the development of traditional, reformulated, and novel oral dosage forms. Little research was conducted to evaluate the applicability of the BCS in developing child-friendly oral dosage forms. This study was conducted to assess the effects of age-related developmental changes in the composition and volume of gastrointestinal fluids on the solubility and performance of oral formulations containing celecoxib. Methods: Solubility studies were conducted at 37 ºC in the pH range of 1.2 to 6.8 in 13 different age-appropriate biorelevant media that reflected the gastric and proximal small environments in fasted and fed states for adults and pediatric populations. Quantities of celecoxib were determined using a validated HPLC method. The permeability class of celecoxib was determined using in vivo pharmacokinetic parameters, and experimental and computational molecular descriptions. Results: The solubility of celecoxib in the adult fed-state simulated gastric fluid was lower than that in the pediatric fed-state gastric media representative of neonates (birth to 28 days) fed soy-based formula. Similarly, the solubility of celecoxib in adult fasted-state simulated intestinal media was lower than that in the pediatric fasted-state intestinal media formulated with bile salt concentrations 50% of the adult levels. However, solubility values of celecoxib were lower in the other pediatric media compared to adult media. The age-appropriate pediatric to adult solubility ratios were outside the 80 to 125% range in 3 and was borderline in 1 out of 9 pediatric to adult solubility ratios. Conclusions: The solubility ratios of celecoxib exhibited significant variability in about 44.4% of the media. This indicated that significant age-related variability could be predicted for oral formulations containing celecoxib intended for pediatric use. Formulation scientists should consider the significant biopharmaceutical considerations when developing child-friendly oral formulations.
{"title":"Development of Child-Friendly Oral Formulations Containing Celecoxib: Biopharmaceutical Considerations for Formulation Scientists","authors":"R. Shawahna, A. Zyoud, Aseel Haj-Yahia, Raheek Taya","doi":"10.35516/jjps.v16i2.1496","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1496","url":null,"abstract":"Purpose: Recently, different international regulatory agencies and task forces have encouraged the pharmaceutical industry to develop child-friendly oral dosage forms. The biopharmaceutical classification system (BCS) has emerged as a tool that facilitates the development of traditional, reformulated, and novel oral dosage forms. Little research was conducted to evaluate the applicability of the BCS in developing child-friendly oral dosage forms. This study was conducted to assess the effects of age-related developmental changes in the composition and volume of gastrointestinal fluids on the solubility and performance of oral formulations containing celecoxib. \u0000Methods: Solubility studies were conducted at 37 ºC in the pH range of 1.2 to 6.8 in 13 different age-appropriate biorelevant media that reflected the gastric and proximal small environments in fasted and fed states for adults and pediatric populations. Quantities of celecoxib were determined using a validated HPLC method. The permeability class of celecoxib was determined using in vivo pharmacokinetic parameters, and experimental and computational molecular descriptions. \u0000Results: The solubility of celecoxib in the adult fed-state simulated gastric fluid was lower than that in the pediatric fed-state gastric media representative of neonates (birth to 28 days) fed soy-based formula. Similarly, the solubility of celecoxib in adult fasted-state simulated intestinal media was lower than that in the pediatric fasted-state intestinal media formulated with bile salt concentrations 50% of the adult levels. However, solubility values of celecoxib were lower in the other pediatric media compared to adult media. The age-appropriate pediatric to adult solubility ratios were outside the 80 to 125% range in 3 and was borderline in 1 out of 9 pediatric to adult solubility ratios. \u0000Conclusions: The solubility ratios of celecoxib exhibited significant variability in about 44.4% of the media. This indicated that significant age-related variability could be predicted for oral formulations containing celecoxib intended for pediatric use. Formulation scientists should consider the significant biopharmaceutical considerations when developing child-friendly oral formulations.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48838128","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1488
Rima Hjazeen
Objectives: This study's principal aim was to investigate community pharmacists' views of continuing professional development (CPD) and to explore pharmacists' perceptions of the most common facilitators and barriers to participation in continuing education (CE). Methods: A series of seven focus group sessions were undertaken with groups of four to seven community pharmacists. Focus group transcripts were thematically analyzed using a qualitative data analysis method. Results: Four key themes were identified: (1) community pharmacists' attitudes toward CPD; (2) perceived motivating factors for CPD; (3) experienced barriers to CPD; (4) and potential strategies for improving pharmacists' CPD. Conclusion: Practicing pharmacists need support now, and changes to undergraduate education are warranted to keep abreast of current developments and changes to practice. Despite limitations, the distinctive nature of this study would have a valuable contribution to the field of professional development. It can inform theory, policy, and practice relating to pharmacists' CPD at both a professional level and governmentally, helping the relevant parties make informed decisions.
