33 results on '"Amr Selim Abu Lila"'
Search Results
2. Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia
- Author
-
Bjad K. Almutairy, El-Sayed Khafagy, Mohammed F. Aldawsari, Abdullah Alshetaili, Hadil Faris Alotaibi, and Amr Selim Abu Lila
- Subjects
Androgenic alopecia ,Bimatoprost ,Dermal delivery ,Skin deposition ,Spanlastics ,Pharmacy and materia medica ,RS1-441 - Abstract
Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 23 full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (−19.9 ± 2.1 mV), Q12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, ex-vivo skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, in vivo studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC0-12h of BIM-SLG was 888.05 ± 72.31 μg/mL.h, which was twice as high as that of naïve BIM gel (AUC0-12h 382.86 ± 41.12 μg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.
- Published
- 2024
- Full Text
- View/download PDF
3. Anticancer potentials of metformin loaded coconut oil nanoemulsion on MCF-7, HepG2 and HCT-116 cell lines
- Author
-
Hadil Faris Alotaibi, El-Sayed Khafagy, Amr Selim Abu Lila, Haifa F. Alotaibe, Serag Eldin Elbehairi, Ashwag S. Alanazi, Mohammad Y. Alfaifi, Jawaher Abdullah Alamoudi, Sarah Salem Alamrani, and Fatma Alzahraa Mokhtar
- Subjects
mcf-7 ,hct-116 ,HepG2 ,nanoemulsion ,metformin ,anticancer ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
AbstractIn order to load metformin in a nano formula and evaluate the produced nano form towards cancer cells, metformin was loaded on natural carrier coconut oil. The formed metformin-loaded coconut oil nanoemulsion was characterized by Zeta potential, particle size, drug content, drug release, and drug stability. The formed nanoemulsion was evaluated towards MCF-7, HepG2, and HCT-116 cell lines. Cell cycle analysis and apoptosis mechanism were studied. The nanoemulsion was created using deionized water, 1.5% Span 20, 1.5% Tween 80, 1.5% coconut oil, and 0.5% Metformin in an ultrasonicator to produce a homogenous solution. The anticancer activities of the metformin-loaded coconut nanoemulsion were highly improved compared to non-formulated metformin with IC50s of 8.3 ± 0.1 µg/ml, 12 ± 1.5 µg/ml, 2.685 ± 0.3 µg/ml for MCF-7, HepG2, and HCT-116 cell lines, respectively. There was a 76.5 ± 2.3 and 78.3 ± 3.2% increase in the number of apoptotic cells of MCF-7 and HepG2 cells after nanoemulsion treatment. This formula may be considered a new anticancer medication.
- Published
- 2023
- Full Text
- View/download PDF
4. An Update on Emergent Nano-Therapeutic Strategies against Pediatric Brain Tumors
- Author
-
Ammu V. V. V. Ravi Kiran, G. Kusuma Kumari, Praveen T. Krishnamurthy, Asha P. Johnson, Madhuchandra Kenchegowda, Riyaz Ali M. Osmani, Amr Selim Abu Lila, Afrasim Moin, H. V. Gangadharappa, and Syed Mohd Danish Rizvi
- Subjects
brain tumors ,childhood cancers ,pediatrics ,nanoparticles ,liposomes ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Pediatric brain tumors are the major cause of pediatric cancer mortality. They comprise a diverse group of tumors with different developmental origins, genetic profiles, therapeutic options, and outcomes. Despite many technological advancements, the treatment of pediatric brain cancers has remained a challenge. Treatment options for pediatric brain cancers have been ineffective due to non-specificity, inability to cross the blood–brain barrier, and causing off-target side effects. In recent years, nanotechnological advancements in the medical field have proven to be effective in curing challenging cancers like brain tumors. Moreover, nanoparticles have emerged successfully, particularly in carrying larger payloads, as well as their stability, safety, and efficacy monitoring. In the present review, we will emphasize pediatric brain cancers, barriers to treating these cancers, and novel treatment options.
- Published
- 2024
- Full Text
- View/download PDF
5. Formulation optimization, in vitro and in vivo evaluation of niosomal nanocarriers for enhanced topical delivery of cetirizine
- Author
-
Mohammed F. Aldawsari, El-Sayed Khafagy, Ehssan H. Moglad, and Amr Selim Abu Lila
- Subjects
Androgenic alopecia ,Cetirizine ,Niosomes ,Span 60 ,Thin film hydration method ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Cetirizine hydrochloride (CTZ), a second-generation anti-histaminic drug, has been recently explored for its effectiveness in the treatment of alopecia. Niosomes are surfactant-based nanovesicular systems that have promising applications in both topical and transdermal drug delivery. The aim of this study was to design topical CTZ niosomes for management of alopecia. Thin film hydration technique was implemented for the fabrication of CTZ niosomes. The niosomes were examined for vesicle size, surface charge, and entrapment efficiency. The optimized niosomal formulation was incorporated into a hydrogel base (HPMC) and explored for physical characteristics, ex vivo permeation, and in vivo dermato-kinetic study. The optimized CTZ-loaded niosomal formulation showed an average size of 403.4 ± 15.6 nm, zeta potential of − 12.9 ± 1.7 mV, and entrapment efficiency percentage of 52.8 ± 1.9%. Compared to plain drug solution, entrapment of CTZ within niosomes significantly prolonged in vitro drug release up to 12 h. Most importantly, ex-vivo skin deposition studies and in vivo dermato-kinetic studies verified superior skin deposition/retention of CTZ from CTZ-loaded niosomal gels, compared to plain CTZ gel. CTZ-loaded niosomal gel permitted higher drug deposition percentage (19.2 ± 1.9%) and skin retention (AUC0-10h 1124.5 ± 87.9 μg/mL.h) of CTZ, compared to 7.52 ± 0.7% and 646.2 ± 44.6 μg/mL.h for plain CTZ gel, respectively. Collectively, niosomes might represent a promising carrier for the cutaneous delivery of cetirizine for the topical management of alopecia.
- Published
- 2023
- Full Text
- View/download PDF
6. Development of Carvedilol Nanoformulation-Loaded Poloxamer-Based In Situ Gel for the Management of Glaucoma
- Author
-
Bjad K. Almutairy, El-Sayed Khafagy, and Amr Selim Abu Lila
- Subjects
carvedilol ,glaucoma ,in situ gel ,poloxamer ,spanlastics ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - 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 (Papp = 6.39 × 10−6 cm/s) compared to plain carvedilol-loaded in situ gel (CRV-ISG; Papp = 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 AUC0–6h 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.
