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Alruwaili NK, Zafar A, Imam SS, et al. Int J Nanomedicine. 2020;15:4717–4737. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of isotonicity images in Figure 8. The corresponding author did cooperate with the investigation and images relating to the isontonicity study were provided. However, despite the authors’ assistance, it was still not clear how the images came to be duplicated, and, as we cannot verify the validity of the published work, we are therefore retracting the article. The authors have been informed and do not agree with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

May Bin-Jumah,1 Sadaf Jamal Gilani,2 Mohammed Asadullah Jahangir,3 Ameeduzzafar Zafar,4 Sultan Alshehri,5,6 Mohd Yasir,7 Chandra Kala,8 Mohamad Taleuzzaman,8 Syed Sarim Imam5 1Biology Department, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 2Department of Basic Health Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 3Department of Pharmaceutics, Nibha Institute of Pharmaceutical Sciences, Rajgir, Nalanda 803116, Bihar, India; 4Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Aljouf, Saudi Arabia; 5Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 6College of Pharmacy, Almaarefa University, Riyadh, Saudi Arabia; 7Department of Pharmacy, College of Health Science, Arsi University, Asella, Ethiopia; 8Faculty of Pharmacy, Maulana Azad University, Jodhpur 342802, Rajasthan, IndiaCorrespondence: Sadaf Jamal GilaniDepartment of Basic Health Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaEmail gilanisadaf@gmail.comSyed Sarim ImamDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaEmail sarimimam@gmail.comPurpose: The topically administered drugs through conventional delivery systems have low bioavailability. Henceforth, the present study was designed to prepare and optimize clarithromycin (CTM)-loaded chitosan nanoparticles (CHNPs) to demonstrate the efficacy against microorganisms.Methods: Clarithromycin-loaded chitosan nanoparticles (CTM-CHNPs) were prepared by ionotropic gelation method. The formulation was optimized by box-Behnken design using the formulation variables like CH (A), STPP concentration (B), and stirring speed (C). Their effects were evaluated on the independent variables like particle size (Y1) and entrapment efficiency (Y2). Further, CTM-CHNPs were evaluated for physicochemical parameters, in-vitro drug release, ex-vivo permeation, bioadhesive study, corneal hydration, histopathology, HET-CAM, and antibacterial study.Results: The optimized formulation (CTM-CHNPopt) showed the low particle size (152± 5 nm), which is desirable for ocular delivery. It also showed high encapsulation (70.05%), zeta potential (+35.2 mV), and was found in a spherical shape. The drug release study revealed a sustained drug release profile (82.98± 3.5% in 12 hours) with Korsmeyer peppas kinetic (R2=0.996) release model. It showed a 2.7-fold higher corneal permeation than CTM-solution. CHNPs did not exhibit any sign of damage to excised goat cornea, which is confirmed by hydration, histopathology, and HET-CAM test. It exhibited significant (P< 0.05) higher antibacterial susceptibility than CTM-solution.Conclusion: The finding of the study concluded that CTM-CHNPs can be used for effective management of bacterial conjunctivitis by increasing the precorneal residence time.Keywords: clarithromycin, chitosan, optimization, nanoparticles, HET-CAM, antimicrobial assessment

Nabil K Alruwaili,1 Ameeduzzafar Zafar,1 Syed Sarim Imam,2 Khalid Saad Alharbi,3 Nasser Hadal Alotaibi,4 Sultan Alshehri,2,5 Nabil A Alhakamy,6 Abdulaziz I Alzarea,1 Muhammad Afzal,3 Mohammed Elmowafy1,7 1Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia; 2Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia; 4Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Kingdom of Saudi Arabia; 5College of Pharmacy, Almaarefa University, Riyadh, Kingdom of Saudi Arabia; 6Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 7Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, EgyptCorrespondence: Ameeduzzafar Zafar Email zzafarpharmacian@gmail.comPurpose: The present study was designed to study the gentamycin (GTM)-loaded stimulus-responsive chitosan nanoparticles to treat bacterial conjunctivitis.Methods: GTM-loaded chitosan nanoparticles (GTM-CHNPs) were prepared by ionotropic gelation method and further optimized by 3-factor and 3-level Box–Behnken design. Chitosan (A), sodium tripolyphosphate (B), and stirring speed (C) were selected as independent variables. Their effects were observed on particle size (PS as Y1), entrapment efficiency (EE as Y2), and loading capacity (LC as Y3).Results: The optimized formulation showed the particle size, entrapment efficiency, and loading capacity of 135.2± 3.24 nm, 60.18± 1.65%, and 34.19± 1.17%, respectively. The optimized gentamycin-loaded chitosan nanoparticle (GTM-CHNPopt) was further converted to the stimulus-responsive sol-gel system (using pH-sensitive carbopol 974P). GTM-CHNPopt sol-gel (NSG5) exhibited good gelling strength and sustained release (58.99± 1.28% in 12h). The corneal hydration and histopathology of excised goat cornea revealed safe to the cornea. It also exhibited significant (p< 0.05) higher ZOI than the marketed eye drop.Conclusion: The finding suggests that GTM-CHNP-based sol-gel is suitable for ocular delivery to enhance the corneal contact time and improved patient compliance.Keywords: chitosan, nanoparticles, gentamycin, histopathology, antimicrobial assessment, HET CAM test

Afzal Hussain,1 Mohammad A Altamimi,1 Sultan Alshehri,1 Syed Sarim Imam,1 Faiyaz Shakeel,1 Sandeep Kumar Singh2 1Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Department of Pharmaceutical Sciences, Birla Institute of Technology, Ranchi, Jharkhand, IndiaCorrespondence: Afzal HussainDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Kingdom of Saudi ArabiaTel +966 5 64591584Email afzal.pharma@gmail.comPurpose: This study demonstrated improved transdermal delivery of rifampicin-loaded cationic nanoemulsion gel to treat systemic and cutaneous tuberculosis using capmul, labrasol, and acconon, which exert anti-Mycobacterium activities. This approach enhanced drug permeation across the skin, increased therapeutic efficacy, and reduced dose-related side effects.Methods: Design Expert® was used to optimize formulations (Smix ratio and capmul as independent factors), which were prepared using a slow spontaneous titration method. The optimized nanoemulsion was incorporated into carbopol gel to allow for topical application and comparative assessments. Nanoemulsions and gels were evaluated for size, size distribution, shape, zeta potential, percent spread, viscosity, in vitro hemolysis, in vitro release, and ex vivo skin permeation and deposition. A mechanistic evaluation was performed using scanning electron microscopy. Furthermore, in vivo pharmacokinetic and irritation studies were performed.Results: The optimized cationic nanoemulsion (OCNE-1) was characterized by small particle size (≤ 100 nm), had optimal viscosity, percent spread, zeta potential, and percent drug release, and was hemocompatible. The OCNE-1T gel exhibited higher permeation flux (51.32 ± 0.5 μg/cm2 hr), permeation coefficient (2.566 ± 0.08 cm/hr), drug deposition (994.404 μg/cm2), and enhancement ratio (7.16) than those of the OCNE-1 nanoemulsion or drug solution. Scanning electron microscopy was used to characterize the mechanism of enhanced permeation. An In vivo study showed that the Cmax and area under the curve following transdermal application were 4.34- and 4.74-fold higher than those following oral administration.Conclusion: Transdermal delivery of rifampicin could be a promising alternative to conventional approaches to treat systemic and local tuberculosis, and other bacterial infections.Keywords: systemic and cutaneous tuberculosis, nanoemulsion gel, transdermal delivery, permeation parameters, bioavailability

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Silymarin (SLR) is a poorly water-soluble bioactive compound with a wide range of therapeutic activities. Nanosized silymarin vesicles (F1-F6) were prepared by the solvent evaporation rehydration method. The silymarin vesicles were evaluated for vesicle size, surface charge, entrapment efficiency, and drug release studies. The optimized SLR lipid vesicle (F3) was further modified with the addition of the cationic polymer chitosan. After that, the modified vesicle (F3C1) was assessed for permeation flux, antimicrobial activity, cell viability, and molecular docking studies. The silymarin vesicles showed nanometric size (<250 nm), low polydispersibility index (<0.05), negative surface charge, and high SLR entrapment (85-95 %). The drug release study result demonstrated a maximum drug release of 91.2 ± 2.8 %. After adding chitosan to the surface, there was a significant change in the size, polydispersibility index, surface charge (positive), and encapsulation efficiency. The drug release was found to be prolonged, and the permeation flux was also increased in comparison to free SLR. A comparative antimicrobial result was observed in comparison to the free SLR and standard drug. The cell viability assay also demonstrated a low IC 50 value for F3C1 against the cell line., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats.

