Enhancing Oral Bioavailability of Simvastatin Using Uncoated and Polymer-Coated Solid Lipid Nanoparticles.

Simvastatin (SVA) is a well-prescribed drug for treating cardiovascular and hypercholesterolemia. Due to the extensive hepatic first-pass metabolism and poor solubility, its oral bioavailability is 5%. Solid lipid nanoparticles (SLNs) and hydrogel-coated SLNs were investigated to overcome the limited bioavailability of SVA. Four different lipids used alone or in combination with two stabilizers were employed to generate 13 SLNs. Two concentrations of chitosan (CS) and alginate (AL) were coating materials. SLNs were studied for particle size, zeta potential, in vitro release, rheology, and bioavailability. The viscosities of both the bare and coated SLNs exhibited shear-thinning behavior. The viscosity of F11 (Chitosan 1%) at 20 and 40 rpm were 424 and 168 cp, respectively. F11 had a particle size of 260.1 ± 3.72 nm with a higher release; the particle size of F11-CS at 1% was 524.3 ± 80.31 nm. In vivo studies illustrated that F11 had the highest plasma concentration when compared with the SVA suspension and coated chitosan (F11 (Chitosan 1%)). Greater bioavailability is measured as (AUC0→24), as compared to uncoated ones. The AUC for F11, F11-CS 1%, and the SVA suspension were 1880.4, 3562.18, and 272 ng·h/mL, respectively. Both bare and coated SLNs exhibited a significantly higher relative bioavailability when compared to that from the control SVA.

Preparation and In Vitro Evaluation of Levofloxacin-Loaded Floating Tables Using Various Rate-Controlling Agents.

Floating tablets are a new approach to extending the time a drug is in the stomach to improve therapy outcomes. Floating tablets were formulated with the drug, the polymers hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), and starch, fillers, and lubricants. The tablets were prepared using the direction compression method. The tablets' physical quality control tests were found to be within acceptable limits. The tablets extended drug release up to 12 h and were uniform in their drug contents. The swelling index of the tablets ranged from 60 ± 0.11 to 66 ± 0.14%, and the tablets were less dense than water. The floating lag time (10 ± 0.23 to 16 ± 0.09 s) and total floating time (>12 h) showed good floating behaviors. The kinetic modeling showed that the drug was released from the tablets by pseudo-diffusion, swelling, erosion, or anomalous non-Fickian diffusion. F6 (starch and CMC) showed higher n values (0.994 ± 0.04), exhibiting pseudo-zero-order drug release kinetics compared to those of other tablets. The dissolution data of the test and reference tables were not similar (P > 0.05). In terms of antimicrobial activity, the zones of inhibition of the test F6 tablet powders (5.3 ± 0.08 mm) and the reference tablet powders (5.9 ± 0.13 mm) were found to be significantly similar (P > 0.05). The study concluded that these floating tablets can improve the gastric residence time and therapeutic outcomes.

Quality by design for sumatriptan loaded nano-ethosomal mucoadhesive gel for the therapeutic management of nitroglycerin induced migraine.

Migraine is a progressive neurological condition often accompanied by nausea and vomiting. Various drugs have recently been used in the treatment of migraine, including sumatriptan (SUT). However, SUT has poor pharmacological effects mainly due to its reduced permeability, blood brain barrier (BBB) effect, half-life and bioavailability. Herein, we developed SUT loaded nano-ethosomes (SUT-NEs) for intranasal (IN) delivery, after their incorporation into chitosan based mucoadhesive gel (SUT-NEsG). The observed mean particle size of SUT-NEs was 109.45 ± 4.03 nm with spherical morphology, mono dispersion (0.191 ± 0.001), negatively charged (-20.90 ± 1.98 mV) and with excellent entrapment efficiency (96.90 ± 1.85 %). Fourier-transform infrared (FTIR) spectra have depicted the compatibility of the components. Moreover, SUT-NEsG was homogeneous having suitable viscosity and mucoadhesive strength. In vitro release and ex vivo permeation analysis showed sustained release and improved permeation of the SUT-NEsG, respectively. Additionally, histopathological studies of nasal membrane affirmed the safety of SUT-NEsG after IN application. In vivo pharmacokinetic study demonstrated improved brain bioavailability of SUT-NEsG as compared to orally administered sumatriptan solution (SUT-SL). Furthermore, significantly enhanced pharmacological effect of SUT-NEsG was observed in behavioral and biochemical analysis, immunohistochemistry for NF-κB, and enzyme linked immuno assay (ELISA) for IL-1ß and TNF-α in Nitroglycerin (NTG) induced migraine model. It can be concluded that migraine may be successfully managed through IN application of SUT-NEsG owing to the direct targeted delivery to the brain.