{"title":"Community Pharmacists’ Perspectives toward Continuing Professional Development: A Qualitative Study","authors":"Rima Hjazeen","doi":"10.35516/jjps.v16i2.1488","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1488","url":null,"abstract":"Objectives: This study's principal aim was to investigate community pharmacists' views of continuing professional development (CPD) and to explore pharmacists' perceptions of the most common facilitators and barriers to participation in continuing education (CE). \u0000Methods: A series of seven focus group sessions were undertaken with groups of four to seven community pharmacists. Focus group transcripts were thematically analyzed using a qualitative data analysis method. \u0000Results: Four key themes were identified: (1) community pharmacists' attitudes toward CPD; (2) perceived motivating factors for CPD; (3) experienced barriers to CPD; (4) and potential strategies for improving pharmacists' CPD. \u0000 Conclusion: Practicing pharmacists need support now, and changes to undergraduate education are warranted to keep abreast of current developments and changes to practice. Despite limitations, the distinctive nature of this study would have a valuable contribution to the field of professional development. It can inform theory, policy, and practice relating to pharmacists' CPD at both a professional level and governmentally, helping the relevant parties make informed decisions.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44378648","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1544
Lujain F. Alzaghari, A. Hammad
Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems. We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions including the prefrontal cortex (PFC) and the nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure on withdrawal-induced anxiety-like behavior were assessed using open field (OF) and light/dark (LD) tests. Sprague-Dawley rats were randomly assigned to 5 experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with aspirin (15mg/kg and 30mg/kg, respectively). Lastly, a group treated only with aspirin (30 mg/kg). Cigarette smoke exposure was performed for 2hr/day, 5days/week, for 31days. Behavioral tests were conducted weekly, 24hrs after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or aspirin 45 min before cigarette exposure for 11 days. Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg aspirin attenuated this effect. Cigarette smoke exposure increased the relative mRNA and the protein level for nuclear factor ĸB (NFĸB) in the PFC and the NAc, and aspirin treatment reversed this effect. In addition, cigarette smoke decreased the relative mRNA and the protein levels of glutamate transporter 1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while aspirin treatment normalized their expression. Thus, cigarette smoke caused neuroinflammation, alterations in relative mRNA glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by aspirin treatment.
{"title":"Aspirin Effect on Tobacco Smoke Withdrawal-Induced Anxiety In Female Rats","authors":"Lujain F. Alzaghari, A. Hammad","doi":"10.35516/jjps.v16i2.1544","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1544","url":null,"abstract":"Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems. We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions including the prefrontal cortex (PFC) and the nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure on withdrawal-induced anxiety-like behavior were assessed using open field (OF) and light/dark (LD) tests. Sprague-Dawley rats were randomly assigned to 5 experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with aspirin (15mg/kg and 30mg/kg, respectively). Lastly, a group treated only with aspirin (30 mg/kg). Cigarette smoke exposure was performed for 2hr/day, 5days/week, for 31days. Behavioral tests were conducted weekly, 24hrs after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or aspirin 45 min before cigarette exposure for 11 days. Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg aspirin attenuated this effect. Cigarette smoke exposure increased the relative mRNA and the protein level for nuclear factor ĸB (NFĸB) in the PFC and the NAc, and aspirin treatment reversed this effect. In addition, cigarette smoke decreased the relative mRNA and the protein levels of glutamate transporter 1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while aspirin treatment normalized their expression. Thus, cigarette smoke caused neuroinflammation, alterations in relative mRNA glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by aspirin treatment.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44009091","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1539
Raffa Aborayya, Amani Abu kwaik, Yasmeen Aladhami, Mais Naser, O. Tarawneh, R. Hamed
Vitamin C, ascorbic acid, is a water-soluble vitamin that is considered as one of the most potent antioxidant agent. It delays early skin aging, protects against harmful free radicals, improves wrinkles appearance under-eye circles, and reduces redness and hyperpigmentation. One of the most common way to deliver vitamin C to the body’s tissue is through skin layers. Nevertheless, the effect of such ingredient might be limited due to the stratum corneum barrier which decreases the ability to reach the site of action. In this study, we provide an innovative strategy of utilization dissolving microneedles (MNs) to enhance skin-drug delivery system and overcome problems associated with the conventional formulations. A delivery system of micro-molds which provide a diverse range of three-dimensional (3D) MNs were used for the fabrication of vitamin C patches. Vitamin C MNs were examined for mechanical force tolerance, drug release, dimensional evaluation, dissolution, insertion, and permeation tests. Drug, polymers, and stabilizers were mixed at different ratios. Hydrogels were filled into the molds, centrifuged and left for air dry for 24-48 h. Appearance was visualized under light microscope. Patches were analyzed to determine percent assay of drug loaded, mechanical force, and penetration through the skin. The amount of vitamin C loaded into MNs was found to be 102%. MNs were easily inserted and dissolved through skin within 30 s. The dissolution rate of MNs were tested by using rat skin to determine the release of vitamin C within several time intervals. The in vitro release of vitamin C loaded MNs showed cumulative release percentage up to 70% in 9-10 h. Therefore, MNs as dermal drug delivery system was successfully developed, providing efficient release of vitamin C through the skin.
