RETRACTED: Alhakamy et al. Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats. Biomolecules 2020, 10, 1006.

The journal retracts the article, "Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats" [...].

L-arginine mitigates bleomycin-induced pulmonary fibrosis in rats through regulation of HO-1/PPAR-γ/ß-catenin axis.

Pulmonary fibrosis is a chronic and progressively deteriorating lung condition that can be replicated in laboratory animals by administering bleomycin, a chemotherapeutic antibiotic known for its lung fibrosis-inducing side effects. L-arginine, a semi-essential amino acid, is recognized for its diverse biological functions, including its potential to counteract fibrosis. This study aimed to evaluate the antifibrotic properties of L-arginine on bleomycin-induced pulmonary fibrosis in rats. The administration of a single intratracheal dose of bleomycin resulted in visible and microscopic damage to lung tissues, an uptick in oxidative stress markers, and an elevation in inflammatory, apoptotic, and fibrotic indicators. A seven-day treatment with L-arginine post-bleomycin exposure markedly improved the gross and histological architecture of the lungs, prevented the rise of malondialdehyde and carbonyl content, and enhanced total antioxidant capacity alongside the activities of antioxidant enzymes. Also, L-arginine attenuated the expression of the pro-fibrotic factors, transforming growth factor-ß and lactate dehydrogenase in bronchoalveolar lavage fluid. In the lung tissue, L-arginine reduced collagen deposition, hydroxyproline concentration, and mucus production, along with decreasing expression of α-smooth muscle actin, tumor necrosis factor-α, caspase-3, matrix metalloproteinase-9, and ß-catenin. Moreover, it boosted levels of nitric oxide and upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), heme oxygenase-1 (HO-1), and E-cadherin and downregulating the expression of ß-catenin. These findings suggest that L-arginine has preventive activities against bleomycin-induced pulmonary fibrosis. This effect can be attributed to the increased production of nitric oxide, which modulates the HO-1/PPAR-γ/ß-catenin axis.

RETRACTED: Alhakamy et al. Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells. Pharmaceutics 2020, 12, 761.

The journal retracts the article, "Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells" [...].

RETRACTED: Alhakamy et al. Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment. Pharmaceutics 2022, 14, 1133.

The journal retracts the article, "Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment" [...].

RETRACTED: Ahmed et al. Omega-3 Self-Nanoemulsion Role in Gastroprotection against Indomethacin-Induced Gastric Injury in Rats. Pharmaceutics 2020, 12, 140.

The journal retracts the article, "Omega-3 Self-Nanoemulsion Role in Gastroprotection against Indomethacin-Induced Gastric Injury in Rats" [...].

RETRACTED: Aldawsari et al. Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment. Pharmaceutics 2021, 13, 783.

The journal retracts the article "Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment" [...].

RETRACTED: Fahmy et al. Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation. Pharmaceutics 2020, 12, 485.

This journal retracts the article "Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation" [...].

RETRACTED: Alhakamy et al. Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells. Pharmaceutics 2020, 12, 346.

The journal retracts the article, "Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells" [...].

RETRACTED: Alhakamy et al. Chitosan-Based Microparticles Enhance Ellagic Acid's Colon Targeting and Proapoptotic Activity. Pharmaceutics 2020, 12, 652.

The journal retracts the article "Chitosan-Based Microparticles Enhance Ellagic Acid's Colon Targeting and Proapoptotic Activity" [...].

RETRACTED: Asfour et al. Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats. Pharmaceutics 2022, 14, 1792.

Pharmaceutics retracted the article "Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats" [...].

RETRACTED: Ahmed et al. Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route. Nanomaterials 2020, 10, 1270.

The Journal retracts the article "Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route" [...].

RETRACTED: Alhakamy et al. Attenuation of Benign Prostatic Hyperplasia by Optimized Tadalafil Loaded Pumpkin Seed Oil-Based Self Nanoemulsion: In Vitro and In Vivo Evaluation. Pharmaceutics 2019, 11, 640.

The journal retracts the article, "Attenuation of Benign Prostatic Hyperplasia by Optimized Tadalafil Loaded Pumpkin Seed Oil-Based Self Nanoemulsion: In Vitro and In Vivo Evaluation" [...].

Optimized bilosome-based nanoparticles enhance cytotoxic and pro-apoptotic activity of costunolide in LS174T colon cancer cells.

