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Article ; Online: Tailoring of Novel Bile Salt Stabilized Vesicles for Enhanced Transdermal Delivery of Simvastatin

El-Sayed Khafagy / Bjad K. Almutairy / Amr Selim Abu Lila

Polymers, Vol 15, Iss 677, p

A New Therapeutic Approach against Inflammation

2023 Volume 677

Abstract: Simvastatin (SMV), a cholesterol-lowering agent, has antioxidant and anti-inflammatory effects. Nevertheless, the oral use of SMV is linked with poor systemic bioavailability owing to its limited aqueous solubility and extensive first-pass metabolism. ... ...

Abstract	Simvastatin (SMV), a cholesterol-lowering agent, has antioxidant and anti-inflammatory effects. Nevertheless, the oral use of SMV is linked with poor systemic bioavailability owing to its limited aqueous solubility and extensive first-pass metabolism. The aim of this study was to evaluate the feasibility of transdermal delivery of SMV using bile salt stabilized vesicles (bilosomes) for enhancing the anti-inflammatory potential of SMV. SMV-loaded bilosomes (SMV-BS) were prepared by the thin film hydration technique and optimized by 3 3 Box–Behnken design. The fabricated SMV-BS were assessed for vesicle size, entrapment efficiency (% EE) and cumulative drug release. The optimized formula was incorporated into HPMC gel and investigated for physical properties, ex vivo permeation, in vivo pharmacokinetic study and anti-inflammatory potential in inflamed paw edema rat model. The optimized SMV-BS showed vesicle size of 172.1 ± 8.1 nm and % EE of 89.2 ± 1.8%. In addition, encapsulating SMV within bilosomal vesicles remarkably sustained drug release over 12 h, compared to plain drug suspension. Furthermore, SMV-loaded bilosomal gel showed a three-fold enhancement in SMV transdermal flux, compared to plain drug suspension. Most importantly, the relative bioavailability of SMV-BS gel was ~2-fold and ~3-fold higher than those of oral SMV suspension and SMV gel, respectively. In carrageenan-induced paw edema model, SMV-BS gel induced a potent anti-inflammatory effect, as evidenced by a remarkable reduction in paw edema, which was comparable to that of the standard anti-inflammatory drug, indomethacin. Collectively, bilosomes might represent a plausible transdermal drug delivery system that could enhance the anti-inflammatory activity of SMV by boosting its skin permeation and its systemic bioavailability.
Keywords	anti-inflammatory ; bilosomes ; rat paw edema ; simvastatin ; transdermal drug delivery ; Organic chemistry ; QD241-441
Subject code	500
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of Carvedilol Nanoformulation-Loaded Poloxamer-Based In Situ Gel for the Management of Glaucoma

Bjad K. Almutairy / El-Sayed Khafagy / Amr Selim Abu Lila

Gels, Vol 9, Iss 12, p

2023 Volume 952

Abstract: The objective of the current study was to fabricate a thermosensitive in situ gelling system for the ocular delivery of carvedilol-loaded spanlastics (CRV-SPLs). In situ gel formulations were prepared using poloxamer analogs by a cold method and was ... ...

Abstract	The objective of the current study was to fabricate a thermosensitive in situ gelling system for the ocular delivery of carvedilol-loaded spanlastics (CRV-SPLs). In situ gel formulations were prepared using poloxamer analogs by a cold method and was further laden with carvedilol-loaded spanlastics to boost the precorneal retention of the drug. The gelation capacity, rheological characteristics, muco-adhesion force and in vitro release of various in situ gel formulations (CS-ISGs) were studied. The optimized formula (F2) obtained at 22% w / v poloxamer 407 and 5% w / v poloxamer 188 was found to have good gelation capacity at body temperature with acceptable muco-adhesion properties, appropriate viscosity at 25 °C that would ease its ocular application, and relatively higher viscosity at 37 °C that promoted prolonged ocular residence of the formulation post eye instillation and displayed a sustained in vitro drug release pattern. Ex vivo transcorneal penetration studies through excised rabbit cornea revealed that F2 elicited a remarkable ( p ˂ 0.05) improvement in CRV apparent permeation coefficient (P app = 6.39 × 10 −6 cm/s) compared to plain carvedilol-loaded in situ gel (CRV-ISG; P app = 2.67 × 10 −6 cm/s). Most importantly, in normal rabbits, the optimized formula (F2) resulted in a sustained intraocular pressure reduction and a significant enhancement in the ocular bioavailability of carvedilol, as manifested by a 2-fold increase in the AUC 0–6h of CRV in the aqueous humor, compared to plain CRV-ISG formulation. To sum up, the developed thermosensitive in situ gelling system might represent a plausible carrier for ophthalmic drug delivery for better management of glaucoma.
Keywords	carvedilol ; glaucoma ; in situ gel ; poloxamer ; spanlastics ; Science ; Q ; Chemistry ; QD1-999 ; Inorganic chemistry ; QD146-197 ; General. Including alchemy ; QD1-65
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cytotoxic and Apoptotic Effect of Rubus chingii Leaf Extract against Non-Small Cell Lung Carcinoma A549 Cells