In photocatalytic removal of organic pollutants, adsorption and degradation are two important processes that take place. Various instrumental techniques and trapping experiments have been used to identify the reactive species and the mechanism of photodegradation. The present work focuses on investigating the mechanism of photo-induced degradation from the comparative characterization of fresh and used samples, isotherm models, competitive adsorption, and desorption studies of pure and Ag + -modified TiO 2 NPs. The comparative characterizations of fresh and used NPs were carried out with FT-IR, EDX, and XRF analyses after methylene blue (MB) degradation. The Ag + doped TiO 2 used in this study was fabricated using simple impregnation technique. The prepared NPs were characterized using techniques including XPS, XRD, SEM/EDX, XRF, UV-DRS, and pH point-zero charge analyses (pH PZC ). The Ag + -modified TiO 2 NPs showed improved efficiency compared to pure TiO 2 NPs using normal compact fluorescent light (CFL). The Langmuir and Freundlich isotherm models were applied to test the adsorption behavior on the surface photocatalysts. The investigational data finest fitted to the Langmuir isotherms model compared to Freundlich model, suggesting the homogeneous monolayer adsorption followed by degradations. The competitive removal of MB in the presence of a photo-generated electrons trapper (Cd 2+ ) was enhanced almost 3-folds (115 mg/L) compared to the removal from a single MB solution (40 mg/L). The characterization of the used samples as well as adsorption in the dark and negligible desorption of used samples support the involvement of the proposed photo-induced degradation mechanism., (© 2023. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Introduction: Triple-negative breast cancer (TNBC) presents unique challenges in diagnosis and treatment. Resveratrol exhibits potential as a therapeutic intervention against TNBC by regulating various pathways such as the PI3K/AKT, RAS/RAF/ERK, PKCδ, and AMPK, leading to apoptosis through ROS-mediated CHOP activationand the expression of DR4 and DR5. However, the clinical efficacy of resveratrol is limited due to its poor biopharmaceutical characteristics and low bioavailability at the tumor site. Nanotechnology offers a promising approach to improving the biopharmaceutical characteristics of resveratrol to achieve clinical efficacy in different cancers. The small dimension (<200 nm) of nanotechnology-mediated drug delivery system is helpful to improve the bioavailability, internalization into the TNBC cell, ligand-specific targeted delivery of loaded resveratrol to tumor site including reversal of MDR (multi-drug resistance) condition., Areas Covered: This manuscript provides a comprehensive discussion on the structure-activity relationship (SAR), underlying anticancer mechanism, evidence of anticancer activity in in-vitro/in-vivo investigations, and the significance of nanotechnology-mediated delivery of resveratrol in TNBC., Expert Opinion: Advanced nano-formulations of resveratrol such as oxidized mesoporous carbon nanoparticles, macrophage-derived vesicular system, functionalized gold nanoparticles, etc. have increased the accumulation of loaded therapeutics at the tumor-site, and avoid off-target drug release. In conclusion, nano-resveratrol as a strategy may provide improved tumor-specific image-guided treatment options for TNBC utilizing theranostic approach.

Silymarin (SL) is a water-insoluble flavonoid used in the treatment of different diseases, but its therapeutic activity is limited due to its low solubility. So, in the present study, SL solid dispersions (SDs) were developed using different carriers like Kollidone VA64 (KL), Soluplus (SP), and Poloxamer 188 (PL) by solvent evaporation (SE), microwave irradiation (MI), and freeze-drying (FD) methods. The phase solubility and saturation solubility studies were assessed to estimate the stability constant as well as the carrier effect. The dissolution studies were performed for prepared SL-SDs (binary and ternary) to select the optimum SL-SDs. The selected SL-SDs (F5, F9) were further characterized for infrared spectroscopy (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM), and X-ray diffraction (XRD). Finally, the comparative cell viability assay (lung cancer cell line) was performed to evaluate the change in activity after the formulation of SDs. The phase solubility and solubility study results displayed marked enhancements in solubility. The dissolution study findings showed significant enhancement in drug release from ternary solid dispersions (F7-F9) > ternary physical mixture (PM3) > binary solid dispersions (F1-F6) > binary physical mixture (PM1, PM2) in comparison to free SL. A greater release was observed from ternary SDs due to the addition of PL in the formulation, which had a synergistic effect on increasing the solubility. IR and NMR spectra revealed no chemical interaction between SL, KL, and PL. DSC, XRD, and SEM all confirmed the transformation of crystalline SL into amorphous SL. The cell viability assay demonstrated significantly enhanced results from ternary solid dispersion (F9) compared to free SL. Based on the study results, it can be said that SL-SDs are an alternative way to deliver drugs orally that can improve solubility and have anti-cancer activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Chrysin (CR) is a water-insoluble drug reported for different therapeutic effects. The microwave irradiation method was used in this study to create a multicomponent inclusion complex (CR-MC) containing CR (drug) and carrier hydroxyl propyl beta cyclodextrin (HP β CD) and L-arginine (LA). The prepared inclusion complex (CR-MC) was evaluated for dissolution study and results were compared with chrysin physical mixture (CR-PM). Further, the samples were assessed for infra-red (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM) and molecular docking. Finally, the cell viability, reactive oxygen species and flow cytometer studies were also assessed to check the potential of the prepared inclusion complex on the human primary glioblastoma cell line ( U87-MG cell). The phase solubility findings revealed a stability constant (773 mol L -1 ) as well as a complexation efficiency of 0.027. The dissolution study displayed a significant increase in CR release from CR-MC (99.03 ± 0.39%) > CR-PM (70.58 ± 1.16%) > pure CR (35.29 ± 1.55%). NMR and IR spectral data revealed no interaction between CR and carriers. SEM and DSC study results revealed the conversion into amorphous form. The molecular docking results illustrated a high docking score, which supports the findings of complex formation. The cell viability, reactive oxygen species, and flow cytometry studies results showed enhanced activity from CR-MC against the tested human primary glioblastoma cell line. From the results it has been observed that chrysin solubility significantly increased after complexation and there in vitro activity also enhanced against cancer cell line., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Silymarin (SIL) is a poorly water-soluble flavonoid reported for different pharmacological properties. Its therapeutic applications are limited due to poor water solubility. In this study, the solubility of silymarin has been enhanced by preparing freeze-dried binary and ternary complexes using beta cyclodextrin (βCD) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS). The stoichiometry of the drug and the carrier was selected from the phase solubility study. The dissolution study was performed to assess the effect of complexation on the release pattern of SIL. The formation of inclusion complexes was confirmed by different physicochemical studies. Finally, a cell viability assay (MCF 7; breast cancer cell line) was performed to compare the activity with free SIL. The phase solubilization results revealed the formation of a stable complex (binary) with a stability constant and complexation efficiency (CE) value of 288 mol L -1 and 0.045%. The ternary sample depicted a significantly enhanced stability constant and CE value (890 mol L -1 and 0.14%). The release study results showed a marked increase in the release pattern after addition of βCD (alone) in the binary mixture (49.4 ± 3.1%) as well as inclusion complex (66.2 ± 3.2%) compared to free SIL (32.7 ± 1.85%). Furthermore, with the addition of TPGS in SIL-βCD (ternary), the SIL release was found to be significantly enhanced from the SIL ternary mixture (79.2 ± 2.13%) in 120 min. However, fast SIL release was achieved with 99.2 ± 1.7% in 45 min for the SIL ternary complex. IR and NMR spectral analysis results revealed the formation of a stable complex with no drug-polymer interaction. The formation of complexes was also confirmed by the molecular docking study (docking scores of 4.1 and -6.4 kcal/mol). The in vitro cell viability result showed a concentration-dependent activity. The IC 50 value of the SIL ternary complex was found to be significantly lower than that of free SIL. The findings of the study concluded that the prepared SIL inclusion complex can be used as an alternative oral delivery system to enhance solubility, dissolution, and biological activity against the tested cancer cell line., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Rheumatoid arthritis causes irreparable damage to joints. The present research sought to check fustin's anti-arthritic efficacy against the complete Freund's adjuvant-induced arthritis paradigm in animals by altering the inflammatory response. In the rats, complete Freund's adjuvant was used to trigger arthritis and they received fustin at 50 and 100 mg/kg for 21 days. At regular intervals, the hind paw volume and arthritic score were assessed. After the trial period, hematological, antioxidant, pro-inflammatory cytokines, and other biochemical parameters were estimated. Fustin-treated rats showed the down-regulation of hind paw volume, arthritic score, and altered hematological parameters (TLC, DLC (neutrophil, lymphocyte, monocyte, eosinophil, basophil)). Furthermore, fustin significantly mitigates proinflammatory cytokine (reduced interleukin, tumor necrosis factor-a (TNF- α ), IL-6, IL-1 β ), oxidative stress (attenuated malondialdehyde (MDA), catalase (CAT), glutathione (GSH), superoxide dismutase (SOD)), attenuated production of prostaglandin E2 and myeloperoxidase (MPO) and improved nuclear factor erythroid 2-related factor (Nrf2) action. Fustin led to the benefit in arthritis-prone animals elicited by complete Freund's adjuvant via pro-inflammatory cytokine., Competing Interests: The authors declare there are no competing interests., (©2023 Alshehri et al.)

