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Sitagliptin (STG) is assigned pharmacologically as a dipeptidyl peptidase-4 enzyme inhibitor. The aforementioned drug, which is taken by mouth either alone or in conjunction with metformin, is used to manage class 2 diabetes. In the proposed study, the ideal utility of the dihydropyridine derivative was applied for STG assessment in an affordable, sensitive, and economical way. The functional amine primary group in STG enables coupling with pentane-2,4-dione to create a fluorescent molecule with the aid of formaldehyde (7.2% v/v) in the reaction. Spectrofluorimetric excitation and emission processes, respectively, at 421.7 and 478.9 nm were used to follow the developed yield of dihydropyridine fluorophore. The experimental circumstances were thoroughly inspected and controlled appropriately. The calibration plot was produced by plotting values of fluorescence intensities against STG concentrations. However, the regulated linearity was observed at STG concentration intervals from 0.1 to 1.5 µg/mL. The effectiveness of the technique was evidenced by a detailed inspection of the ICH criteria. The technique for monitoring STG in various dosage forms and/or spiking biological fluids was effectively used for research purposes. The presently developed method utility for pentane-2,4-dione is a simple, effective, and quick alternative tool for quality control and clinical study assays of STG.

In this study, nickel tungstate (NiW) nanospheres were synthesized using a facile hydrothermal method. The morphology of the NiW nanospheres was found to vary with hydrothermal reaction time (4, 6, 8, and 10 h) at a constant reaction temperature. Different physico-chemical tools such as XRD, FESEM, EDAX and Elemental Mapping are used for the characterization of NiW sample. X-ray diffraction (XRD) analysis revealed that the NiW material exhibited a monoclinic crystal system with a P2/c space group. The Field Emission scanning electron microscopy (FE-SEM) analysis reveals a spherical morphology. Electrochemical measurements of NiW electrodes were conducted in a 1 M KOH electrolyte within a potential window of 0 to 0.5 V vs SCE. The NiW electrode synthesized after a 4 h reaction time exhibited a specific capacitance of 857 F/g at a scan rate of 5 mV/s. The specific capacitance determined from the GCD curve was 783 F/g at a current density of 5 mA/cm2. Additionally, the NiW-4 electrode exhibits an excellent energy density of 27.4 Wh/kg at a power density of 1645 W/kg and outstanding cyclic stability with 86.24 % retention after 5000 charge/discharge cycles. These findings suggest that the synthesized NiW could serve as a highly efficient electrode material for energy storage applications.

The objective of the proposed investigation is the development and validation of a green stability-indicating reverse-phase high-performance thin-layer chromatographic method to determine croconazole hydrochloride (CCZ). The developing system used was an 80:20 v/v mixture of acetone and water. The measurement of CCZ was done at 198 nm. With the use of the Analytical Eco-Scale (AES), ChlorTox, and Analytical GREEnness (AGREE) tools, greenness was evaluated. The linearity was demonstrated by the present method in the 25–1,200 ng/band range. The present approach was additionally reliable, accurate, sensitive, precise, and green. An exceptional greenness profile was demonstrated by the AES, total ChlorTox, and AGREE scales, which were determined to be 89, 1.08 g, and 0.82, respectively. The greenness metrics of the present method were much better than the reported high-performance liquid chromatography approach. Under acid and oxidative degradation circumstances, CCZ was shown to be unstable, while under alkaline and thermal-stress settings, it was sufficiently stable. Furthermore, the stability-indicating component determined by analytical method identified CCZ in the presence of its degradation products. Commercial CCZ cream was found to contain 0.98% w/w of CCZ. The investigation’s results suggested that CCZ in commercially available creams might be regularly examined with the help of the recommended green technology.

So far, no documented method for simultaneously analyzing lesinurad (LND) and febuxostat (FBX) has been reported for either traditional high-performance thin-layer chromatography (HPTLC) or a green HPTLC technique. In order to determine LND and FBX simultaneously in commercially available fixed-dose combo tablets, this study devised a normal-phase HPTLC method that is fast, sensitive, and green. The green eluents for the simultaneous analysis of LND and FBX were a mixture of ethyl acetate:ethanol:water at 70:20:10 (v/v/v) ratio. The new approach’s greenness was predicted utilizing four distinct greenness tools: the National Environmental Method Index, Analytical Eco-Scale, ChlorTox, and Analytical GREENness approaches, and the results revealed a significantly greener profile. The current method operated on a linear scale between 30 and 1,000 ng·band−1. It was confirmed that the current approach is sensitive, accurate, precise, robust, and green. The LND and FBX contents of commercially available tablet products A and B were found to be within the range of 100 ± 2%, indicating that the existing methodology for simultaneously determining LND and FBX in pharmaceutical combination products is applicable. The results of the current methodology indicated that LND and FBX could be consistently measured in pharmaceutical combination products simultaneously using the current approach.