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. ß-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (ß- and hydroxy propyl ß-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-ß- and hydroxy propyl ß-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6')-Ib. The blaIMP and aac (6')-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.

Preformulation-Assisted Design of Ketorolac Tromethamine for Effective Ophthalmic Delivery.

Background: The eye is a highly protected organ from ocularly administered drugs; drug- and formulation-related factors contribute significantly to ocular bioavailability. There has been a growing interest in using nonsteroidal anti-inflammatory drugs in ophthalmology for treating postoperative pain, inflammation, and seasonal allergic conjunctivitis. A preformulation-assisted design boosts efficacy and reduces dose requirements. Methods: This work aims to study the preformulation characteristics of ketorolac tromethamine to improve ocular performance and future formulation development through developing an high-performance liquid chromatography (HPLC) stability-indicating assay, forced degradation under stress conditions, solubility, as well as partition and distribution coefficient measurements. An isocratic HPLC with diode array detector method was developed and validated. Accelerated degradation under different stressors (acid, alkali, heat, and oxidative) was studied. In addition, solubility, partition, and distribution were investigated at different pHs of 3.5-7.4. Results: The results indicated that the developed HPLC method was simple, rapid (retention time ≃3 min), sensitive, selective, robust, and stability indicating. The drug seems more chemically sensitive to acid degradation (∼30% and 40% of the drug was degraded under 0.1 M and 1 M HCl at 60°C for 24 h, respectively). Another significant degradation was recorded in the following order: Oxidative > alkali > heat (phosphate-buffered saline) > heat (distilled water). Being a weak ionizable drug, both water and lipid solubility, as measured through partition coefficients, it demonstrated pH-dependency. Conclusion: For the optimum balance of water and lipid solubility required for penetration through the lipophilic corneal epithelial barrier, ketorolac eye drops would be better formulated between pH 5.5 and 6.6 than being formulated at the physiological fluid pH 7.4, where the drug is extremely hydrophilic and less permeable.

Chitosan/Solid-Lipid Nanoparticles Hybrid Gels for Vaginal Delivery of Estradiol for Management of Vaginal Menopausal Symptoms.

Hormonal replacement therapy is the mainstay treatment to improve quality of life and reduce mortality. With the increasing number of young women with early menopause, women now live longer (increased life expectancy). However, poor patient compliance with oral estrogen therapy has emerged. Intravaginal estrogen therapy can provide significant benefits with minimal risk for postmenopausal women with symptoms of the lower urinary tract and vaginal area but who do not want to take oral estrogen. In this study, estradiol-loaded solid lipid nanoparticles (SLPs) were prepared from compritol ATO 888 and precirol ATO 5, and two different stabilizers (Pluronic F127 and Tween 80) were studied. Selected SLPs (F3 and F6) were coated with different concentrations of the mucoadhesive and sustained-release polymer chitosan. Furthermore, gelation time, viscosity, mucoadhesion, ex vivo permeation, and in vitro irritation for vaginal irritation were studied. Particle sizes ranged between 450-850 nm, and EE% recorded 50-83% for the six SLPs depending on the type and amount of lipids used. Cumulative % drug release was significantly enhanced and was recorded at 51% to 83%, compared to that (less than 20%) for the control suspension of estradiol. Furthermore, extensive thermal gelation and mucoadhesion were recorded for chitosan-coated SLPs. Up to 2.2-fold increases in the permeation parameters for SLPs gels compared to the control suspension gel were recorded, revealing a slight to moderate irritation on Hela cell lines. These findings demonstrated chitosan-coated estradiol SLPs as novel and promising vaginal mucoadhesive hybrid nanogels.

Formulation and In-Vitro/Ex-Vivo Characterization of Pregelled Hybrid Alginate-Chitosan Microparticles for Ocular Delivery of Ketorolac Tromethamine.