{"title":"Development and Physiochemical Characteristics of Vitamin C-loaded Microneedles","authors":"Raffa Aborayya, Amani Abu kwaik, Yasmeen Aladhami, Mais Naser, O. Tarawneh, R. Hamed","doi":"10.35516/jjps.v16i2.1539","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1539","url":null,"abstract":"Vitamin C, ascorbic acid, is a water-soluble vitamin that is considered as one of the most potent antioxidant agent. It delays early skin aging, protects against harmful free radicals, improves wrinkles appearance under-eye circles, and reduces redness and hyperpigmentation. One of the most common way to deliver vitamin C to the body’s tissue is through skin layers. Nevertheless, the effect of such ingredient might be limited due to the stratum corneum barrier which decreases the ability to reach the site of action. In this study, we provide an innovative strategy of utilization dissolving microneedles (MNs) to enhance skin-drug delivery system and overcome problems associated with the conventional formulations. A delivery system of micro-molds which provide a diverse range of three-dimensional (3D) MNs were used for the fabrication of vitamin C patches. Vitamin C MNs were examined for mechanical force tolerance, drug release, dimensional evaluation, dissolution, insertion, and permeation tests. Drug, polymers, and stabilizers were mixed at different ratios. Hydrogels were filled into the molds, centrifuged and left for air dry for 24-48 h. Appearance was visualized under light microscope. Patches were analyzed to determine percent assay of drug loaded, mechanical force, and penetration through the skin. The amount of vitamin C loaded into MNs was found to be 102%. MNs were easily inserted and dissolved through skin within 30 s. The dissolution rate of MNs were tested by using rat skin to determine the release of vitamin C within several time intervals. The in vitro release of vitamin C loaded MNs showed cumulative release percentage up to 70% in 9-10 h. Therefore, MNs as dermal drug delivery system was successfully developed, providing efficient release of vitamin C through the skin.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45106940","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1463
Worood H Ismail, Osama H. Abusara, Balqis A. Ikhmais, Hassan Abul‐Futouh, Suhair Sunoqrot, Ali I. M. Ibrahim
Natural products are known to exhibit antimicrobial, anticancer, and antioxidant activities. Among these natural products is cinnamon which contains cinnamaldehyde. Cinnamaldehyde and its derivatives have been reported to have anticancer and antioxidant activities. Coniferyl aldehyde, a non-cytotoxic compound and a cinnamaldehyde derivative, has also been shown to have anticancer activity. In this study, several derivatives of coniferyl aldehyde were synthesized and evaluated for their anticancer and antioxidant activities. Compounds 1, 2, 4, and 8-11 showed cytotoxic activity against H1299 cell line, a non-small cell lung cancer cells, with 4 being the most potent with IC50 value of 6.7 μM. The antioxidant assay experiment showed that compounds 1, 2, and 4 resulted in half the scavenging activity of vitamin C at all tested concentrations. The coniferyl aldehyde itself showed dose-dependent antioxidant activity, with a proposed free radical stabilization mechanism. Thus, our study showed that the synthesized coniferyl aldehyde derivatives exhibit anticancer and antioxidant activities, which might act as potential therapeutic agents.