- Published
- 2023
- Full Text
- View/download PDF
7. Manganese chloride (MnCl2) induced novel model of Parkinson’s disease in adult Zebrafish; Involvement of oxidative stress, neuroinflammation and apoptosis pathway
- Author
-
Abhishek.P.R. Nadig, Bader Huwaimel, Ahmed Alobaida, El-Sayed Khafagy, Hadil Faris Alotaibi, Afrasim Moin, Amr Selim Abu Lila, Suman, Sahyadri. M, and K.L. Krishna
- Subjects
Manganese Chloride ,Non-motor symptoms ,Tyrosine hydroxylase ,Pro-inflammatory cytokines ,Parkinson's disease ,Zebrafish ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder imposing a severe health and socioeconomic burden worldwide. Existing pharmacological approaches for developing PD are poorly developed and do not represent all the characteristics of disease pathology. Developing cost-effective, reliable Zebrafish (ZF) model will meet this gap. The present study was conceived to develop a reliable PD model in the ZF using manganese chloride (MnCl2). Here, we report that chronic exposure to 2 mM MnCl2 for 21 days produced non-motor and motor PD-like symptoms in adult ZF. Compared with control fish, MnCl2-treated fish showed reduced locomotory activity, indicating a deficit in motor function. In the light-dark box test, MnCl2-treated fish exhibited anxiety and depression-like behavior. MnCl2-treated fish exhibited a less olfactory preference for amino acids, indicating olfactory dysfunction. These behavioral symptoms were associated with decreased dopamine and increased DOPAC levels. Furthermore, oxidative stress-mediated apoptotic pathway, decreased brain derived neurotropic factor (BDNF) and increased pro-inflammatory cytokines levels were observed upon chronic exposure to MnCl2 in the brain of ZF. Thus, MnCl2-induced PD in ZF can be a cost-effective PD model in the drug discovery process. Moreover, this model could be potentially utilized to investigate the molecular pathways underlying the multifaceted pathophysiology which leads to PD using relatively inexpensive species. MnCl2 being heavy metal may have other side effects in addition to neurotoxicity. Our model recapitulates most of the hallmarks of PD, but not all pathological processes are involved. Future studies are required to recapitulate the complete pathophysiology of PD.
- Published
- 2022
- Full Text
- View/download PDF
8. Nano-Formulating Besifloxacin and Employing Quercetin as a Synergizer to Enhance the Potency of Besifloxacin against Pathogenic Bacterial Strains: A Nano-Synergistic Approach
- Author
-
Turki Al Hagbani, Syed Mohd Danish Rizvi, Shazi Shakil, and Amr Selim Abu Lila
- Subjects
besifloxacin ,eye infection ,gold nanoparticles ,quercetin ,resistant pathogens ,synergistic effect ,Chemistry ,QD1-999 - Abstract
The present study applied a nano-synergistic approach to enhance besifloxacin’s potency via nano-formulating besifloxacin on gold nanoparticles (Besi-AuNPs) and adding quercetin as a natural synergistic compound. In fact, a one-pot AuNP synthesis approach was applied for the generation of Besi-AuNPs, where besifloxacin itself acted as a reducing and capping agent. Characterization of Besi-AuNPs was performed by spectrophotometry, DLS, FTIR, and electron microscopy techniques. Moreover, antibacterial assessment of pure besifloxacin, Besi-AuNPs, and their combinations with quercetin were performed on Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. UV-spectra showed a peak of AuNPs at 526 nm, and the electron microscopy-based size was estimated to be 15 ± 3 nm. The effective MIC50 concentrations of besifloxacin after loading on AuNPs were reduced by approximately 50% against the tested bacterial strains. Interestingly, adding quercetin to Besi-AuNPs further enhanced their antibacterial potency, and isobologram analysis showed synergistic potential (combination index below 1) for different quercetin and Besi-AuNP combinations. However, Besi-AuNPs and quercetin combinations were most effective against Gram-positive S. aureus in comparison to Gram-negative P. aeruginosa and E. coli. Their potent activity against S. aureus has its own clinical significance, as it is one the main causative agents of ocular infection, and besifloxacin is primarily used for treating infectious eye diseases. Thus, the outcomes of the present study could be explored further to provide better medication for eye infections caused by resistant pathogens.
- Published
- 2023
- Full Text
- View/download PDF
9. Ocular Delivery of Bimatoprost-Loaded Solid Lipid Nanoparticles for Effective Management of Glaucoma
- Author
-
Sandeep Divate Satyanarayana, Amr Selim Abu Lila, Afrasim Moin, Ehssan H. Moglad, El-Sayed Khafagy, Hadil Faris Alotaibi, Ahmad J. Obaidullah, and Rompicherla Narayana Charyulu
- Subjects
bimatoprost ,central composite design ,glaucoma ,HET-CAM test ,solid lipid nanoparticles (SLNs) ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Glaucoma is a progressive optic neuropathy characterized by a rise in the intraocular pressure (IOP) leading to optic nerve damage. Bimatoprost is a prostaglandin analogue used to reduce the elevated IOP in patients with glaucoma. The currently available dosage forms for Bimatoprost suffer from relatively low ocular bioavailability. The objective of this study was to fabricate and optimize solid lipid nanoparticles (SLNs) containing Bimatoprost for ocular administration for the management of glaucoma. Bimatoprost-loaded SLNs were fabricated by solvent evaporation/ultrasonication technique. Glyceryl Monostearate (GMS) was adopted as solid lipid and poloxamer 407 as surfactant. Optimization of SLNs was conducted by central composite design. The optimized formulation was assessed for average particle size, entrapment efficiency (%), zeta potential, surface morphology, drug release study, sterility test, isotonicity test, Hen’s egg test-chorioallantoic membrane (HET-CAM) test and histopathology studies. The optimized Bimatoprost-loaded SLNs formulation had an average size of 183.3 ± 13.3 nm, zeta potential of −9.96 ± 1.2 mV, and encapsulation efficiency percentage of 71.8 ± 1.1%. Transmission electron microscopy (TEM) study revealed the nearly smooth surface of formulated particles with a nano-scale size range. In addition, SLNs significantly sustained Bimatoprost release for up to 12 h, compared to free drug (p < 005). Most importantly, HET-CAM test nullified the irritancy of the formulation was verified its tolerability upon ocular use, as manifested by a significant reduction in mean irritation score, compared to positive control (1% sodium dodecyl sulfate; p < 0.001). Histopathology study inferred the absence of any signs of cornea tissue damage upon treatment with Bimatoprost optimized formulation. Collectively, it was concluded that SLNs might represent a viable vehicle for enhancing the corneal permeation and ocular bioavailability of Bimatoprost for the management of glaucoma.
- Published
- 2023
- Full Text
- View/download PDF
10. Piperine-Loaded In Situ Gel: Formulation, In Vitro Characterization, and Clinical Evaluation against Periodontitis
- Author
-
Poornima K. Gopalakrishna, Rajamma Abburu Jayaramu, Sateesha Shivally Boregowda, Shruthi Eshwar, Nikhil V. Suresh, Amr Selim Abu Lila, Afrasim Moin, Hadil Faris Alotaibi, Ahmad J. Obaidullah, and El-Sayed Khafagy
- Subjects
anti-inflammatory ,anti-plaque ,in situ gel ,periodontitis ,piperine ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
Periodontitis is an inflammatory disorder associated with dysbiosis and characterized by microbiologically related, host-mediated inflammation that leads to the damage of periodontal tissues including gingiva, connective tissues, and alveolar bone. The aim of this study was to develop an in situ gel consisting of piperine. Eight in situ gel formulations were designed by varying the concentration of deacylated gellan gum cross-linked with sodium tripolyphosphate, and poloxamer-407. The prepared gels were evaluated for gelation temperature, gelation time, viscosity, piperine-loading efficiency, and piperine release. Finally, the optimized formula was evaluated for anti-inflammatory effectiveness among human patients during a 14-day follow-up. The optimized in situ gel formulation exhibited a gelation temperature of 35 ± 1 °C, gelling of 36 ± 1 s, excellent syringeability, and piperine loading of 95.3 ± 2.3%. This formulation efficiently sustained in vitro drug release for up to 72 h. In vivo studies revealed an efficient sol-to-gel transformation of optimized in situ gel formulation at physiological conditions, permitting an efficient residence time of the formulation within a periodontitis pocket. Most importantly, a clinical study revealed that treatment with the optimized formulation elicited a significant reduction in the mean plaque score (p = 0.001), gingival index (p = 0.003), and pocket depth (p = 0.002), and exerted a potent anti-inflammatory potential, compared to the control group. Collectively, piperine-loaded in situ gel might represent a viable therapeutic approach for the management of gingival and periodontal diseases.
