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It is now widely accepted that various subsets of hybrid fiber composites reinforced with combined natural and synthetic fibers can significantly expand the applicability of composite-based materials in design and technology practice. The already existing unnatural circumstances on the planet put natural fibers far ahead of traditions in the field of materials thanks to their biodegradability characteristics, availability and over-term endurance and corrosion resistance. At the same time, composites are rapidly taking their place in many industries and sectors of the economy as metals in as much as it is economically and energetically justified. This study evaluates the mechanical properties of hybrid composites reinforced with glass, hemp, and sisal fibers. Using a hand lay-up method with epoxy resin, composite laminates were fabricated and tested for tensile, flexural, impact strengths and hardness test in accordance with ASTM standards. The experimental results revealed that glass-sisal fiber composites achieved the highest tensile strength of 69.1 MPa, while glass-hemp-sisal fiber composites exhibited superior flexural strength of 15.22 MPa and impact strength of 137.45 kJ/m2while best hardness value was 24.73 HV for glass-sisal fibre composite. These findings underscore the potential of glass-sisal-hemp fiber-reinforced epoxy composites as viable alternatives to traditional synthetic fiber-reinforced materials in automotive industry where there are no structural loadings i.e. automobile interiors; offering enhanced mechanical performance and sustainability.

Background: Differentiating malignancy from benign diseases is the key to successful management of adnexal masses. Risk of malignancy algorithm (ROMA) has been used for this purpose. We have prospectively studied the diagnostic value of ROMA in patients presented with adnexal masses. Methods: We prospective calculated ROMA values prior to surgery for adnexal masses. The risk calculated was then correlated with the histological findings, and results were analyzed according to menopausal status. ROMA cutoff value was determined using ROC curve, and sensitivity, specificity and predictive values were calculated. Statistics were performed on SPSS software (version 20.0). Results: There were 94 patients with adnexal masses included in the study, 65 (69.1%) had epithelial ovarian cancer and 29 (30.9%) were diagnosed benign on histopathology. In both pre- and postmenopausal patients, ROMA values were significantly higher in patients with malignancy compared to those with benign disease (p < 0.05). ROMA score was of a significant diagnostic value in both premenopausal (AUC = 0.914, Z = 10.81, p < 0.001) and postmenopausal patients (AUC = 0.975, Z = 21.51, p < 0.001). In premenopausal females, ROMA > 13.3% was able to discriminate malignant from benign patients with 97.06% sensitivity and 85.00% specificity. The positive and negative predictive values were 91.7% and 94.4%. Similarly, in postmenopausal females, ROMA value of > 76% achieved 87.10% sensitivity and 100.00% specificity in discriminating malignant from benign patients with 100% positive and 69.2% negative predictive value. The overall accuracy of ROMA in pre- and postmenopausal patients was 87.0% and 85%, respectively. Conclusions: ROMA is a useful and accurate test for differentiating epithelial ovarian cancer from benign ovarian masses. Further studies are needed to compare performance of ROMA with the Risk of Malignancy Index (RMI), CA 125 and HE4. Such comparative studies will be helpful to the clinician in deciding the best diagnostic tool for women with adnexal masses.

Surgical site infection (SSI) remains the most common complication of surgery around the world. WHO does not make recommendations for changing gloves and instruments before wound closure owing to a lack of evidence. This study aimed to test whether a routine change of gloves and instruments before wound closure reduced abdominal SSI.

The modulational instability (MI) of electrostatic waves, i.e., slow and fast electrostatic modes, is investigated in a magnetized plasma in the presence ion pressure anisotropy. The anisotropic ion pressure is defined using the double adiabatic Chew–Goldberger–Low (CGL) theory. The nonlinear Schrödinger equation (NLSE) is derived to study the amplitude modulation of obliquely propagating electrostatic waves in a magnetized plasma using the Krylov-Bogoliubov–Mitropolsky (KBM) method. The dispersive and nonlinear coefficients, i.e., $P$ and $Q$ , respectively, of NLSE are obtained which depends on system parameters such as plasma density, the magnetic field intensity, wave propagation angle $\theta $ , and ion parallel and perpendicular temperatures (anisotropy effects), respectively. The modulationally unstable regions ( $PQ>0$ ) of modulated slow [or ion-acoustic wave (IAW)] and fast [or ion-cyclotron wave (ICW)] electrostatic modes are investigated numerically in a magnetized plasma with ion temperature anisotropy, and the contour plots of product $PQ>0$ with wave propagation angle $\theta $ and critical wave numbers are also presented. It is found that the unstable regions for modulated IAW and ICW are extended to large wave propagation angle $\theta $ and its corresponding critical wave numbers in the presence of ion temperature anisotropy in comparison to cold ions’ case. The existence of magnetized plasma with ion pressure anisotropy in different space plasma regions and in the laboratory experiments is also pointed out.