El-Sayed Khafagy / Ahmed Al Saqr / Hadil Faris Alotaibi / Amr Selim Abu Lila

Processes, Vol 10, Iss 8, p

2022 Volume 1537

Abstract: Rubus chingii is a traditional Chinese medicinal herbal that has been used since ancient times for its great dietary and medicinal values. Recent reports have underscored the promising cytotoxic effect of R. chingii extracts against a wide variety of ... ...

Abstract	Rubus chingii is a traditional Chinese medicinal herbal that has been used since ancient times for its great dietary and medicinal values. Recent reports have underscored the promising cytotoxic effect of R. chingii extracts against a wide variety of cancer cells. Therefore, in the current study, we aim to explore the anticancer potential of the Rubus chingii ethanolic leaf extract ( R cL-EtOH) against non-small cell lung cancer A549 cells. R cL-EtOH efficiently exerted a cytotoxic effect against A549 cells in a dose dependent manner, whilst, it exhibited non-significant toxic effects on normal murine macrophage cells, signifying its safety against normal cells. The reduced viability of A549 cells was reaffirmed by the acridine orange/ethidium bromide double staining, which confirmed the induction of apoptosis in R cL-EtOH-treated A549 cells. In addition, R cL-EtOH instigated the dissipation of mitochondrial membrane potential (ΔΨm) with mutual escalation in ROS generation in a dose-dependent manner. Furthermore, R cL-EtOH increased caspase-3, caspase-9 levels in A549 cells post-exposure to R cL-EtOH, which was concomitantly followed by altered mRNA expression of apoptotic (anti-apoptotic: Bcl-2, Bcl XL pro-apoptotic: Bax, Bad). To sum up, the R cL-EtOH-instigated apoptotic cell death within A549 cells was assumed to be accomplished via targeting mitochondria, triggering increased ROS generation, with subsequent activation of caspase cascade and altering the expression of gene regulating apoptosis. Collectively, R cL-EtOH might represent a plausible therapeutic option for the management of lung cancer.
Keywords	anti-cancer ; apoptosis ; mitochondrial membrane potential ; reactive oxygen species (ROS) ; Rubus chingii ; Chemical technology ; TP1-1185 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ophthalmic Bimatoprost-Loaded Niosomal In Situ Gel

Mohammed F. Aldawsari / Ehssan H. Moglad / Hadil Faris Alotaibi / Hamad M. Alkahtani / El-Sayed Khafagy

Polymers, Vol 15, Iss 21, p

Preparation, Optimization, and In Vivo Pharmacodynamics Study

2023 Volume 4336

Abstract: This study aimed at formulating the antiglaucoma agent, Bimatoprost (BMT), into niosomal in situ gel (BMT-ISG) for ocular delivery. Niosomes containing cholesterol/span 60 entrapping BMT were fabricated using a thin-film hydration method. The fabricated ... ...

Abstract	This study aimed at formulating the antiglaucoma agent, Bimatoprost (BMT), into niosomal in situ gel (BMT-ISG) for ocular delivery. Niosomes containing cholesterol/span 60 entrapping BMT were fabricated using a thin-film hydration method. The fabricated niosomes were optimized and characterized for entrapment efficiency () and size. The optimized BMT-loaded niosomal formulation prepared at a cholesterol/span 60 ratio of 1:2 exhibited the highest entrapment (81.2 ± 1.2%) and a small particle size (167.3 ± 9.1 nm), and they were selected for incorporation into in situ gelling systems (BMT-ISGs) based on Pluronic F127/Pluronic F68. Finally, the in vivo efficiency of the BMT-ISG formulation, in terms of lowering the intraocular pressure (IOP) in normotensive male albino rabbits following ocular administration, was assessed and compared to that of BMT ophthalmic solution. All the formulated BMT-ISGs showed sol–gel transition temperatures ranging from 28.1 °C to 40.5 ± 1.6 °C. In addition, the BMT-ISG formulation sustained in vitro BMT release for up to 24 h. Interestingly, in vivo experiments depicted that topical ocular administration of optimized BMT-ISG formulation elicited a significant decline in IOP, with maximum mean decreases in IOP of 9.7 ± 0.6 mm Hg, compared to BMT aqueous solution (5.8 ± 0.6 mm Hg). Most importantly, no signs of irritation to the rabbit’s eye were observed following topical ocular administration of the optimized BMT-ISG formulation. Collectively, our results suggested that niosomal in situ gels might be a feasible delivery vehicle for topical ocular administration of anti-glaucoma agents, particularly those with poor ocular bioavailability.
Keywords	bimatoprost ; in situ gel ; glaucoma ; niosomes ; ocular delivery ; Organic chemistry ; QD241-441
Subject code	540
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Screening of Apoptosis Pathway-Mediated Anti-Proliferative Activity of the Phytochemical Compound Furanodienone against Human Non-Small Lung Cancer A-549 Cells