- Published
- 2023
- Full Text
- View/download PDF
11. In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives
- Author
-
Amr Selim Abu Lila, Mohammed Amran, Mohamed A. Tantawy, Ehssan H. Moglad, Shadeed Gad, Hadil Faris Alotaibi, Ahmad J. Obaidullah, and El-Sayed Khafagy
- Subjects
antitumor activity ,Ehrlich ascites carcinoma ,MTT assay ,nanocapsule ,pyridine derivatives ,Pharmacy and materia medica ,RS1-441 - Abstract
This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.
- Published
- 2023
- Full Text
- View/download PDF
12. Development and Characterization of Pullulan-Based Orodispersible Films of Iron
- Author
-
Maram Suresh Gupta, Tegginamath Pramod Kumar, Dinesh Reddy, Kamla Pathak, Devegowda Vishakante Gowda, A. V. Naresh Babu, Alhussain H. Aodah, El-Sayed Khafagy, Hadil Faris Alotaibi, Amr Selim Abu Lila, Afrasim Moin, and Talib Hussin
- Subjects
anemia ,iron ,orodispersible film ,plasticizer ,pullulan ,Pharmacy and materia medica ,RS1-441 - Abstract
Iron deficiency is the principal cause of nutritional anemia and it constitutes a major health problem, especially during pregnancy. Despite the availability of various non-invasive traditional oral dosage forms such as tablets, capsules, and liquid preparations of iron, they are hard to consume for special populations such as pregnant women, pediatric, and geriatric patients with dysphagia and vomiting tendency. The objective of the present study was to develop and characterize pullulan-based iron-loaded orodispersible films (i-ODFs). Microparticles of iron were formulated by a microencapsulation technique, to mask the bitter taste of iron, and ODFs were fabricated by a modified solvent casting method. Morphological characteristics of the microparticles were identified by optical microscopy and the percentage of iron loading was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The fabricated i-ODFs were evaluated for their morphology by scanning electron microscopy. Other parameters including thickness, folding endurance, tensile strength, weight variation, disintegration time, percentage moisture loss, surface pH, and in vivo animal safety were evaluated. Lastly, stability studies were carried out at a temperature of 25 °C/60% RH. The results of the study confirmed that pullulan-based i-ODFs had good physicochemical properties, excellent disintegration time, and optimal stability at specified storage conditions. Most importantly, the i-ODFs were free from irritation when administered to the tongue as confirmed by the hamster cheek pouch model and surface pH determination. Collectively, the present study suggests that the film-forming agent, pullulan, could be successfully employed on a lab scale to formulate orodispersible films of iron. In addition, i-ODFs can be processed easily on a large scale for commercial use.
- Published
- 2023
- Full Text
- View/download PDF
13. Clinical Resistant Strains of Enterococci and Their Correlation to Reduced Susceptibility to Biocides: Phenotypic and Genotypic Analysis of Macrolides, Lincosamides, and Streptogramins
- Author
-
Amr Selim Abu Lila, Tareq Nafea Alharby, Jowaher Alanazi, Muteb Alanazi, Marwa H. Abdallah, Syed Mohd Danish Rizvi, Afrasim Moin, El-Sayed Khafagy, Shams Tabrez, Abdullah Ali Al Balushi, and Wael A. H. Hegazy
- Subjects
Enterococci ,macrolides ,lincosamides ,streptogramins ,Enterococci faecalis ,Enterococci faecium ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Enterococci are troublesome nosocomial, opportunistic Gram-positive cocci bacteria showing enhanced resistance to many commonly used antibiotics. This study aims to investigate the prevalence and genetic basis of antibiotic resistance to macrolides, lincosamides, and streptogramins (MLS) in Enterococci, as well as the correlation between MLS resistance and biocide resistance. From 913 clinical isolates collected from King Khalid Hospital, Hail, Saudi Arabia, 131 isolates were identified as Enterococci spp. The susceptibility of the clinical enterococcal isolates to several MLS antibiotics was determined, and the resistance phenotype was detected by the triple disk method. The MLS-involved resistance genes were screened in the resistant isolates. The current results showed high resistance rates to MLS antibiotics, and the constitutive resistance to all MLS (cMLS) was the most prevalent phenotype, observed in 76.8% of resistant isolates. By screening the MLS resistance-encoding genes in the resistant isolates, the erythromycin ribosome methylase (erm) genes that are responsible for methylation of bacterial 23S rRNA were the most detected genes, in particular, ermB. The ereA esterase-encoding gene was the most detected MLS modifying-encoding genes, more than lnuA (adenylation) and mphC (phosphorylation). The minimum inhibitory concentrations (MICs) of commonly used biocides were detected in resistant isolates and correlated with the MICs of MLS antibiotics. The present findings showed a significant correlation between MLS resistance and reduced susceptibility to biocides. In compliance with the high incidence of the efflux-encoding genes, especially mefA and mefE genes in the tolerant isolates with higher MICs to both MLS antibiotics and biocides, the efflux of resistant isolates was quantified, and there was a significant increase in the efflux of resistant isolates with higher MICs as compared to those with lower MICs. This could explain the crucial role of efflux in developing cross-resistance to both MLS antibiotics and biocides.