Here we present the fabrication of a multilayer resistive memory device (ReRAM) utilizing AlCr2O4/MXene nanocomposite. Comprehensive investigations into the structural and morphological properties of the nanostructures were conducted using various characterization techniques. The fabricated device was tested by measuring I-V characteristics at different current applications which encompasses all previous results. The band gap value for the nanocomposite was reduced to 2.42 eV while that for AlCr2O4was measured at 3.25 eV via photoluminescence spectrum. Average particle size of the AlCr2O4/MXene nanocomposite was determined to be 25 nm through powder X-ray diffraction analysis. Crystallographic analysis revealed that all crystal peaks conform to the R-3c (167) space group, indicative of a standard hexagonal crystal structure. Energy-dispersive X-ray readings provided further confirmation that all required elements are present in the sample, affirming successful synthesis of the nanocomposite. Notably, the nanocomposite demonstrated exceptional performance as an electrode material in ReRAM, as evidenced by its current-voltage characteristics, making the AlCr2O4/MXene nanocomposite suitable for a wide range of next-generation device applications.

The integrins belong to the cell-surface polypeptide family and are the mediating partners among the cells, and extracellular matrix (ECM). They are also involved in the biological processes of cell migration, wound healing, blood clotting, immunological response generation, tissue morphogenesis, leucocyte reticulations, and angiogenesis and are therefore very relevant in stem cell technology and are useful as biomarkers, diagnostic probes, and drug-target ligands. The ανβ3 (alpha-nu-beta3) integrin antagonists are an excellent target example for designing and developing newer drug candidates, drug leads and templates for various diseases, and physiological malfunctioning, including cancers. The current review examines the ανβ3 integrin structural features involved in the drug design and its antagonistic ligands and highlights the development of anti-ανβ3 integrin-antagonists as nano-architectural design-based nanomedicine, especially for cancer chemotherapy. The perspectival review discusses the ανβ3 integrin structure, mode of action, involved pathways, and the concepts utilized in nanomedicine design, and ligands related to integrins. It also covers the latest thyrointegrin approaches toward the development of anti-angiogenesis agents and entails the anti-angiogenesis approach to cancer growth inhibition through targeting by the anti-integrin ligands and related chemical entities. The current perspective on the nano-architectural design approach for the known anti-integrin compounds is also outlined.

This work reports the synthesis of NaCr2O4/GO nanocomposite using co-precipitation method for energy storage applications. Characterizations e.g., scanning electron microscopy (SEM) and X-ray diffraction (XRD) were performed to investigate the important optical and structural properties. The Crystalline size is seen to decrease from 28 nm for sodium chromite to 16.56 nm for nanocomposite NaCr2O4/GO. Raman results showed the existence of characteristic peaks for NaCr2O4/GO. Using cyclic voltammetry, the specific capacitance for NaCr2O4/GO was measured to be 455.5 F/g. The NaCr2O4/GO nanohybrids depicted significantly higher values of specific capacitance combined with extremely low charge transfer resistance, useful for various applications.

In the present work, the nanoparticles of spinel bismuth Chromites (BiCr2O4) are prepared using sol gel method. We have developed a novel technique to achieve longer stability and higher ionic storage of MXene/BiCr2O4nanocomposite by using co-precipitation method. Structural and morphological properties of the prepared nano-structures are thoroughly investigated. The band gap is seen to reduce from 2.08 eV for MXene to 1.90eV for MXene/BiCr2O4nanocomposite which encompasses all the earlier stated values. The average particle size of nanocomposite MXene/BiCr2O4is 11.15 nm. The EDX analysis is performed to confirm the elemental composition of the prepared nano-composites. Composite electrodes are then electro-polymerized on the coating of glassy carbon electrode. The value of specific capacitance is measured to be 455.0 F/g, suggesting the plausible usage of the synthesized material in super capacitance applications. The prepared MXene/BiCr2O4nanocomposites can be used as efficient promoters and electrode materials, based on the attractive properties like reduced band gap, high electrochemical stability, and excellent value of specific capacitance.

Tumors of facial skin are common in upper part of central subunit of face. Defects after resection require a flap, which is pliable, thin, and has a good colour match. Among the various local flaps available paramedian forehead flap is a good option.

Lithium–sulfur (Li–S) batteries have been recognized as one of the most promising candidates for next-generation portable electronic devices, owing to their extremely high energy density and low cost. However, the dissolution of lithium polysulfides (LiPSs) and consequent “shuttle effect” seriously hinder the practical deployment of Li–S batteries. Herein, multi-metal oxide nanorods named attapulgite are proposed as multifunctional ionic sieve to immobilize LiPSs and further promote the regulation of LiPSs. Attapulgite, consisting of Al, Mg, Fe, Si and O ions, possesses more polar sites to immobilize LiPSs in comparison with single metal oxides. In addition, the catalytic nature (Fe ions) of attapulgite avails the LiPSs conversion reaction, which is further confirmed by the linear sweep voltammetry and electrochemical impedance spectroscopy. Benefited from the synergistic effect of multi-metal oxide and conductive carbon, the Li–S battery with the modified separator delivers remarkable discharge capacities of 1059.4 mAh g−1and 792.5 mAh g−1for the first and 200th cycle at 0.5 C, respectively. The work presents an effective way to improve the electrochemical performance of Li–S batteries by employing attapulgite nanorods assisted separator surface engineering.