Piperine is an alkaloid, but its therapeutic efficacy is limited due to poor aqueous solubility. In this study, piperine nanoemulsions were prepared using oleic acid (oil), Cremophore EL (surfactant), and Tween 80 (co-surfactant) using the high-energy ultrasonication approach. The optimal nanoemulsion (N2) was further evaluated using transmission electron microscopy, release, permeation, antibacterial, and cell viability studies based on minimal droplet size and maximum encapsulation efficiency. The prepared nanoemulsions (N1-N6) showed a transmittance of more than 95%, a mean droplet size between 105 ± 4.11 and 250 ± 7.4 nm, a polydispersity index of 0.19 to 0.36, and a ζ potential of -19 to -39 mV. The optimized nanoemulsion (N2) showed significantly improved drug release and permeation compared with pure piperine dispersion. The nanoemulsions were stable in the tested media. The transmission electron microscopy image showed a spherical and dispersed nanoemulsion droplet. The antibacterial and cell line results of piperine nanoemulsions were significantly better than the pure piperine dispersion. The findings suggested that piperine nanoemulsions may be a more advanced nanodrug delivery system than conventional ones., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: The effect of europinidin on alcoholic liver damage in rats was examined in this research., Methods: A total of 24 Wistar rats were grouped in the same way into four groups: normal control (normal), ethanol control (EtOH), europinidin low dose (10 mg/kg), and europinidin higher dose (20 mg/kg). The test group rats were orally treated with europinidin-10 and europinidin-20 for 4 weeks, whereas 5 mL/kg distilled water was administered to control rats. In addition, 1 h after the last dose of the above-mentioned oral treatment, 5 mL/kg (i.p.) EtOH was injected to induce liver injury. After 5 h of EtOH treatment, samples of blood were withdrawn for biochemical estimations., Results: Administration of europinidin at both doses restored all of the estimated serum, i.e., liver function tests (ALT, AST, ALP), biochemical test (Creatinine, albumin, BUN, direct bilirubin, and LDH), lipid assessment (TC and TG), endogenous antioxidants (GSH-Px, SOD, and CAT), malondialdehyde (MDA), nitric oxide (NO), cytokines (TGF-β, TNF-α, IL-1β, IL-6, IFN-γ, and IL-12), caspase-3, and nuclear factor kappa B (NF-κB) associated with the EtOH group., Conclusion: The results of the investigation showed that europinidin had favorable effects in rats given EtOH and may have hepatoprotective potential property., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

We attempted to develop green nanoemulsions (ENE1-ENE5) using capryol-C90 (C90), lecithin, Tween 80, and N -methyl-2-pyrrolidone (NMP). HSPiP software and experimentally obtained data were used to explore excipients. ENE1-ENE5 nanoemulsions were prepared and evaluated for in vitro characterization parameters. An HSPiP based QSAR (quantitative structure-activity relationship) module established a predictive correlation between the Hansen solubility parameter (HSP) and thermodynamic parameters. A thermodynamic stability study was conducted under stress conditions of temperature (from -21 to 45 °C) and centrifugation. ENE1-ENE5 were investigated for the influence of size, viscosity, composition, and exposure time on emulsification (5-15 min) on %RE (percent removal efficiency). Eventually, the treated water was evaluated for the absence of the drug using electron microscopy and optical emission spectroscopy. HSPiP program predicted excipients and established the relationship between enoxacin (ENO) and excipients in the QSAR module. The stable green nanoemulsions ENE-ENE5 possessed the globular size range of 61-189 nm, polydispersity index (PDI) of 0.1-0.53, viscosity of 87-237 cP, and ζ potential from -22.1 to -30.8 mV. The values of %RE depended upon the composition, globular size, viscosity, and exposure time. ENE5 showed %RE value as 99.5 ± 9.2% at 15 min of exposure time, which may be due to the available maximized adsorption surface. SEM-EDX (scanning electron microscopy-X-ray dispersive energy mode) and inductively coupled plasma-optical emission spectroscopy (ICP-OES) negated the presence of ENO in the treated water. These variables were critical factors for efficient removal of ENO during water treatment process design. Thus, the optimized nanoemulsion can be a promising approach to treat water contaminated with ENO (a potential pharmaceutical antibiotics)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The primary aim of this study is to develop an economical, stable, and effective heterogeneous catalyst for wastewater remediation via the Fenton oxidation process. For this purpose, Fe 3 O 4 -montmorillonite alginate (FeMA) composite beads were synthesized by entrapping Fe 3 O 4 -montmorillonite in calcium alginate beads. The performance of the catalysts was evaluated via the Fenton degradation of ofloxacin (OFL), an antibiotic that is frequently detected in water bodies. The physiochemical properties of the FeMA composite beads were characterized using X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscope/energy dispersive X-ray (FESEM/EDX), Brunauer-Emmett-Teller (BET) analysis, Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA). FeMA composite beads were found to have a higher surface area, higher porosity, and better thermal stability compared to pristine alginate beads. The composite beads were subsequently used for Fenton degradation of ofloxacin (OFL) in an aqueous solution. The effects of Fe 3 O 4 -montmorillonite loading on alginate, FeMA composite beads dosage, initial solution pH, initial OFL concentration, different oxidants, H 2 O 2 dosage, reaction temperature, and inorganic salts on Fenton degradation of OFL in aqueous solution was investigated. The results revealed that the percentage of OFL degradation reached about 80 % under optimized conditions, while the total organic carbon (TOC) removal reached about 53 %. The entrapment of Fe 3 O 4 -montmorillonite in alginate beads results in less iron ions leaching compared to previous observation, and the efficiency remains constant over the five cycles investigated. The kinetics of the Fenton degradation process are best fitted to the pseudo-first-order kinetic model. It is therefore believed that FeMA composite beads can be a promising material for wastewater remediation via the Fenton oxidation process., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Miconazole nitrate (MN) is a poorly water-soluble and antifungal drug used for fungal infections. The present research work was designed to develop topical MN-loaded bilosomes (BSs) for the improvement of therapeutic efficacy. MZBSs were prepared by using the thin-film hydration method and further optimized by using the Box-Behnken statistical design (BBD). The optimized miconazole bilosome (MZBSo) showed nano-sized vesicles, a low polydispersity index, a high entrapment efficiency, and zeta potential. Further, MZBSo was incorporated into the gel using carbopol 934P and chitosan polymers. The selected miconazole bilosome gel (MZBSoG2) demonstrated an acceptable pH (6.4 ± 0.1), viscosity (1856 ± 21 cP), and spreadability (6.6 ± 0.2 cm 2 ). Compared to MZBSo (86.76 ± 3.7%), MZBSoG2 showed a significantly ( p < 0.05) slower drug release (58.54 ± 4.1%). MZBSoG2 was found to be a non-irritant because it achieved a score of zero (standard score) in the HET-CAM test. It also exhibited significant antifungal activity compared to pure MZ against Candida albicans and Aspergillus niger . The stability study results showed no significant changes after stability testing under accelerated conditions. MZ-loaded gels could serve as effective alternative carriers for improving therapeutic efficacy.