{"title":"Design, Synthesis, and Biological Activity of Coniferyl Aldehyde Derivatives as Potential Anticancer and Antioxidant Agents","authors":"Worood H Ismail, Osama H. Abusara, Balqis A. Ikhmais, Hassan Abul‐Futouh, Suhair Sunoqrot, Ali I. M. Ibrahim","doi":"10.35516/jjps.v16i2.1463","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1463","url":null,"abstract":"Natural products are known to exhibit antimicrobial, anticancer, and antioxidant activities. Among these natural products is cinnamon which contains cinnamaldehyde. Cinnamaldehyde and its derivatives have been reported to have anticancer and antioxidant activities. Coniferyl aldehyde, a non-cytotoxic compound and a cinnamaldehyde derivative, has also been shown to have anticancer activity. In this study, several derivatives of coniferyl aldehyde were synthesized and evaluated for their anticancer and antioxidant activities. Compounds 1, 2, 4, and 8-11 showed cytotoxic activity against H1299 cell line, a non-small cell lung cancer cells, with 4 being the most potent with IC50 value of 6.7 μM. The antioxidant assay experiment showed that compounds 1, 2, and 4 resulted in half the scavenging activity of vitamin C at all tested concentrations. The coniferyl aldehyde itself showed dose-dependent antioxidant activity, with a proposed free radical stabilization mechanism. Thus, our study showed that the synthesized coniferyl aldehyde derivatives exhibit anticancer and antioxidant activities, which might act as potential therapeutic agents.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47051175","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1485
I. Almasri
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR.
{"title":"Design, Synthesis and Biological Evaluation of Novel Pyrazolotriazolopyrimidine Derivatives as Potential Anticancer Agents","authors":"I. Almasri","doi":"10.35516/jjps.v16i2.1485","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1485","url":null,"abstract":"Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations of 7 and 11 µM, respectively. The results from docking experiments with EGFR suggested the binding of compound 1 at the ATP binding site of EGFR. Furthermore, the crystal structure of compound 3 (7-(4-bromophenyl)-9-(pyridin-4-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine) was determined by single crystal X-ray analysis. Our work represents a promising starting point for the development of a new series of compounds targeting EGFR.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45691523","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1530
Eliza Hasen
Background: Nowadays, the pharmacological activities of many natural phytochemicals have a huge impact on pharmaceutical research and drug development. Hence, numerous studies have been conducted to investigate plants' efficacy, fractions, and isolated pure compounds to discover new therapeutic agents. Aim: This study aimed to evaluate the potential activity of coriander essential oil (CEO) on bacterial biofilm and immune cells. Methods: CEO has been extracted from the seeds through the hydrodistillation method, and its chemical composition was analyzed using gas chromatography (GC) and Nuclear magnetic resonance (NMR). The antibacterial activity of CEO was assessed using different bacterial strains (P. aeruginosa, S. aureus, S. epidermidis and E. coli), both in planktonic and biofilm forms. In addition, this activity has been investigated individually and in combination with selected antibiotics (Gentamicin and Ciprofloxacin), using the bacterial enumeration following the MBEC Assay® protocol. Pyocianin (PYO) has been measured using a plate reader on 690 nm absorbance, where wells tested were treated with different CEO concentrations (12.5, 25, 50 and 100 mg/mL). An MTT assay was also used to examine the CEO'seffect on the viability of RAW 246.7 murine macrophages. Data were analyzed using GraphPad Prism 9 software. Results: Six major compounds were identified in CEO; Linalool was the most predominant. Regarding the activity of the CEO on planktonic bacteria, cell count was obtained and calculated as log reductions; significant log reductions (p<0.05) were measured on 300 mg/mL of CEO for all P. aeruginosa, S. aureus, S. epidermidis and E. coli, 2.00, 6.73, 6.93 and 7.68 respectively. While for the bacterial biofilm, a significant (p<0.05) log reduction in the cell count was obtained at 300 mg/mL of CEO for all of P. aeruginosa, S. aureus, S. epidermidis and E. coli, 2.22, 5.33, 5.83 and 6.76, respectively. Minimum inhibitory concentrations (MIC) of the combination of antibiotics Gentamicin (0.60, 0.15, 1.22, 0.3 µg/mL) or Ciprofloxacin (0.075, 0.03, 0.004 and 0.002 µg/mL) for all P. aeruginosa, S. aureus, S. epidermidis and E. coli, respectively, with 50 mg/mL of CEO on planktonic and biofilm bacteria. PYO measurements obtained showed anti-quorum sensing activity of CEO, the absorbance detecting PYO levels, was decreasing as the concentration of CEO was increasing, absorbances were (0.66, 0.075, 0.097 and 0.11), whereas the control of P. aeruginosa was (0.124). On the other hand, the antibacterial/antibiofilm concentrations were cytotoxic (percentage of viability <80%) to macrophages and the safe level was (0.30 mg/mL) of CEO. Conclusion: These results indicated that CEO may have a promising role in bacterial biofilm eradication, which may help manage and prevent chronic infections in the future. However, more investigations are required to understand the exact mechanism and improve its safety on immune cells.
