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In the current study, the toxic effects of gefitinib-loaded solid lipid nanoparticles (GFT-loaded SLNs) upon human breast cancer cell lines (MCF-7) were investigated. GFT-loaded SLNs were prepared through a single emulsification–evaporation technique using glyceryl tristearate (Dynasan™ 114) along with lipoid® 90H (lipid surfactant) and Kolliphore® 188 (water-soluble surfactant). Four formulae were developed by varying the weight of the lipoid™ 90H (100–250 mg), and the GFT-loaded SLN (F4) formulation was optimized in terms of particle size (472 ± 7.5 nm), PDI (0.249), ZP (−15.2 ± 2.3), and EE (83.18 ± 4.7%). The optimized formulation was further subjected for in vitro release, stability studies, and MTT assay against MCF-7 cell lines. GFT from SLNs exhibited sustained release of the drug for 48 h, and release kinetics followed the Korsmeyer–Peppas model, which indicates the mechanism of drug release by swelling and/or erosion from a lipid matrix. When pure GFT and GFT–SLNs were exposed to MCF-7 cells, the activities of p53 (3.4 and 3.7 times), caspase-3 (5.61 and 7.7 times), and caspase-9 (1.48 and 1.69 times) were enhanced, respectively, over those in control cells. The results suggest that GFT-loaded SLNs (F4) may represent a promising therapeutic alternative for breast cancer. [ABSTRACT FROM AUTHOR]

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study's goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box–Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment. [ABSTRACT FROM AUTHOR]

In the current study, diosmin (DSM)-loaded beta-cyclodextrin (β-CD)-based nanosponges (NSPs) using diphenylcarbonate (DPC) as a cross-linker were prepared. Four different DSM-loaded NSPs (D-NSP1-NSP4) were developed by varying the molar ratio of β-CD: DCP (1:15–1:6). Based on preliminary evaluations, NSPs (D-NSP3) were optimized for size (412 ± 6.1 nm), polydispersity index (PDI) (0.259), zeta potential (ZP) (−10.8 ± 4.3 mV), and drug loading (DL) (88.7 ± 8.5%), and were further evaluated by in vitro release, scanning electron microscopy (SEM), and in vitro antioxidant studies. The NSPs (D-NSP3) exhibited improved free radical scavenging activity (85.58% at 100 g/mL) compared to pure DSM. Dissolution efficiency (%DE) was enhanced to 71.50% (D-NSP3) from plain DSM (58.59%). The D-NSP3 formulation followed the Korsmeyer–Peppas kinetic model and had an n value of 0.529 indicating a non-Fickian and controlled release by diffusion and relaxation. The D-NSP3 showed cytotoxic activity against MCF-7 breast cancer, as evidenced by caspase 3, 9, and p53 activities. According to the findings, DSM-loaded NSPs might be a promising therapy option for breast cancer. [ABSTRACT FROM AUTHOR]

In the current study, lipid-polymer hybrid nanoparticles (LPHNPs) fabricated with lipoid-90H and chitosan, sunitinib malate (SM), an anticancer drug was loaded using lecithin as a stabilizer by employing emulsion solvent evaporation technique. Four formulations (SLPN1–SLPN4) were developed by varying the concentration of chitosan polymer. Based on particle characterization, SLPN4 was optimized with size (439 ± 5.8 nm), PDI (0.269), ZP (+34 ± 5.3 mV), and EE (83.03 ± 4.9%). Further, the optimized formulation was characterized by FTIR, DSC, XRD, SEM, and in vitro release studies. In-vitro release of the drug from SPN4 was found to be 84.11 ± 2.54% as compared with pure drug SM 24.13 ± 2.67%; in 48 h, release kinetics followed the Korsmeyer–Peppas model with Fickian release mechanism. The SLPN4 exhibited a potent cytotoxicity against MCF-7 breast cancer, as evident by caspase 3, 9, and p53 activities. According to the findings, SM-loaded LPHNPs might be a promising therapy option for breast cancer. [ABSTRACT FROM AUTHOR]

A key factor in dosage form development is selection of a suitable solvent for the solubility of drugs. Solubility data of osimertinib (OSM) are scarce in the research literature. In current study, thermodynamic solubility of OSM in eight different pharmaceutically useful solvents namely, water, ethanol, propylene glycol (PG), ethyl acetate (EA), isopropyl myristate (IPM), dichloromethane (DCM), Transcutol-HP (THP), and polyethylene glycol-400 (PEG-400) at the temperature from (298.2 to 318.2) K under air pressure of 0.1 MP were determined. The solid state characterization confirmed no transformation of OSM into polymorphs. The mole-fraction solubility of OSM was obtained greatest in PEG-400 (7.33 × 10−3) and least in water (3.69 × 10−5) at 318.2 K. The solubility data of OSM was regressed by "Apelblat and van't Hoff models" with overall deviations of 1.64 and 2.37%, respectively. Ideal solubility was calculated much higher than experimental solubilities of OSM at different temperatures. The activity coefficients were calculated with the help of ideal solubilities, and found highest molecular interaction between OSM and PEG-400. Thermodynamic parameters confirmed endothermic and entropy driven dissolution in all investigated solvents. • Thermodynamic solubility studies of osimertinib in pharmaceutically useful solvents • Solid state characterization of osimertinib before and after equilibration by DSC and PXRD • Calculation of mole-fraction solubility in all investigated solvents • Calculation of ideal solubility and thermodynamic parameters [ABSTRACT FROM AUTHOR]

Purpose: To develop poly-lactic-co-glycolic acid (PLGA) -based nanoparticles (NPs) for the delivery of sunitinib malate (STM) to colon cancer cells. Methods: Three different formulations (F1 - F3) were developed by nano-precipitation technique using various concentrations of PLGA. The NPs were evaluated for particle size, polydispersity index, zeta potential, drug entrapment, and drug loading, using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Furthermore, in vitro drug release and anticancer studies were carried out on the formulations. Results: Among the three NPs, optimized NP (F3) of STM was chosen for in vitro anti-cancer study against H-29 human colon cancer cells lines based on its particle size (132.9 nm), PDI (0.115), zeta potential (-38.12 mV), entrapment efficiency (52.42%), drug loading (5.24%), and drug release (91.26% in 48 h). A significant anti-cancer activity of the optimized NPs was observed, relative to free STM. Conclusion: These findings suggest that STM-loaded NPs possess significant anti-cancer activity against human colon cancer HT-29 cells lines. [ABSTRACT FROM AUTHOR]