Ahmed Al Saqr / El-Sayed Khafagy / Mohammed F. Aldawsari / Khaled Almansour / Amr S. Abu Lila

Life, Vol 12, Iss 114, p

2022 Volume 114

Abstract: Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma Curcumae , has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the ... ...

Abstract	Furanodienone (FDN), a major bioactive component of sesquiterpenes produced from Rhizoma Curcumae , has been repeatedly acknowledged for its intrinsic anticancer efficacy against different types of cancer. In this study, we aimed to investigate the cytotoxic potential of furanodienone against human lung cancer (NSCLC A549) cells in vitro, as well as its underlying molecular mechanisms in the induction of apoptosis. Herein, we found that FDN significantly inhibited the proliferation of A549 cells in a dose-dependent manner. In addition, treatment with FDN potentially triggered apoptosis in A549 cells via not only disrupting the nuclear morphology, but by activating capsase-9 and caspase-3 with concomitant modulation of the pro- and antiapoptotic gene expression as well. Furthermore, FDN revealed its competence in inducing cell cycle arrest at G0/G1 phase in A549 cells, which was associated with decreased expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4), along with increased expression of CDK inhibitor p21Cip1. Intriguingly, FDN treatment efficiently downregulated the Wnt signaling pathway, which was correlated with increased apoptosis, as well as cell cycle arrest, in A549 cells. Collectively, FDN might represent a promising adjuvant therapy for the management of lung cancer.
Keywords	A549 cells ; anticancer ; apoptosis ; cell cycle arrest ; non-small cell lung carcinoma ; phyto-compound ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients’ Survival

Nesreen M. Sabry / Tamer M. Naguib / Ahmed M. Kabel / El-Sayed Khafagy / Hany H. Arab / Walid A. Almorsy

Medicina, Vol 58, Iss 394, p

A Randomized Controlled Trial

2022 Volume 394

Abstract: Background and Objectives : Diarrhea induced by chemotherapy may represent a life-threatening adverse effect in cancer patients receiving chemotherapy. FOLFOX, an effective treatment for colon cancer, has been associated with diarrhea with high severity, ...

Abstract	Background and Objectives : Diarrhea induced by chemotherapy may represent a life-threatening adverse effect in cancer patients receiving chemotherapy. FOLFOX, an effective treatment for colon cancer, has been associated with diarrhea with high severity, particularly with higher doses. Management of diarrhea is crucial to increase the survival of cancer patients and to improve the quality of life. Glutamine is an abundant protein peptide found in blood and has a crucial role in boosting immunity, increasing protein anabolism, and decreasing the inflammatory effects of chemotherapy on the mucosal membranes, including diarrhea. This study aimed to provide evidence that parenteral L-alanyl L-glutamine dipeptide may have a positive influence on the incidence of diarrhea, treatment response, and the overall survival in colon cancer patients treated with modified FOLFOX-6 (mFOLFOX-6). Materials and Methods : Forty-four stage II and III colon cancer patients were included in this study where they were treated with the standard colon cancer chemotherapy mFOLFOX-6 and were randomly allocated into glutamine group and placebo group, each of 22 patients. Results : L-alanyl L-glutamine dipeptide was found to be significantly effective in decreasing the frequency and severity of diarrhea when compared to the placebo group, particularly after four and six cycles of mFOLFOX-6. There was no significant difference between the studied groups regarding to the overall survival. Conclusion : L-alanyl L-glutamine dipeptide can be considered as an add-on with chemotherapy to improve the quality of life and the overall survival of colon cancer patients.
Keywords	colon cancer ; L-alanyl L-glutamine dipeptide ; FOLFOX ; diarrhea ; patients’ survival ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Experimental Design and Optimization of Nano-Transfersomal Gel to Enhance the Hypoglycemic Activity of Silymarin