{"title":"The Potential Effects of the Essential Oil of Coriander Seeds on Bacterial Biofilm and Immune Cells","authors":"Eliza Hasen","doi":"10.35516/jjps.v16i2.1530","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1530","url":null,"abstract":"Background: Nowadays, the pharmacological activities of many natural phytochemicals have a huge impact on pharmaceutical research and drug development. Hence, numerous studies have been conducted to investigate plants' efficacy, fractions, and isolated pure compounds to discover new therapeutic agents. Aim: This study aimed to evaluate the potential activity of coriander essential oil (CEO) on bacterial biofilm and immune cells. Methods: CEO has been extracted from the seeds through the hydrodistillation method, and its chemical composition was analyzed using gas chromatography (GC) and Nuclear magnetic resonance (NMR). The antibacterial activity of CEO was assessed using different bacterial strains (P. aeruginosa, S. aureus, S. epidermidis and E. coli), both in planktonic and biofilm forms. In addition, this activity has been investigated individually and in combination with selected antibiotics (Gentamicin and Ciprofloxacin), using the bacterial enumeration following the MBEC Assay® protocol. Pyocianin (PYO) has been measured using a plate reader on 690 nm absorbance, where wells tested were treated with different CEO concentrations (12.5, 25, 50 and 100 mg/mL). An MTT assay was also used to examine the CEO'seffect on the viability of RAW 246.7 murine macrophages. Data were analyzed using GraphPad Prism 9 software. Results: Six major compounds were identified in CEO; Linalool was the most predominant. Regarding the activity of the CEO on planktonic bacteria, cell count was obtained and calculated as log reductions; significant log reductions (p<0.05) were measured on 300 mg/mL of CEO for all P. aeruginosa, S. aureus, S. epidermidis and E. coli, 2.00, 6.73, 6.93 and 7.68 respectively. While for the bacterial biofilm, a significant (p<0.05) log reduction in the cell count was obtained at 300 mg/mL of CEO for all of P. aeruginosa, S. aureus, S. epidermidis and E. coli, 2.22, 5.33, 5.83 and 6.76, respectively. Minimum inhibitory concentrations (MIC) of the combination of antibiotics Gentamicin (0.60, 0.15, 1.22, 0.3 µg/mL) or Ciprofloxacin (0.075, 0.03, 0.004 and 0.002 µg/mL) for all P. aeruginosa, S. aureus, S. epidermidis and E. coli, respectively, with 50 mg/mL of CEO on planktonic and biofilm bacteria. PYO measurements obtained showed anti-quorum sensing activity of CEO, the absorbance detecting PYO levels, was decreasing as the concentration of CEO was increasing, absorbances were (0.66, 0.075, 0.097 and 0.11), whereas the control of P. aeruginosa was (0.124). On the other hand, the antibacterial/antibiofilm concentrations were cytotoxic (percentage of viability <80%) to macrophages and the safe level was (0.30 mg/mL) of CEO. Conclusion: These results indicated that CEO may have a promising role in bacterial biofilm eradication, which may help manage and prevent chronic infections in the future. However, more investigations are required to understand the exact mechanism and improve its safety on immune cells.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44211050","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 : 2023-07-24DOI: 10.35516/jjps.v16i2.1545
Ruwa Zuhier Obaid, R. Abu-Huwaij, R. Hamed