Innovative hybrid chitosan-sodium alginate (Ch-Ag) microparticles (MPs) were fabricated using both the ionic gelation method as well as the pre-gelation technique. The hybrid Ch-Ag MPs were studied for size, zeta potential, morphology, mucoadhesion, in-vitro release, corneal permeation, and ocular irritation using lens and corneal epithelial cell lines. The average particle size ranged from 1322 nm to 396 nm. The zeta potential for the prepared formulations showed an increase with increasing Ch concentrations up to a value of >35 mV; the polydispersity index (PDI) of some optimized MPs was around 0.1. Compared to drug-free MPs, ketorolac-loaded Ch-Ag MPs demonstrated a drug proportion-dependent increase in their size. SEM, as well as TEM of KT-loaded MPs, confirmed that the formed particles were quasi-spherical to elliptical in shape. The KT release from the MPs demonstrated a prolonged release profile in comparison to the control KT solution. Further, mucoadhesion studies with porcine mucin revealed that the KT-loaded MPs had effective mucoadhesive properties, and polymeric particles were stable in the presence of mucin. Corneal permeation was studied on bovine eyes, and the results revealed that Ch-based MPs were capable of showing more sustained KT release across the cornea compared with that for the control drug solution. Conclusively, the cytotoxicity assay confirmed that the investigated MPs were non-irritant and could confer protection from direct drug irritation of KT on the ocular surface. The MTT cytotoxicity assay confirmed that KT-loaded MPs showed acceptable and reasonable tolerability with both human lens and corneal epithelial cell lines compared to the control samples.

Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.

M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention.

Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection.

Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds' immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.

Carvedilol Precipitation Inhibition by the Incorporation of Polymeric Precipitation Inhibitors Using a Stable Amorphous Solid Dispersion Approach: Formulation, Characterization, and In Vitro In Vivo Evaluation.

An amorphous solid dispersion (ASD) of carvedilol (CVL) was prepared via the solvent evaporation method, using cellulose derivatives as polymeric precipitation inhibitors (PPIs). The prepared ASDs existed in the amorphous phase, as revealed by X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). The Fourier-transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) results confirmed the compatibility between CVL and the polymers used. The ASDs characteristics were evaluated, with no change in viscosity, a pH of 6.8, a polydispersity index of 0.169, a particle size of 423-450 nm, and a zeta potential of 3.80 mV. Crystal growth inhibition was assessed for 180 min via an infusion precipitation study in simulated intestinal fluid (SIF). The interactions between the drug and polymers were established in great detail, using nuclear magnetic resonance (NMR) spectroscopy, nuclear Overhauser effect spectroscopy (NOESY), and Raman spectroscopy studies. Dielectric analysis was employed to determine the drug-polymer interactions between ion pairs and to understand ion transport behavior. In vivo oral kinetics and irritation studies performed on Wistar rats have demonstrated promising biocompatibility, stability, and the enhanced bioavailability of CVL. Collectively, the stable ASDs of CVL were developed using cellulose polymers as PPIs that would inhibit drug precipitation in the gastrointestinal tract and would aid in achieving higher in vivo drug stability and bioavailability.

Design, Preparation and Evaluation of Supramolecular Complexes with Curcumin for Enhanced Cytotoxicity in Breast Cancer Cell Lines.

Curcumin is one of the most researched phytochemicals by pharmacologists and formulation scientists to unleash its potential therapeutic benefits and tackle inherent biopharmaceutic problems. In this study, the native ß-cyclodextrin (CD) and three derivatives, namely, Captisol (sulfobutyl ether ß-CD), hydroxypropyl ß-cyclodextrin, and hydroxyethyl ß-cyclodextrin were investigated for inclusion complexes with curcumin using two preparation methods (physical mixing and solvent evaporation). The prepared complexes were studied for docking, solubility, FTIR, DSC, XRD, and dissolution rates. The best-fitting curcumin: cyclodextrins (the latter of the two CDs) were evaluated for cytotoxicity using human breast cell lines (MCF-7). Dose-dependent cytotoxicity was recorded as IC50% for curcumin, curcumin: hydroxyethyl ß-cyclodextrin, and curcumin: hydroxypropyl ß-cyclodextrin were 7.33, 7.28, and 19.05 µg/mL, respectively. These research findings indicate a protective role for the curcumin: hydroxypropyl ß-cyclodextrin complex on the direct cell lines of MCF-7.