A fast, sensitive, and green reverse-phase “high-performance thin-layer chromatography” approach for the simultaneous estimation of ibuprofen (IBF), caffeine (CAF), and paracetamol (PCM) in marketed formulations was established and verified in this study. The binary combination of acetone and water (80:20 v/v) was used as the green eluent system. The current method’s greenness was predicted using four different approaches, namely National Environmental Method Index, Analytical Eco-Score (89), ChlorTox (1.08 g), and the Analytical GREENness (83) approaches, which demonstrated an outstanding greener profile. The present approach was linear in the range of 25–800 ng·band−1for the simultaneous estimation of IBF, CAF, and PCM. In addition, the current method was accurate (% recoveries = 100 ± 2), precise (%CV < 2%), robust (%CV < 2), sensitive (LOD = 1.13–2.71 ng·band−1and LOQ = 3.39–8.10 ng·band−1), and green. The amount of IBF, CAF, and PCM in commercial tablets was determined to be 99.51%, 98.25%, and 100.64%, respectively. The present method for the simultaneous determination of IBF, CAF, and PCM in marketed tablets is supported by these data. The findings of this study suggested that the current approach may be consistently applied to analyze IBF, CAF, and PCM in marketed tablets.

The performance of multiparametric magnetic resonance imaging (mpMRI) and subsequent biopsy in monitoring prostate cancer in men on active surveillance (AS) have not been defined clearly. In this systematic review, we aimed to review current literature about the usage of MRI examination in men with low-risk prostate cancer during active surveillance. For that, we searched seven databases to include all studies reporting magnetic resonance imaging in the AS of low-risk prostate cancer. We finally included 11 studies with 1237 patients included. Our results showed an adequate sensitivity and specificity of both modalities to detect disease progression; including disease upgrading and upstaging. However, the performance in the prediction of unfavorable disease was inferior to the detection of upgrading and upstaging. In terms of MRGB, the previous literature agreed on the superiority of using a combination of different biopsy schemes to get a better progression section. Noteworthy, mp-MRI and MRGB had a good predictive value limited to the first year, with TRUSGB showing a superior role in detecting patients with a GS ≥ 7, after that. In conclusion, both of mpMRI and MRGB have shown an adequate performance on assessing disease progression in the AS of low-risk prostate cancer patients. They can be used for disease staging and grading for successful treatment planning.

Quercetin (QT, 3,3′,4′,5,7-pentahydroxyflavone), is a natural flavonoid with nutritional value and acts as a potential free-radical scavenger (antioxidant). QT has also been explored for its anti-cancer as well as anti-proliferative activities against numerous cancerous cells. Moreover, QT exhibits significant pro-apoptotic activity against tumor cells and is well established to control the growth of different carcinoma cells at various phases of the cell cycle. Hence, it can reduce the burden of human solid cancer and metastasis. Both these activities have been established in a diverse class of human cell lines in-vitro as well as in animal models (in-vivo). Apart from the promising therapeutic activities of QT molecule, their applications have been limited due to some major concerns, including low oral bioavailability and poor aqueous solubility. Also, rapid gastrointestinal digestion of QT seems to be a key barrier for its clinical translations for oral drug delivery in conventional dosage form. Henceforth, to overcome these drawbacks, QT is loaded with liposomal systems, which exhibit promising outcomes in the upregulation of QT by the epithelial system and also improved its targeting at the site of action. Furthermore, Liposomes based Drug Delivery Systems (LDDS) have showed significant therapeutic activity with conjugated drug moiety and exhibit safety, biocompatibility, biodegradability, and mitigated toxicity despite having certain limitations associated with physiological and biological barriers. Herein, in this review, we have focused on the mechanism related with the chemotherapeutic activity of QT and also discussed the promising activity of QT-loaded LDDS as a potent chemotherapeutic agent for cancer therapy.

•The prevalence of NBD in our cohort was found to be in one in six patients with BD.•Symptoms of NBD commonly include headache, weakness, and unsteadiness.•The most commonly involved sites on imaging were the diencephalon, basal ganglia and hemispheres.•Favorable outcomes were seen in most NBD patients in our cohort.