Marwa H. Abdallah / Amr S. Abu Lila / Seham Mohammed Shawky / Khaled Almansour / Farhan Alshammari / El-Sayed Khafagy / Tarek Saad Makram

Polymers, Vol 14, Iss 508, p

2022 Volume 508

Abstract: Current advancements in the research investigations focused at using natural products to generate novel dosage forms with a potential therapeutic impact. Silymarin is a natural product obtained from the herb Silybum marianum that has been shown to have ... ...

Abstract	Current advancements in the research investigations focused at using natural products to generate novel dosage forms with a potential therapeutic impact. Silymarin is a natural product obtained from the herb Silybum marianum that has been shown to have remarkable hypoglycemic activity. Owing to the low enteral absorption, instability in stomach secretion, and poor solubility of Silymarin, it was better to be produced as a topical dosage form. A three-factor, three-level Box Behnken (3 3 BB) design was constructed to develop 15 formulations using three independent variables (phospholipid concentration, surfactant concentration, and sonication time) and two dependent variables (encapsulation efficiency and in vitro drug release). The optimized formula was added to HPMC gel and the resulting transfersomal gel was investigated for its characteristics, in vitro, ex vivo and hypoglycemic behaviors. The pH of the Silymarin-loaded transfersomal gel was 7.05, the spreadability was 55.35 mm, and the viscosity was 6.27 Pa. Furthermore, Silymarin loaded transfersomal gel had the greatest transdermal flux (92.41 µg/cm 2 ·h), which was much greater than all other formulations. In vivo observations revealed that Silymarin loaded transfersomal gel significantly reduced blood glucose levels, compared to either Silymarin gel or oral Silymarin suspension. The findings show that the developed transfersomal gel could be an effective carrier for Silymarin transdermal delivery.
Keywords	Silymarin ; transfersomes ; Box Behnken Design ; hypoglycemic effect ; transdermal application ; Organic chemistry ; QD241-441
Subject code	333
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pulmonary Targeting of Levofloxacin Using Microsphere-Based Dry Powder Inhalation

Turki Al Hagbani / Bhavya Vishwa / Amr S. Abu Lila / Hadil Faris Alotaibi / El-Sayed Khafagy / Afrasim Moin / Devegowda V. Gowda

Pharmaceuticals, Vol 15, Iss 560, p

2022 Volume 560

Abstract: The objective of the current study was to develop poly (lactic-co-glycolic acid) (PLGA) microspheres loaded with the anti-tuberculosis (anti-TB) fluoroquinolone, Levofloxacin (LVX), in the form of dry powder inhalation (DPI). LVX-loaded microspheres were ...

Abstract	The objective of the current study was to develop poly (lactic-co-glycolic acid) (PLGA) microspheres loaded with the anti-tuberculosis (anti-TB) fluoroquinolone, Levofloxacin (LVX), in the form of dry powder inhalation (DPI). LVX-loaded microspheres were fabricated by solvent evaporation technique. Central Composite Design (CCD) was adopted to optimize the microspheres, with desired particle size, drug loading, and drug entrapment efficiency, for targeting alveolar macrophages via non-invasive pulmonary delivery. Structural characterization studies by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction analysis revealed the absence of any possible chemical interaction between the drug and the polymer used for the preparation of microspheres. In addition, the optimized drug-loaded microspheres exhibited desired average aerodynamic diameter of 2.13 ± 1.24 μm and fine particle fraction of 75.35 ± 1.42%, indicating good aerosolization properties. In vivo data demonstrated that LVX-loaded microspheres had superior lung accumulation, as evident by a two-fold increase in the area under the curve AUC 0–24h , as compared with plain LVX. Furthermore, LVX-loaded microspheres prolonged drug residence time in the lung and maintained a relatively high drug concentration for a longer time, which contributed to a reduced leakage in the systemic circulation. In conclusion, inhalable LVX-loaded microspheres might represent a plausible delivery vehicle for targeting pulmonary tuberculosis via enhancing the therapeutic efficacy of LVX while minimizing its systemic off-target side effects.
Keywords	inhalable microspheres ; levofloxacin ; lung targeting ; pulmonary drug delivery ; tuberculosis ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The flavonoid hesperidin methyl chalcone as a potential therapeutic agent for cancer therapy