Quercetin is the most abundant antioxidant found in the human diet. Low aqueous solubility of quercetin limits its bioavailability and hence therapeutic effects. Therefore, the aim of the present study was to develop a poly lactide-co-glycolic acid (PLGA) polymer based nanoparticles of quercetin with a view to improve its aqueous solubility and examine the effect on its antioxidant and diuretic properties. Nanoparticles of quercetin were developed by single emulsion-solvent evaporation technique and evaluated in vitro for differential scanning calorimetry (DSC), Fourier transforms infra-red (FTIR) spectroscopy, particle size, polydispersity index and drug entrapment efficiency. Among the five different formulations (F1, F2, F3, F4 and F5), F2 and F3 were optimized with an average particle size of 189 nm and 186 nm and high entrapment values of 86.48%, 83.71%, respectively. SEM images of confirmed that prepared nanoparticles were spherical in shape with a smooth surface. In vitro release and anti-oxidant activity confirmed significant results. Furthermore, its in vivo diuretic activity was much better as compared to pure quercetin. The overall results suggest that PLGA polymer based nanoparticle could be a potential option for quercetin delivery. [ABSTRACT FROM AUTHOR]

Objective: Insulin is a hormone used in the treatment of diabetes mellitus. Multiple injections of insulin every day may causes pain, allergic reactions at injection site, which lead to low patient compliance. The aim of this work was to develop and evaluate an efficient solid lipid nanoparticle (SLN) carrier for oral delivery of insulin. Methods: SLNs were prepared by double emulsion solvent evaporation (w/o/w) technique, employing glyceryltrimyristate (Dynasan 114) as lipid phase and soy lecithin and polyvinyl alcohol as primary and secondary emulsifier, respectively, and evaluatedin vitrofor particle size, polydispersity index (PDI) and drug entrapment. Results: Among the eight different developed formulae (F1–F8), F7 showed an average particle size (99 nm), PDI (0.021), high entrapment of drug (56.5%). The optimized formulation (F7) was further evaluated by FT-IR, DSC, XRD,in vitrorelease, permeation, stability, bioavailability and pharmacological studies. Insulin-loaded SLNs showed better protection from gastrointestinal environment as evident from the relative bioavailability, which was enhanced five times as compared to the insulin solution. A significant enhancement of relative bioavailability of insulin was observed, i.e. approximately five times of pure insulin solution when loaded in SLN (8.26% versus 1.7% only). [ABSTRACT FROM PUBLISHER]

With an attempt to improve the solubility of poorly water-soluble bioactive compound diosmin, its inclusion complexation was investigated with β-cyclodextrin (β-CD) in the presence and/or absence of ternary component, hydroxypropyl methyl cellulose (HPMC) and polyethylene glycol 6000 (PEG 6000). The complexes of diosmin were prepared by kneading technique. Phase solubility studies confirmed a stoichiometry of 1:1 (diosmin:β-CD) molar ratio with an A L -type of phase solubility curve. The stability constants and complexation efficiency of binary systems were significantly improved in the presence of ternary components HPMC and PEG 6000. The formation of inclusion complexes were confirmed by FTIR, powder XRD, DSC, SEM and 1 H NMR spectral analyses. In vitro drug release studies and anti-oxidant activity showed promising results when diosmin was complexed in binary and/or ternary system. These results indicated the suitability of β-CD in enhancing the solubility and in vitro bioactivity of diosmin. [ABSTRACT FROM AUTHOR]

The objective of the current research is to develop ZnO-Manjistha extract (ZnO-MJE) nanoparticles (NPs) and to investigate their transdermal delivery as well as antimicrobial and antioxidant activity. The optimized formulation was further evaluated based on different parameters. The ZnO-MJE-NPs were prepared by mixing 10 mM ZnSO4·7H2O and 0.8% w/v NaOH in distilled water. To the above, a solution of 10 mL MJE (10 mg) in 50 mL of zinc sulfate was added. Box–Behnken design (Design-Expert software 12.0.1.0) was used for the optimization of ZnO-MJE-NP formulations. The ZnO-MJE-NPs were evaluated for their physicochemical characterization, in vitro release activity, ex vivo permeation across rat skin, antimicrobial activity using sterilized agar media, and antioxidant activity by the DPPH free radical method. The optimized ZnO-MJE-NP formulation (F13) showed a particle size of 257.1 ± 0.76 nm, PDI value of 0.289 ± 0.003, and entrapment efficiency of 79 ± 0.33%. Drug release kinetic models showed that the formulation followed the Korsmeyer–Peppas model with a drug release of 34.50 ± 2.56 at pH 7.4 in 24 h. In ex vivo studies ZnO-MJE-NPs-opt permeation was 63.26%. The antibacterial activity was found to be enhanced in ZnO-MJE-NPs-opt and antioxidant activity was found to be highest (93.14 ± 4.05%) at 100 µg/mL concentrations. The ZnO-MJE-NPs-opt formulation showed prolonged release of the MJE and intensified permeation. Moreover, the formulation was found to show significantly (p < 0.05) better antimicrobial and antioxidant activity as compared to conventional suspension formulations. [ABSTRACT FROM AUTHOR]

Mitochondria are semiautonomous doubly membraned intracellular components of cells. The organelle comprises of an external membrane, followed by coiled structures within the membrane called cristae, which are further surrounded by the matrix spaces followed by the space between the external and internal membrane of the organelle. A typical eukaryotic cell contains thousands of mitochondria within it, which make up 25% of the cytoplasm present in the cell. The organelle acts as a common point for the metabolism of glucose, lipids, and glutamine. Mitochondria chiefly regulate oxidative phosphorylation-mediated aerobic respiration and the TCA cycle and generate energy in the form of ATP to fulfil the cellular energy needs. The organelle possesses a unique supercoiled doubly stranded mitochondrial DNA (mtDNA) which encodes several proteins, including rRNA and tRNA crucial for the transport of electrons, oxidative phosphorylation, and initiating genetic repair processors. Defects in the components of mitochondria act as the principal factor for several chronic cellular diseases. The dysfunction of mitochondria can cause a malfunction in the TCA cycle and cause the leakage of the electron respiratory chain, leading to an increase in reactive oxygen species and the signaling of aberrant oncogenic and tumor suppressor proteins, which further alter the pathways involved in metabolism, disrupt redox balance, and induce endurance towards apoptosis and several treatments which play a major role in developing several chronic metabolic conditions. The current review presents the knowledge on the aspects of mitochondrial dysfunction and its role in cancer, diabetes mellitus, infections, and obesity. [ABSTRACT FROM AUTHOR]

The objective of this study was to measure and correlate the solubility of poorly water-soluble bioactive compound silymarin in five different green solvents namely water, ethanol, isopropyl alcohol (IPA), polyethylene glycol-400 (PEG-400) and β-cyclodextrin (β-CD) solution (20mM) from (298.15 to 333.15) K at atmospheric pressure of 0.1MPa using the shake flask method. The experimental solubilities of silymarin were regressed by Apelblat equation and root mean square deviations (RMSDs) between calculated and experimental solubility were determined. The RMSD values were observed in the range of 0.022–2.374. However, the correlation coefficients were observed in the range of 0.997–0.999 in all green solvents investigated. The solubility of silymarin was found to be increased with temperature in all green solvents investigated. The mole fraction solubility of silymarin was found to be highest in PEG-400 (0.243 at 298.15K) as compared to β-CD (2.10×10−2 at 298.15K), ethanol (1.67×10−2 at 298.15K), IPA (4.484×10−3 at 298.15K) and water (1.46×10−5 at 298.15K). Based on these results, silymarin was considered as practically insoluble in water, soluble in ethanol, IPA & β-CD solution and freely soluble in PEG-400. [ABSTRACT FROM AUTHOR]