Pharmaceuticals and personal care products (PPCPs) are one of the emerging pollutants (EPs) groups that attracted the environmentalist’s attention according to the increase in their demand. Diclofenac (DFC) is an anti-inflammatory medication used as a first-line treatment for pain. Around 15% of DFC is unmetabolized after human consumption, leading to an increase in the opportunity to release DFC into the environment. DFC may build up in the environment over time, which increases its negative impacts on the ecosystem. Several biological, physical, and chemical techniques have been applied to treat DFC. This review provides an overview of the photodegradation of DFC including photodegradation efficiency, mechanism, the role of physicochemical parameters, and toxicity assessment. Generally, the photodegradation systems showed high efficiency in the removal. However, each experiment has been applied under different experimental conditions and different parameters such as the type and dosage of catalyst, the chosen wavelength of the radiation, pH, temperature, and additive concentration. This led to the differentiation in the photodegradation efficiency and photodegradation rate of DFC. We revealed that the physicochemical parameters of the photocatalytic process are a double edge sword. On the one hand, raising their values up to a certain point might help the treatment work well. On the other hand, a significant rise has a negative impact on the effectiveness of the treatment and raises the expense of the treatment operation. The toxicity tests indicated that most frequent DFC by-products are not safe, and their release into the environment may negatively affect the ecosystem. This review may provide a useful recommendation for future researchers who want to treat DFC by photodegradation and enables them to enhance the applicability of photodegradation.

The aim of the study was to prepare lansoprazole (LNS)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles in order to improve the physicochemical stability associated with LNS. We synthesized LNS-loaded PLGA nanoparticles in the presence of magnesium oxide as alkalizer to improve the release of LNS and stability against photodegradation. The LNS-encapsulated PLGA nanoparticles were developed by the nanoprecipitation/solvent evaporation method, resulting in a particle size of 246.7 ± 3.4 nm, polydispersity index (PDI) of 0.126, percent drug entrapment (PDE) of 82.85 ± 4.5%, percent drug loading (PDL) of 3.54 ± 0.34%, and pH of 8.10 ± 0.56. The developed nanoparticles were further evaluated for in vitrorelease and resistance to photodegradation by NMR spectroscopy and LC-MS. The sustained release of the drug was confirmed after the encapsulation of LNS in the PLGA matrix. The protection of LNS in the PLGA matrix against photodegradation was confirmed by NMR and LC-MS studies. The LC-MS of UV-exposed samples of pure LNS and LNS-loaded PLGA nanoparticles at 254 nm showed the same (M + 1) peak at 370 m/e, and the base peak at 369 m/eaccounted for the unchanged structure of LNS inside PLGA nanoparticles. Overall, it was proved that PLGA nanoparticles in the presence of magnesium oxide are an efficient carrier to deliver and protect LNS from physicochemical instability.

Background: The poor oral bioavailability of newly discovered chemical entities and marketed formulations are usually related to poor aqueous solubility or poor permeability, leading to drug failure in the development phases or therapeutic failure in a clinical setting. However, advancement in drug formulations and delivery technologies have enabled scientists to improve the bioavailability of formulations by enhancing solubility or permeability. Objective: This study reports the enhancement of the oral bioavailability of ibrutinib (IBR), a poorly soluble anticancer drug in Wistar albino rats. Methods: IBR loaded nanoparticles were formulated through the nanoprecipitation method by utilizing poly lactide-co-glycolide (PLGA) as a safe, biodegradable and biocompatible polymer, and poloxamer or pluronic 127 as a stabilizer. Animals were administered with a dose of 10 mg/kg of IBR suspension or an equivalent amount of IBR loaded nanoparticles. Plasma samples were extracted and analyzed by state of the art UPLC-MS/MS technique. Pharmacokinetic (PK) parameters and bioavailability were calculated by non-compartmental analysis. Results: There was an approximately 4.2-fold enhancement in the oral bioavailability of IBR-loaded nanoparticles, as compared to the pure IBR suspension. The maximum plasma concentration (Cmax; 574.31 ± 56.20 Vs 146.34 ± 5.37 ng/mL) and exposure (AUC; 2291.65 ± 263.83 vs 544.75 ± 48.33 ng* h/mL) of IBR loaded nanoparticles were significantly higher than those exhibited through pure IBR suspension. Conclusion: The outcomes of the present study suggested the potential of PLGA nanoparticles in the enhancement of bioavailability and the therapeutic efficacy of IBR.