- Published
- 2023
- Full Text
- View/download PDF
14. Ganetespib with Methotrexate Acts Synergistically to Impede NF-κB/p65 Signaling in Human Lung Cancer A549 Cells
- Author
-
Gehad Subaiea, Syed Mohd Danish Rizvi, Hemant Kumar Singh Yadav, Turki Al Hagbani, Marwa Helmy Abdallah, El-Sayed Khafagy, Hosahalli Veerabhadrappa Gangadharappa, Talib Hussain, and Amr Selim Abu Lila
- Subjects
anticancer ,ganetespib ,lung cancer ,methotrexate ,NF-κB/p65 signaling ,NSCLC ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Among the various types of cancer, lung cancer accounts for the highest number of fatalities across the globe. A combination of different cancer chemotherapeutics is regarded as an effective strategy for clinical management of different cancers. Ganetespib (GAN) is a well-established hsp90 inhibitor with enhanced pharmacological properties in comparison with its first-generation counterparts. Previous preclinical studies have shown that GAN exerts significant effects against cancer cells; however, its therapeutic effects against non-small cell lung cancer (NSCLC) A549 cells, achieved by modulating the expression of the NF-κB/p65 signaling pathway, remains unexplored. In this study, the combinatorial effect of GAN and methotrexate (MTX) against lung carcinomas was investigated through both in silico and in vitro studies. A combinatorial treatment regimen of GAN/MTX exerted more significant cytotoxic effects (p < 0.001) against A549 cells than individual treatments. The GAN/MTX combination also instigated nuclear fragmentation followed by augmentation in intracellular ROS levels (p < 0.001). The elevated ROS in A549 cells upon exposure to GAN/MTX combinatorial regimen was concomitantly accompanied with a remarkable reduction in mitochondrial viability. In addition, it was observed that the GAN/MTX combination succeeded in elevating caspase-3 activity and downregulating the expression levels of anti-apoptotic mediators Bcl2 and survivin in NSCLC A549 cells. Most importantly, the GAN/MTX combinatorial regimen impeded the activation of the NF-kB/p65 signaling pathway via repression of the expression of E-cadherin and N-cadherin, which was confirmed by molecular docking studies. Collectively, these findings demonstrated the synergistic effect of the GAN/MTX combinatorial regimen in suppressing the growth of A549 cells by modulating the NF-κB/p65 signaling pathway.
- Published
- 2023
- Full Text
- View/download PDF
15. Antibiotic-Loaded Gold Nanoparticles: A Nano-Arsenal against ESBL Producer-Resistant Pathogens
- Author
-
Syed Mohd Danish Rizvi, Amr Selim Abu Lila, Afrasim Moin, Talib Hussain, Mohammad Amjad Kamal, Hana Sonbol, and El-Sayed Khafagy
- Subjects
antibiotic resistance ,bacterial pathogens ,ESBLs ,gold nanoparticles ,nano-therapeutics ,Pharmacy and materia medica ,RS1-441 - Abstract
The advent of new antibiotics has helped clinicians to control severe bacterial infections. Despite this, inappropriate and redundant use of antibiotics, inadequate diagnosis, and smart resistant mechanisms developed by pathogens sometimes lead to the failure of treatment strategies. The genotypic analysis of clinical samples revealed that the rapid spread of extended-spectrum β-lactamases (ESBLs) genes is one of the most common approaches acquired by bacterial pathogens to become resistant. The scenario compelled the researchers to prioritize the design and development of novel and effective therapeutic options. Nanotechnology has emerged as a plausible groundbreaking tool against resistant infectious pathogens. Numerous reports suggested that inorganic nanomaterials, specifically gold nanoparticles (AuNPs), have converted unresponsive antibiotics into potent ones against multi-drug resistant pathogenic strains. Interestingly, after almost two decades of exhaustive preclinical evaluations, AuNPs are gradually progressively moving ahead toward clinical evaluations. However, the mechanistic aspects of the antibacterial action of AuNPs remain an unsolved puzzle for the scientific fraternity. Thus, the review covers state-of-the-art investigations pertaining to the efficacy of AuNPs as a tool to overcome ESBLs acquired resistance, their applicability and toxicity perspectives, and the revelation of the most appropriate proposed mechanism of action. Conclusively, the trend suggested that antibiotic-loaded AuNPs could be developed into a promising interventional strategy to limit and overcome the concerns of antibiotic-resistance.
- Published
- 2023
- Full Text
- View/download PDF
16. Nano-Conversion of Ineffective Cephalosporins into Potent One against Resistant Clinical Uro-Pathogens via Gold Nanoparticles
- Author
-
Syed Mohd Danish Rizvi, Talib Hussain, Farhan Alshammari, Hana Sonbol, Nabeel Ahmad, Syed Shah Mohammed Faiyaz, Mohammad Amjad Kamal, El-Sayed Khafagy, Afrasim Moin, and Amr Selim Abu Lila
- Subjects
antibiotic resistance ,cefotetan ,cefixime ,clinical pathogens ,gold nanoparticles ,Chemistry ,QD1-999 - Abstract
Infections caused by resistant bacterial pathogens have increased the complications of clinicians worldwide. The quest for effective antibacterial agents against resistant pathogens has prompted researchers to develop new classes of antibiotics. Unfortunately, pathogens have acted more smartly by developing resistance to even the newest class of antibiotics with time. The culture sensitivity analysis of the clinical samples revealed that pathogens are gaining resistance toward the new generations of cephalosporins at a very fast rate globally. The current study developed gold nanoparticles (AuNPs) that could efficiently deliver the 2nd (cefotetan-CT) and 3rd (cefixime-CX) generation cephalosporins to resistant clinical pathogens. In fact, both CT and CX were used to reduce and stabilize AuNPs by applying a one-pot synthesis approach, and their characterization was performed via spectrophotometry, dynamic light scattering and electron microscopy. Moreover, the synthesized AuNPs were tested against uro-pathogenic resistant clinical strains of Escherichia coli and Klebsiella pneumoniae. CT-AuNPs characteristic SPR peak was observed at 542 nm, and CX-AuNPs showed the same at 522 nm. The stability measurement showed ζ potential as −24.9 mV and −25.2 mV for CT-AuNPs and CX-AuNPs, respectively. Scanning electron microscopy revealed the spherical shape of both the AuNPs, whereas, the size by transmission electron microscopy for CT-AuNPs and CX-AuNPs were estimated to be 45 ± 19 nm and 35 ± 17 nm, respectively. Importantly, once loaded onto AuNPs, both the cephalosporin antibiotics become extremely potent against the resistant strains of E. coli and K. pneumoniae with MIC50 in the range of 0.5 to 0.8 μg/mL. The findings propose that old-generation unresponsive antibiotics could be revived into potent nano-antibiotics via AuNPs. Thus, investing efforts, intellect, time and funds for a nano-antibiotic strategy might be a better approach to overcome resistance than investing the same in the development of newer antibiotic molecule(s).
- Published
- 2023
- Full Text
- View/download PDF
17. Tailoring of Novel Bile Salt Stabilized Vesicles for Enhanced Transdermal Delivery of Simvastatin: A New Therapeutic Approach against Inflammation
- Author
-
El-Sayed Khafagy, Bjad K. Almutairy, and Amr Selim Abu Lila
- Subjects
anti-inflammatory ,bilosomes ,rat paw edema ,simvastatin ,transdermal drug delivery ,Organic chemistry ,QD241-441 - 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 33 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.