Temperature-dependent solubilitydata of bioactive compound hesperidinhas not been reported in any solvent in the literature so far. Therefore,the aim of the current study was to measure the solubility of bioactivecompound hesperidin in six different pure solvents namely water, ethanol,isopropyl alcohol (IPA), propylene glycol (PG), poly(ethylene glycol)-400(PEG-400), and 1-butanol from (298.15 to 333.15) K using the shakeflask method. The experimental solubilities of hesperidin were regressedby Apelblat equation with root-mean-square deviations in the rangeof 6.32·10–7to 0.184 in all solvents investigated.The correlation coefficients in pure solvents were observed in therange of 0.995 to 0.999. The mole fraction solubility of hesperidinwas found to be higher in PEG-400 (6.33·10–3at 298.15 K) and PG (5.35·10–4at 298.15K) as compared to water (1.47·10–7at 298.15K), ethanol (3.45·10–5at 298.15 K), IPA (1.53·10–5at 298.15 K), and 1-butanol (3.15·10–4at 298.15 K). The data of the current study could be useful in crystallization/purificationand formulation development of hesperidin in the chemical/pharmaceuticalindustry. [ABSTRACT FROM AUTHOR]

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations. [ABSTRACT FROM AUTHOR]

Niosomes represent an emerging class of novel vesicular systems. They are composed of nonionic surfactants which are biodegradable and relatively nontoxic. They were developed as stable and inexpensive alternatives to liposomes. Since their early introduction to cosmetic industry their role has diversified to other application areas. They are now being ardently explored as potential carriers for sustained and targeted drug delivery. In addition to conventional, oral, and parenteral routes, they are amenable to be delivered by ocular, transdermal, vaginal, and inhalation routes. Delivery of biotechnological products including vaccine delivery with niosomes is also an interesting and promising research area. The introduction of provesicular approach in the form of proniosomes has further increased the relevance of these systems. More concerted research efforts, however, are still required to realize the full potential of these novel systems. This review considers the current status and explores the potential of niosomes in drug delivery with special attention to their role in drug targeting. Their methods of preparation, formulation aspects, advantages, limitations, and applications are also discussed. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to investigate the feasibility of proniosomes as transdermal drug delivery system for losartan potassium. Different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24 h. The permeability parameters such as flux, permeability coefficient, and enhancement ratio were significant for PNG-2 compared with other formulations ( P < 0.05). This optimized PNG-2 was fabricated in the form of transdermal patch using HPMC gel as a suitable base. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is, 24 h through rat skin. In vivo pharmacokinetic study of PNP-H showed a significant increase in bioavailability (1.93 times) compared with oral formulation of losartan potassium. The formulation appeared to be stable when stored at room temperature (30 ± 2°C) and at refrigeration temperature (4 ± 2°C) for 45 days. [ABSTRACT FROM AUTHOR]

Sildenafil citrate (SLC) is a frequently used medication (Viagra®) for the treatment of erectile dysfunction (ED). Due to its poor solubility, SLC suffers from a delayed onset of action and poor bioavailability. Hence, the aim of the proposed work was to prepare and evaluate solid dispersions (SDs) with hydrophilic polymers (Kolliphor® P188, Kollidon® 30, and Kollidon®-VA64), in order to enhance the dissolution and efficacy of SLC. The SLC-SDs were prepared using a solvent evaporation method (at the ratio drug/polymer, 1:1, w/w) and characterized by Differential Scanning Calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Scanning electron microscope (SEM), drug content, yield, and in vitro release studies. Based on this evaluation, SDs (SLC-KVA64) were optimized, with a maximum release of drug (99.74%) after 2 h for all the developed formulas. The SDs (SLC-KVA64) were further tested for sexual behavior activity in male rats, and significant enhancements in copulatory efficiency (81.6%) and inter-copulatory efficiency (44.9%) were noted in comparison to the pure SLC drug, when exposed to the optimized SLC-KVA64 formulae. Therefore, SD using Kollidon®-VA64 could be regarded as a potential strategy for improving the solubility, in vitro dissolution, and therapeutic efficacy of SLC. [ABSTRACT FROM AUTHOR]

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188. [ABSTRACT FROM AUTHOR]

Despite progress in cancer treatments, it remains a leading cause of death worldwide. Current chemotherapy is often hampered by side effects, tissue damage, and drug resistance. To overcome these limitations, research is exploring new approaches to improve chemotherapy efficacy and reduce its side effects. A promising strategy involves combining chemotherapeutic drugs with phytochemicals, which are active compounds derived from plants. Nanotechnology plays a crucial role in delivering these often‐hydrophobic drugs, enhancing their bioavailability and solubility. This research area represents a significant convergence of nanotechnology with both conventional pharmaceuticals and botanical compounds. Global studies are increasingly demonstrating the potential of these combination therapies to inhibit cancer cell growth in laboratory and preclinical models. These studies suggest synergistic or additive effects that lead to improved treatment outcomes. This article focuses on recent advancements in nano‐drug delivery systems, specifically those designed for the simultaneous delivery of chemotherapeutic drugs and phytochemicals. It explores the selection of phytochemicals based on their anticancer properties, outlines the design considerations for nanocarriers, and discusses how physicochemical characteristics influence drug release kinetics. Additionally, the review examines nanoformulations that integrate synthetic drugs with natural components, highlighting the potential of herbal oils and medicines in cancer treatment. [ABSTRACT FROM AUTHOR]

The aim of the current study was to evaluate the therapeutics potential of eluxadoline (ELX) loaded solid lipid nanoparticles (SLNs) in ulcerative colitis. ELX loaded SLNs were prepared using three different lipids according to the solvent emulsification technique. The optimization of prepared SLNs (F1-F3) were carried out based on size, PDI, zeta potential, percent drug entrapment (%EE), and loading (%DL). The lipid (stearic acid) based SLNs (F2) was optimized with particle size (266.0 ± 6.4 nm), PDI (0.217 ± 0.04), zeta potential (31.2 ± 5.19 mV), EE (65.0 ± 4.8%), and DL (4.60 ± 0.8%). The optimized SLNs (F2) was further evaluated by DSC, FTIR, SEM, in vitro release, and stability studies, which confirmed the successful encapsulation of ELX in SLNs. The efficacy of optimized SLNs (F2) in comparison to the pure ELX drug was assessed in acetic acid induced colitis rat models. It was observed that the delivery of ELX by SLNs alleviated the induced acetic acid colitis significantly. Thus, ELX loaded SLNs delivery to the colon has a significant potential to be developed for the treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