Background: Previously reported data suggest that hibiscetin, isolated from roselle , contains delphinidin-3-sambubioside and cyanidin-3-sambubioside including anthocyanidins and has a broad range of physiological effects. In this study, we aim to analyze the effect of hibiscetin neuroprotective ability in rats against 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD)., Methods: To investigate possible toxicities in animals, oral acute toxicity studies of hibiscetin were undertaken, and results revealed the safety of hibiscetin in animals with a maximum tolerated dose. Wistar rats were divided into four groups ( n = 6); (group-1) treated with normal saline, (group-2) hibiscetin (10 mg/kg) only, (group-3) 3-NPA only, and (group-4) 3-NPA +10 mg/kg hibiscetin. The efficacy of hibiscetin 10 mg/kg was studied with the administration of 3-NPA doses for the induction of experimentally induced HD symptoms in rats. The mean body weight (MBW) was recorded at end of the study on day 22 to evaluate any change in mean body weight. Several biochemical parameters were assessed to support oxidative stress (GSH, SOD, CAT, LPO, GR, and GPx), alteration in neurotransmitters (DOPAC, HVA, 5-HIAA, norepinephrine, serotonin, GABA, and dopamine), alterations in BDNF and cleaved caspase (caspase 3) activity. Additionally, inflammatory markers, i.e., tumor necrosis factor alpha (TNF-α), interleukins beta (IL-1β), and myeloperoxidase (MPO) were evaluated., Results: The hibiscetin-treated group exhibits a substantial restoration of MBW than the 3-NPA control group. Furthermore, 3-NPA caused a substantial alteration in biochemical, neurotransmitter monoamines, and neuroinflammatory parameters which were restored successfully by hibiscetin., Conclusion: The current study linked the possible role of hibiscetin by offering neuroprotection in experimental animal models.

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2- a ]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2 ; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC 50 = 4.33-6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