- Published
- 2023
- Full Text
- View/download PDF
18. Biosynthesis of Silver Nanoparticles Using Commiphora mukul Extract: Evaluation of Anti-Arthritic Activity in Adjuvant-Induced Arthritis Rat Model
- Author
-
Anupama Singh, Sateesha Shivally Boregowda, Afrasim Moin, Amr Selim Abu Lila, Mohammed F. Aldawsari, El-Sayed Khafagy, Hadil Faris Alotaibi, and Rajamma Abburu Jayaramu
- Subjects
anti-inflammatory ,arthritic score ,guggul ,rheumatoid arthritis ,silver nanoparticles ,Pharmacy and materia medica ,RS1-441 - Abstract
Rheumatoid arthritis (RA) is a major global public health challenge, and novel therapies are required to combat it. Silver nanoparticles (AgNPs) have been employed as delivery vehicles of anti-inflammatory drugs for RA therapy, and it has been recently realized that AgNPs have anti-inflammatory action on their own. However, their conventional synthesis processes might result in cytotoxicity and environmental hazards. Instead, the use of natural products as a reducing and stabilizing agent in the biosynthesis of silver nanoparticles has arisen as an option to decrease the cytotoxic and environmental concerns associated with chemical synthesis of AgNPs. In this study, we challenged the efficacy of Commiphora mukul (guggul) aqueous extract as a reducing and/or capping agent for the biosynthesis of AgNPs. Guggul-mediated biosynthesized silver nanoparticles (G-AgNPs) were characterized via UV-vis spectroscopy, dynamic light scattering, and scanning electron microscopy. In addition, their anti-arthritic potential was evaluated in an adjuvant-induced arthritis (AIA) model. The fabricated NPs showed an absorption peak at 412 nm, corresponding to the typical surface plasmon resonance band of AgNPs. The synthesized G-AgNPs were nearly spherical, with a particle size of 337.6 ± 12.1 nm and a negative surface charge (−18.9 ± 1.8 mV). In AIA rat model, synthesized G-AgNPs exerted a potent anti-inflammatory action, as manifested by a remarkable reduction in paw volume (>40%) along with elicitation of a minimal arthritic score, compared to control rats. In addition, when compared to arthritic rats, treatment with G-AgNPs efficiently restored the activity of antioxidant enzyme, superoxide dismutase, and catalase, indicating the efficiency of synthesized G-AgNPs in alleviating the oxidative stress associated with RA. Finally, histological examination revealed comparatively lower inflammatory cells infiltration in ankle joint tissue upon treatment with G-AgNPs. Collectively, biosynthesized G-AgNPs might represent a plausible therapeutic option for the management of RA.
- Published
- 2022
- Full Text
- View/download PDF
19. Gold Nanoparticle-Based Resuscitation of Cefoxitin against Clinical Pathogens: A Nano-Antibiotic Strategy to Overcome Resistance
- Author
-
Ahmed Alafnan, Syed Mohd Danish Rizvi, Abdullah S. Alshammari, Syed Shah Mohammed Faiyaz, Amr Selim Abu Lila, Ahmed A. Katamesh, El-Sayed Khafagy, Hadil Faris Alotaibi, and Abo Bakr F. Ahmed
- Subjects
gold nanoparticles ,drug delivery tool ,Gram-negative pathogens ,cefoxitin ,nano-antibiotic ,Chemistry ,QD1-999 - Abstract
Gold nanoparticles have gained popularity as an effective drug delivery vehicle due to their unique features. In fact, antibiotics transported via gold nanoparticles have significantly enhanced their potency in the recent past. The present study used an approach to synthesize gold nanoparticles in one step with the help of cefoxitin antibiotic as a reducing and stabilizing agent. Cefoxitin is a second-generation cephalosporin that loses its potential due to modification in the porins (ompK35 and ompK36) of Gram-negative pathogens. Thus, the present study has developed an idea to revive the potential of cefoxitin against clinical Gram-negative pathogens, i.e., Escherichia coli and Klebsiella pneumoniae, via applying gold nanoparticles as a delivery tool. Prior to antibacterial activity, characterization of cefoxitin–gold nanoparticles was performed via UV–visible spectrophotometry, dynamic light scattering, and electron microscopy. A characteristic UV–visible scan peak for gold nanoparticles was observed at 518 nm, ζ potential was estimated as −23.6 ± 1.6, and TEM estimated the size in the range of 2–12 nm. Moreover, cefoxitin loading efficiency on gold nanoparticles was calculated to be 71.92%. The antibacterial assay revealed that cefoxitin, after loading onto the gold nanoparticles, become potent against cefoxitin-resistant E. coli and K. pneumoniae, and their MIC50 values were estimated as 1.5 μg/mL and 2.5 μg/mL, respectively. Here, gold nanoparticles effectively deliver cefoxitin to the resistant pathogens, and convert it from unresponsive to a potent antibiotic. However, to obtain some convincing conclusions on the human relevance, their fate and toxicity need to be evaluated.
- Published
- 2022
- Full Text
- View/download PDF
20. Vardenafil-Loaded Bilosomal Mucoadhesive Sponge for Buccal Delivery: Optimization, Characterization, and In Vivo Evaluation
- Author
-
Mohammed F. Aldawsari, El-Sayed Khafagy, Hadil Faris Alotaibi, and Amr Selim Abu Lila
- Subjects
bilosomes ,buccal delivery ,cGMP ,mucoadhesive sponge ,vardenafil ,Organic chemistry ,QD241-441 - Abstract
Vardenafil (VDF) is a relatively new phosphodiesterase-5 inhibitor that has limited oral bioavailability (≈15%). The objective of this study was to develop bilosome-based mucoadhesive buccal sponge for augmenting the oral bioavailability of VDF. VDF-loaded bilosomes were fabricated and optimized using a Box-Behnken design. The optimized VDF-loaded bilosomal formulation was assessed for surface morphology, particle size, thermal characteristics, and in vitro release. Afterwards, the optimized bilosomal formulation was incorporated into a cellulose-based matrix to obtain buccal sponge, which was evaluated for ex vivo permeation studies, in vivo oral bioavailability, and in vivo serum concentration of cyclic guanosine monophosphate (cGMP). The mean particle size and entrapment efficiency (%) of optimized bilosome formulation were 282.6 ± 9.5 nm and 82.95 ± 3.5%, respectively. In vitro release studies at pH 6.8 emphasized the potential of optimized bilosomal formulation to sustain VDF release for 12 h. Ex vivo permeation study using sheep buccal mucosa indicated significant enhancement in penetration of VDF from bilosomal buccal sponge compared to plain VDF gel. Pharmacokinetic study in Albino rats showed ~5 fold increase in relative bioavailability with bilosomal buccal sponge, compared to VDF suspension. In addition, VDF-loaded bilosomal buccal sponge triggered higher serum levels of cGMP, a biomarker of VDF in vivo efficacy, compared to oral VDF suspension. To sum up, bilosomes might represent a potential nanocarrier for buccal delivery of VDF, enhancing its oral bioavailability and therapeutic efficacy.