A biocompatible, biodegradable and FDA-approved polymer [Poly lactic-co-glycolic acid (PLGA)] was used to prepare the nanoparticles (NPs) to observe the effect of solvents, stabilizers and their concentrations on the physical properties of the PLGA-NPs, following the encapsulation and in vitro release of Indomethacin (IND). PLGA-NPs were prepared by the single-emulsion solvent evaporation technique using dichloromethane (DCM)/chloroform as the organic phase with Polyvinyl-alcohol (PVA)/Polyvinylpyrrolidone (PVP) as stabilizers to encapsulate IND. The effects of different proportions of PVA/PVP with DCM/chloroform on the physiochemical properties (particle size, the polydispersity index, the zeta potential by Malvern Zetasizer and morphology by SEM) of the NPs were investigated. DSC was used to check the physical state, the possible complexation of PLGA with stabilizer(s) and the crystallinity of the encapsulated drug. Stabilizers at all concentrations produced spherical, regular-shaped, smooth-surfaced discrete NPs. Average size of 273.2–563.9 nm was obtained when PVA (stabilizer) with DCM, whereas it ranged from 317.6 to 588.1 nm with chloroform. The particle size was 273.2–563.9 nm when PVP was the stabilizer with DCM, while it was 381.4–466.6 nm with chloroform. The zeta potentials of PVA-stabilized NPs were low and negative (−0.62 mV) while they were comparatively higher and positive for PVP-stabilized NPs (+17.73 mV). Finally, drug-loaded optimal NPs were composed of PLGA (40 mg) and IND (4 mg) in 1 mL DCM/chloroform with PVA/PVP (1–3%), which resulted in sufficient encapsulation (54.94–74.86%) and drug loading (4.99–6.81%). No endothermic peak of PVA/PVP appeared in the optimized formulation, which indicated the amorphous state of IND in the core of the PLGA-NPs. The in vitro release study indicated a sustained release of IND (32.83–52.16%) from the PLGA-NPs till 72 h and primarily followed the Higuchi matrix release kinetics followed by Korsmeyer–Peppas models. The cell proliferation assay clearly established that the organic solvents used to prepare PLGA-NPs had evaporated. The PLGA-NPs did not show any particular toxicity in the HepG2 cells within the dose range of IND (250–500 µg/mL) and at an equivalent concentration of PLGA-NPs (3571.4–7142.7 µg/mL). The cytotoxicity of the hepatotoxic drug (IND) was reduced by its encapsulation into PLGA-NPs. The outcomes of this investigation could be implemented to prepare PLGA-NPs of acceptable properties for the encapsulation of low/high molecular weight drugs. It would be useful for further in vitro and in vivo applications to use this delivery system. [ABSTRACT FROM AUTHOR]

In the current study, solubility, thermodynamics and molecular interaction of delafloxacin (DFLX) in water, ethanol, transcutol-HP (THP) and three different alkylimidazolium based ionic liquids were conducted at temperature range "T = 298.2 K to 318.2 K" and pressure " p = 0.1 MPa". The solid phase characterization of initial and equilibrated DFLX by DSC, FTIR and PXRD confirmed no significant change in crystallinity of the drug. The maximum mole fraction solubility of DFLX at " T = 318.2" was measured in THP (5.44 × 10−3), followed by [BMIM]PF 6 ] (1.87 × 10−3). The measured solubilities of DFLX were well regressed by "Apelblat and van't Hoff model" with overall RMSD values of 1.66% and 2.42%, respectively. The lowest activity coefficients were measured in THP followed by BMMHFP, which indicated highest molecular interaction between DFLX-THP followed by DFLX-[BMIM]PF 6 ]. • Solubility studies of delafloxacin in environmental friendly ionic liquid solvents. • Solid state characterization of delafloxacin before and after equilibration by DSC, FTIR and PXRD. • Estimation of mole-fraction solubility in all investigated solvents. • Calculation of ideal solubility and thermodynamic parameters. [ABSTRACT FROM AUTHOR]

Delafloxacin (DFL) is a novel potent and broad-spectrum fluoroquinolone group of antibiotics effective against both Gram-positive and negative aerobic and anaerobic bacteria. In this study, DFL-loaded stearic acid (lipid) chitosan (polymer) hybrid nanoparticles (L-P-NPs) have been developed by single-emulsion-solvent evaporation technique. The mean particle size and polydispersity index (PDI) of optimized DFL-loaded L-P-NPs (F1-F3) were measured in the range of 299–368 nm and 0.215–0.269, respectively. The drug encapsulation efficiency (EE%) and loading capacity (LC%) of DFL-loaded L-P-NPs (F1-F3) were measured in the range of 64.9–80.4% and 1.7–3.8%, respectively. A sustained release of DFL was observed from optimized DFL-loaded L-P-NPs (F3). Minimum inhibitory concentration (MIC) values of the DFL-loaded L-P-NPs (F3) appeared typically to be four-fold lower than those of delafloxacin in the case of Gram-positive strains and was 2-4-fold more potent than those of delafloxacin against Gram-negative strains. The pharmacokinetic study in rats confirmed that the bioavailability (both rate and extent of absorption) of DFL-loaded L-P-NPs was significantly higher (2.3-fold) than the delafloxacin normal suspension. These results concluded that the newly optimized DFL-loaded L-P-NPs were more potent against both Gram-positive and negative strains of bacteria and highly bioavailable in comparison to delafloxacin normal suspension. [ABSTRACT FROM AUTHOR]

Estimating the solubility and solution thermodynamics parameters of aliskiren hemifumarate (AHF) in three different room temperature ionic liquids (RTILs), Transcutol-HP (THP) and water are interesting as there is no solubility data available in the literature. In the current study, the solubility and solution thermodynamics of AHF in three different RTILs, THP and water at the temperature range from 298.2 to 318.2 K under air pressure 0.1 MP were evaluated. The solid phase evaluation by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) indicated no conversion of AHF into polymorph. The mole fraction solubility of AHF was found to be highest in 1-hexyl-3-methylimidazolium hexafluorophosphate (HMMHFP) ionic liquid (7.46 × 10−2) at 318.2 K. The obtained solubility values of AHF was regressed by the Apelblat and van't Hoff models with overall root mean square deviations (RMSD) of 0.62% and 1.42%, respectively. The ideal solubility of AHF was higher compared to experimental solubility values at different temperatures. The lowest activity coefficient was found in HMMHFP, which confirmed highest molecular interaction between AHF–HMMHFP. The estimated thermodynamic parameters confirmed endothermic and entropy driven dissolution of AHF in different RTILs, THP, and water. [ABSTRACT FROM AUTHOR]

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues. [ABSTRACT FROM AUTHOR]

