Synthesis of Triazole-Based Nonionic Surfactants for Nanostructured Drug Delivery: Investigation of Their Physicochemical and Biological Aspects

Synthesis of novel nonionic surfactants has attracted attention of synthetic chemists due to the issues of the currently used commercial surfactants. The synthesis of three biocompatible triazole-based nonionic surfactants is reported for nanovesicular drug loading. The surfactants were synthesized in a three-step reaction and characterized using ¹HNMR and mass spectroscopy techniques. They were investigated for their critical micelle concentration (CMC) using a UV–Visible spectrophotometer. Their biocompatibility was investigated against cell culture and in blood. All the synthesized nonionic surfactants were further explored for their nanovesicular drug loading using clarithromycin as a model hydrophobic drug. Nonionic surfactants revealed lower CMC in 35–45 μM and were less hemolytic and cytotoxic. They were capable of self-assembling in nanosize niosomal vesicles encapsulating increased amounts of drug. The results suggest the synthesized nonionic surfactants as biocompatible nanotechnology-based drug-delivery vehicles.     

Formulation and characterisation of a self‐nanoemulsifying drug delivery system of amphotericin B for the treatment of leishmaniasis

This study was aimed to develop a self‐nanoemulsifying drug delivery system (SNEDDS) for amphotericin B (AmB) potential use in leishmaniasis through topical and oral routes. Two formulations, formulation A and formulation B (FA and FB) of AmB loaded SNEDDS were developed by mixing their excipients through vortex and sonication. The SNEDDS formulation FA and FB displayed a mean droplet size of 27.70 ± 0.5 and 30.17 ± 0.7 nm and zeta potential −11.4 ± 3.25 and −13.6 ± 2.75 mV, respectively. The mucus permeation study showed that formulation FA and FB diffused 1.45 and 1.37%, respectively in up to 8 mm of mucus. The cell permeation across Caco‐2 cells monolayer was 10 and 11%, respectively. Viability of Caco‐2 cells was 89% for FA and 86.9% for FB. The anti‐leishmanial activities of FA in terms of IC₅₀ were 0.017 µg/ml against promastigotes and 0.025 µg/ml against amastigotes, while IC₅₀ values of FB were 0.031 and 0.056 µg/ml, respectively. FA and FB killed macrophage harboured Leishmania parasites in a dose‐dependent manner and a concentration of 0.1 µg/ml killed 100% of the parasites. These formulations have the potential to provide a promising tool for AmB use through oral and topical routes in leishmaniasis therapy.Inspec keywords: nanomedicine, drops, microorganisms, electrokinetic effects, cellular biophysics, drug delivery systems, monolayers, drugs, diseasesOther keywords: self‐nanoemulsifying drug delivery system, topical routes, oral routes, SNEDDS formulation, mucus permeation study, cell permeation, leishmaniasis treatment, amphotericin B, zeta potential, Caco‐2 cell monolayer, vortex, sonication, droplet size, Caco‐2 cell viability, antileishmanial activity, promastigotes, amastigotes, Leishmania parasites     

Magnetization reversal and ferrimagnetism in Pr1−x Nd x MnO3

Detailed magnetic properties of Pr_{1? x} Nd _x MnO₃ (x = 0.3, 0.5 and 0.7) have been reported. All the samples crystallize in orthorhombic perovskite structure with Pnma space group. Magnetization measurements under field cooled (FC) protocal reveal magnetization reversal at low temperatures and low magnetic field. This indicates clear evidence of two magnetic sublattices aligned opposite to each other. There is a well-defined maximum around 48 K in the x = 0.7 sample (i.e. Pr_0.3Nd_0.7MnO₃) in the χ′ value which is identified as paramagnetic to ferrimagnetic transition. The peak value shifts to higher temperature with decrease of x and width of the maximum broadened. It is also observable that with decrease of Nd, both the value of χ′ and χ″ decrease. An attempt is made to explain the magnetization reversal within the framework of available models.     