Costunolide (COST) is a sesquiterpene lactone that belongs to the germacranolide group, and occurs mainly in Saussurea lappa Clarke. Although COST inhibits the proliferation and metastasis of cancer cells and induces their apoptosis, it suffers poor water solubility and cellular permeability. Therefore, this study aimed to enhance the anti-proliferative activity of COST in LS174T colon cancer cells through its inclusion in bilosomal nanoformulation (COST-BILs). The optimized BIL formula contained cholesterol and Span-85 in a molar ratio of 1:5 as well as bile salt at a molar concentration of 0.5 mM, with entrapment efficiency of 63.4 ± 3.59 % and particle size of 119.7 ± 3.63 nm. The optimized COST-BILs showed a potent cytotoxic effect against LS174T cells with an IC50 of 6.20 µM; meanwhile, raw COST had an IC50 of 15.78 µM. Safety and relative selectivity were confirmed in the normal human colonic epithelial cells (HCoEpC). Cell cycle analysis indicated that both raw COST and COST-BILs significantly increased the fraction of LS174T cells in the sub-G1 phase. This was accompanied by a significant enhancement of early, late, and total apoptosis, as indicated by annexin-V staining. In addition, COST-BILs exhibited more potent activity in up-regulating CASP3, TP53, and BAX, and in down-regulating the expression of BCL2 mRNA as compared to raw COST. Further, the prepared formula enhanced the release of cytochrome C as well as the generation of reactive oxygen species (ROS) and reduced the integrity of mitochondrial membranes. In conclusion, the loading of COST on BILs significantly enhances its pro-apoptotic activity in LS174T cells.

Protein C and protein S deficiencies are associated with increased risk of deep vein thrombosis in pregnant women using oral contraceptives.

BACKGROUND: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). OBJECTIVE: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT). MATERIALS AND METHODS: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed. RESULTS: The study found that women with DVT had significantly lower levels of PC and PS compared with controls ( P  < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS. CONCLUSION: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

Taif Rose Oil Ameliorates UVB-Induced Oxidative Damage and Skin Photoaging in Rats via Modulation of MAPK and MMP Signaling Pathways.

Short-wave UVB (ultraviolet B) causes rapid oxidative damage to the skin. Rose water is obtained mainly from the petals of Rosa damascena Mill. (Rosaceae) and used traditionally to hydrate dry skin and reduce signs of aging. This work aimed at evaluating the possible protective potential of the prepared eco-friendly Taif rose oil nanoemulsion (ROSE-NANO) against UVB-induced photoaging in adult male Wistar rats. Taif rose oil (ROSE) was obtained from R. damascene by classical steam distillation and formulated in emulgel (100 mg/g). In addition, the oil was formulated in ROSE-NANO-loaded emulgel (50 and 100 mg/g) to enhance the effect of ROSE. All prepared formulas were tested topically for their potential protective effect in UV-induced skin photoaging. The obtained results demonstrated that application of ROSE-NANO-loaded emulgel resulted in superior antiaging potency over ROSE emulgel based on histological studies as well as biochemical evaluations via amendment in CAT and SOD activities, decreasing the concentration of the inflammatory markers and preventing collagen fragmentation through reduction of MMP-9 content in fibroblasts. Moreover, a significant decrease in mRNA expression of NF-KB, JNK, ERK1/2, and p38 MAPK genes was observed. In conclusion, the current study provides scientific evidence for the traditional use of rose oil in skin aging. Moreover, the NANO formula showed promising efficacy as a skin photoprotector against UV-induced oxidative damage and skin aging.

Spanlastics as a Potential Platform for Enhancing the Brain Delivery of Flibanserin: In Vitro Response-Surface Optimization and In Vivo Pharmacokinetics Assessment.

Flibanserin was licensed by the United States Food and Drug Administration (FDA) as an oral non-hormonal therapy for pre-menopausal women with inhibited sexual desire disorder. However, it suffers from susceptibility to first-pass metabolism in the liver, low aqueous solubility, and degradation in the acidic stomach environment. Such hurdles result in a limited oral bioavailability of 33%. Thus, the aim of the study was to utilize the principles of nanotechnology and the benefits of an intranasal route of administration to develop a formulation that could bypass these drawbacks. A response-surface randomized D-optimal strategy was used for the formulation of flibanserin spanlastics (SPLs) with reduced size and increased absolute zeta potential. Two numerical factors were studied, namely the Span 60: edge activator ratio (w/w) and sonication time (min), in addition to one categorical factor that deals with the type of edge activator. Particle size (nm) and zeta potential (mV) were studied as responses. A mathematical optimization method was implemented for predicting the optimized levels of the variables. The optimized formulation was prepared using a Span: sodium deoxycholate ratio of 8:2 w/w; a sonication time of 5 min showed particle sizes of 129.70 nm and a zeta potential of -33.17 mV. Further in vivo assessment following intranasal administration in rats showed boosted plasma and brain levels, with 2.11- and 2.23-fold increases (respectively) compared to raw FLB. The aforementioned results imply that the proposed spanlastics could be regarded as efficient drug carriers for the trans-nasal delivery of drugs to the brain.

Hybrid nanoparticulate system of Fluvastatin loaded phospholipid, alpha lipoic acid and melittin for the management of colon cancer.

As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.

Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats.