Boswellia sacra and its derivatives exhibit notable bioactive properties, which have been the subject of extensive scientific research; however, their potential applications in food packaging remain largely untapped. In the current study, cellulose, sodium alginate, and gelatin composite edible films were fabricated with the addition of different concentrations (0.2% and 0.3%) of the ethanolic fraction of Boswellia sacra oleo gum resin (BSOR). The resultant films were examined for their physical, chemical, mechanical, barrier, optical, and antioxidant properties. Moreover, the films were characterized using Scanning Electron Microscopy (SEM), X‐ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) to study the impact of incorporating BSOR on the morphological, crystalline, and chemical properties of the films. The addition of BSOR increased the film thickness (0.026–0.08 mm), water vapor permeability (0.210–0.619 (g.mm)/(m2.h.kPa), and the intensity of the yellow color (3.01–7.20) while reducing the values of both tensile strength (6.67–1.03 MPa) and elongation at break (83.50%–48.81%). SEM and FTIR analysis confirmed the interaction between the BSOR and film‐forming components. The antioxidant properties of the edible films were significantly increased with the addition of BSOR. The comprehensive findings of the study demonstrated that BSOR possesses the potential to serve as an efficient natural antioxidant agent in the fabrication of edible films. [ABSTRACT FROM AUTHOR]

The objective of the current investigation is the development and characterization of in-situ ophthalmic formulation of fluconazole for sustained release at the eye site for a prolong period of time. Sol-gel fluconazole in-situ formulation was prepared by thermo-responsive pluronic F127, Na+ activated sodium alginate alone and in combination, characterization parameters include FTIR spectroscopy, Visual assessment and clarity test, Gelling ability test, pH testing, drug assay, In-vitro drug release and optimized formulation was evaluated for In-vitro antifungal studies by comparing with marketed formulation of fluconazole. Optimized formulation F8 composed of fluconazole (0.3%w/v), Pluronic F127(1%w/v), sodium alginate (0.5%w/v), sodium chloride (0.9w/v), benzalkonium Chloride (0.01%w/v) and acetate buffer pH 4 up to 100%w/v), showed drug-polymer compatibility as per FTIR, high gelling consistency on contact with simulated physiological conditions, 6.9 pH, drug assay was estimated (99.89±0.78 %) with 100% in-vitro drug released for about 6 hours. The in-vitro antifungal study was found to be 18.87±0.65 mm; 20.76±0.23 mm in comparison to marketed fluconazole conventional gel formulation (15.98±0.98 mm; 18.98±0.76 mm) for Candida albicans and Aspergillus niger pathogenic fungal strains respectively. Prepared in-situ ophthalmic sol-gel formulation of fluconazole could be considered as efficient delivery system to sustained the drug at the target site and effectively eradicating deeply rooted pathogenic fungal stains. [ABSTRACT FROM AUTHOR]

To develop diagnostic imaging approaches, this paper emphasizes the transformational potential of merging geophysics with health sciences. Diagnostic imaging technology improvements have transformed the health sciences by enabling earlier and more precise disease identification, individualized therapy, and improved patient care. This review article examines the connection between geophysics and diagnostic imaging in the field of health sciences. Geophysics, which is typically used to explore Earth's subsurface, has provided new uses of its methodology in the medical field, providing innovative solutions to pressing medical problems. The article examines the different geophysical techniques like electrical imaging, seismic imaging, and geophysics and their corresponding imaging techniques used in health sciences like tomography, magnetic resonance imaging, ultrasound imaging, etc. The examination includes the description, similarities, differences, and challenges associated with these techniques and how modified geophysical techniques can be used in imaging methods in health sciences. Examining the progression of each method from geophysics to medical imaging and its contributions to illness diagnosis, treatment planning, and monitoring are highlighted. Also, the utilization of geophysical data analysis techniques like signal processing and inversion techniques in image processing in health sciences has been briefly explained, along with different mathematical and computational tools in geophysics and how they can be implemented for image processing in health sciences. The key findings include the development of machine learning and artificial intelligence in geophysics-driven medical imaging, demonstrating the revolutionary effects of data-driven methods on precision, speed, and predictive modeling. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies. [ABSTRACT FROM AUTHOR]

Umifenovir is one of the most often prescribed antiviral medications for the prevention and treatment of COVID-19 and other viral infections. Herein, a UPLC-MS/MS method is developed through using ibrutinib as an internal standard (IS) for quantifying umifenovir in plasma samples. Both umifenovir and the IS were analytically separated on an Acquity BEH C18 column with a total run time of only 2.5 min. At a flow rate of 0.3 mLmin−1, acetonitrile:15 mM ammonium acetate (80:20) was employed as the mobile phase composition. Electrospray ionization in positive mode was used for ionization of the samples. Detection and quantification were performed in multiple reaction monitoring mode with parent-to-daughter ionization of 477.05 → 279.02 and 441.16 → 84.4 for umifenovir and the IS, respectively. The method was validated through following international guidelines for bioanalytical method validation, and all parameters were within the acceptable limits. Moreover, the eco-scale method using AGREE software was used for the evaluation of greenness, and results showed that the method is very environmentally friendly. The validated assay was successfully employed in the bioavailability assessment of a newly developed formulation of kneaded ternary umifenovir/β-cyclodextrin with 1% poloxamer 188 (KDB). [ABSTRACT FROM AUTHOR]

Gelatin (bovine/porcine)-based edible films are considered as an excellent carrier for essential oils (EOs) to preserve food quality and extend their shelf life. Spearmint essential oil (SEO) is known for its potential antioxidant and antimicrobial effects; nevertheless, its food applications are limited due to the volatile nature of its active components. Thus, edible films loaded with essential oil can be an alternative to synthetic preservatives to improve their food applications. In the present study, the effect of SEO addition was investigated on the physicochemical properties of bovine and porcine gelatin films, and antioxidant activity was assessed. GCMS (Gas chromatography mass spectrometry) analysis revealed the presence of carvone (55%) and limonene (25.3%) as major components. The incorporation of SEO into the films decreased the opacity, moisture content, water solubility, and elongation at break of bovine and porcine gelatin films. However, with the addition of EO, the thickness and water vapor permeability of bovine and porcine-based gelatin films increased. Moreover, the addition of SEO increased the tensile strength (TS) of the porcine-based film, whereas bovine samples demonstrated a decrease in tensile strength. XRD (X-ray diffraction) findings revealed a decrease in the percentage crystallinity of both types of gelatin films. SEM (scanning electron microscope) results showed the changes in the morphology of films after the addition of SEO. Antioxidant properties significantly (p < 0.05) increased with the incorporation of EO when compared with control films. Therefore, the addition of SEO to gelatin-based edible films could be an effective approach to prepare an active food packaging material to prevent food oxidation. [ABSTRACT FROM AUTHOR]

This study aimed to develop three-dimensional (3D) baricitinib (BAB) pills using polylactic acid (PLA) by fused deposition modeling. Two strengths of BAB (2 and 4% w/v) were dissolved into the (1:1) PEG-400 individually, diluting it with a solvent blend of acetone and ethanol (27.8:18:2) followed by soaking the unprocessed 200 cm~6157.94 mg PLA filament in the solvent blend acetone—ethanol. FTIR spectrums of the 3DP1 and 3DP2 filaments calculated and recognized drug encapsulation in PLA. Herein, 3D-printed pills showed the amorphousness of infused BAB in the filament, as indicated by DSC thermograms. Fabricated pills shaped like doughnuts increased the surface area and drug diffusion. The releases from 3DP1 and 3DP2 were found to be 43.76 ± 3.34% and 59.14 ± 4.54% for 24 h. The improved dissolution in 3DP2 could be due to the higher loading of BAB due to higher concentration. Both pills followed Korsmeyer–Peppas' order of drug release. BAB is a novel JAK inhibitor that U.S. FDA has recently approved to treat alopecia areata (AA). Therefore, the proposed 3D printed tablets can be easily fabricated with FDM technology and effectively used in various acute and chronic conditions as personalized medicine at an economical cost. [ABSTRACT FROM AUTHOR]