Phospholipid-based liposomal vesicles are among the most effective delivery options currently available for various classes of anticancer drugs. The patents granted to inventions disclosing details on liposomal delivery module by the US Patent and Trademark Office, European Patent Office, and world patent holdings through WIPO (World Intellectual Property Organization) patenting have been sorted based upon liposome, and anticancer keywords within the abstract and claims sections of the patents for the period between 2000 and 2019, thereby disclosing novel liposome formulations encapsulating single, or combination of chemotherapeutic agents that have been far more chemically and physiologically stable, therapeutically efficacious, and comparatively less toxic than their nonliposomal free-drug counterparts. The added stability, site-specific transport, and payload delivery, enhanced bioavailability, fast body clearance, and biocompatibility together with the controlled and sustained delivery-related benefits claimed in the patent literature have been exclusively discussed with a focus on the last 5-year period.

Phospholipid-based liposomal vesicles are among the most effective delivery options currently available for various classes of anticancer drugs. The patents granted to inventions disclosing details on liposomal delivery module by the US Patent and Trademark Office, European Patent Office, and world patent holdings through WIPO (World Intellectual Property Organization) patenting have been sorted based upon liposome, and anticancer keywords within the abstract and claims sections of the patents for the period between 2000 and 2019, thereby disclosing novel liposome formulations encapsulating single, or combination of chemotherapeutic agents that have been far more chemically and physiologically stable, therapeutically efficacious, and comparatively less toxic than their nonliposomal free-drug counterparts. The added stability, site-specific transport, and payload delivery, enhanced bioavailability, fast body clearance, and biocompatibility together with the controlled and sustained delivery-related benefits claimed in the patent literature have been exclusively discussed with a focus on the last 5-year period.

The strontium-doped iron chromite nanoparticles were synthesized using the sol-gel method. Using the co-precipitation method, two-dimensional MXene-based nanocomposite is synthesized. This is the first synthesis of MXene with doped spinel chromites. The characterization of nanocomposite Fe1−xSrxCr2O4/MXene is done using XRD, SEM, EDS, Raman spectroscopy, photoluminescence spectrum (PL), and zeta potential. In nanocomposites, Fe1−xSrxCr2O4/MXene, x = 0.2, 0.4, 0.6, 0.8 strong intensity peaks were observed as compared to MXene parent material. From SEM results it was depicted that spinel chromite Fe1−xSrxCr2O4nanoparticles were attached to the surface of MXene. From the PL spectrum, the band gap values for MXene are 3.33 eV and decreased to 2.06 eV for nanocomposites Fe1−xSrxCr2O4/MXene. The zeta potential has been achieved with negative values. The obtained results made this nanocomposite unique and beneficial for electrochemical applications and due to a noticeable reduction in band gap values it has potential applications in optical devices.

Thymoquinone (TMQ), present in Nigella sativaL., exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties. Poor aqueous solubility, low oral bioavailability, hepatic first-pass metabolic constraints, and pH instability have limited TMQ’s in vivouse in clinical settings. This study designed and prepared thermodynamically stable, self-emulsified, nanoscale vesicles with the ternary diagram assistance to produce self-nanoemulsifying drug delivery system (SNEDDS). The TMQ-SNEDDS preparations used clove oil, isopropyl myristate (IPM) (1:1), Labrasol, and Transcutol-P. The SNEDDS mean droplet size varied between 72.85 and 98.42 nm, and approximately >70% TMQ was released within the first 4 h. The peak plasma concentration values of TMQSNE3and TMQ suspension were 420.31 ± 35.23 and 98.51 ± 9.97 μg/mL, respectively, whereas time to achieve the peak plasma concentration values were 0.75 ± 0.12 and 1.0 ± 0.30 h, respectively. The area under the curve from time 0 to t(AUC0–t) and the area under the moment curve from time 0 to t(AUMC0–t) of TMQSNE3were found to be 1838.63 ± 55.73 µg h/mL and 1909.59 ± 382.81 µg h/mL, respectively, which were highly significant (p< 0.05) in comparison with AUC0–t(389.36 ± 87.08 μg h/mL) and AUMC0–t(390.31 ± 184.55 μg h/mL) of the TMQ suspension. The relative bioavailability of TMQ was enhanced by 4.7-folds for the optimized TMQSNEDDSthan that of the free drug suspension. The SNEDDS enhanced the bioavailability, which, in turn, positively affected the therapeutic efficacy of this naturally bioactive compound, TMQ, which has delivery and bioavailability problems owing to poor aqueous solubility.