- Published
- 2022
- Full Text
- View/download PDF
21. Delafloxacin-Capped Gold Nanoparticles (DFX-AuNPs): An Effective Antibacterial Nano-Formulation of Fluoroquinolone Antibiotic
- Author
-
Amr Selim Abu Lila, Bader Huwaimel, Ahmed Alobaida, Talib Hussain, Zeeshan Rafi, Khalid Mehmood, Marwa H. Abdallah, Turki Al Hagbani, Syed Mohd Danish Rizvi, Afrasim Moin, and Abobakr F. Ahmed
- Subjects
antibiotic resistance ,delafloxacin ,fluoroquinolone ,gold nanoparticles ,nano-formulations ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
New antibiotics are seen as ‘drugs of last resort’ against virulent bacteria. However, development of resistance towards new antibiotics with time is a universal fact. Delafloxacin (DFX) is a new fluoroquinolone antibiotic that differs from existing fluoroquinolones by the lack of a protonatable substituent, which gives the molecule a weakly acidic nature, affording it higher antibacterial activity under an acidic environment. Furthermore, antibiotic-functionalized metallic nanoparticles have been recently emerged as a feasible platform for conquering bacterial resistance. In the present study, therefore, we aimed at preparing DFX-gold nano-formulations to increase the antibacterial potential of DFX. To synthesize DFX-capped gold nanoparticles (DFX-AuNPs), DFX was used as a reducing and stabilizing/encapsulating agent. Various analytical techniques such as UV-visible spectroscopy, TEM, DLS, FTIR and zeta potential analysis were applied to determine the properties of the synthesized DFX-AuNPs. The synthesized DFX-AuNPs revealed a distinct surface plasmon resonance (SPR) band at 530 nm and an average size of 16 nm as manifested by TEM analysis. In addition, Zeta potential results (−19 mV) confirmed the stability of the synthesized DFX-AuNPs. Furthermore, FTIR analysis demonstrated that DFX was adsorbed onto the surface of AuNPs via strong interaction between AuNPs and DFX. Most importantly, comparative antibacterial analysis of DFX alone and DFX-AuNPs against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) verified the superior antibacterial activity of DFX-AuNPs against the tested microorganisms. To sum up, DFX gold nano-formulations can offer a promising possible solution, even at a lower antibiotic dose, to combat pathogenic bacteria.
- Published
- 2022
- Full Text
- View/download PDF
22. Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin
- Author
-
Ravi Gundadka Shriram, Afrasim Moin, Hadil Faris Alotaibi, El-Sayed Khafagy, Ahmed Al Saqr, Amr Selim Abu Lila, and Rompicherla Narayana Charyulu
- Subjects
anti-oxidant activity ,hepatoprotective effect ,phospholipid ,phytosomes ,Silymarin ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Silymarin, a phyto-constituent derived from the plant Silybum marianum, has been widely acknowledged for its hepatoprotective activities. Nevertheless, its clinical utility is adversely hampered by its poor water-solubility and its limited oral bioavailability. The aim of this study was to investigate the efficacy of phospholipid-based phytosomes for enhancing the oral bioavailability of silymarin. The phytosomes were prepared using the solvent evaporation technique and were optimized using a full factorial design. The optimized silymarin phytosomal formulation was then characterized for particle size, surface morphology, aqueous solubility, and in vitro drug release. Furthermore, in vivo antioxidant activity, hepatoprotective activity and oral bioavailability of the optimized formula were investigated in a rat model. The prepared silymarin phytosomes were discrete particles with a porous, nearly smooth surface and were 218.4 ± 2.54 nm in diameter. In addition, the optimized silymarin phytosomal formulation showed a significant improvement in aqueous solubility (~360 µg/mL) compared to pure silymarin and manifested a higher rate and extent of silymarin release from the optimized formula in dissolution studies. The in vivo assessment studies revealed that the optimized silymarin phytosomal formulation efficiently exerted a hepatoprotective effect in a CCl4-induced hepatotoxicity rat model via restoring the normal levels of antioxidant enzymes and ameliorating cellular abnormalities caused by CCl4-intoxication. Most notably, as compared to pure silymarin, the optimized silymarin phytosomal formulation significantly improved silymarin oral bioavailability, as indicated by a 6-fold increase in the systemic bioavailability. Collectively, phytosomes might represent a plausible phospholipid-based nanocarrier for improving the oral bioavailability of phyto-constituents with poor aqueous solubility.
- Published
- 2022
- Full Text
- View/download PDF
23. Cefotaxime Mediated Synthesis of Gold Nanoparticles: Characterization and Antibacterial Activity
- Author
-
Turki Al Hagbani, Syed Mohd Danish Rizvi, Talib Hussain, Khalid Mehmood, Zeeshan Rafi, Afrasim Moin, Amr Selim Abu Lila, Farhan Alshammari, El-Sayed Khafagy, Mohamed Rahamathulla, and Marwa H. Abdallah
- Subjects
bacterial resistance ,cefotaxime sodium ,cephalosporin ,gold nanoparticles ,MIC50 ,Organic chemistry ,QD241-441 - Abstract
Cefotaxime (CTX) is a third-generation cephalosporin antibiotic with broad-spectrum activity against Gram negative and Gram positive bacteria. However, like other third-generation cephalosporin antibiotics, its efficacy is declining due to the increased prevalence of multidrug-resistant (MDR) pathogens. Recent advances in nanotechnology have been projected as a practical approach to combat MDR microorganisms. Therefore, in the current study, gold nanoparticles (AuNPs) were prepared using cefotaxime sodium, which acted as a reducing and capping agent, besides having well-established antibacterial activity. The synthesized cefotaxime-loaded gold nanoparticles (C-AuNPs) were characterized by UV-Visible spectroscopy, FTIR, TEM and DLS. In addition, the in vitro antibacterial activity of C-AuNPs was assessed against both Gram-positive and Gram-negative bacteria. UV-Visible spectroscopy verified the formation of C-AuNPs, while TEM and DLS verified their nano-size. In addition, CTX loading onto AuNPs was confirmed by FTIR. Furthermore, the colloidal stability of the synthesized C-AuNPs was ascribed to the higher net negative surface charge of C-AuNPs. Most importantly, the synthesized C-AuNPs showed superior antibacterial activity and lower minimum inhibitory concentration (MIC) values against Gram-negative (Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria, compared with pure CTX. Collectively, CTX was successfully adopted, as reducing and capping agent, to synthesize stable, nano-sized spherical C-AuNPs. Furthermore, loading CTX onto AuNPs could efficiently restore and/or boost the antibacterial activity of CTX against resistant Gram-negative and Gram-positive bacteria.
- Published
- 2022
- Full Text
- View/download PDF
24. Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model
- Author
-
Ekta Singh, Riyaz Ali M. Osmani, Rinti Banerjee, Amr Selim Abu Lila, Afrasim Moin, Khaled Almansour, Hany H. Arab, Hadil Faris Alotaibi, and El-Sayed Khafagy
- Subjects
drug delivery ,nanotherapeutics ,rheumatoid arthritis ,leflunomide ,polymeric nanoparticle ,poly-ε-caprolactone ,Pharmacy and materia medica ,RS1-441 - Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy might represent a promising strategy to treat rheumatoid arthritis without eliciting systemic adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) nanoparticles (Lfd-NPs) were prepared and assessed as a local drug delivery system capable of alleviating RA-associated inflammation. Lfd-NPs were optimized using the Quality by Design (QbD) approach, applying a 32 full factorial design. In vitro drug release from NPs was examined in simulated synovial fluid. In addition, the in vivo efficacy of Lfd-NPs was evaluated in the Adjuvant Induced Arthritis (AIA) rodent model. Sustained drug release in simulated synovial fluid was observed for up to 168 h. A gradual reduction in paw volume and knee diameter was observed over the course of treatment, indicating the regression of the disease. In addition, significant reductions in serum proinflammatory markers and cytokines, including the C-reactive protein (CRP), rheumatoid factor (RF), TNF-α, IL1-β, and IL-6, were verified upon treatment with Lfd-NPs, suggesting the modulation of immune responses at the pathological site. Most importantly, no remarkable signs of toxicity were observed in Lfd-NP-treated animals. Collectively, intra-articularly administered Lfd-NPs might represent a potential therapeutic alternative to systemically administered drugs for the treatment of rheumatoid arthritis, without eliciting systemic adverse effects.