Syed M.D. Rizvi / Manjunatha P. Mudagal / Sateesha S. Boregowda / Talib Hussain / Turki Al Hagbani / Marwa H. Abdallah / El-Sayed Khafagy / Arshad Hussain / Fahad A. Yousif Adam / Amr S. Abu Lila

Arabian Journal of Chemistry, Vol 16, Iss 6, Pp 104769- (2023)

Molecular docking, in vitro cytotoxicity, and in vivo antitumor activity

2023

Abstract: Hesperidin methyl chalcone (HMC) is a methylation product of the flavanone hesperidin, a flavonoid derived from citrus fruits. Many reports have emphasized the analgesic, anti-inflammatory and antioxidant properties of HMC. However, the anticancer ... ...

Abstract	Hesperidin methyl chalcone (HMC) is a methylation product of the flavanone hesperidin, a flavonoid derived from citrus fruits. Many reports have emphasized the analgesic, anti-inflammatory and antioxidant properties of HMC. However, the anticancer potential of HMC has not been fully elucidated. The objective of this study was to assess the possible anticancer potential of HMC. MTT assay was carried out to assess the in vitro cytotoxicity of HMC against using A549 cancer cell line. In addition, the in vivo antitumor activity of HMC was screened against murine Ehrlich ascites carcinoma (EAC) model, in terms of tumor volume, tumor weight, life span, hematological and biochemical parameters, and compared with that of the anticancer agent, hesperetin. HMC was efficient to suppress the cell viability of A549 cancer cells with an IC50 value of 51.12 µM, which was comparable to that of the anticancer agent hesperetin (IC50 = 49.12 µM). Similarly, in Ehrlich ascites carcinoma model, HMC significantly inhibited the growth of Ehrlich ascites carcinoma with mutual increase in the life span of HMC-treated mice, compared to EAC control. Most importantly, HMC showed a good safety profile as evidenced by restoring hematological profile count of RBCs, WBCs, and hemoglobin to the normal levels. HMC also efficiently reduced the oxidative stress in EAC-bearing mice via increasing the levels of GSH, SOD and Catalase. Collectively, HMC exerted a potent anticancer activity and data presented in this work suggest the usefulness of HMC as a promising candidate in cancer therapy.
Keywords	Cancer ; Ehrlich ascites carcinoma ; Flavonoid ; Hesperidin methyl chalcone ; Molecular docking ; MTT assay ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Prospective Cohort Study of COVID-19

Mardheya Al. Kharusi / Naffesa Al Sheikh / Maiya Alhajri / Seif Ali Al. Mandhri / El-Sayed Khafagy / Ehssan H. Moglad / Hadil Faris Alotaibi / Wael A. H. Hegazy

Healthcare, Vol 11, Iss 1025, p

Evaluation of the Early Role of IL-1 and IL-6 Antagonists in Improving the Outcome of the Illness and Reduction in the Risk of Death

2023 Volume 1025

Abstract: The COVID-19 pandemic had a profound impact on global health, economies, and social systems. The crucial factor that determines the success of COVID-19 treatments is preventing the need for mechanical ventilation and intensive care admission. In the ... ...

Abstract	The COVID-19 pandemic had a profound impact on global health, economies, and social systems. The crucial factor that determines the success of COVID-19 treatments is preventing the need for mechanical ventilation and intensive care admission. In the context of COVID-19, several treatments have been found to play a role in the disease’s progression and severity. Interleukins (ILs) have been identified as key mediators of the cytokine storm that can occur in severe cases of COVID-19, leading to respiratory failure and other complications. For instance, IL-1 antagonist (anakinra) and IL-6 antagonist (tocilizumab) are supposed to be promising treatments as well as cortisones for COVID-19. This prospective study aims to evaluate the effectiveness of anakinra or tocilizumab in addition to cortisone in preventing the progression of mild to moderate COVID-19 cases to severe intensive care admission. Biochemical and hematological parameters, such as D-dimer, ferritin, LDH, CRP, and white blood cells (WBCs), were measured after treatment with either anakinra or tocilizumab in addition to cortisone or cortisone alone. The study also recorded the number of deaths and patients admitted to intensive care. The results indicate that anakinra significantly improved outcomes and decreased the number of intensive care admissions compared to tocilizumab or cortisone alone. Therefore, anakinra may play a vital role in controlling the progression of COVID-19, and its use in mild to moderate cases may prevent the worsening of the disease to severe stages.
Keywords	COVID-19 ; COVID-19 treatment ; Interleukins ; IL-1 antagonist ; IL-6 antagonist ; anakinra ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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