In this research, batch adsorption of anionic dye Eosin-B (EB) onto anion exchange membrane (AEM) (BI) from aqueous solution has been investigated at room temperature. The effect of some operating conditions such as contact time, membrane dosage, initial dye concentration and temperature on the percentage removal of EB from aqueous solution has been investigated in detail. Moreover, adsorption kinetics has been analyzed using different models such as pseudo-first-order, pseudo-second-order, Elovich, liquid film diffusion, modified Freundlich and Bangham models. Results show that adsorption data fits to the pseudo-second order kinetics very well. Non-linear isotherms containing two parameters and three parameters isotherms have been applied on experimental data. Different thermodynamic parameters such as Gibb’s free energy (DG°), enthalpy (DH°), and entropy (DS°) have been calculated, which shows that adsorption of EB onto anion exchange membrane (B1) is an exothermic process.

The lithium-sulfur (Li-S) battery has been considered as a promising energy storage system due to its high energy density (2600 Wh kg[?]1) and low cost. However, Li-S battery still exhibits significant challenge for commercial application due to the "shuttle effect". Here, we prepare a composite of Cr2O3-decorated carbon nanofibers (Cr-CNFs) inherited from natural collagen fibers of solid leather wastes (SLWs) and design a multifunctional separator coating for high-performance Li-S batteries. The physical blocking effect of the fibrous morphology of Cr-CNFs and the chemical adsorption by nano Cr2O3 phase in Cr-CNFs could synergistically trap polysulfides to suppress the shuttle effect in Li-S batteries. Moreover, the Cr-CNFs can form conductive network in the as-prepared separator coating, which facilitates the efficient utilization of active materials, due to its specific fibrous structure. Our results demonstrate a superior capacity retention ([?]810 mAh g[?]1 after 260 cycles at 0.2 C, < 0.1% decay rate per cycle), long cycle life, and high coulombic efficiency (>95%) for the Li-S batteries built with our Cr-CNFs separator coating. The high performance of Li-S battery with Cr-CNFs separator coating as well as the efficient reutilization of SLWs make the Cr-CNFs a promising material for Li-S batteries.

Lithium-sulfur battery, which has high theoretical specific capacity and energy density, is considered to be one of the next-generation of rechargeable batteries. But the "shuttle effect" still hinders its application. Here, carbon/gelatin microcapsule (C/GM) as a micro-reactor for sulfur cathode to suppress "shuttle effect" is prepared. The submicron-sulfur particles, which are synthesized with the regulation of gelatin, are encapsulated in the C/GM so that a region-limited electrochemical reaction can be realized. Benefiting from the micro-reactor inhibiting the dissolution of polysulfide, the initial discharge specific capacity of lithium-sulfur battery with C/GM cathode is up to 1259.0 mAh/g and still retains 961.0 mAh/g after 100 cycles. Due to the sustainable source and facile method, the C/GM cathode is promising for the application of lithium-sulfur batteries.

Serine protease, Human Neutrophil Elastase (HNE), has been shown to be useful in medical science, however, its over production and malfunctioning may produce devastating effects and cause serious damage to the host. Unfortunately, the present approved drug, sivelestat, only alleviates the symptoms of the diseases caused by malfunction of HNE but not the disease progression. Therefore, there is a crucial need to search potent and safer molecules as elastase inhibitors and to develop better anti-inflammatory drugs in future. In addition, nature is the best architect that may provide a safer future drug candidate as HNEproduction/ activity inhibitor. Since phenolic natural products are already known as antiinflammatory compounds, either by acting as antioxidants or by any other mechanism, thus, this review article summarizes the discovery and elastase inhibitory activity of ?180 phenolics isolated from diverse natural sources during more than one decade, i.e. 2005-2017.

Phyllodes tumours are rare neoplasms that comprise less than 1% breast tumours and are unique in a way that they occur exclusively in the female breast. These tumours are biphasic fibroepithelial neoplasms of breast which are generally classified as benign, borderline and malignant. Given its infrequent description in the literature, guideline regarding management is based on small-scale retrospective clinical trials or case reports. We describe here a giant malignant phyllodes tumour that we encountered in our centre. 50-year-old female presented with rapidly enlarging breast swelling since 6 months. On local examination, there was huge breast swelling measuring 41 × 37 × 22 cm swelling on left breast with lobulated appearance and dilated veins over it with fixity to the skin and underlying muscle but not to the chest wall. Imaging was done using CECT of the local part with thorax which was suggestive of 42.5 × 35 × 24 cm tumour in subcutaneous plane infiltrating parts of underlying muscle. After adequate preoperative preparation and optimization, patient underwent left radical mastectomy under general anaesthesia. The defect was closed primarily. Final histopathology revealed 40 × 32 × 22 cm encapsulated malignant phyllodes tumour high grade with mitotic rate of 32 per high-power field and margins clear. Axillary lymph nodes showed no disease. Multidisciplinary tumour board meeting recommended adjuvant treatment in form of chemotherapy consisting of Ifosfamide and Adriamycin along with chest wall radiation. Patient on follow-up showed a healthy wound, and sutures were removed. Patient received six cycles of chemotherapy followed by radiation to the chest wall. The term giant phyllodes is used when the tumour size exceeds 10 cm in maximum diameter. In the available literature search, only a few reports have specifically commented on the giant phyllodes tumour, an entity that presents the surgeon with several unique management problems. This case is one of the largest malignant phyllodes tumour resected among the few that have been reported. Size described ranges from 15 to 50 cm. Surgery typically requires mastectomy as clear margins are not possible with local excision. Defect can be closed primarily or coverage can be provided in form of flap or split-thickness skin graft. Usually, adjuvant chemotherapy as well as radiation is given in cases with high-grade malignant phyllodes tumour but yet there is no guidelines regarding the same.