The effective and preventive treatment of HIV is one of the difficult challenges worldwide. It requires the development of an effective prophylactic strategy to prevent HIV/AIDS. This study aimed to synthesize Cabotegravir (CAB)-biodegradable gold (Au) nanoparticles by using pectin as a reducer and stabilizer. CAB-GNPs were prepared by the slightly modified  Turkevich  method. CAB-GNPs were optimized using Box Behnken design for independent variables gold chloride (A), pectin (B) and pH range (C). The effects of independent variables were observed on particle size (Y 1 ) and encapsulation efficiency (Y 2 ). The results of the study revealed that the optimized nanoparticles (GLN7) had a particle size of 3.9 ± 0.1 nm and encapsulation efficiency of 97.2 ± 3.9%. TEM study showed the spherical shape particles. The in-vitro drug release revealed 62.1 ± 0.5% release of CAB in simulated gastric buffer (pH 1.2) and 45.5 ± 2.8% in physiological buffer (pH 7.4). In-vitro cytotoxicity study and antibacterial activity depicted the safety of the prepared NPs by showing lesser toxicity than pure CAB. From the results, our experimental outcomes concluded that CAB gold nanoparticles composed of pectin may constitute a preferred embodiment for the delivery of CAB., Competing Interests: Conflict of interestNone., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Molecular pharmaceutics play a critical role in the drug delivery system, representing the direct interconnection of drug bioavailability with its molecular form. There is a diversity in the molecular structures by which it affects its properties, such as amorphous form, crystalline form, partialamorphous molecular dispersion, and disordered state. The active pharmaceutical ingredient (API) and the excipients utilized in the formulation process contain various divergent modes used in the formulation process. They include better formulations of any type to obtain good quality pharmaceutical products. This review reveals how the molecular states affect the API and are important in maintaining the quality of dosage forms. Furthermore, the physio-chemical properties of the components and various pharmaceutical approaches employed in the formulation of dosage forms are studied from the point of view of molecular pharmaceutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aβ42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The purpose of this research is to synthesize environmentally friendly nanosorbents for the novel adsorption of diesel range organics (DRO) from contaminated water. Central composite design (CCD) analysis of response surface methodology (RSM) was employed in a model fitting of the variables predicting the adsorption efficiency of Moringa oleifera-functionalized zerovalent iron particles (ZINPs) for the removal of DRO. The effects of the reaction parameters on the response were screened using 2 4 factorial designs to determine the statistically significant independent variables. A quadratic model predicting the DRO adsorption efficiency of ZINPs with an F value of 276.84 (p value < 0.0001) was developed. Diagnostic plots show that the predicted values were in excellent agreement with actual experimental values (R 2  = 0.99). The maximum percentage removal of DRO of 92.6% was achieved after optimization, using the synthesized ZINPs after 8 h of contact between DRO substrates and ZINPs at pH of 8, the temperature of 25 °C, with an adsorbent dosage of 2 g/L and at composite desirability of 1. Characterization of ZINPs revealed the formation of quasi nanospheres and nanocubes with an average particle diameter of 50.9 ± 9.7, a crystallite size of 15.31 nm, a crystallinity index of 32.47% and a pore width of 75.69-88.59 nm. The adsorption equilibrium data modelling of ZINPs for adsorption of DRO was best described by Langmuir isotherm with the maximum monolayer coverage capacity of 7.194 mg/g. The separation factor [Formula: see text], indicated favourable adsorption. The adsorption kinetic data were consistent with pseudo-second-order kinetics indicating probable chemisorption., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We evaluated mechanistic insights into luteolin (LUT)-loaded elastic liposomes (OLEL1) permeated across rat skin. HSPiP software-based parameters, thermal analysis, infrared analysis, and morphological evaluations were employed to understand mechanistic observations of drug permeation and deposition. HSPiP provided HSP values (δ d , δ p , and δ h ) of OLEL1 (based on composition), LUT, excipients, and rat skin (literature value and by-default value). Rat skin was studied via Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), fluorescence microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) studies. The δ d and δ h estimation of the skin and phosphatidylcholine showed close relation in terms of δ d and δ h . Similarly, OLEL1 and the skin might interact with each other mainly through δ d and δ p forces as evidenced by the predicted values. The untreated skin showed characteristic stretching and vibrations as compared to lower frequencies caused by OLEL1. DSC showed changes in the thermal behavior of the skin after OLEL1 treatment as compared to the untreated skin. Visualization of these changes was evident under fluorescence microscopy and SEM for confirmed substantial reversible surface perturbation of the skin protein layer for improved vesicle permeation and subsequent internalization with the inner skin matrix. The AFM study confirmed the nanoscale surface roughness variation caused substantially by OLEL1 and OLEL1 placebo as compared to the untreated control and drug solution. Thus, the study clearly demonstrated mechanistic insights into LUT-loaded vesicles across rat skin for enhanced permeation and drug deposition., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Contaminated wastewater released from hospital, domestic, and industrial sources is a major challenge to aquatic animals and human health. In this study, we addressed removal of erythromycin (ERN) from contaminated water employing water/ethanol/Transcutol/Labrafil M 1944 CS (LabM) green nanoemulsions as a nanocarrier system. ERN is a major antibiotic contaminant harming aquatic and human lives. Green nanoemulsions were prepared and evaluated for size, size distribution (measuring polydispersity index), stability, zeta potential, refractive index, and viscosity. Transmission electron microscopy (TEM) was used to visualize morphological behavior. The treated-water was analyzed for ERN by the spectroscopy, scanning electron microscopy-energy-dispersive X-ray analysis mode (SEM-EDX), and inductively coupled plasma-optical emission spectroscopy (ICP-OES) techniques. We studied factors (composition, size, viscosity, and time of exposure) affecting removal efficiency (%RE). The obtained green nanoemulsions (ENE1-ENE5) were stable and clear (<180 nm). ENE5 had the smallest size (58 nm), a low polydispersity index value (0.19), optimal viscosity (∼121.7 cP), and a high negative zeta potential value (-25.4 mV). A high %RE value (98.8%) was achieved with a reduced size, a high water amount, a low Capryol 90 content, and optimal viscosity as evidenced by the obtained results. Moreover, contact time had insignificant effect on %RE. UV-vis spectroscopy, SEM-EDX, and ICP-OES confirmed the absence of ERN from the treated water. Conclusively, ERN can easily be removed from polluted water employing green nanoemulsions prepared from the optimized excipients, and evaluated characteristics., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The work aimed to enhance chrysin (CHR) water solubility, dissolution, and in vitro antibacterial as well as cell viability. Chrysin binary, as well as ternary inclusion complex, were prepared using the spray drying method. The influence of an auxiliary component (poloxamer; PLX) was also assessed after being incorporated into the chrysin HP βCD complex (CHR-BC) and formed as a chrysin ternary complex (CHR-TC). The phase solubility investigation was carried out in order to assess the complexation efficiency and stability constant. The samples were assessed for the dissolution test, physicochemical evaluation, antibacterial activity, and cell viability tests were also assessed. The results of the phase solubility investigation showed that the stability constant for the binary system (268 M -1 ) was lower than the ternary system (720 M -1 ). The complex stability was validated by the greater stability constant value. The dissolution results showed that pure CHR had a limited release of 32.55 ± 1.7% in 60 min, while prepared CHR-TC and CHR-BC both demonstrated maximum CHR releases of 99.03 ± 2.34% and 71.95 ±2.1%, respectively. The dissolution study's findings revealed that the release of CHR was much improved over that of pure CHR. A study using a scanning electron microscope showed that CHR-TC contains more agglomerated and amorphous components. The higher conversion of crystalline CHR into an amorphous form is responsible for the structural alterations that are observed. After complexation, the distinctive peaks of pure CHR changed due to the complexation with HP βCD and PLX. The antimicrobial and cell viability results revealed improved antimicrobial activity as well as a lower IC50 value than pure CHR against the tested anticancer cell line (MCF7).

Abstract: Persistent pulmonary hypertension of the newborn (PPHN) is a condition caused by failure of pulmonary vascular adaptation at birth, resulting in severe hypoxia. Several therapeutic modalities are being tried in developing countries where established therapies (inhaled nitric oxide and extracorporeal membrane oxygenation) are widely unavailable. This study aimed to assess the efficacy of milrinone versus sildenafil as available alternative therapeutics in treating PPHN. Forty neonates (&gt;34 weeks) admitted to neonatal intensive care units with evidence of PPHN were randomly allocated to receive either oral sildenafil (0.5-2 mg/kg/6 hours) or intravenous milrinone (0.25-0.75 mic/kg/min). Primary outcomes included improvements in systolic pulmonary artery pressure and oxygen saturation index (OSI) at 24 and 48 hours after treatment. Secondary outcomes included the duration of hospitalization and mechanical ventilation. The ClinicalTrials identifier is NCT04391478. Both groups showed significant improvement in the post-treatment hemodynamic variables compared with pretreatment levels ( P &lt; 0.05 for all parameters). Systolic pulmonary artery pressure and OSI values significantly improved in both study groups compared with baseline ( P &lt; 0.001). The 24-hour and 48-hour post-treatment OSI values were much lower in the milrinone group than those in the sildenafil group ( P &lt; 0.05). The length of hospital stay was significantly shorter in the milrinone group than that in the sildenafil group ( P &lt; 0.05). There were no significant differences in the duration of mechanical ventilation, incidence of intracranial hemorrhage and pulmonary hemorrhage, or mortality between the 2 groups ( P &gt; 0.05). In conclusion, milrinone and sildenafil are effective and well-tolerated in neonates with PPHN, particularly when inhaled nitric oxide and extracorporeal membrane oxygenation are not available. Milrinone is superior to sildenafil in improving oxygenation without lowering blood pressure parameters., Competing Interests: We confirm that this work is original and has neither been published and nor is it currently under consideration for publication elsewhere. There are no prior publications or submissions with any overlapping information, including studies and patients. The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Among women, breast cancer (B·C.) is a common form of cancer that can strike either developed or developing countries. In addition to pregnancy-related variables, hormone therapy lifestyle factors (e.g., physical inactivity, smoking, and alcohol use) may all influence the progression of B·C. The creation of anti-B·C. medication carriers with better stability, controlled and targeted administration, and the goal of minimizing unwanted effects has taken a lot of time and effort. Naturally generated biopolymers-based pharmaceutical delivery techniques have attracted attention for their potential use in treating B·C. It's been shown that natural polymers can deliver high medication concentrations to the desired place and provide prolonged release of pharmaceuticals useful in treating B.C. Alginate is one of the most commonly used drug carriers for delayed and targeted release. In present review will discuss the utilization of sodium alginate as an carrier of anticancer drug, such as paclitaxel, doxorubicin, tamoxifen, curcumin, and others., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The clinical application of phytochemicals such as thymoquinone (THQ) is restricted due to their limited aqueous solubility and oral bioavailability. Developing mucoadhesive nanocarriers to deliver these natural compounds might provide new hope to enhance their oral bioavailability. Herein, this investigation aimed to develop THQ-loaded lipid-polymer hybrid nanoparticles (THQ-LPHNPs) based on natural polymer chitosan. THQ-LPHNPs were fabricated by the nanoprecipitation technique and optimized by the 3-factor 3-level Box−Behnken design. The optimized LPHNPs represented excellent properties for ideal THQ delivery for oral administration. The optimized THQ-LPHNPs revealed the particles size (PS), polydispersity index (PDI), entrapment efficiency (%EE), and zeta potential (ZP) of <200 nm, <0.25, >85%, and >25 mV, respectively. THQ-LPHNPs represented excellent stability in the gastrointestinal milieu and storage stability in different environmental conditions. THQ-LPHNPs represented almost similar release profiles in both gastric as well as intestinal media with the initial fast release for 4 h and after that a sustained release up to 48 h. Further, the optimized THQ-LPHNPs represent excellent mucin binding efficiency (>70%). Cytotoxicity study revealed much better anti-breast cancer activity of THQ-LPHNPs compared with free THQ against MDA-MB-231 and MCF-7 breast cancer cells. Moreover, ex vivo experiments revealed more than three times higher permeation from the intestine after THQ-LPHNPs administration compared to the conventional THQ suspension. Furthermore, the THQ-LPHNPs showed 4.74-fold enhanced bioavailability after oral administration in comparison with the conventional THQ suspension. Therefore, from the above outcomes, mucoadhesive LPHNPs might be suitable nano-scale carriers for enhanced oral bioavailability and therapeutic efficacy of highly lipophilic phytochemicals such as THQ.