- Published
- 2022
- Full Text
- View/download PDF
25. Development and Evaluation of Clove and Cinnamon Supercritical Fluid Extracts-Loaded Emulgel for Antifungal Activity in Denture Stomatitis
- Author
-
Meenakshi Srinivas Iyer, Anil Kumar Gujjari, Sathishbabu Paranthaman, Amr Selim Abu Lila, Khaled Almansour, Farhan Alshammari, El-Sayed Khafagy, Hany H. Arab, and Devegowda Vishakante Gowda
- Subjects
Candida albicans ,clove extracts ,cinnamon extracts ,denture stomatitis ,super critical fluid extraction ,Science ,Chemistry ,QD1-999 ,Inorganic chemistry ,QD146-197 ,General. Including alchemy ,QD1-65 - Abstract
Denture stomatitis (DS), usually caused by Candida infection, is one of the common denture-related complications in patients wearing dentures. Clove and cinnamon oils have been acknowledged for their anti-inflammatory, antimicrobial activity, and antifungal effects in the oral cavity. The aim of this study, therefore, was to prepare clove/cinnamon oils-loaded emulgel and to assess its efficacy in treating Candida albicans-associated denture stomatitis. Central composite design was adopted to formulate and optimize clove/cinnamon extracts-loaded emulgel. The formulated preparations were assessed for their physical appearance, particle size, viscosity, spreadability, and in-vitro drug release. In addition, in-vivo therapeutic experiments were conducted on 42 patients with denture stomatitis. The prepared emulgel formulations showed good physical characteristics with efficient drug release within 3 h. In addition, in-vivo antifungal studies revealed that the optimized formula significantly (p < 0.001) reduced Candida colony counts from the denture surface, compared to commercially available gel (240.38 ± 27.20 vs. 398.19 ± 66.73 CFU/mL, respectively). Furthermore, the optimized formula and succeeded in alleviating denture stomatitis-related inflammation with a better clinical cure rate compared to commercially available gel Collectively, herbal extracts-loaded emulgel might be considered an evolution of polyherbal formulations and might represent a promising alternative to the existing allopathic drugs for the treatment of denture stomatitis, with better taste acceptability and no side effects.
- Published
- 2022
- Full Text
- View/download PDF
26. Enhancement of Vancomycin Potential against Pathogenic Bacterial Strains via Gold Nano-Formulations: A Nano-Antibiotic Approach
- Author
-
Turki Al Hagbani, Hemant Yadav, Afrasim Moin, Amr Selim Abu Lila, Khalid Mehmood, Farhan Alshammari, Salman Khan, El-Sayed Khafagy, Talib Hussain, Syed Mohd Danish Rizvi, and Marwa H. Abdallah
- Subjects
gold nanoparticles ,antibiotic resistance ,vancomycin ,metallic nanoparticles ,transmission electron microscopy ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
The remarkable rise of antibiotic resistance among pathogenic bacteria poses a significant threat to human health. Nanoparticles (NPs) have recently emerged as novel strategies for conquering fatal bacterial diseases. Furthermore, antibiotic-functionalized metallic NPs represent a viable nano-platform for combating bacterial resistance. In this study, we present the use of vancomycin-functionalized gold nanoparticles (V-GNPs) to battle pathogenic bacterial strains. A facile one-pot method was adopted to synthesize vancomycin-loaded GNPs in which the reducing properties of vancomycin were exploited to produce V-GNPs from gold ions. UV–Visible spectroscopy verified the production of V-GNPs via the existence of a surface plasmon resonance peak at 524 nm, whereas transmission electron microscopy depicted a size of ~24 nm. Further, dynamic light scattering (DLS) estimated the hydrodynamic diameter as 77 nm. The stability of V-GNPs was investigated using zeta-potential measurements, and the zeta potential of V-GNPs was found to be −18 mV. Fourier transform infrared spectroscopy confirmed the efficient loading of vancomycin onto GNP surfaces; however, the loading efficiency of vancomycin onto V-GNPs was 86.2%. Finally, in vitro antibacterial studies revealed that V-GNPs were much more effective, even at lower concentrations, than pure vancomycin. The observed antibacterial activities of V-GNPs were 1.4-, 1.6-, 1.8-, and 1.6-fold higher against Gram-negative Escherichia coli, Klebsiella oxytoca, and Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus, respectively, compared to pure vancomycin. Collectively, V-GNPs represented a more viable alternative to pure vancomycin, even at a lower antibiotic dose, in conquering pathogenic bacteria.
- Published
- 2022
- Full Text
- View/download PDF
27. In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives
- Author
-
Khafagy, Amr Selim Abu Lila, Mohammed Amran, Mohamed A. Tantawy, Ehssan H. Moglad, Shadeed Gad, Hadil Faris Alotaibi, Ahmad J. Obaidullah, and El-Sayed
- Subjects
antitumor activity ,Ehrlich ascites carcinoma ,MTT assay ,nanocapsule ,pyridine derivatives - Abstract
This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.
- Published
- 2023
- Full Text
- View/download PDF
28. Coleus aromaticus Ethanolic Leaves Extract Mediates Inhibition of NF-κB Signaling Pathway in Lung Adenocarcinoma A549 Cells
- Author
-
Gehad Subaiea, Ahmed Alafnan, Abdulwahab Alamri, Talib Hussain, Shimaa Mahmoud Hassoun, Amr Selim Abu Lila, El-Sayed Khafagy, and Ahmed A. Katamesh
- Subjects
Process Chemistry and Technology ,Chemical Engineering (miscellaneous) ,Bioengineering ,A549 ,apoptosis ,Coleus aromaticus extract ,NF-κB ,non-small cell lung carcinoma ,ROS - Abstract
Lung cancer is the second leading cause of cancer-related mortalities globally. Failure in diagnosis at early stages and limited effective chemotherapeutics has severely impeded the clinical management of patients suffering from lung carcinoma. At present, researchers across the world are focused on exploring biologically active natural products for treating various cancers, which can thus be further investigated for their chemotherapeutical potential. Coleus aromaticus is a common herb used in culinary practices and has previously been shown to possess various medicinal characteristics. In the present study, the anti-cancer effects of ethanolic extract of C. aromaticus leaves (EtOH-LCa) against non-small cell lung carcinoma (NSCLC) A549 cells were screened. It was observed that EtOH-LCa reduced the viability of A549 cells and obstructed the cell cycle progression in a concentration-dependent manner. Importantly, EtOH-LCa succeeded in instigating the production of reactive oxygen species (ROS) (p < 0.001) within A549 cells. The elevation in ROS levels was concomitantly followed by the disruption of nuclear morphology and the loss in mitochondria viability within A549 cells. In addition, EtOH-LCa was successful in increasing the activity of caspases-3, which further aided in increasing apoptosis. Most importantly, EtOH-LCa decreased NF-κB expression (p < 0.05) along with modulating mRNA expression of pro-/anti-apoptotic genes; Bax, Bad, Bcl-2 and Bcl-XL within NSCLC A549 cells. Collectively, it could be concluded that EtOH-LCa possessed considerable anti-cancer effects against NSCLC A549 cells; however, further molecular studies are warranted to completely establish the chemotherapeutical potential of EtOH-LCa.