Doxorubicin (DOX) is an anthracycline antineoplastic agents, which interacts with DNA and shows sever toxicity due to its lack of specificity. The cytotoxic effect of zinc oxide nanoparticles (ZnO NPs) is mainly concerned in changing the cytoskeleton and nucleoskeleton of proteins and/or producing reactive oxygen species (ROS) in cells exposed to ZnO NPs. The green synthesis of ZnO NPs from plant extracts has been recently employed as a simple, eco-friendly, safe, and cost- and time-effective approach with higher stability and reproducibility. Phoenix dactylifera, due to its chemical component (tannins, phenolic acid, and carotenoids), was employed in the preparation of ZnO NPs. The main objective of this study is to greenly synthesize ZnO NPs conjugated with DOX (DOX-ZnO NPS) and loaded into various types of gel preparations (hydrogel and oleogel). P.dactylifera solution extract was mixed with 0.6M zinc acetate at 1:1 v/v ratio to prepare ZnO NPs. The prepared NPs was characterized by UV-vis spectroscopy, particles size, PDI, and zeta potential. The maximum wavelength of ZnO NPs was detected at 360 nm. Dialysis method was used to determine the effect of ZnO NPs on enhancing DOX release. The cumulative amount of DOX was calculated via UV-vis spectroscopy at 480 nm after 48 h. Spherical nanoparticles of size range 15.35–28.74 nm and -22mV zeta potential was obtained. The rheological results showed that both gel formulations exhibited a pseudoplastic (shear-thinning) flow and viscoelastic behavior. The in vitro release studies showed that ZnO NPs enhanced the release of DOX, where the amount of DOX released from DOX-ZnO NPs hydrogel and oloegel was higher than that of DOX-hydrogel and oleogel. In addition, DOX-ZnO NPs hydrogel showed a faster release that DOX-ZnO NPs oleogel. Therefore, an eco-friendly and low-cost greenly synthesized ZnO NPs were successfully developed, conjugated with DOX, and loaded into hydrogels and oleogels for dermal delivery.
{"title":"Development and Characterization of Anticancer Model Drug Conjugated to Biosynthesized Zinc Oxide Nanoparticles Loaded into Different Topical Skin Formulations","authors":"Ruwa Zuhier Obaid, R. Abu-Huwaij, R. Hamed","doi":"10.35516/jjps.v16i2.1545","DOIUrl":"https://doi.org/10.35516/jjps.v16i2.1545","url":null,"abstract":"Doxorubicin (DOX) is an anthracycline antineoplastic agents, which interacts with DNA and shows sever toxicity due to its lack of specificity. The cytotoxic effect of zinc oxide nanoparticles (ZnO NPs) is mainly concerned in changing the cytoskeleton and nucleoskeleton of proteins and/or producing reactive oxygen species (ROS) in cells exposed to ZnO NPs. The green synthesis of ZnO NPs from plant extracts has been recently employed as a simple, eco-friendly, safe, and cost- and time-effective approach with higher stability and reproducibility. Phoenix dactylifera, due to its chemical component (tannins, phenolic acid, and carotenoids), was employed in the preparation of ZnO NPs. The main objective of this study is to greenly synthesize ZnO NPs conjugated with DOX (DOX-ZnO NPS) and loaded into various types of gel preparations (hydrogel and oleogel). P.dactylifera solution extract was mixed with 0.6M zinc acetate at 1:1 v/v ratio to prepare ZnO NPs. The prepared NPs was characterized by UV-vis spectroscopy, particles size, PDI, and zeta potential. The maximum wavelength of ZnO NPs was detected at 360 nm. Dialysis method was used to determine the effect of ZnO NPs on enhancing DOX release. The cumulative amount of DOX was calculated via UV-vis spectroscopy at 480 nm after 48 h. Spherical nanoparticles of size range 15.35–28.74 nm and -22mV zeta potential was obtained. The rheological results showed that both gel formulations exhibited a pseudoplastic (shear-thinning) flow and viscoelastic behavior. The in vitro release studies showed that ZnO NPs enhanced the release of DOX, where the amount of DOX released from DOX-ZnO NPs hydrogel and oloegel was higher than that of DOX-hydrogel and oleogel. In addition, DOX-ZnO NPs hydrogel showed a faster release that DOX-ZnO NPs oleogel. Therefore, an eco-friendly and low-cost greenly synthesized ZnO NPs were successfully developed, conjugated with DOX, and loaded into hydrogels and oleogels for dermal delivery.","PeriodicalId":14719,"journal":{"name":"Jordan Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42203261","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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