The aim of this work was to study the healing activity of amitriptyline (Amitrip) in rat diabetic wounds. A nanoformula of the drug was prepared as Amitrip-based biodegradable PEG-PLGA self-assembled nanoparticles (Amitrip-NPs) with a mean particle size of 67.4 nm. An in vivo investigation was conducted to evaluate the wound-healing process of Amitrip-NPs in streptozotocin-induced diabetic rats. Wound contraction was accelerated in rats treated with Amitrip-NPs. Histological examinations confirmed these findings, with expedited remodeling and collagen deposition in the NPs-treated animals. The formula showed anti-inflammatory activities as demonstrated by inhibition of interleukin-6 (IL-6) expression and tumor necrosis factor-α (TNF-α) expression, as well as enhanced expression of interleukin-10 (IL-10). In addition, Amitrip-NPs protected against malondialdehyde (MDA) buildup and superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic exhaustion. The pro-collagen activity of Amitrip-NPs was confirmed by the observed enhancement of hydroxyproline wounded skin content, upregulation of Col 1A1 mRNA expression and immune expression of collagen type IV expression. Further, Amitrip-NPs significantly increased expression transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-B (PDGF-B) and cluster of differentiation 31 (CD31). In conclusion, the developed Amitrip-NPs expedited wound healing in diabetic rats. This involves anti-inflammatory, antioxidant, pro-collagen and angiogenic activities of the prepared NPs. This opens the gate for evaluating the usefulness of other structurally related tricyclic antidepressants in diabetic wounds.

Colon Targeted Eudragit Coated Beads Loaded with Optimized Fluvastatin-Scorpion Venom Conjugate as a Potential Approach for Colon Cancer Therapy: In Vitro Anticancer Activity and In Vivo Colon Imaging.

Preclinical studies suggest that most of statins or 3­hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors possess pleiotropic anticancer activity. The aim of the present work was to investigate the conjugation of the statin fluvastatin (FLV) with scorpion venom (SV), a natural peptide with proven anticancer properties, to enhance FLV cytotoxic activity and prepare colon targeted FLV-SV nanoconjugate beads for management of colon cancer. Response surface design was applied for the optimization of FLV-SV nanoconjugates. FLV-SV particle size and zeta potential were selected as responses. Cytotoxicity of optimized FLV-SV nanoconjugates was carried out on Caco2 cell line. Colon targeted alginate coated Eudragit S100 (ES100) beads for the optimized formula were prepared with the utilization of barium sulfate (BaSO4) as radiopaque contrast substance. Results revealed that optimized FLV-SV nanoconjugates showed a size of 71.21 nm, while the zeta potential was equal to 29.13 mV. Caco2 cells were considerably more sensitive to the FLV-SV formula (half-maximal inhibitory concentration (IC50) = 11.91 µg/mL) compared to SV and FLV used individually, as shown by values of IC50 equal to 30.23 µg/mL and 47.68 µg/mL, respectively. In vivo imaging of colon targeted beads, carried out by employing real-time X-ray radiography, confirmed the efficiency of colon targeted beads. Overall our results indicate that the optimized FLV-SV nanoconjugate loaded alginate coated ES100 beads could represent a promising approach for colon cancer with efficient colon targeting ability.

2-Methoxyestradiol TPGS Micelles Attenuate Cyclosporine A-Induced Nephrotoxicity in Rats through Inhibition of TGF-ß1 and p-ERK1/2 Axis.

The immunosuppressant cyclosporine A (CSA) has been linked to serious renal toxic effects. Although 2-methoxyestradiol (2ME) possesses a wide range of pharmacological abilities, it suffers poor bioavailability after oral administration. The purpose of this study was to evaluate the potential of 2ME loaded D-ɑ-tocopheryl polyethylene glycol succinate (TPGS) micelles to prevent CSA-induced nephrotoxicity in rats. A 2ME-TPGS was prepared and showed particle size of 44.3 ± 3.5 nm with good entrapment efficiency and spherical structures. Male Wistar rats were divided into 5 groups, namely: Control, Vehicle, CSA, CSA + 2ME-Raw, and CSA + 2ME-Nano. CSA was injected daily at a SC dose of 20 mg/kg. Both 2ME-Raw and 2ME-Nano were given daily at oral doses of 5 mg/kg. Treatments continued for three successive weeks. 2ME-TPGS exerted significant protective effects against CSA nephrotoxicity. This was evidenced in ameliorating deterioration of renal functions, attenuation of pathological changes in kidney tissues, exerting significant anti-fibrotic, antioxidant, and anti-inflammatory effects together with significant anti-apoptotic effects. Western blot analyses showed both 2ME-Raw and 2ME-Nano significantly inhibited protein expression of TGF-ß1 and phospho-ERK (p-ERK). It was observed that 2ME-TPGS, in almost all experiments, exerted superior protective effects as compared with 2ME-Raw. In conclusion, 2ME loaded in a TPGS nanocarrier possesses significant protective activities against CSA-induced kidney injury in rats. This is attributable to 2ME anti-fibrotic, antioxidant, anti-inflammatory, and anti-apoptotic activities which are mediated at least partly by inhibition of TGF-ß1/p-ERK axis.