Near infra-red absorbing Quinolizidine fused curcuminoid-BF2 chelate and its applications in photodynamic therapy using MCF-7 and A549 cells.

Metal-free near-infrared absorbing photosensitizers (PS) have been considered promising candidates for photodynamic therapy. Curcumin, curcuminoid, and its derivatives have therapeutic values due to their anti-inflammatory, antifungal, and antiproliferative properties. Curcuminoid-BF2 chelates have also been studied as cell imaging probes, however, their applications in photodynamic therapy are rare. In this article, we describe the synthesis and therapeutic evaluation of quinolizidine fused curcuminoid-BF2 chelate (Quinolizidine CUR-BF2) containing an acid-sensitive group. This donor-acceptor-donor curcuminoid-BF2 derivative exhibits absorption and emission in the deep red region with an absorption band maximum of ∼647 nm and a weak emission band at approximately 713 nm. It is interesting to note that this derivative has a high molar extinction coefficient (164,655 M-1cm-1). Quinolizidine CUR-BF2 possesses intramolecular charge transfer properties, facilitating the production of singlet oxygen (1O2), which plays a crucial role in cell death. Additionally, Quinolizidine CUR-BF2 can enable the selective release of active ingredients in an acidic medium (pH 5). Furthermore, the nanoaggregates of PS were prepared by encapsulating Quinolizidine CUR-BF2 within Pluronic F127 block co-polymer for better water-dispersibility and enhanced cellular uptake. Dark cytotoxicity of nanoaggregates was found to be negligible, whereas they exhibited significant photoinduced cytotoxicity towards cancer cells (MCF-7 and A549) under irradiation of 635 nm light. Further, the cell death pathway using Quinolizidine CUR-BF2 nanoaggregates as PS is found to occur through apoptosis. Specifically, the present study deals with the successful preparation of Quinolizidine CUR-BF2 nanoaggregates for enhanced water-dispersibility and cellular uptake as well as the efficacy evaluation of developed nanoaggregates for photodynamic therapy.

Superior Interfacial Contact Yields Efficient Electron Transfer Rate and Enhanced Solar Photocatalytic Hydrogen Generation in M/C3N4 Schottky Junctions.

Various literature studies (Table 6) have reported that dispersion of metal nanoparticles (NPs) on graphitic carbon nitride g-C3N4 (M/CN) has considerably improved the photocatalytic hydrogen yield. It is understood that metal NPs create active sites on the surface of CN and act as a cocatalyst. However, the precise changes induced by different metal NPs on the surface of CN still elude us. Here, we report a thorough understanding and comparison of the morphology, metal-support interactions, interfacial charge transfer kinetics, and band characteristics in different M/CN (M = Pt, Pd, Au, Ag, Cu) correlated with photocatalytic activity. Among all metals, Pt/CN was found to be the best performer both under sunlight and UV-visible irradiation. Under sunlight, maximum H2@ 2.7 mmol/h/g was observed over Pt/CN followed by Pd/CN > Au/CN > Ag/CN > Cu/CN ≈ CN. The present study revealed that among all metals, Pt formed superior interfacial contact with g-C3N4 as compared to other metals. The maximum Schottky barrier height (Φb,Pt) of 0.66 V was observed at Pt/CN followed by Φb,Au/CN (0.46 V) and Φb,Pd/CN (0.05 V). The presence of electron-deficient Pt in Pt-XPS, decrease in the intensity of d-DOS of Pt near the Fermi level in VB-XPS, increase in CB tail states, and cathodic shift in Vfb in MS plots sufficiently confirmed strong metal-support interactions in Pt/CN. Due to the SPR effect, Au and Ag NPs suffered from agglomeration and poor dispersion during photodeposition. Finely dispersed Pt NPs (2-4 nm, 53% dispersion) successfully competed with shallow/deep trap states and drove the photogenerated electrons to active metallic sites in a drastically reduced time period as investigated by femtosecond transient absorption spectroscopy. Typically, an interfacial electron transfer rate, KIET,avg, of 2.5 × 1010 s-1 was observed for Pt/CN, while 0.087 × 1010 s-1 was observed in Au/CN. Band alignment/potentials at M/CN Schottky junctions were derived and most favorable in Pt/CN with CB tail states much above the water reduction potential; however, in the case of Pd, these extend much below the H+/H2 potential and hence behave like deep trap states. Thus, in Pd/CN (τ0 = 4200 ps, 49%) and Ag/CN (3870 ps, 53%), electron deep trapping dominates over charge transfer to active sites. The present study will help in designing futuristic new cocatalyst-photocatalyst systems.