Background: The poor oral bioavailability of newly discovered chemical entities and marketed formulations are usually related to poor aqueous solubility or poor permeability, leading to drug failure in the development phases or therapeutic failure in a clinical setting. However, advancement in drug formulations and delivery technologies have enabled scientists to improve the bioavailability of formulations by enhancing solubility or permeability. Objective: This study reports the enhancement of the oral bioavailability of ibrutinib (IBR), a poorly soluble anticancer drug in Wistar albino rats. Methods: IBR loaded nanoparticles were formulated through the nanoprecipitation method by utilizing poly lactide-co-glycolide (PLGA) as a safe, biodegradable and biocompatible polymer, and poloxamer or pluronic 127 as a stabilizer. Animals were administered with a dose of 10 mg/kg of IBR suspension or an equivalent amount of IBR loaded nanoparticles. Plasma samples were extracted and analyzed by state of the art UPLC-MS/MS technique. Pharmacokinetic (PK) parameters and bioavailability were calculated by non-compartmental analysis. Results: There was an approximately 4.2-fold enhancement in the oral bioavailability of IBR-loaded nanoparticles, as compared to the pure IBR suspension. The maximum plasma concentration (Cmax; 574.31 ± 56.20 Vs 146.34 ± 5.37 ng/mL) and exposure (AUC; 2291.65 ± 263.83 vs 544.75 ± 48.33 ng* h/mL) of IBR loaded nanoparticles were significantly higher than those exhibited through pure IBR suspension. Conclusion: The outcomes of the present study suggested the potential of PLGA nanoparticles in the enhancement of bioavailability and the therapeutic efficacy of IBR.

Background: Nano drug delivery systems have the potential to address the challenges of delivering BCS Class II and IV drugs like furosemide. The purpose of the current study is to prepare stable nanosuspension and investigate in vitro dissolution performance of the model compound furosemide using quality by design (QbD) approach. Methods: Nanosuspension batches with uniform particle size were prepared for furosemide using the antisolvent precipitation method. A quality by design (Qbd) approach was explored to understand the impact of process parameters (stirring time, stirring speed, temperature, and injection rate) and material attributes (drug concentration, stabilizer type, drug: stabilizer ratio, and antisolvent: solvent ratio) on the quality attributes of furosemide nanosuspension using a full factorial experimental design. Multiple linear regression and ANOVA were employed to estimate and identify the critical process parameters and material attributes. Injection rate and stirring time were identified as the most critical process parameters’ affecting the quality attributes of furosemide nanosuspension. Results: Individual material attributes did not show significant impact on the average particle size of the nanocrystals, however two-way interactions between material attributes (stabilizer type/drug concentration and stabilizer type/antisolvent: solvent ratio) significantly affected nanosuspension particle size distribution. Solid state characterization (PXRD, DSC and SEM) did not exhibit any changes of physical form during preparation and optimization of the furosemide nanosuspension. Dissolution of the furosemide nanocrystals in gastric media was significantly higher than that observed for micronized furosemide suspension and raw furosemide powder. Stability study data suggests that optimized batches of furosemide nanosuspensions were stable for three months at 4°C and ambient conditions. Conclusion: The antisolvent precipitation method can produce stable furosemide nanosuspensions with desirable quality attributes and enhancement of dissolution rate in the gastric medium as compared to the raw furosemide powder and microsuspension.

This study intended to optimize apigenin (APG) nanoparticle formulation prepared by planetary ball milling to enhance its dissolution rate and bioavailability using a design of experiment (DoE). In this study, polyvinyl pyrrolidone (PVP K30) was used as a nanoparticle stabilizer. The independent parameters of milling speed, milling ball size, and drug to solvent ratio were evaluated for their impacts on APG nanoparticles concerning the nanoparticle size (Y1), zeta potential (Y2), and drug dissolution efficiency after 60 min, notated as % DE60(Y3). The milling ball size showed a significant antagonistic effect (P= 0.0210) on the size of APG nanoparticles, while milling speed had an agonistic effect on the zeta potential values of drug nanoparticles, ranging from low to medium speed levels. In addition, ANOVA analysis indicated that the effect of the drug-to-solvent ratio on the % DE60of APG from the nanoparticle formulations was antagonistically significant (P= 0.015), and the quadratic effect of milling speed (AA) also had a significant antagonistic effect (P= 0.025) on the % DE60. Risk assessment analytical tools revealed that milling ball size and milling speed significantly affect the nanoparticle size. The drug/solvent ratio exerted a strong impact on % DE60. Furthermore, the maximum plasma concentration (Cmax) of the optimized APG nanoparticle formula increased by four folds. In addition, AUC0–t(ng·mL−1·h−1) for APG nanoparticle (353.7 ± 185.3 ng·mL−1·h−1) was higher than that noticed in the case of the untreated drug (149 ± 137.5 ng·mL−1·h−1) by more than two folds.