- Published
- 2023
- Full Text
- View/download PDF
29. Manganese chloride (MnCl
- Author
-
Abhishek P R, Nadig, Bader, Huwaimel, Ahmed, Alobaida, El-Sayed, Khafagy, Hadil Faris, Alotaibi, Afrasim, Moin, Amr Selim Abu, Lila, Suman, Sahyadri, M, and K L, Krishna
- Subjects
Oxidative Stress ,Dopamine ,Brain-Derived Neurotrophic Factor ,Neuroinflammatory Diseases ,Animals ,3,4-Dihydroxyphenylacetic Acid ,Cytokines ,Parkinson Disease ,Apoptosis ,Amino Acids ,Zebrafish - Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder imposing a severe health and socioeconomic burden worldwide. Existing pharmacological approaches for developing PD are poorly developed and do not represent all the characteristics of disease pathology. Developing cost-effective, reliable Zebrafish (ZF) model will meet this gap. The present study was conceived to develop a reliable PD model in the ZF using manganese chloride (MnCl
- Published
- 2022
30. Inflammation targeted nanomedicines: Patents and applications in cancer therapy
- Author
-
Thaggikuppe Krishnamurthy Praveen, Hosahalli Veerabhadrappa Gangadharappa, Amr Selim Abu Lila, Afrasim Moin, Khalid Mehmood, Kamsagara Linganna Krishna, Talib Hussain, Ahmed Alafnan, Shazi Shakil, and Syed Mohd Danish Rizvi
- Subjects
Inflammation ,Cancer Research ,Nanomedicine ,Drug Delivery Systems ,Neoplasms ,Humans ,Nanotechnology - Abstract
Evident role of inflammation in cancer development and progression prompted the application of anti-inflammatory medications as a therapeutic strategy. The major bottleneck for the anti-inflammatory drugs is targeted delivery to the cancerous cell. Nanotechnology has provided safe and effective way for targeted cancer therapy. However, the complex and heterogeneous traits of cancer, incomplete information on fate and behavior of nanomedicines in human body, and lack of large-scale commercial production have slowed down the pace of nanomedicines development. To shift the paradigm from conventional cancer therapeutics to anti-inflammatory nano-therapeutics, thorough understanding of the strategies, progress, success, challenges and future perspectives are needed. The present review highlights all these aspects in addition to innovations patented on them. In fact, patent plays a vital role in protection of innovations, and further translation of lab-scale outcomes into bedside medications. Thus, the review introspects and recognizes the glitches in successful clinical translation of anti-inflammatory nanomedicines.
- Published
- 2022
31. Cytotoxic and Apoptotic Effect of Rubus chingii Leaf Extract against Non-Small Cell Lung Carcinoma A549 Cells
- Author
-
El-Sayed Khafagy, Ahmed Al Saqr, Hadil Faris Alotaibi, and Amr Selim Abu Lila
- Subjects
Process Chemistry and Technology ,Chemical Engineering (miscellaneous) ,anti-cancer ,apoptosis ,mitochondrial membrane potential ,reactive oxygen species (ROS) ,Rubus chingii ,Bioengineering - 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 (RcL-EtOH) against non-small cell lung cancer A549 cells. RcL-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 RcL-EtOH-treated A549 cells. In addition, RcL-EtOH instigated the dissipation of mitochondrial membrane potential (ΔΨm) with mutual escalation in ROS generation in a dose-dependent manner. Furthermore, RcL-EtOH increased caspase-3, caspase-9 levels in A549 cells post-exposure to RcL-EtOH, which was concomitantly followed by altered mRNA expression of apoptotic (anti-apoptotic: Bcl-2, BclXL; pro-apoptotic: Bax, Bad). To sum up, the RcL-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, RcL-EtOH might represent a plausible therapeutic option for the management of lung cancer.
- Published
- 2022
32. Doxorubicin Expands in Vivo Secretion of Circulating Exosome in Mice
- Author
-
Sherif E, Emam, Hidenori, Ando, Amr Selim, Abu Lila, Shinya, Kobayashi, Taro, Shimizu, Keiichiro, Okuhira, Yu, Ishima, and Tatsuhiro, Ishida
- Subjects
Male ,Mice ,Mice, Inbred BALB C ,Antibiotics, Antineoplastic ,Doxorubicin ,Injections, Intravenous ,Models, Animal ,Animals ,Exosomes ,Exocytosis ,Spleen ,Polyethylene Glycols - Abstract
Modulation of tumor immunity is a known factor in the antitumor activity of many chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are released by almost all types of cells, which includes cancer cells. These vesicles play a crucial role in tumor immunity. Many in vitro studies have reproduced the aggressive secretion of exosomes following treatment with conventional anticancer drugs. Nevertheless, how chemotherapeutic agents including nanomedicines such as Doxil
- Published
- 2018
33. Ex-vivo/in-vitro anti-polyethylene glycol (PEG) immunoglobulin M production from murine splenic B cells stimulated by PEGylated liposome
- Author
-
Amr Selim, Abu Lila, Masako, Ichihara, Taro, Shimizu, Tatsuhiro, Ishida, and Hiroshi, Kiwada
- Subjects
Male ,B-Lymphocytes ,Mice ,Mice, Inbred BALB C ,Immunoglobulin M ,Liposomes ,Animals ,Cells, Cultured ,Spleen ,Polyethylene Glycols - Abstract
We have reported that PEGylated liposomes lose their long-circulating properties when injected twice into the same animal within a certain interval (the accelerated blood clearance (ABC) phenomenon). We assumed that this phenomenon was triggered via the abundant secretion of anti-polyethylene glycol (PEG) immunoglobulin M (IgM) in response to the first dose of PEGylated liposomes and that the spleen played an important role in the production of anti-PEG IgM. However, no direct evidence has yet confirmed this suspicion. In the current study, we verified, both in vitro and ex vivo, that spleen cells are indeed responsible for the production of anti-PEG IgM in response to PEGylated liposomes. In this study, spleen cells obtained from either naïve mice or mice pre-treated with PEGylated liposomes induced the production of anti-PEG IgM in a dose- and time-dependent manner, upon incubation with PEGylated liposomes. In addition, we confirmed that among the different fractions of splenic B cells, IgM-positive B cells, rather than CD45R-positive or CD19-positive splenic B cells, which are presumed to be the marginal zone B (MZB) cells, are the major cells producing anti-PEG IgM in the response to stimulation by PEGylated liposomes. These results may provide new insights into the mechanisms underlying the anti-PEG IgM production in response to the stimulation by PEGylated liposomes.
- Published
- 2013
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.