In individuals with sepsis-related neurodegenerative illness, sleep and circadian rhythm disturbance are common. The alteration in genomic expression linked with the immune-directed oxidative stress-inflammatory axis is thought to cause these individuals' abnormal sleep. On the other hand, sleep is linked to normal brain activity through common neurotransmitter systems and regulatory mechanisms. Ailments (ranging from cognitive to metabolic abnormalities) are seldom related to aberrant sleep that is made worse by sleep disturbance, which throws off the body's sleep-wake cycle. PubMed/Springer link /Public library of science/ScienceDirect/ Mendeley/Medline and Google Scholar were used to find possibly relevant studies. For the literature search, many keywords were considered, both individually and in combination. 'Sepsis,' 'Epidemiology of sepsis,' 'Sepsis-related hyper inflammation,' 'Relationship of sepsis-associated clock gene expression and relationship of inflammation with the reprogramming of genetic alterations' were some of the key terms utilized in the literature search. Our main objective is to understand better how traumatic infections during sepsis affect CNS processes, particularly sleep, by investigating the pathobiology of circadian reprogramming associated with immune-directed oxidative stress-inflammatory pathway responsive gene expression and sleep-wake behaviour in this study., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The nano-drug delivery system has gained greater acceptability for poorly soluble drugs. Alogliptin (ALG) is a FDA-approved oral anti-hyperglycemic drug that inhibits dipeptidyl peptidase-4. The present study is designed to prepare polymeric ALG nanoparticles (NPs) for the management of diabetes. ALG-NPs were prepared using the nanoprecipitation method and further optimized by Box−Behnken experimental design (BBD). The formulation was optimized by varying the independent variables Eudragit RSPO (A), Tween 20 (B), and sonication time (C), and the effects on the hydrodynamic diameter (Y1) and entrapment efficiency (Y2) were evaluated. The optimized ALG-NPs were further evaluated for in vitro release, intestinal permeation, and pharmacokinetic and anti-diabetic activity. The prepared ALG-NPs show a hydrodynamic diameter of between 272.34 nm and 482.87 nm, and an entrapment efficiency of between 64.43 and 95.21%. The in vitro release data of ALG-NPs reveals a prolonged release pattern (84.52 ± 4.1%) in 24 h. The permeation study results show a 2.35-fold higher permeation flux than pure ALG. ALG-NPs exhibit a significantly (p < 0.05) higher pharmacokinetic profile than pure ALG. They also significantly (p < 0.05) reduce the blood sugar levels as compared to pure ALG. The findings of the study support the application of ALG-entrapped Eudragit RSPO nanoparticles as an alternative carrier for the improvement of therapeutic activity.

In this study, moxifloxacin (MX)-loaded bilosome (BS) in situ gel was prepared to improve ocular residence time. MX-BSs were prepared using the thin-film hydration method. They were optimized using a Box−Behnken design (BBD) with bile salt (A, sodium deoxycholate), an edge activator (B, Cremophor EL), and a surfactant (C, Span 60) as process variables. Their effects were assessed based on hydrodynamic diameter (Y1), entrapment efficacy (Y2), and polydispersity index (Y3). The optimized formulation (MX-BSop) depicted a low hydrodynamic diameter (192 ± 4 nm) and high entrapment efficiency (76 ± 1%). Further, MX-BSop was successfully transformed into an in situ gel using chitosan and sodium alginate as carriers. The optimized MX-BSop in situ gel (MX-BSop-Ig4) was further evaluated for gelling capacity, clarity, pH, viscosity, in vitro release, bio-adhesiveness, ex vivo permeation, toxicity, and antimicrobial properties. MX-BSop-Ig4 exhibited an optimum viscosity of 65.4 ± 5.3 cps in sol and 287.5 ± 10.5 cps in gel states. The sustained release profile (82 ± 4% in 24 h) was achieved with a Korsmeyer−Peppas kinetic release model (R2 = 0.9466). Significant bio-adhesion (967.9 dyne/cm2) was achieved in tear film. It also exhibited 1.2-fold and 2.8-fold higher permeation than MX-Ig and a pure MX solution, respectively. It did not show any toxicity to the tested tissue, confirmed by corneal hydration (77.3%), cornea histopathology (no internal changes), and a HET-CAM test (zero score). MX-BSop-Ig4 exhibited a significantly (p < 0.05) higher antimicrobial effect than pure MX against Staphylococcus aureus and Escherichia coli. The findings suggest that bilosome in situ gel is a good alternative to increase corneal residence time, as well as to improve therapeutic activity.

Objectives : Malvidin, a dietary anthocyanin can be a potent drug for the treatment of neuronal toxicity. The investigation was aimed to study the antioxidant role of malvidin against aluminum chloride (AlCl 3 )-induced neurotoxicity in rats. Methods : To evaluate the neuroprotective role of malvidin, the rats were divided into four different groups: group I received saline, group II received AlCl 3 , and groups III and IV were administered with 100 and 200 mg/kg malvidin after AlCl 3 for 60 days. During the evaluation period, all the groups were subjected to a behavioral test. On the 61st day of the study, rat brains were removed and used for a neurochemical assay. Results : From the present study, malvidin ameliorated the effects of AlCl 3 on behavioral parameters. Biochemical investigation revealed that oral treatment of malvidin shows neuroprotective effects through regulation of antioxidant levels and neuroinflammation in the AlCl 3 -exposed rats. Conclusion : The results indicate that malvidin possesses antioxidant activity via acetylcholinesterase inhibition and regulation of oxidative stress in neuronal cells. Hence, malvidin could be a potential drug in correcting Alzheimer's disease., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Lung cancer is the dominant emerging factor in cancer-related mortality around the globe. Therapeutic interventions for lung cancer are not up to par, mainly due to reoccurrence/relapse, chemoresistance, and late diagnosis. People are currently interested in miRNAs, which are small double-stranded (20-24 ribonucleotides) structures that regulate molecular targets (tumor suppressors, oncogenes) involved in tumorigeneses such as cell proliferation, apoptosis, metastasis, and angiogenesis via post-transcriptional regulation of mRNA. Many studies suggest the emerging role of miRNAs in lung cancer diagnostics, prognostics, and therapeutics. Therefore, it is necessary to intensely explore the miRNOME expression of lung tumors and the development of anti-cancer strategies. The current review focuses on the therapeutic, diagnostic, and prognostic potential of numerous miRNAs in lung cancer.