Enhancement of oral bioavailability of anti-HIV drug rilpivirine HCl through nanosponge formulation*

Objective: To synthesize β cyclodextrin nanosponges using a novel and efficient microwave mediated method for enhancing bioavailability of Rilpivirine HCl (RLP).

Significance: Belonging to BCS class II RLP has pH dependent solubility and poor oral bioavailability. However, a fatty meal enhances its absorption hence the therapy indicates that the dosage form be consumed with a meal. But then it becomes tedious and inconvenient to continue the therapy for years with having to face the associated gastric side effects such as nausea.

Method: Microwave synthesizer was used to mediate the poly-condensation reaction between β-cyclodextrin and cross-linker diphenylcarbonate. Critical parameters selected were polymer to cross-linker ratio, Watt power, reaction time and solvent volume. Characterization studies were performed using FTIR, DSC, SEM, ¹H-NMR and PXRD. Molecular modeling was applied to confirm the possibility of drug entrapment. In vitro drug dissolution followed by oral bioavailability studies was performed in Sprawley rats. Samples were analyzed using HPLC.

Results: Microwave synthesis yields para-crystalline, porous nanosponges (～205?nm). Drug entrapment led to enhancement of solubility and a two-fold increase in drug dissolution (P?C_max and AUC_0-∞ increases significantly (C_max of NS～ 586?±?5.91?ng/mL; plain RLP ～310?±?5. 74?ng/mL).

Conclusion: The approach offers a comfortable dosing zone for AIDs patients, negating the requirement of consuming the formulation in a fed state due to enhancement in drugs’ oral bioavailability.     

Improving Routine Immunization Coverage Through Optimally Designed Predictive Models

Routine immunization (RI) of children is the most effective and timely public health intervention for decreasing child mortality rates around the globe. Pakistan being a low-and-middle-income-country (LMIC) has one of the highest child mortality rates in the world occurring mainly due to vaccine-preventable diseases (VPDs). For improving RI coverage, a critical need is to establish potential RI defaulters at an early stage, so that appropriate interventions can be targeted towards such population who are identified to be at risk of missing on their scheduled vaccine uptakes. In this paper, a machine learning (ML) based predictive model has been proposed to predict defaulting and non-defaulting children on upcoming immunization visits and examine the effect of its underlying contributing factors. The predictive model uses data obtained from Paigham-e-Sehat study having immunization records of 3,113 children. The design of predictive model is based on obtaining optimal results across accuracy, specificity, and sensitivity, to ensure model outcomes remain practically relevant to the problem addressed. Further optimization of predictive model is obtained through selection of significant features and removing data bias. Nine machine learning algorithms were applied for prediction of defaulting children for the next immunization visit. The results showed that the random forest model achieves the optimal accuracy of 81.9% with 83.6% sensitivity and 80.3% specificity. The main determinants of vaccination coverage were found to be vaccine coverage at birth, parental education, and socio-economic conditions of the defaulting group. This information can assist relevant policy makers to take proactive and effective measures for developing evidence based targeted and timely interventions for defaulting children.     

Comparative Study of Effect of Surfactant-Polymer Interactions on Properties of Alkyl Polyglucosides and Alpha Olefin Sulphonate

The properties of Alpha Olefin Sulphonate (AOS) and Alkyl polyglucosides (APG) were studied in the presence and absence of nonionic polymers such as polyethylene glycol, poly vinyl pyrrolidone and methyl cellulose and hydroxy propyl cellulose. Properties like surface tension, foaming, viscosity and emulsification were studied at a constant concentration of polymer (0.1%) and varying concentrations of surfactant. It was found that at low surfactant concentrations there is an association between surfactant and polymer at the liquid/air surface in the case of an anionic surfactant and a nonionic polymer, which is not seen in the case of nonionic surfactants and nonionic polymers. A nonionic polymer reduces the surface tension of AOS by forming a surfactant-polymer complex which in turn increases the foamability, emulsifying property and viscosity of solution. APG does not show any effect on its surface tension in the presence of nonionic polymers but its foamability and emulsifying properties are improved. Reduction in surface tension is not the only reason behind increased foamability in the presence of the polymer. Higher molecular weight polymers give a rich, creamy foam because of increased viscosity in the surfactant solution as compared to lower molecular weight polymers.     