The objective of this study was to investigate the extrudability, drug release, and stability of fenofibrate (FF) formulations utilizing various hot-melt extrusion processing parameters and polyvinylpyrrolidone (PVP) polymers of various molecular weights. The different PVP grades selected for this study were Kollidon®12 PF (K12), Kollidon®30 (K30), and Kollidon®90 F (K90). FF was extruded with these polymers at three drug loadings (15%, 25%, and 35% w/w). Additionally, for FF combined with each of the successfully extruded PVP grades (K12 and K30), the effects of two levels of processing parameters for screw design, screw speed, and barrel temperature were assessed. It was found that the FF with (K90) was not extrudable up to 35% drug loading. With low drug loading, the polymer viscosity significantly influenced the release of FF. The crystallinity remaining was vital in the highest drug-loaded formulation dissolution profile, and the glass transition temperature of the polymer significantly affected its stability. Modifying the screw configuration resulted in more than 95% post-extrusion drug content of the FF–K30 formulations. In contrast to FF–K30 formulations, FF release and stability with K12 were significantly influenced by the extrusion temperature and screw speed.

The objective of this study was to enhance the solubility as well as to mask the intensely bitter taste of the poorly soluble drug, Mefenamic acid (MA). The taste masking and solubility of the drug was improved by using Eudragit®E PO in different ratios via hot melt extrusion (HME), solid dispersion technology. Differential scanning calorimetry (DSC) studies demonstrated that MA and E PO were completely miscible up to 40% drug loads. Powder X-ray diffraction analysis indicated that MA was converted to its amorphous phase in all of the formulations. Additionally, FT-IR analysis indicated hydrogen bonding between the drug and the carrier up to 25% of drug loading. SEM images indicated aggregation of MA at over 30% of drug loading. Based on the FT-IR, SEM and dissolution results for the extrudates, two optimized formulations (20% and 25% drug loads) were selected to formulate the orally disintegrating tablets (ODTs). ODTs were successfully prepared with excellent friability and rapid disintegration time in addition to having the desired taste-masking effect. All of the extruded formulations and the ODTs were found to be physically and chemically stable over a period of 6 months at 40 °C/75% RH and 12 months at 25 °C/60% RH, respectively.

Genistein (GT) is a poorly water-soluble flavonoid and reported for different biological activity. The present work was designed to prepare the inclusion complex using β-Cyclodextrins (β-CDs) as complexing agent and D -α-Tocopherol polyethylene glycol 1000 succinate (TPGS) as ternary substance to enhance the solubility and in vitroactivity. The inclusion complex was prepared by solvent evaporation method and characterized for different physicochemical parameters. The selected GT ternary inclusion complex was further evaluated for in vitroantioxidant and cell viability study against breast cancer cell line. The phase solubility study result data revealed significantly marked enhancement in the solubility of GT. The complexation efficiency (CE) and stability constant (Ks) of GTBIC and GTTIC2 was found to 0.31% and 0.48% as well as 419.67 M-1and 654.98 M-1, respectively. The saturation solubility results depicted a significant (p < 0.05) enhancement in the saturation solubility (2.61 and 5.27-fold) of GT. Genistein ternary inclusion complex (GTTIC2) prepared with TPGS (0.05%, w/w) showed the maximum release pattern 96.5 ± 3.98% in 90 min. The DSC and XRD spectra showed the transformation of crystalline GT into the amorphous state after complexation. The infrared (IR) and nuclear magnetic resonance (NMR) spectra confirms the formation of inclusion complex by showing changes in the characteristic peaks. GTTIC2 formulation exhibited significantly greater in-vitroantioxidant and cell viability activity against MCF7 cell than pure GT. The improved activity can be attributed to the enhanced solubility of Genistein by effective complexation in β-CDs and TPGS.

The current research was portrayed to design and optimize the Chitosan (CH) coated Buspirone-loaded nanostructured lipid carriers (BPE-CH-NLCs) for nose to brain delivery. NLCs were developed by solvent diffusion evaporation technique, coated with CH, and then optimized to the maximum efficiency using the quality by design (QbD) based Box-Behnken design (BBD). Glyceryl monostearate (GMS) & oleic acid mixture and tween 80 were used as a lipid and surfactant, respectively. The prepared NLCs were subjected to in-vitrocharacterization. In-vivopharmacokinetic and neuro-pharmacokinetic (drug targeting efficiency-DTE, direct transport percentage-DTP) parameters were evaluated on Wister rats. The results revealed that the optimized formulation exhibited acceptable PS (190.98 ± 4.72 nm), ZP (+17.47 mV), and EE (80.53 ± 1.26% w/w), and the TEM image showed that the drug was incorporated adequately in NLCs. DSC findings exposed that the drug was present in amorphous form within the NLCs. The optimized formulation exhibited 27.61 months shelf life and was found to be stable under studied conditions. The value of AUC (bioavailability) for BPE-CH-NLCs administered i.n was found to be 3.06 folds compared to BPE-CH-NLCs administered i.v, and 2.17 folds compared to BPE-Sol administered i.n. A higher value of DTE (1462.49%) for developed NLCs confirmed the brain targeting efficiency of these lipid nanoparticles. DTP value for BPE-CH-NLCs (93.16%) was significantly (p < 0.05) higher than BPE-Sol (81.63%), indicating the efficient targeting potential of lipid nanoparticles compared to drug solutions. Finally, it could be possible to infer that GMS-Oleic acid-based NLCs coated with CH might be effective carriers to administer BPE to the brain via the nasal route.