The quality and safety of food products greatly depend on the physiochemical properties of the food packaging material. There is an increasing trend in the utilization of protein-based biopolymers for the preparation of edible films and coating due to their film-forming properties. Various studies have reported the preparation of protein-based edible films with desirable mechanical and barrier properties. The mechanical attributes of the protein-based food packaging materials can be enhanced by incorporating various components in the film composition such as plasticizers, surfactants, crosslinkers, and various bioactive compounds, including antimicrobial and antioxidant compounds. This review article summarizes the recent updates and perspective on the mechanical attributes such as Tensile Strength (TS), Elongation at Break (EAB), and Young's Modulus (YM) of edible films based on different proteins from plants and animal sources. Moreover, the effects of composite materials such as other biopolymers, bioactive compounds, essential oils, and plasticizers on the mechanical properties of protein-based edible films are also discussed. [ABSTRACT FROM AUTHOR]

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides. [ABSTRACT FROM AUTHOR]

Aqueous extract of fruit obtained from Ficus racemosa enriched with phenolic components was used for the first time to fabricate chitosan (CS) and sodium alginate (SA)-based edible films. The edible films supplemented with Ficus fruit aqueous extract (FFE) were characterized physiochemically (using Fourier transform infrared spectroscopy (FT-IR), Texture analyser (TA), Thermogravimetric analysis (TGA), scanning electron microscopy (SEM), X-ray diffraction (XRD), and colourimeter) and biologically (using antioxidant assays). CS–SA–FFA films showed high thermal stability and high antioxidant properties. The addition of FFA into CS–SA film decreased transparency, crystallinity, tensile strength (TS), and water vapour permeability (WVP) but ameliorate moisture content (MC), elongation at break (EAB) and film thickness. The overall increase in thermal stability and antioxidant property of CS–SA–FFA films demonstrated that FFA could be alternatively used as a potent natural plant-based extract for the development of food packaging material with improved physicochemical and antioxidant properties. [ABSTRACT FROM AUTHOR]

Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4′,7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the wound healing effects of clove oil (CO) via its encapsulation into nanoemulsion. Optimized nanoemulsion (droplet size of 29.10 nm) was selected for wound healing investigation, collagen determination, and histopathological examination in rats. Optimized nanoemulsion presented significant would healing effects in rats as compared to pure CO. Nanoemulsion also presented significant enhancement in leucine content (0.61 mg/g) as compared to pure CO (0.50 mg/g) and negative control (0.31 mg/g). Histopathology of nanoemulsion treated rats showed no signs of inflammatory cells. These results suggested that nanoemulsion of CO was safe and nontoxic. [ABSTRACT FROM AUTHOR]

Sinapic acid (SA) has been reported as a poorly soluble bioactive compound due to its dissolution rate and oral bioavailability, which are very poor. Therefore, in the current research work, different self-nanoemulsifying drug delivery systems (SNEDDS) of SA were developed for enhancement of its in vitro dissolution (drug release) and bioactivity. Different SA-loaded SNEDDS were prepared by low-energy emulsification methods, characterized and evaluated for various physicochemical and in vitro parameters such as thermodynamic stability, self-nanoemulsification efficiency, droplet size, polydispersity index (PDI), zeta potential (ZP), refractive index (RI), the % of transmittance (% T ) and drug release profile. In vitro dissolution rate of SA was significantly enhanced from SNEDDS in comparison with SA suspension. The optimized SNEDDS of SA with droplet size of 12.4 nm, PDI value of 0.158, ZP value of − 32.8 mV, RI value of 1.335, % T value of 98.7% and drug release profile of 96.8% was selected for in vitro antioxidant and in vivo anti-inflammatory studies. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay indicated significant antioxidant activity of optimized SA SNEDDS (IC50 = 4.52 μg/ml) in comparison with free SA (IC50 = 7.62 μg/ml) and standard ascorbic acid (IC50 = 40.78 μg/ml). In vivo anti-inflammatory studies in rats also indicated that SA in optimized SNEDDS was significantly efficacious than SA suspension. Free SA as well as SA in SNEDDS was proved to be an excellent antioxidant in comparison with standard ascorbic acid. The results obtained in the current research work indicated the great potential of SNEDDS in the enhancement of in vitro dissolution rate and therapeutic efficacy of poorly soluble bioactive compounds such as SA. [ABSTRACT FROM AUTHOR]

Due to genetic changes in DNA (deoxyribonucleic acid) sequences, cancer continues to be the second most prevalent cause of death. The traditional target-directed approach, which is confronted with the importance of target function in healthy cells, is one of the most significant challenges in anticancer research. Another problem with cancer cells is that they experience various mutations, changes in gene duplication, and chromosomal abnormalities, all of which have a direct influence on the potency of anticancer drugs at different developmental stages. All of these factors combine to make cancer medication development difficult, with low clinical licensure success rates when compared to other therapy categories. The current review focuses on the pathophysiology and molecular aspects of common cancer types. Currently, the available chemotherapeutic drugs, also known as combination chemotherapy, are associated with numerous adverse effects, resulting in the search for herbal-based alternatives that attenuate resistance due to cancer therapy and exert chemo-protective actions. To provide new insights, this review updated the list of key compounds that may enhance the efficacy of cancer treatment. [ABSTRACT FROM AUTHOR]

The abundant synthesis and accretion of melanin inside skin can be caused by activation of melanogenic enzymes or increase in number of melanocytes. Melasma is defined as hyperpigmented bright or dark brown spots which are symmetrically distributed and have serrated and irregular borders. The three general categories of pigmentation pattern include centro facial pattern, malar pattern, and mandibular pattern. Exposure to UV rays, heat, use of cosmetics and photosensitizing drugs, female sex hormonal therapies, aberrant production of melanocyte stimulating hormone, and increasing aesthetic demands are factors which cause the development of melasma disease. This review gives a brief overview regarding the Fitzpatrick skin phototype classification system, life cycle of melanin, mechanism of action of anti-hyperpigmenting drugs, and existing pharmacotherapy strategies for the treatment of melasma. The objectives of this review are focused on role of cutting-edge nanotechnology-based strategies, such as lipid-based nanocarriers, i.e., lipid nanoparticles, microemulsions, nanoemulsions, liposomes, ethosomes, niosomes, transfersomes, aspasomes, invasomes penetration-enhancing vesicles; inorganic nanocarriers, i.e., gold nanoparticles and fullerenes; and polymer-based nanocarriers i.e., polymeric nanoparticles, polymerosomes, and polymeric micelles for the management of hyperpigmentation. [ABSTRACT FROM AUTHOR]