Bulk thermal expansion studies of BiCaSrCu2O x and Bi2CaSr2Cu2O x

The compounds BiCaSrCu₂O _x and Bi₂CaSr₂Cu₂O _x were prepared by ceramic techniques and characterized by X-ray powder diffractometry (XRD) and microthermogravimetry (TG) and their bulk thermal expansion measurements were carried out using dilatometry in the temperature range 298T1073 K in air. The results have been analyzed and are compared with those obtained earlier for YBa₂Cu₃O₇. The XRD analysis shows that both BiCaSrCu₂O _x and Bi₂CaSr₂Cu₂O _x are single phase in nature, having an orthorhombic symmetry. The TG analysis carried out in oxygen, air, and nitrogen shows negligible weight loss (R~0.1%) on heating to 1073 K, indicating that these two compounds, unlike YBa₂Cu₃O₇, are quite stable. The analysis of bulk thermal expansion data reveals that the average linear thermal expansion coefficient ( ₁) for both BiCaSrCu₂O _x and Bi₂CaSr₂Cu₂O _x is almost the same ( ₁ 10.5×10^–6 K^–1) and is found to be nearly half of that for YBa₂Cu₃O₇ ( ₁ 18×10^–6 K^–1), suggesting that the interatomic bonding in both BiCaSrCu₂O _x and Bi₂CaSr₂Cu₂O _x is stronger as compared to YBa₂Cu₃O₇.     

Rising Up: Hierarchical Metal–Organic Frameworks in Experiments and Simulations

Controlled synthesis across several length scales, ranging from discrete molecular building blocks to size‐ and morphology‐controlled nanoparticles to 2D sheets and thin films and finally to 3D architectures, is an advanced and highly active research field within both the metal–organic framework (MOF) domain and the overall material science community. Along with synthetic progress, theoretical simulations of MOF structures and properties have shown tremendous progress in both accuracy and system size. Further advancements in the field of hierarchically structured MOF materials will allow the optimization of their performance; however, this optimization requires a deep understanding of the different synthesis and processing techniques and an enhanced implementation of material modeling. Such modeling approaches will allow us to select and synthesize the highest‐performing structures in a targeted rational manner. Here, recent progress in the synthesis of hierarchically structured MOFs and multiscale modeling and associated simulation techniques is presented, along with a brief overview of the challenges and future perspectives associated with a simulation‐based approach toward the development of advanced hierarchically structured MOF materials.     

Bioactive,nutritional composition,heavy metal and pesticide residue of four Chinese jujube cultivars

This study aims to conduct a detailed investigation on four cultivars grown in northwest China, concentrating on the analysis of the bioactive contents, nutrients, heavy metal concentrations, and pesticide residue contents. Those Chinese jujubes consist of 51.99–71.75% edible part, 82.35–89.63% carbohydrates, 4.43–6.01% protein, 0.48–0.63% lipid, 2.80–4.80% polysaccharide, 45.64–88.97 mg/100 g ascorbic acid, 132.16–196.58 mg/100 g phenolics and 101.17–132.04 mg/100 g flavonoids in dry matter. In those four Chinese jujube cultivars, sulfur amino acids are the first limiting amino acids for adults, and aromatic amino acids are for children. The amount of heavy metal and pesticide residue concentrations in those jujubes was way below the limit. All four cultivars were found to have different nutritional values except for the carbohydrates; they had higher rates of carbohydrates and polysaccharide than those previously reported ones from Eastern China; and they are a better source for carbohydrates, vitamin C and functional amino acids.