The selection of suitable functional excipients with low toxicity index and having P-glycoprotein inhibitory characteristics represents a major innovative step in designing a promising formulation for oral chemotherapy. This study was aimed at investigating the chemosensitizing effect of selected pharmaceutical excipients to improve the in vivo pharmacokinetic performance of VP-16. The pharmaceutical excipients having P-glycoprotein inhibitory activity were screened by shake flask method for their VP-16 solubilization capacity. The cumulative amount of VP-16 was determined with or without the selected pharmaceutical excipients at three different concentrations (0.1 % w/v, 0.5 % w/v and 1 % w/v) by an everted gut sac technique. Moreover, pharmacokinetic studies were also performed to determine the oral bioavailability assessment of VP-16 in albino male Wistar rats. The absorptive transport from mucosal-to-serosal (M→S) and secretory transport from serosal-to-mucosal (S→M) for VP-16 solution over 90 min were found to be (3.58 ± 0.32) × 10−6and (14.63 ± 3.11) × 10−6cm/s, respectively, with a net efflux of 4.08. Addition of verapamil (200 µM), a P-glycoprotein inhibitor, elevated the transport from M→S[Pappfrom (3.58 ± 0.32) to (9.66 ± 1.55) × 10–6cm/s, p< 0.05] and lowered the S→M[Pappfrom (14.63 ± 3.11) to (13.35 ± 2.01) × 10–6cm/s, p< 0.01], with a net efflux of 1.38. The relative bioavailability of VP-16 following oral administration (4.5 mg/kg) in rats was increased significantly (p< 0.01) in presence of Labrasol micellar solution at a concentration of 5 % (w/v) when compared with VP-16 solution alone. The findings suggest that pharmaceutical excipients may be employed in the development of drug delivery systems to improve the oral bioavailability of drugs having low solubility and/or less permeability as a result of substantial P-glycoprotein mediated efflux.

Solid lipid nanoparticles (SLNs), the spheroidal-shaped, colloids state lipophilic-natured, innovative nanoscale particulate materials, are being concurrently prepared by the quality-by-design approach for cellular and sub-cellular delivery of drugs and other payloads with facilitated physicochemical characteristics for targeted delivery. The delivery of drugs, other pharmaceuticals and biopharmaceutical materials, and genes to the diseased body organs, tissues, and cellular mass have been developed as promising nanocarriers for different high-incidence cancers and other disease therapies, including the Alzheimer’s, Parkinson’s, and tuberculosis. SLNs have evolved as favorable lipid-based formulation, and have served as oral and intravenous carriers that targeted the drug with stable and sterile transport, sustained delivery, controlled drug/payload deloading, and requisite biodistributions. SLNs advantages, shortcomings, and bottlenecks have been discussed with plausible remediation strategies. The laboratory-scale and bulk preparations, use of different lipids in various preparation, surface coatings, physicochemical properties of the final product, and characterization protocols are also encompassed, as are the routes of administrations, specific-sites-targeting, and on-site outreach with biocompatibility, bioavailability, and the absorption, distribution, metabolism, and excretion and pharmacokinetics, and pharmacodynamics inputs with relevance to the therapy. Plausible applications in complex and genetic disorders, and as personalized medicine, also of traditional and alternative medicine prospects, are also discussed.

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The oral absorption of etoposide is mainly limited by its active efflux out of the cells by P-glycoprotein (P-gp) and metabolized by cytochrome P450. Therefore, an attempt was aimed to investigate the effect of etoposide-loaded self-nanoemulsifying drug delivery system (SNEDDS) on the absorption of etoposide. The transport of SNE3 formulation across rat intestine was significantly (p < 0.001) higher than that of drug solution alone as well as in presence of verapamil, used as P-gp inhibitor. Results of fluorescence activating cell sorting assay showed a 61.3 ± 2.56% intracellular uptake of fluorescence marker Rhodamine B loaded in SNEDDS while plain Rhodamine B solution showed only a 15.3 ± 1.62% uptake. Confocal laser scanning microscopy study showed significantly higher penetration i.e., 83.71 μm across the GI membrane as compared to plain Rhodamine B solution which showed penetration up to 21.67 μm. Mechanism of P-gp inhibition was confirmed by measuring ATPase activity in the DC-3F/ADX cell model. Moreover, histopathology revealed that epithelial membrane of rat intestine treated with SNE3 was free of abrasion and atrophy. The aforementioned results suggest that the inhibitory effect of SNEDDS on the activity of both P-gp and cytochrome P450 may enhance the oral absorption of etoposide.