Objectives of present investigation were to develop novel high throughput green UPLC-MS/MS methods for quality control of desmopressin formulations. Two liquid chromatographic methods: Method-I based on isocratic elution and method-II based on gradient elution were developed and validated. Methods were green, since less amount of organic solvent (≤75 ​μL, per sample run time) was utilized in mobile phase. Mobile phase (0.1% formic acid in ACN, and in water), flow rate was 300 ​μL/min. Desmopressin retention time and sample run time for Method-I were 0.59 and 1.0 ​min, respectively. Retention time and sample run time for method-II were 2.03 and 2.5 ​min, respectively. Double charged ions [M ​+ ​2H]2+of desmopressin (m/z535.33 ​> ​120) were monitored in multi-reaction monitoring mode. Desmopressin was directly analyzed in water samples. Calibration curves were prepared between 50 and 600 ​ng/mL. The values of r2were 0.999. Assay and dissolution study of desmopressin formulation was successfully performed using these methods. Desmopressin was found to adsorb or react with different type of materials while handling. The specific filters (Chromafil® Xtra PTFE-45/25 0.45 ​μm, syringe filter) and tubes (glass tubes or Neutral graduated micro test tubes) were used for handling desmopressin samples.

Luteolin is a valuable natural drug for the treatment of oxidative stress associated diseases, but its use is hindered by gastric instability and poor bioavailability. Given that hybrid polymeric nanoparticles may have potential applications in the design of oral drug delivery systems, this study aims to develop luteolin loaded hybrid polylactic acid/Eudragit L100 nanoparticles. By nanoprecipitation, different formulations were prepared, optimized and characterized in terms of physicochemical properties, stability and in vivoperformance. The optimum formulation presented particle size of 452.23 ± 22.4 nm, zeta potential of 0.92 mV ± 0.04, entrapment efficiency of 71.02 ± 14.6% and loading efficiency of 11.21 ± 3.1%, in accordance with the values predicted created by Box-Behnken design. In vitro,the system was capable of protection of luteolin in simulated gastric fluid, while a release study confirmed the controlled luteolin release pattern. Interaction between system components was verified through infrared and thermal analysis. The maximum plasma concentration of luteolin in the optimized formulation was significantly improved (212.2 %, p < 0.05) when compared to conventional luteolin suspension whereas the relative bioavailability accounted 2.61-fold. In vivopharmacodynamic studies in CCL4toxicity induced model revealed faint liver, kidney and testicular changes in terms of biochemical and histological evaluation. The findings of this study revealed that hybrid polylactic acid/Eudragit L100 nanoparticles are responsible for improved pharmacological efficacy of orally administered luteolin, thereby indicating the benefits of using such system to overcome the problems facing luteolin oral delivery.

Cancer is the second well-known cause of death. Approx 18.1 million cancer cases have been recorded worldwide (9.5 million men and 8.5 million women) in 2018. In the case of women, 25.4% of cases were of breast cancer, 6.9% of cervical cancer, and it is the fourth most common cancer in women. About 3.6% of ovarian cancer from the total number of new cases diagnosed in 2018. With this expanding global burden, prevention of cancer in women is one of the most serious public health challenges of the 21st century. Nanotechnology offers advantageous drug delivery systems that support its ability to deliver therapeutic and diagnostic purpose. Nanoformulation is frequently employed precisely to aim the target organ, to maintain the bioactivity of drug load, preferentially accumulate the drug at the target site as well as reducing the cytotoxicity. There are various nanoformulation based chemotherapeutic delivery systems have been used by the US-FDA for clinical trials for treatment of breast, cervical and ovarian cancer. These delivery systems include lipid-based nanoformulation, vesicular nanosystem, polymeric nanoparticles, inorganic nanoparticle, carbon nanotubes, and theranaustic formulation. Doxil® and Abraxane® are the first anticancer nanoformulation available in the market. The aim of this review summarized potential research on nanoformulation used in the diagnosis and therapy of cancer.