The fustin plant-derived bioflavonoid obtained from a common plant known as lacquer tree from family Anacardiaceae, formally known as Rhus verniciflua Stokes, is known to exert a variety of therapeutic properties. The current investigation proved the anti-ulcerative property of fustin on ethanol-induced gastric ulcers in an experimental animal model. The fustin 50 and 100 mg/kg was studied in an experimental rat model by performing an 8 day protocol. The ulcer index, pH, total acidic content, and biochemical parameters such as glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT), malondialdehyde (MDA), interleukin-1β, prostaglandin E-2, tumor necrosis factor-α (TNF-α), myeloperoxidase, and nitric oxide (NO) in serum were measured. The gastric parameter such as ulcer index, pH, and acidic content was maintained in the fustin groups compared to the ethanol control group. Clinical presentation of gastric ulcers includes a significant increase in serum levels, GSH, SOD, and CAT and decreased MDA, TNF-α, interleukin-1β, and prostaglandin E-2 parameters in contrast to normal groups. The treatment regimen with fustin has significantly restored all serum parameters in test groups. The current study helps to develop reasonable phytochemical options for the innervations of chemical-induced gastric ulcers., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.

The present research work was designed to prepare Azithromycin (AM)-loaded nano lipid carriers (NLs) for ocular delivery. NLs were prepared by the emulsification-homogenization method and further optimized by the Box Behnken design. AM-NLs were optimized using the independent constraints of homogenization speed (A), surfactant concentration (B), and lipid concentration (C) to obtain optimal NLs (AM-NLop). The selected AM-NLop was further converted into a sol-gel system using a mucoadhesive polymer blend of sodium alginate and hydroxyl propyl methyl cellulose (AM-NLopIG). The sol-gel system was further characterized for drug release, permeation, hydration, irritation, histopathology, and antibacterial activity. The prepared NLs showed nano-metric size particles (154.7 ± 7.3 to 352.2 ± 15.8 nm) with high encapsulation efficiency (48.8 ± 1.1 to 80.9 ± 2.9%). AM-NLopIG showed a more prolonged drug release (98.6 ± 4.6% in 24 h) than the eye drop (99.4 ± 5.3% in 3 h). The ex vivo permeation result depicted AM-NLopIG, AM-IG, and eye drop. AM-NLopIG exhibited significant higher AM permeation (60.7 ± 4.1%) than AM-IG (33.46 ± 3.04%) and eye drop (23.3 ± 3.7%). The corneal hydration was found to be 76.45%, which is within the standard limit. The histopathology and HET-CAM results revealed that the prepared formulation is safe for ocular use. The antibacterial study revealed enhanced activity from the AM-NLopIG.

Apigenin (AGN) is a potent phytochemical with strong antioxidant and anticancer potential. But its therapeutic efficacy is limited due to its high lipophilic characteristics. Therefore, the present investigation aimed to develop AGN-loaded polymer-lipid hybrid nanoparticles (AGN-PLHNPs). Herein, we successfully developed AGN-PLHNPs and optimized them by a 33-Box-Behnken de-sign. The poly (lactic-co-glycolic acid) (PLGA; coded as F1), phospholipon 90 G (PL-90G; coded as F2), and poloxamer 188 (P-188; coded as F3) were considered as the independent factors while particle size (PS; coded as R1), entrapment efficiency (%EE; R2), and cumulative drug release (%CDR; R3) were selected as dependent responses. The average PS, %EE, and %CDR of the AGN-PLHNPs were observed in the range of 101.93 nm to 175.26 nm, 58.35% to 81.14%, and 71.21% to 93.31%, respectively. The optimized AGN-PLHNPs revealed better homogeneity (poly-dispersity index < 0.2) and colloidal stability with high zeta potential (>25 mV). It also exhibited fast release in the initial 4 h after that sustained release up to 48 h of study. Moreover, the results of both DPPH as well as ABTS assays revealed significant improvement in the antioxidant activity. Furthermore, the optimized AGN-PLHNPs exhibited enhanced cytotoxicity efficacy against MCF-7 as well as MDA-MB-231 breast cancer cell lines.

Piperine (PPN), one of the most investigated phytochemicals, is known to have excellent therapeutic efficacy against a variety of ailments including breast cancer. However, its physicochemical properties such as poor aqueous solubility restrict its clinical application. Therefore, the present investigation was designed to develop PPN encapsulated lipid polymer hybrid nanoparticles (PPN-LPHNPs) to overcome the limitation. The developed PPN-LPHNPs were optimized by the three-factor, three-level Box−Behnken design (33-BBD). The optimized PPN-LPHNPs were then evaluated for their drug release profile, cytotoxicity assay against MDA-MB-231 and MCF-7 cells, and gastrointestinal stability as well as colloidal stability. In addition, the optimized PPN-LPHNPs were evaluated for ex vivo intestinal permeation and in vivo pharmacokinetic in albino Wistar rats. As per the results, the optimized PPN-LPHNPs showed a small average particles size of <160 nm with a low (<0.3) polydispersity index, and highly positive surface charge (>+20 mV). PPN-LPHNPs revealed excellent gastrointestinal as well as colloidal stability and sustained release profiles up to 24 h. Furthermore, PPN-LPHNPs revealed excellent cytotoxicity against both MDA-MB-231 and MCF-7 cancer cells compared to the free PPN. Moreover, animal studies revealed that the PPN-LPHNPs exhibited a 6.02- and 4.55-fold higher intestinal permeation and relative oral bioavailability, respectively, in comparison to the conventional PPN suspension. Thus, our developed LPHNPs present a strong potential for improved delivery of PPN.

A cephalexin (CEP) self-nanoemulsifying drug delivery system (SNEDDS) was developed in this study to improve the drug's oral administration. The CEP-SNEDDS was made utilizing an aqueous titration method employing Lauroglycol 90, Poloxamer 188, and Transcutol-HP. Box-Behnken design (BBD) with three factors at three levels was used for optimization, and their impacts on globule size (nm), transmittance (percent), and emulsification time (s) were assessed. The optimized formulation (Opt-F3) was further tested for zeta potential, refractive index, percent transmittance, thermodynamic stability, in-vitro release, ex vivo permeability, antibacterial activity, and bioavailability. The chosen formulation (Opt-F3) had a globule size of 87.25 ± 3.16 nm, PDI of 0.25, zeta potential of -24.37 mV, self-emulsification duration of 52 ± 1.7 s, and percentage transmittance of 99.13 ± 1.5%, viscosity of 96.26 ± 2.72 cp, and refractive index of 1.29 ± 0.1. It showed a sustained release profile (94.28 ± 5.92 percent in 24 h). The Opt-F3 formulation had 3.95 times the permeability of CEP-dispersion. In comparison to CEP-dispersion, it also demonstrated greater antibacterial efficacy against tested Gram-positive and Gram-negative pathogens. The oral bioavailability of Opt-F3 is 3.48 times higher than that of CEP-dispersion, according to an in-vivo investigation. It has been determined that the prepared CEP-SNEDDS may be an advantageous carrier for CEP delivery.