Introduction:The ATP-binding cassette superfamily contains membrane transporter proteins that transport a wide range of diverse compounds across cellular membranes. The P-glycoprotein (P-gp) is an important member of this family and a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of many clinically active drugs. The inhibition of this efflux transporter by various P-gp inhibitors forms a distinctive approach in improving bioavailability and conquering drug resistance. Most P-gp inhibitors exhibit limitations associated with their safety and unwanted pharmacokinetic interactions, thereby restraining their clinical applicability.Areas covered:This review explores the investigations on the feasibility and applicability of various classes of P-gp inhibitors as described in recent patents for enhanced drug delivery.Expert opinion:Several candidates presently under development look promising as P-gp inhibitors, e.g., tariquidar and elacridar. Pharmaceutical excipients currently constitute the most promising class of P-gp inhibitors and are considered safe and pharmaceutically acceptable for use in formulations. In addition, lipid-based excipients and thiolated polymers play an active role in affecting P-gp-mediated transport not only by altering the membrane fluidity or ATPase activity but by down regulating P-gp expression. An additional overture such as the prodrug derivatization of P-gp substrates is a feasible approach to bypass P-gp-mediated efflux.

This review focuses on nano-structured delivery devices prepared from biodegradable and biocompatible natural and synthetic polymers, organic raw materials, metals, metal oxides, and their other compounds that culminated in the preparation of various nano-entities depending on the preparative techniques, and starting raw materials’ utilizations. Many nanoparticles (NPs) made of polymeric, metallic, magnetic, and non-magnetic origins, liposomes, hydrogels, dendrimers, and other carbon-based nano-entities have been produced. Developments in nanomaterial substrate and end products’ design, structural specifications, preparative strategies, chemo-biological interfacing to involve the biosystems interactions, surface functionalization, and on-site biomolecular and physiology-mediated target-specific delivery concepts, examples, and applications are outlined. The inherent toxicity, and safety of the design concepts in nanomaterial preparation, and their applications in biomedical fields, especially to the organs, cellular and sub-cellular deliveries are deliberated. Bioapplications, the therapeutic delivery modules’ pharmacokinetics and medicinal values, nanopharmaceutical designs, and their contributions as nano-entities in the healthcare biotechnology of drug delivery domains have also been discussed. The importance of site-specific triggers in nano-scale deliveries, the inherent and induced structural specifications of numerous nanomaterial entities belonging to NPs, nano-scale composites, nano-conjugates, and other nano-devices of organic and inorganic origins, near biological systems are detailed. Modifications that provide nano-deliveries of their intrinsic therapeutic actions, through structural and physicochemical characteristics modifications, and the proven success of various nano-delivery devices and currently available commercial nanomedicinal and nanopharmaceutical products are also provided.

Background: Complete cytoreduction (CC) is one of the most important prognostic factors for epithelial ovarian cancer (EOC). Response to neoadjuvant chemotherapy (NACT) is potentially important to predict CC as well as counseling the patients. We aimed to study if RECIST 1.1 response predicts CC in EOC following NACT. Materials and Methods: This prospective observational study included 59 patients of EOC planned for NACT followed by interval debulking surgery (IDS). Response to NACT was assessed by RECIST 1.1 criteria. The level of cytoreduction during IDS was correlated with the radiological response. A Chi-square test was used for the group comparison. Results: Half (50%) of patients had an objective response to NACT. CC was feasible in a total of 35 (62.5%) patients. Both response and cytoreduction levels were independent of clinical parameters. We observed 100% CC rates in CR, 95.8% in PR, 50% in SD and 12.5% in PD categories. RECIST 1.1 response was found significantly (p&lt; 0.01) associated with levels of cytoreduction. The sensitivity, specificity, positive predictive value and negative predictive value of RECIST to predict CC were 77.1%, 95.2%, 96.4% and 71.4%, respectively. Conclusions: RECIST 1.1 predicts CC in responders (CR/PR) well. We suggest against denying surgery solely based on RECIST criteria in the SD or PD patients. Given its imprecision in these circumstances, patient characteristics such as performance status, perioperative risk and comorbidities should be taken into account. The role of newer antineoplastic agents, three-dimensional or functional imaging and diagnostic laparoscopy should be explored further for predicting CC.

endo- and exo-Norborneols have been phosphorylated with phosphorus oxychloride, and phenylphosphorodichloridate to the corresponding phosphorodichloridates and phenylphosphorochloridates. With thiophosphoryl chloride, both isomeric norborneols gave the dichloridothioates. When the norborneols (2 mol. equivs.) were treated with phosphorus oxy-chloride (1 mol. equiv.) the corresponding phosphorrchloridates were isolated. The various liquid phosphorochloridates and dichloridothioates were characterized as solid derivatives, e.g. phenylhydrazides, diamidates, and hydrazones. Several of the phosphorohydrazides have been reacted with isocyanates and phenylisothiocyanate to form the carbamoyl and N-phenylthiocarbamoyl derivatives. exo-Norbornyl O-phenylphosphorochloridate by partial hydrolysis (aq. pyridine) gave the corresponding P1:P2-diphenylpyrophosphate; exo-norbornyl N-phenylphosphoramidic chloride similarly afforded the P1: P2-dianilinopyrophosphate. The aqueous hydrolysis of exo- and endo-norbornylphosphorodichloridates is discussed in terms of competing reactions between substitution at carbon and substitution at phosphorus. The spectral data of the phosphorylated derivatives are briefly discussed.