The study investigated a comparative assessment of binary ethosomes (ETHOs) and elastic liposomes (ELPs) for transdermal delivery of acyclovir sodium (ACV-Na). Optimized binary ETHO (ETHO2) and ELPs (ELP3) were evaluated for vesicle size, entrapment efficiency, elasticity, extruded volume, in vitrodrug release, morphology, ex vivoskin permeation, and drug deposition (albino rat skin). In vivostudies were performed to evaluate transepidermal water loss (TEWL) and skin irritation. The components of ELP3 and ETHO2 (ethanol, propylene glycol, Tween 80, lipids) had a significant impact on in vitroand in vivoparameters. ETHO2 showed convincing findings as compared to ELP3. The permeation steady-state flux (Jss) and enhancement ratio (ER) were significantly (p˂0.05) enhanced in ETHO2 (Jss= 87.6±4.8 μg/cm2/h and ER= 7.3) as compared to drug solution (DS) (Jss= 12±2.6 μg/cm2/h) and marketed cream (Jss= 52±7.0 μg/cm2/h and ER= 4.3). The findings of TEWL and scanning electron microscopy confirmed better permeation of ETHO2. Hemolysis and Draize studies confirmed the hemocompatibility and non-irritant behavior of formulations, respectively. Conclusively, ETHO2 can be a suitable alternative to classical vesicular systems for transdermal application against infections caused by the herpes simplex virus.

High lipophilicity, low bioavailability, and hostile gastrointestinal (GI) environment is the major concern in oral administration of thymoquinone (TQ). Herein, we developed chitosan (CS) modified solid lipid nanoparticles (SLNs) to improve oral bioavailability. SLNs were systematically optimized by using a three-factor three-level QbD approach. The optimized TQ-CS-SLNs were successfully evaluated for various in vitro and ex vivo experiments and further evaluated for its bioavailability in Wistar albino rats. The developed TQ-CS-SLNs showed particle size, polydispersity index, and drug entrapment in the range between 135.61-211.36 nm, 0.17- 0.29, and 65.14-91.78%. The zeta potential of TQ-CS-SLNs was found to be +12.52 ± 1.21 mV. Moreover, TQ-CS-SLNs showed a controlled release profile during 24 h of study. In addition, optimized TQ-CS-SLNs showed excellent mucoadhesion with 67.26 ± 2.18% mucoadhesive efficiency. The intestinal permeation and confocal microscopy revealed higher permeation of TQ-CS-SLNs compared to TQ suspension. Furthermore, bioavailability results revealed that the optimized TQ-CS-SLNs represents ∼3.53 fold improved oral bioavailability of TQ compared to TQ suspension. Therefore, from the findings, it was concluded that the CS-SLNs could be an effective nanoplatforms for improved oral bioavailability of TQ.

We aimed to identify a suitable solvent [dimethyl acetamide (DMA), ethyl acetate, (EA), N-methyl pyrrolidone (NMP), cremophor-EL (CEL), transcutol-HP (THP), polyethylene glycol 400 (PEG-400), limonene and ethanol] based on experimental solubility, thermodynamic/computational parameters for subcutaneous (sub-Q) delivery. The “vanʼt Hoff” model validated solubility values in several solvents at “T = 298.2K–318.2K” and “p = 0.1 MPa”. In silicoprediction study was carried out for sub-Q delivery using GastroPlus. The selected KETO-DMA construct was evaluated for cellular interaction, cellular uptake (L929 cells), cytotoxicity (L929 and J774A.1) and antifungal activities (C. albicans, C. glabrata, C. Tropicalis, and A. niger). The maximum mole fractional solubility of KETO were found in three solvents such as DMA (4.8 × 10−2) ˃ EA (2.8 × 10−2) ˃ NMP (11.7 × 10−3) at “T = 318.2 K”. Analysis confirmed “endothermic and entropy” driven solubilisation process. GastroPlus predicted pharmacokinetics parameters were influenced with nonsaturable metabolic clearance in subcutaneous tissue of human. Interaction study of KETO-DMA solution with Candidacells showed maximized cellular internalization. KETO-DMA solution exhibited poor cellular uptake by L929 cell lines (murine fibroblast cells) compared to KETO aqueous solution which was further supported with cytotoxicity study in L929 and J774A.1 cell lines. Reduced MIC values of KETO-DMA solution as compared to KETO aqueous solution against four strains corroborated improved efficacy of KETO probably due to augmented solubility in DMA and lack of surfactant. Thus, KETO-DMA solution can be a suitable construct for sub-Q delivery to control fungal infections.