Diabetes is one of the world's most important public health issues, impacting both public health and socioeconomic advancement; moreover, current pharmacotherapy is still insufficient. The natural flavonoid rosinidin has a long history of use in pharmaceuticals and nutritional supplements, but its role in diabetes has been unknown. The current study was intended to confirm the anti-diabetic activity of rosinidin in our laboratory setting, along with its mechanism. Streptozotocin (60 mg/kg, ip) treatment used to induce type II diabetes in rats and the test medication rosinidin was then administered orally (at doses of 10 mg/kg and 20 mg/kg) for biochemical and histopathological analysis. Treatment with rosinidin reduced negative consequences of diabetes. Rosinidin exerted a protective effect on a number of characteristics, including anti-diabetic responses (lower blood glucose, higher serum insulin and improved pancreatic function) and molecular mechanisms (favorable effects on lipid profiles, total protein, albumin, liver glycogen, proinflammatory cytokine, antioxidant and oxidative stress markers, AST, ALT and urea). Furthermore, the improved pancreatic architecture observed in tissues substantiated the favourable actions of rosinidin in STZ-induced diabetic rats.

Multiple sclerosis is a chronic autoimmune disorder that leads to the demyelination of nerve fibers, which is the major cause of non-traumatic disability all around the world. Herbal plants Nepeta hindustana L., Vitex negundo L., and Argemone albiflora L., in addition to anti-inflammatory and anti-oxidative effects, have shown great potential as neuroprotective agents. The study was aimed to develop a neuroprotective model to study the effectiveness of herbal plants ( N. hindustana , V. negundo , and A. albiflora ) against multiple sclerosis. The in vivo neuroprotective effects of ethanolic extracts isolated from N. hindustana , V. negundo , and A. albiflora were evaluated in lipopolysaccharides (LPS) induced multiple sclerosis Wistar rat model. The rat models were categorized into seven groups including group A as normal, B as LPS induced diseased group, while C, D, E, F, and G were designed as treatment groups. Histopathological evaluation and biochemical markers including stress and inflammatory (MMP-6, MDA, TNF-α, AOPPs, AGEs, NO, IL-17 and IL-2), antioxidant (SOD, GSH, CAT, GPx), DNA damage (Isop-2α, 8OHdG) as well as molecular biomarkers (RAGE, Caspase-8, p38) along with glutamate, homocysteine, acetylcholinesterase, and myelin binding protein (MBP) were investigated. The obtained data were analyzed using SPSS version 21 and GraphPad Prism 8.0. The different extract treated groups (C, D, E, F, G) displayed a substantial neuroprotective effect regarding remyelination of axonal terminals and oligodendrocytes migration, reduced lymphocytic infiltrations, and reduced necrosis of Purkinje cells. The levels of stress, inflammatory, and DNA damage markers were observed high in the diseased group B, which were reduced after treatments with plant extracts. The antioxidant activity was significantly reduced in diseased induced group B, however, their levels were raised after treatment with plant extract. Group F (a mélange of all the extracts) showed the most significant change among all other treatment groups (C, D, E, G). The communal dose of selected plant extracts regulates neurodegeneration at the cellular level resulting in restoration and remyelination of axonal neurons. Moreover, 400 mg/kg dose of three plants in conjugation (Group F) were found to be more effective in restoring the normal activities of all measured parameters than independent doses (Group C, D, E) and is comparable with standard drug nimodipine (Group G) clinically used for the treatment of multiple sclerosis. The present study, for the first time, reported the clinical evidence of N. hindustana , V. negundo , and A. albiflora against multiple sclerosis and concludes that all three plants showed remyelination as well neuroprotective effects which may be used as a potential natural neurotherapeutic agent against multiple sclerosis.

We prepared apigenin (APG)-loaded bilosomes (BLs) and evaluated them for vesicle size, zeta-potential and encapsulation efficiency. The formulations were prepared with cholesterol (CHL), sodium deoxy cholate (SDC), Tween 80 (T80) and phosphatidylcholine (PC) using solvent evaporation method. The prepared formulations showed the optimum result was coated with much mucoadhesive polymer chitosan (CH, 0.25 and 0.5% w/v). The chitosan-coated bilosomes (CH-BLs) were further evaluated for surface morphology, drug−polymer interaction, mucoadhesion, permeation, antimicrobial activity and cell viability. The prepared APG-BLs showed nano-metric size (211 ± 2.87 nm to 433 ± 1.98 nm), polydispersibility index <0.5, negative zeta potential (−15 to −29 mV) and enhanced encapsulation efficiency (69.5 ± 0.93 to 81.9 ± 1.3%). Based on these findings, selected formulation (F2) was further coated with chitosan and showed a marked increase in vesicle size (298 ± 3.56 nm), a positive zeta potential (+17 mV), superior encapsulation efficiency (88.1 ± 1.48%) and improved drug release (69.37 ± 1.34%). Formulation F2C1 showed significantly enhanced permeation and mucoadhesion (p < 0.05) compared to formulation F2 due to the presence of CH as a mucoadhesive polymer. The presence of CH on the surfaces of BLs helps to open the tight membrane junctions and leads to enhanced permeation. A TEM study revealed non-aggregated smooth surface vesicles. The antimicrobial and cell viability assessment revealed better effects in terms of zone of inhibition and cell line assessment against two different cancer cell line. From the study, it can be concluded that APG-CHBLs could be a superior alternative to conventional delivery systems.

In the present research study, we formulate bilosomes (BMs) of diclofenac (DC) for oral delivery for enhancement of therapeutic efficacy (anti-inflammatory disease). The BMS were prepared by thin film hydration method and optimized by Box−Behnken design (BBD) using cholesterol (A), lipid (B), surfactant (C), and bile salt (D) as formulation factors. Their effects were evaluated on vesicle size (Y1) and entrapment efficacy (Y2). The optimized DC-BMs-opt showed a vesicle size of 270.21 ± 3.76 nm, PDI of 0.265 ± 0.03, and entrapment efficiency of 79.01 ± 2.54%. DSC study result revealed that DC-BMs-opt exhibited complete entrapment of DC in BM matrix. It also depicted significant enhancement (p < 0.05) in release (91.82 ± 4.65%) as compared to pure DC (36.32 ± 4.23%) and DC-liposomes (74.54 ± 4.76%). A higher apparent permeability coefficient (2.08 × 10−3 cm/s) was also achieved compared to pure DC (6.6 × 10−4 cm/s) and DC-liposomes (1.33 × 10−3 cm/s). A 5.21-fold and 1.43-fold enhancement in relative bioavailability was found relative to pure DC and DC liposomes (DC-LP). The anti-inflammatory activity result showed a significant (p < 0.05) reduction of paw edema swelling compared to pure DC and DC-LP. Our findings revealed that encapsulation of DC in BMs matrix is a good alternative for improvement of therapeutic efficacy.

Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder affecting females in their reproductive age. The early diagnosis of PCOS is complicated and complex due to overlapping symptoms of this disease. The most accepted diagnostic approach today is the Rotterdam Consensus (2003), which supports the positive diagnosis of PCOS when patients present two out of the following three symptoms: biochemical and clinical signs of hyperandrogenism, oligo, and anovulation, also polycystic ovarian morphology on sonography. Genetic variance, epigenetic changes, and disturbed lifestyle lead to the development of pathophysiological disturbances, which include hyperandrogenism, insulin resistance, and chronic inflammation in PCOS females. At the molecular level, different proteins and molecular and signaling pathways are involved in disease progression, which leads to the failure of a single genetic diagnostic approach. The genetic approach to elucidate the mechanism of pathogenesis of PCOS was recently developed, whereby four phenotypic variances of PCOS categorize PCOS patients into classic, ovulatory, and non-hyperandrogenic types. Genetic studies help to identify the root cause for the development of this PCOS. PCOS genetic inheritance is autosomal dominant but the latest investigations revealed it as a multigene origin disease. Different genetic loci and specific genes have been identified so far as being associated with this disease. Genome-wide association studies (GWAS) and related genetic studies have changed the scenario for the diagnosis and treatment of this reproductive and metabolic condition known as PCOS. This review article briefly discusses different genes associated directly or indirectly with disease development and progression.