Novel Drug Delivery Systems as an Emerging Platform for Stomach Cancer Therapy.

Cancer has long been regarded as one of the world's most fatal diseases, claiming the lives of countless individuals each year. Stomach cancer is a prevalent cancer that has recently reached a high number of fatalities. It continues to be one of the most fatal cancer forms, requiring immediate attention due to its low overall survival rate. Early detection and appropriate therapy are, perhaps, of the most difficult challenges in the fight against stomach cancer. We focused on positive tactics for stomach cancer therapy in this paper, and we went over the most current advancements and progressions of nanotechnology-based systems in modern drug delivery and therapies in great detail. Recent therapeutic tactics used in nanotechnology-based delivery of drugs aim to improve cellular absorption, pharmacokinetics, and anticancer drug efficacy, allowing for more precise targeting of specific agents for effective stomach cancer treatment. The current review also provides information on ongoing research aimed at improving the curative effectiveness of existing anti-stomach cancer medicines. All these crucial matters discussed under one overarching title will be extremely useful to readers who are working on developing multi-functional nano-constructs for improved diagnosis and treatment of stomach cancer.

Anti-Proliferative Potential of Quercetin Loaded Polymeric Mixed Micelles on Rat C6 and Human U87MG Glioma Cells.

Quercetin (Qu) is a natural flavonoid present in many commonly consumed food items and is also identified as a potential anticancer agent. The present study evaluates the Qu-loaded polymeric mixed micelles (Qu-PMMs) against C6 and U87MG glioma cell lines. The Box-Behnken Design (BBD) was employed to study the influence of independent variables such as Soluplus, Vitamin-E polyethyleneglycol-1000 succinate (E-TPGS), and poloxamer 407 concentrations on dependent variables including particle size (PS), polydispersity index (PDI), and percentage entrapment efficiency (%EE) of the prepared Qu-PMMs. The Qu-PMMs were further characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), and were assessed for in vitro drug release, effect on cell viability, migration, cellular uptake, and apoptosis assays. The PS, PDI, and % EE of the optimized PMMs were 107.16 ± 1.06 nm, 0.236 ± 0.053, and 77.46 ± 1.94%, respectively. The FTIR and XRD revealed that the Qu was completely entrapped inside the PMMs. The SEM analysis confirmed the spherical shape of micelles. The in vitro cell viability study showed that the Qu-PMMs had 1.7 times higher cytotoxicity against C6 and U87MG cells than Qu pure drug (Qu-PD). Furthermore, Qu-PMMs demonstrated superior cellular uptake, inhibited migration, and induced apoptosis when tested against C6 and U87MG cells than pure Qu. Thus, the polymeric mixed micelle (PMMs) enhanced the therapeutic effect of Qu and can be considered an effective therapeutic strategy to treat Glioma.

Development and Characterization of Oral Raft Forming In Situ Gelling System of Neratinib Anticancer Drug Using 32 Factorial Design.

Neratinib (NTB) is an irreversible inhibitor of pan-human epidermal growth factor receptor (HER-2) tyrosine kinase and is used in the treatment of breast cancer. It is a poorly aqueous soluble drug and exhibits extremely low oral bioavailability at higher pH, leading to a diminishing of the therapeutic effects in the GIT. The main objective of the research was to formulate an oral raft-forming in situ gelling system of NTB to improve gastric retention and drug release in a controlled manner and remain floating in the stomach for a prolonged time. In this study, NTB solubility was enhanced by polyethylene glycol (PEG)-based solid dispersions (SDs), and an in situ gelling system was developed and optimized by a two-factor at three-level (32) factorial design. It was analyzed to study the impact of two independent variables viz sodium alginate [A] and HPMC K4M [B] on the responses, such as floating lag time, percentage (%) water uptake at 2 h, and % drug release at 6 h and 12 h. Among various SDs prepared using PEG 6000, formulation 1:3 showed the highest drug solubility. FT-IR spectra revealed no interactions between the drug and the polymer. The percentage of drug content in NTB SDs ranged from 96.22 ± 1.67% to 97.70 ± 1.89%. The developed in situ gel formulations exhibited a pH value of approximately 7. An in vitro gelation study of the in situ gel formulation showed immediate gelation and was retained for a longer period. From the obtained results of 32 factorial designs, it was observed that all the selected factors had a significant effect on the chosen response, supporting the precision of design employed for optimization. Thus, the developed oral raft-forming in situ gelling system of NTB can be a promising and alternate approach to enhance retention in the stomach and to attain sustained release of drug by floating, thereby augmenting the therapeutic efficacy of NTB.