o-Methoxyphenyl-, N-phenyl-N',N'-dimethyl, and N-3-acetylphenyl-urea with chlorosulfonic acid gave 4-methoxy-3-ureido, 4-(N',N'-dimethylureido)-, and N-3-acetylureido-benzenesulfonyl chlorides respectively.However, attempts to chlorosulfonate phenylthiourea were unsuccessful; the product was the zwitterionic sulfonic acid which did not give the sulfonyl chloride with phosphorus pentachloride.N-Phenyl-N'-p-tolyl urea by reaction with chlorosulfonic acid afforded the corresponding 4-sulfonyl chloride. N-Phenyl-N'-2-pyridyl- and N-phenyl-N'-2-thiazolyl thioureas reacted similarly. In contrast, N-phenyl-N'-2'-pyridylurea only gave the bis-sulfonyl chloride.Selected ureido-sulfonyl chlorides have been condensed with hydrazine and sodium azide and some reactions of the sulfonyl azides examined.Acetylation of phenylurea gave only the N-(3-acetyl)- or the S-acetyl derivative depending on the conditions. Contrary to previous work, it is not considered that the N-(l-acetyl) phenylthiourea is formed.

The phosphorylation of 1- and 2-adamantanols and of 1-adamantylamine with POCl3, PSCl3, PhOP(O)Cl2, 4-ClC6H4OP(O)Cl2, and PCl3 is described and the conversion of the obtained phosphorochloridates into a number of derivatives such as phenylhydrazides, diamidates, hydrazides, hydrazones and azides is reported.

Pyrrolidine, morpholine, and β-hydroxyethylmorpholine have been phosphorylated with phosphorus oxychloride, phenylphosphorodichloridate, p-chlorophenylphosphorodichloridate and thiophosphoryl chloride. The resultant phosphorodichloridates have been condensed with a wied range of nucleophilic reagents, e.g. amines, hydrazines, phenols and isobutanol. Piperazine with phosphorus oxychloride (2 mols) gave the N(1) N(4)-diphosphorotetrachloridate, which was characterized as the tetracyclohexylamidate. β-Hydroxyethylpiperazine was similarly phosphorylated to the N,O-diphosphorotetrachloridate which was characterized as the tetraphenylhydrazidate.Condensation of pyrrolidine (2 mols) with phosphorus oxychloride (1 mol) afforded N,N'-dipyrrolidinophosphorochloridate which was reacted with phenylhydrazide and sodium azide. The phosphoroazide with triphenylphosphine afforded the corresponding triphenylphosphinimine. N-Phenyl N'-pyrrolidinophosphorochloridate with aqueous pyridine gave the corresponding pyrophosphoramide and the stability of the pyrophosphoramide towards hydrolysis was examined. 1,2-Cyclohexanediol was phosphorylated with phenylphosphorodichloridate and thiophosphorylchloride. Trans-4-t-Butylcyclohexyl N,N'-diphenylhydrazinophosphorothioate by reaction with formaldehyde gave a tetra-azaphosphorine P-sulfide. Trans-4-t-Butylcyclohexyl N-phenyl N'-phenylphosphorodiamidic hydrazide reacted with 1,4-dibromobut-2-ene to give a 1,2-diazahex-4-ene.

Borneol (1 mol. equiv.) has been phosphorylated with phosphorus oxy(thio)chloride to the phosphorodichloridate; condensation with phenylphosphorodichloridate similarly afforded the phenylphosphorochloridate. The phosphorochloridates were characterized by preparation of various solid derivatives, such as diamidates, hydrazides, and phenylhydrazides.With phosphorus trichloride, borneol gave the phosphorodichloridite which was characterized as the anilinium phosphite and by formation of the N, N1-diphenyldiamidite.Reaction of borneol (2 mol. equivs.) with phosphorus oxychloride gave bis(bornyl) phosphorochloridate, characterized as solid derivatives, e.g. the phosphate, hydrazide, phenylhydrazide, and cyclohexylamidate.In contrast attempts to phosphorylate isoborneol (exo-OH) with, for instance, phosphorus oxychloride, thiophosphoryl chloride and phosphorus trichloride were unsuccessful as was the preparation of bis(isobornyl) phosphorochloridate.Possible explanations for this failure are briefly discussed.

The specific binding of 1,9-dimethylmethylene blue (DMB) with glycosaminoglycans (GAGs) was studied including molecular analysis of the GAG species using mass spectrometry. The dye solution was unstable under any storage conditions. Inorganic analysis showed that the purity of the dye was variable from different sources. False negative results could be obtained when using impure dye. Binding of the dye with GAG resulted in the formation of a complex with an absorption maximum at 525 nm. The absorbance of the complex was linearly correlated with GAG concentration up to 150mg/L. The specific molar extinction coefficients of individual GAG molecules were calculated in relation to the molar absorbance of the GAG-dye complex and the carbon and nitrogen contents of the GAGs. The results indicated that binding of dye occurred at both the ionized sulphate and carboxyl groups on the GAG molecules. Improvements of the DMB-binding method for the measurement of GAGs are suggested.