Olaparib (OLA) is an anticancer agent that acts by inhibiting the poly (ADP-ribose)-polymerase-I (PARP-I). Due to its low solubility and low permeability, it has been placed as a BCS Class-IV drug and hence its clinical use is limited. In this study, we develop the nanocrystals of OLA as a way to improve its solubility and other performances. The OLA-NCs were prepared by antisolvent precipitation method through homogenization and probe sonication technique using a novel amphiphilic polymeric stabilizer (Soluplus®). Particle characterization resulted approximately 103.13 nm, polydispersity-index was 0.104 with positive zeta-potential of +8.67 mV. The crystal morphology by SEM of OLA-NCs (with and without mannitol) exhibited nano-crystalline prism-like structures as compared to the elongated OLA-pure. The DSC, XRD and FTIR were performed to check the interaction of Soluplus, mannitol and OLA did not exhibit any physical interaction among the OLA, Soluplus® and mannitol that is indicated by the presence of parent wave number peak. Two-fold increased solubility of OLA was found in PBS with Soluplus® from the NCs (69.3 ± 6.2 µgmL−1) as compared to pure drug (35.6 ± 7.2 µgmL−1). In vitro release of drug from OLA-NCs was higher (78.2%) at 12 h at pH 6.8 and relatively lower (53.1%) at pH 1.2. In vitro cellular cytotoxicity and anticancer effects were examined on MCF-7 cells. OLA-NCs were found effectively potent to MCF-7 cells compared with OLA-pure with approximately less than half IC50 value during MTT assay. Estimation of p53, Caspase-3 and Caspase-9 in MCF-7 cells indicated that OLA-NCs have significantly (p < 0.05) increased their expressions. After single oral dose in rats, 12 h plasma drug concentration-time profile indicated approximately 2.06-, 2.29-, 2–25- and 2.62-folds increased Cmax, AUC0-12 h, AUC0-∞ and AUMC0-∞, respectively, from the NCs as compared to OLA-pure. Storage stability indicated that the OLA-NCs was physically and chemically stable at 4 °C, 25 °C and 40 °C up to 6-months. Overall, OLA-NCs were deliberated; its potential feasibility to overwhelm the formulation challenges related to poorly soluble drugs and its future clinical applications. [ABSTRACT FROM AUTHOR]

A brand-new nano-crystal (NC) version of the hydrophobic drug Paclitaxel (PT) were formulated for cancer treatment. A stable NC formulation for the administration of PT was created using the triblock co-polymer Pluronic F127. To achieve maximum entrapment effectiveness and minimal particle size, the formulation was improved using the central composite design by considering agitation speed and vacuum pressure at five levels (coded as +1.414, +1, 0, −1, and −1.414). According to the Design Expert software's predictions, 13 runs were created and evaluated for the chosen responses. The formulation prepared with an agitation speed of 1260 RPM and a vacuum pressure of 77.53 mbar can meet the requirements of the ideal formulation in order to achieve 142.56 nm of PS and 75.18% EE, according to the level of desirability (D = 0.959). Folic acid was conjugated to Pluronic F127 to create folate receptor-targeted NC. The drug release profile of the nano-crystals in vitro demonstrated sustained release over an extended period. Folate receptor (FR)-targeted NC (O-PT-NC-Folate) has also been prepared by conjugating folic acid to Pluronic F127. MTT test is used to validate the targeting efficacy on the FR-positive human oral cancer cell line (KB). At pharmacologically relevant concentrations, the PT nano-crystal formulation did not cause hemolysis. Compared to non-targeted NC of PT, the O-PT-NC-Folate showed a comparable but more sustained anti-cancer effect, according to an in vivo anti-tumor investigation in NCI/ADR-RES cell lines. The remarkable anti-tumor effectiveness, minimal toxicity, and simplicity of scale-up manufacturing of the NC formulations indicate their potential for clinical development. Other hydrophobic medications that are formulated into nano-systems for improved therapy may benefit from the formulation approach. [ABSTRACT FROM AUTHOR]

The present study was aimed to develop chitosan-coated enamel adhesive device of CAP-P 407 (Cellulose acetate phthalate-Poloxamer 407), loaded with MNC (Minocycline) for sustained release and site-specific drug delivery system for the carious lesion. The average tensile strength and in-vitro drug release of uncoated dental film were found to be 15.97 kg/mm2 and 98.11% in 24 h, respectively. The average in-vitro mucoadhesion time and tooth adhesion strength of the finished product was found to be 249 minutes and 268 g, respectively. In-vitro antimicrobial study showed the drug concentration is well above MIC even after 8 hours of drug release. [ABSTRACT FROM AUTHOR]

The goal of this study was to optimize and formulate apigenin (APG)-loaded pegylated chitosan nanoparticles (PEGylated-CNPs) via ionic gelation techniques using the Box–Behnken design (BBD). Three individual variables, X1(chitosan: TPP concentration), X2 (PEG-400 concentration), and X3 (sonication time), were investigated for their influence on response variables (Y1—particle size (PS); Y2—drug entrapment efficiency (DEE); and Y3—zeta potential (ZP). The optimized formula of APG-PEGylated CNPs was picked from the statistical design and was then examined for physical, morphological, release characterization, anti-oxidant, and anti-tumor potential. The average PS, PDI, %DEE, and ZP were found to be 139.63 ± 5.67 nm, 0.296 ± 0.014, 79.55 ± 3.12%, and 24.68 ± 1.84 mV, respectively. The optimized APG formulation was chosen and reformulated based on the desirability function. Results of the observed and predicted values of responses through the BBD process were found to be nearly identical. The resulting APG-PEGylated CNPs were spherical and smooth, according to surface morphology studies. The release study revealed that PEGylated-CNPs exhibited biphasic release patterns distinguished by an initial burst release of APG only at early phases accompanied by a delayed release near 24 h. Furthermore, APG-PEGylated CNPs demonstrated statistically increased antioxidant activities and cytotoxicity against MCF-7 cells compared to pure APG. Based on the findings, it is possible to conclude that BBD was efficient in optimizing the PEGylated CNPs formulation and recognizing the impacts of formulation variables. In conclusion, the developed formulation has a significant potential for anticancer therapy. [ABSTRACT FROM AUTHOR]

In the current work, we fabricated gelatin–casein-based edible films (GC-EFs) crosslinked with gallic acid (GA). We analyzed the physiochemical characteristics, crystallinity, thermal stability, and surface properties of the EFs using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). It was found that the edible films possessed a semi-crystalline structure. Addition of GA enhanced the thermal stability of the edible films as well as the surface properties of the films. It was found that a higher concentration of GA (4–5% w/v) significantly improved the surface properties, observed in the surface and cross-sectional examination of SEM micrographs. EFs containing higher amounts of GA showed more compact and denser structures with smoother and more homogeneous surfaces than the control samples. In addition, swelling degree (SD), thickness, water solubility (WS), moisture content (MC), and water vapor permeability (WVP) were found to be low in EFs containing more GA concentration. Mechanical parameters revealed that the Young modulus (Ym) and tensile strength (TS) increased with a rise in GA concentration, and elongation at break (EB) reduced with a rise in GA concentration. In transparency and color analysis, it was observed that GA positively affected the transparency of the edible films. [ABSTRACT FROM AUTHOR]