Design and Development of Neomycin Sulfate Gel Loaded with Solid Lipid Nanoparticles for Buccal Mucosal Wound Healing.

Drug administration to the wound site is a potential method for wound healing. The drug retention duration should be extended, and drug permeability through the buccal mucosal layer should be regulated. Oral wounds can be caused by inflammation, ulcers, trauma, or pathological lesions; if these wounds are not treated properly, they can lead to pain, infection, and subsequent undesirable scarring. This study aimed to develop Kolliphor-407 P-based gel containing neomycin sulfate (NES) loaded in solid lipid nanoparticles (SLNs) and enhance the antimicrobial activity. By considering lipid concentrations and achieving the lowest particle size (Y1) and maximum entrapment (EE-Y2) effectiveness, the formulation of NES-SLN was optimized using the Box-Behnken design. For the selected responses, 17 runs were formulated (as anticipated by the Design-Expert software) and evaluated accordingly. The optimized formulation could achieve a particle size of 196.25 and EE of 89.27% and was further utilized to prepare the gel formulation. The NES-SLN-G formula was discovered to have a smooth, homogeneous structure and good mechanical and rheological properties. After 24 h of treatment, NES-SLN-G showed a regulated in vitro drug release pattern, excellent ex vivo permeability, and increased in vitro antibacterial activity. These findings indicate the potential application of NES-SLN-loaded gels as a promising formulation for buccal mucosal wound healing.

The Unique Carboxymethyl Fenugreek Gum Gel Loaded Itraconazole Self-Emulsifying Nanovesicles for Topical Onychomycosis Treatment.

The novel itraconazole (ITZ) nail penetration enhancing self-emulsifying nanovesicles (ITZ-nPEVs) loaded in carboxymethyl fenugreek gum (CMFG) gel circumvent the systemic onychomycosis treatment. The ITZ-nPEVs were prepared by the thin film hydration technique, and the particle size (PS), zeta potential (ZP), drug content (DC), entrapment efficiency (% EE), deformity index (DI), viscosity, morphology, and physical stability of the ITZ-nPEVs were measured. In terms of nail hydration, transungual drug absorption, and antifungal efficacy against Candida albicans, the chosen ITZ-nPEVs, nPEV-loaded CMFG (CMFG-ITZ-nPEVs) gel, and the commercialized Itrostred gel were compared. The ITZ-nPEVs showed spherical structure with high DC, % EE, low PS and PDI and positive ZP of ITZ ranging from 95.36 to 93.89 mg/5 mL and 95.36-96.94%, 196.55-252.5 nm, 0.092-0.49, and +11.1 to +22.5 mV, respectively. Compared to the Itrostred gel, the novel ITZ-nPEVs exhibited hydration enhancement factor for 24 h (HE24) of 1.53 and 1.39 drug uptake enhancement factor into nail clippings. Moreover, zone of inhibitions for ITZ-nPEVs (27.0 ± 0.25 mm) and CMFG-ITZ-nPEVs (33.2 ± 0.09 mm) against Candida albicans were significantly greater than that of Itrostred gel (22.9 ± 0.44 mm). For clinical investigation on onychomycotic patients, a nail penetration enhancer containing ITZ-nPEV-loaded CMFG gel presents a highly promising approach.

A Novel Curcumin Arginine Salt: A Solution for Poor Solubility and Potential Anticancer Activities.