The self-generating nano-emulsifying drug delivery system (SNEDDS) is among the most effective approaches to enhance the oral bioavailability of a therapeutic agent, especially of a hydrophobic or poorly-water soluble drug. The methodology for SNEDDS preparation has been established on a number of therapeutic agents from several pharmacological classes. The requisite studies have validated the concept, and detailed experimentations in pharmaceutical, pharmacokinetics, and pharmacodynamics evaluations have corroborated the feasibility of SNEDDS formulation in providing higher levels of drug uploading, transport, dissolution, and intestinal permeation together with enhanced bioavailability at the site, and enhanced therapeutic effectiveness of the drug administered through oral route. The anti-cancer and anti-diabetic drugs having solubility issues, poor absorption, unwanted toxicity, and low bioavailability at the site of action have been dealt-with by the SNEDDS technology. The present review encompasses the SNEDDS technology applications primarily in these segments of drugs, and natural bioactive agents as well as synthetic agents for several bioactivities. It analyses the SNEDDS formulation approaches both in liquid and solid-SNEDDS based formulations, the absorption differences, bioavailability, and overall therapeutic effectiveness of these SNEDDS based products in comparison to the free drug behavior and other forms of drug delivery modalities as well as administration routes.

Purpose: Epithelial ovarian cancer is the second most common gynaecological malignancy among Indian women. Primary debulking surgery remains the standard of care in advanced operable ovarian cancer patients, but is associated with morbidity. Neoadjuvant chemotherapy followed by delayed primary cytoreductive surgery may be a better treatment strategy in advanced ovarian cancer. We present our experience of neoadjuvant chemotherapy in advanced ovarian cancer with special emphasis on treatment outcomes. Methods: A retrospective analysis of advanced epithelial ovarian carcinoma (stages III and IV) patients treated at the Department of Surgical Oncology at King George’s Medical University, Lucknow, between 2012 and 2016 was done. Results: A total of 128 patients with advanced ovarian carcinoma were treated during this period. Median age at diagnosis was 46 years. Among these patients, 115 underwent surgery, of which 57.4% were optimally cytoreduced. Papillary serous adenocarcinoma was the most common histological subtype (78.1%). Recurrence was seen in 73% of patients, with a median time to recurrence 16 months (range 6.5–37 months). They were managed with second-line chemotherapy and surgery. Median overall survival in this study for optimally cytoreduced stage III patients was 38 months and 17 months for optimally cytoreduced stage IV patients. Median progression-free survival for stage III was 13 months and stage IV was 6 months. Conclusion: Neoadjuvant chemotherapy facilitates surgery in advanced ovarian cancer and helps in assessing chemotherapy responsiveness. It provides an opportunity to modify systemic treatment if there is no response to therapy or disease progression.

The lithium-sulfur (Li-S) battery has been considered as a promising energy storage system due to its high energy density (2600 Wh kg−1) and low cost. However, Li-S battery still exhibits significant challenge for commercial application due to the “shuttle effect”. Here, we prepare a composite of Cr2O3-decorated carbon nanofibers (Cr-CNFs) inherited from natural collagen fibers of solid leather wastes (SLWs) and design a multifunctional separator coating for high-performance Li-S batteries. The physical blocking effect of the fibrous morphology of Cr-CNFs and the chemical adsorption by nano Cr2O3phase in Cr-CNFs could synergistically trap polysulfides to suppress the shuttle effect in Li-S batteries. Moreover, the Cr-CNFs can form conductive network in the as-prepared separator coating, which facilitates the efficient utilization of active materials, due to its specific fibrous structure. Our results demonstrate a superior capacity retention (∼810 mAh g−1after 260 cycles at 0.2 C, < 0.1% decay rate per cycle), long cycle life, and high coulombic efficiency (>95%) for the Li-S batteries built with our Cr-CNFs separator coating. The high performance of Li-S battery with Cr-CNFs separator coating as well as the efficient reutilization of SLWs make the Cr-CNFs a promising material for Li-S batteries.

Lithium-sulfur battery, which has high theoretical specific capacity and energy density, is considered to be one of the next-generation of rechargeable batteries. But the “shuttle effect” still hinders its application. Here, carbon/gelatin microcapsule (C/GM) as a micro-reactor for sulfur cathode to suppress “shuttle effect” is prepared. The submicron-sulfur particles, which are synthesized with the regulation of gelatin, are encapsulated in the C/GM so that a region-limited electrochemical reaction can be realized. Benefiting from the micro-reactor inhibiting the dissolution of polysulfide, the initial discharge specific capacity of lithium-sulfur battery with C/GM cathode is up to 1259.0 mAh/g and still retains 961.0 mAh/g after 100 cycles. Due to the sustainable source and facile method, the C/GM cathode is promising for the application of lithium-sulfur batteries.