A novel, sensitive, and low-cost HPLC method for the rapid determination of favipiravir (FVR) in rat plasma was developed and validated, and the effect of vitamin C on FVR pharmacokinetic parameters was investigated. FVR and oxcarbazepine (IS) were separated using a mobile phase of 50% acetonitrile and 50% water (with 0.25% trifluoroacetic acid) at 1.0 mL/min flow rate and detected at λmax 289 nm. The intra- and interday values for FVR in plasma were less than 15%, with low, medium, and high QC levels for the relative recovery rate, according to ICH guidelines. Cmax values in the control and experimental groups were 558 ± 124.42 and 979.13 ± 138.10 ng/mL, respectively; t1/2 values were 7.15 ± 1.60 and 9.09 ± 1.14 h, AUC(0-t) values were 5697.70 ± 536.58 and 7381.62 ± 1577.58 ng.h/mL, and AUC(0-∞) values were 5697.70 ± 536.58 and 8192.36 ±  1721.67, respectively. According to the results, the experimental group's Cmax of FVR was 75.17% higher than the control group's, the Vz/F was lower, and the t1/2 was 1.86 h longer. The technique developed for determining FVR in plasma was useful for FVR pharmacokinetics and food–drug interaction investigations. [ABSTRACT FROM AUTHOR]

Biopolymers-based composite edible films are gaining interest in the food packaging industry due to their sustainable nature and diverse biological activities. In the current study, we used sodium alginate (SA) and casein (CA) for the fabrication of composite film using the casting method. We also added orange oil to the edible film and assessed its impact on the biological, chemical, physical, and barrier properties of the films. The fabricated films were analyzed using X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). It was observed that CA–SA films loaded with 1.5% OEO had better visual attributes, and a further increase in oil concentration was not found to be as favorable. Mechanical assessment of the films revealed that CA–SA-OEO (1.5%) film showed lower puncture deformation and higher puncture force values. XRD data showed that all samples exhibited peaks at similar positions (21° of 2θ) with different intensities. In FTIR analysis, characteristic peaks of the film components (sodium alginate, casein, and orange oil) were reported at corresponding positions. The thermal stability of films was enhanced after the addition of the OEO (1.5%), however, a greater increase in OEO caused a decrease in the thermal stability, observed during TGA analysis. Moreover, the surface of the blank CA–SA film (FL1) was found to be rough (with cracks) compared to CA–SA films (FL2) containing 1.5% OEO. Additionally, FL2 was found to be relatively better than the other samples in terms of swelling degree (SD), thickness, water solubility (WS), oxygen permeability (OP), water vapor permeability (WVP), moisture content (MC), and transparency (T). [ABSTRACT FROM AUTHOR]

The main characteristic feature of diabetes mellitus is the disturbance of carbohydrate, lipid, and protein metabolism, which results in insulin insufficiency and can also lead to insulin resistance. Both the acute and chronic diabetic cases are increasing at an exponential rate, which is also flagged by the World Health Organization (WHO) and the International Diabetes Federation (IDF). Treatment of diabetes mellitus with synthetic drugs often fails to provide desired results and limits its use to symptomatic treatment only. This has resulted in the exploration of alternative medicine, of which herbal treatment is gaining popularity these days. Owing to their safety benefits, treatment compliance, and ability to exhibit effects without disturbing internal homeostasis, research in the field of herbal and ayurvedic treatments has gained importance. Medicinal phytoconstituents include micronutrients, amino acids, proteins, mucilage, critical oils, triterpenoids, saponins, carotenoids, alkaloids, flavonoids, phenolic acids, tannins, and coumarins, which play a dynamic function in the prevention and treatment of diabetes mellitus. Alkaloids found in medicinal plants represent an intriguing potential for the inception of novel approaches to diabetes mellitus therapies. Thus, this review article highlights detailed information on alkaloidal phytoconstituents, which includes sources and structures of alkaloids along with the associated mechanism involved in the management of diabetes mellitus. From the available literature and data presented, it can be concluded that these compounds hold tremendous potential for use as monotherapies or in combination with current treatments, which can result in the development of better efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

Considering the importance of benzothiazepine pharmacophore, an attempt was carried out to synthesize novel 1,5-benzothiazepine derivatives using polyethylene glycol-400 (PEG-400)-mediated pathways. Initially, different chalcones were synthesized and then subjected to a cyclization step with benzothiazepine in the presence of bleaching clay and PEG-400. PEG-400-mediated synthesis resulted in a yield of more than 95% in less than an hour of reaction time. Synthesized compounds 2a–2j were investigated for their in vitro cytotoxic activity. Moreover, the same compounds were subjected to systematic in silico screening for the identification of target proteins such as human adenosine kinase, glycogen synthase kinase-3β, and human mitogen-activated protein kinase 1. The compounds showed promising results in cytotoxicity assays; among the tested compounds, 2c showed the most potent cytotoxic activity in the liver cancer cell line Hep G-2, with an IC50 of 3.29 ± 0.15 µM, whereas the standard drug IC50 was 4.68 ± 0.17 µM. In the prostate cancer cell line DU-145, the compounds displayed IC50 ranges of 15.42 ± 0.16 to 41.34 ± 0.12 µM, while the standard drug had an IC50 of 21.96 ± 0.15 µM. In terms of structural insights, the halogenated phenyl substitution on the second position of benzothiazepine was found to significantly improve the biological activity. This characteristic feature is supported by the binding patterns on the selected target proteins in docking simulations. In this study, 1,5-benzothiazepines have been identified as potential anticancer agents which can be further exploited for the development of more potent derivatives. [ABSTRACT FROM AUTHOR]

For a few decades, globally, erectile dysfunction (ED) has become more prominent even in young adults and represents a mounting health concern causing a significant effect on men's quality of life. There is an expectation that by the end of 2025, the number of ED cases can rise to 322 million. We aimed to comprehensively analyze the scientific output of scholarly articles and studies in the field of ED (2016–2021). Data from scholarly articles were collected using Pubmed, and clinical trials-related information was accessed from the clinical trials website. An extensive patent search was conducted using databases such as USPTO (United States patent and trademark office) and EPO (European patent office), WIPO (World Intellectual Property Organization), etc. Owing to the high market value of ED drugs, considerable interest was attained to grab the opportunities. The race to replace the phosphodiesterase type 5 inhibitor (PDE5 inhibitor-PDE5i) can be identified as evident from the significant number of patents filed and the inventions cleared with clinical trials. Some other intriguing interventions are identified for ED treatment but have yet to gain public acceptance. The current analysis confirms the overall evolution and unexplored corners of research on ED treatment strategies with a current global projection. [ABSTRACT FROM AUTHOR]