Curcumin is a natural polyphenolic compound with well-known anticancer properties. Poor solubility and permeability hamper its use as an anticancer pharmaceutical product. In this study, L-arginine, a basic amino acid and a small hydrophilic molecule, was utilized to form a salt with the weak acid curcumin to enhance its solubility and potentiate the anticancer activities of curcumin. Two methods were adopted for the preparation of curcumin: L-arginine salt, namely, physical mixing and coprecipitation. The ion pair or salt was characterized for docking, solubility, DSC, FTIR, XRD, in vitro dissolution, and anticancer activities using MCF7 cell lines. The molecular docking suggested a salt/ion-pair complex between curcumin and L-arginine. Curcumin solubility was increased 335- and 440-fold by curcumin in L-arginine, physical, and co-precipitated mixtures, respectively. Thermal and spectral analyses supported the molecular docking and formation of a salt/ion pair between curcumin and L-arginine. The cytotoxicity of curcumin L-arginine salt significantly improved (p < 0.05) by 1.4-fold, as evidenced by the calculated IC50%, which was comparable to Taxol (the standard anticancer drug but with common side effects).

Superfast Synthesis of Stabilized Silver Nanoparticles Using Aqueous Allium sativum (Garlic) Extract and Isoniazid Hydrazide Conjugates: Molecular Docking and In-Vitro Characterizations.

Green synthesis of silver nanoparticles (AgNPs) was synthesized from fresh garlic extract coupled with isoniazid hydrazide (INH), a commonly used antibiotic to treat tuberculosis. A molecular docking study conducted with the selected compounds compared with anthranilate phosphoribosyltransferase (trpD) from Mycobacterium tuberculosis. The aqueous extract of garlic was prepared and mixed with silver nitrate (AgNO3) solution for the superfast synthesis of stable AgNPs. INH was then conjugated with AgNPs at different ratios (v/v) to obtain stable INH-AgNPs conjugates (AgNCs). The resulting AgNCs characterized by FTIR spectra revealed the ultrafast formation of AgNPs (<5 s) and perfectly conjugated with INH. The shifting of λmax to longer wavelength, as found from UV spectral analysis, confirmed the formation of AgNCs, among which ideal formulations (F7, F10, and F13) have been pre-selected. The zeta particle size (PS) and the zeta potential (ZP) of AgNPs were found to be 145.3 ± 2.1 nm and -33.1 mV, respectively. These data were significantly different compared to that of AgNCs (160 ± 2.7 nm and -14.4 mV for F7; 208.9 ± 2.9 nm and -19.8 mV for F10; and 281.3 ± 3.6 nm and -19.5 mV for F13), most probably due to INH conjugation. The results of XRD, SEM and EDX confirmed the formation of AgNCs. From UV spectral analysis, EE of INH as 51.6 ± 5.21, 53.6 ± 6.88, and 70.01 ± 7.11 %, for F7, F10, and F13, respectively. The stability of the three formulations was confirmed in various physiological conditions. Drug was released in a sustainable fashion. Besides, from the preferred 23 compounds, five compounds namely Sativoside R2, Degalactotigonin, Proto-desgalactotigonin, Eruboside B and Sativoside R1 showed a better docking score than trpD, and therefore may help in promoting anti-tubercular activity.

Chemosensitization and mitigation of Adriamycin-induced cardiotoxicity using combinational polymeric micelles for co-delivery of quercetin/resveratrol and resveratrol/curcumin in ovarian cancer.

This work looks to improve the efficacy of Adriamycin (ADR) while mitigating its cardiotoxicity using combinations of micellar resveratrol (R): quercetin (Q) (mRQ) or R: curcumin (C) (mRC) in healthy mice and ovarian cancer xenograft models. Ovarian cancer cells, ES2-Luc, or A2780ADR are inoculated in mice (n =4/group) and sorted into eight cohorts. Mice are treated weekly for 4 weeks with ADR, ADR+mRQ, ADR+mRC, or controls (saline, empty micelles, ADR+EM, mRQ, or mRC). To evaluate the degree of cardioprotection, serum is collected to determine the cardiac Troponin I (cTnI). Cardiac tissue is collected for morphological evaluation and evaluation of creatine kinase levels. Our results indicate that mRQ+ADR is statistically significant in tumor reduction in xenograft models. In healthy mice, the left ventricular ejection fraction and fractional shortening in the ADR treated group is most compromised. Co-administration of mRQ with ADR can reduce ADR dosing through chemosensitization while being cardioprotective.