The study aimed to investigate rifampicin (RIF) loaded cationic nanoemulsion (NE) for increased efficacy, facilitated intestinal permeability and GastroPlus™ based prediction. Formulations were prepared and characterized for robustness to dilution, cloud point and stability to varied pH. Morphological transition of M. tuberculosisH37Rvwas studied by a transmission electron microscopy (TEM), % inhibition study and cytoplasmic content analysis. The ex vivopermeation and confocal laser scanning microscopy (CLSM) studies were conducted using duodenum, jejunum and ileum. Results of robustness ensured stability to dilution, pH and temperature (˃ 37 °C). The Smix(surfactant to co-surfactant) ratio (2:1 and 3:1) possessed maximized % inhibition due to LAB and AC8. The Peffvalues of cationic NE were 2.25, 1.96 and 2.0 fold higher than DS (drug solution) for duodenum, jejunum and ileum, respectively, whereas enhancement ratios were 2.25-, 1.94- and 2.0 fold higher than DS. A CLSM showed 3.22-, 2.89-, and 1.1 fold higher % fluorescence intensity from duodenum, jejunum and ileum, respectively. GastroPlus™ predicted 100% regional absorption of RIF-cationic NE and considerable effect of globular size, permeability and nanonization on pharmacokinetics (PK) parameters. Conclusively, the cationic NE can be a promising approach for increased efficacy of RIF and augmented oral absorption to control tuberculosis.

Conventional oral isoniazid (INH) causes severe side effects, toxicity and poor patient compliance. INH loaded elastic liposomes (ELs) were fabricated with phosphatidylcholine (PC) and edge activators (EA) possessing innate anti-tubercular activity. A full factorial design was applied to two factors (PC as X1and EA as X2) and four dependent variables (size as Y1, zeta potential as Y2, % entrapment as Y3and flux as Y4). The optimized formulation (OEL) was characterized for comparison. To confirm mechanistic views of permeation/deposition and penetration across the rat skin, a differential scanning calorimeter (DSC), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used. The F18 had the least vesicle size (~78.6 nm) and optimum zeta potential (+25.31 mV) as per formulations comprised of the sodium deoxycholate and span 80. The OEL (X1~ 82.5 mg and X2~ 30.5 mg) exhibited a good correlation between the predicted and the observed values with maximum desirability (0.943) and no observed interaction (factors). Morphological and extrusion studies ensured the spherical and deformable vesicle of the OEL. All the ELs were hemocompatible and showed sustained drug release as per diffusion studies (n < 0.5). The permeation flux of the OEL was 1.8-, 1.4-, 1.8-, 1.6- and 8.2 fold higher than those for F3, F7, F11, F15, and the drug solution, respectively. The DSC and SEM showed reversible perturbation whereas the CLSM corroborated penetration into the skin. Thus, the ELs could be an effective approach controlling cutaneous and systemic tuberculosis.

The purpose of this investigation was to ameliorate the solubility and dissolution rate of luteolin (LUT) in aqueous phase by LUT: β-cyclodextrin (β CD) binary and LUT: β-cyclodextrin (β CD) : Pluronic F127 (PLF) ternary complex. Phase solubility study was performed with β CD as well as with β CD-PLF to assess the solubilizing efficiency. The solid complexes were prepared by solvent evaporation (SE), and microwave irradiation (MI) techniques. The in-vitrodissolution study was performed for the developed systems. The selected ternary complex was evaluated for solid state characterization, anti-oxidant effect and further molecular docking study was performed to provide structural insights and to identify the favorable role of β CD in improving the solubility of LUT. The key results of phase solubility studies indicated that 6.23 fold and 10 folds increase in LUT solubility with β CD and β CD-PLF respectively in comparison to pure LUT solubility. The formulation TIC-MI showed maximum drug release 97.06 ± 4.23% followed by TIC-SE (83.679 ± 3.78%)  >  BIC-MI (76.35 ± 3.57%)  >  BIC-SE (57.39 ± 2.11%)  >  TNPM (42.72 ± 2.45%) > BNPM (26.16 ± 1.71%). Most importantly IR, NMR study results revealed that there is no interaction was observed between LUT and used excipients. The antioxidant effect of the complex was found higher than that of LUT. The docking results demonstratethat LUT is completely embedded into the β CD cavity. Therefore, LUT: β CD: PLF ternary complex prepared by MI method found to be efficient with improved solubility, dissolution and antioxidant effect.