Multifunctional ZnO nanostructures: a next generation nanomedicine for cancer therapy, targeted drug delivery, bioimaging, and tissue regeneration.

Zinc oxide nanostructures (ZnO NSs) are one of the most versatile and promising metal oxides having significant importance in biomedical fields, especially for therapeutic and diagnostic purposes. ZnO possesses unique physio-chemical and biological properties such as photo-chemical stability, corrosion resistance, mechanical properties, biocompatibility, higher targeting capability, and ROS-triggered cytotoxicity. These ZnO NSs have enhanced potential for various biomedical applications such as cancer therapy, drug delivery, bioimaging, tissue engineering, etc. Furthermore, ZnO possesses excellent luminescent properties that make it useful for bioimaging and image-guided targeted drug delivery, thereby reducing the unwanted side effects of chemotherapeutic agents. Besides, these characteristics, enhanced permeability and retention effect, electrostatic interaction, ROS production, and pH-dependent dissolution of ZnO also make it potential aspirant as therapeutic that are suggested as key parameters for cytotoxic and cell death mechanismsviaapoptosis, autophagy, and mitophagy mechanisms. Here, the recent progress and advances of ZnO NSs in bioimaging, drug delivery, and tissue engineering are discussed along with the advantages, limitations, and future advancement for biological applications.

Technetium-99m labeled core shell hyaluronate nanoparticles as tumor responsive, metastatic skeletal lesion targeted combinatorial theranostics.

Achieving target specific delivery of chemotherapeutics in metastatic skeletal lesions remains a major challenge. Towards this, a dual drug loaded, radiolabeled multi-trigger responsive nanoparticles having partially oxidized hyaluronate (HADA) conjugated to alendronate shell and palmitic acid core were developed. While the hydrophobic drug, celecoxib was encapsulated in the palmitic acid core, the hydrophilic drug, doxorubicin hydrochloride was linked to the shell via a pH responsive imine linkage. Hydroxyapatite binding studies showed affinity of alendronate conjugated HADA nanoparticles to bones. Enhanced cellular uptake of the nanoparticles was achieved via HADA-CD44 receptor binding. HADA nanoparticles demonstrated trigger responsive release of encapsulated drugs in the presence of hyaluronidase, pH and glucose, present in excess in the tumor microenvironment. Efficacy of the nanoparticles for combination chemotherapy was established by >10-fold reduction in IC50 of drug loaded particles with a combination index of 0.453, as compared to free drugs in MDA-MB-231 cells. The nanoparticles could be radiolabeled with the gamma emitting radioisotope technetium-99m (99mTc) through a simple, 'chelator free', procedure with excellent radiochemical purity (RCP) (>90 %) and in vitro stability. 99mTc-labeled drug loaded nanoparticles reported herein constitutes a promising theranostic agent to target metastatic bone lesions. STATEMENT OF HYPOTHESES: Technetium-99m labeled, alendronate conjugated, dual targeting, tumor responsive, hyaluronate nanoparticle for tumor specific drug release and enhanced therapeutic effect, with real-time in vivo monitoring.

Recent advances in active targeting of nanomaterials for anticancer drug delivery.

One of the challenges in cancer chemotherapy is the low target to non-target ratio of therapeutic agents which incur severe adverse effect on the healthy tissues. In this regard, nanomaterials have tremendous potential for impacting cancer therapy by altering the toxicity profile of the drug. Some of the striking advantages provided by the nanocarriers mediated targeted drug delivery are relatively high build-up of drug concentration at the tumor site, improved drug content in the formulation and enhanced colloidal stability. Further, nanocarriers with tumor-specific moieties can be targeted to the cancer cell through cell surface receptors, tumor antigens and tumor vasculatures with high affinity and accuracy. Moreover, it overcomes the bottleneck of aimless drug biodistribution, undesired toxicity and heavy dosage of administration. This review discusses the recent developments in active targeting of nanomaterials for anticancer drug delivery through cancer cell surface targeting, organelle specific targeting and tumor microenvironment targeting strategies. Special emphasis has been given towards cancer cell surface and organelle specific targeting as delivery of anticancer drugs through these routes have made paradigm change in cancer management. Further, the current challenges and future prospects of nanocarriers mediated active drug targeting are also demonstrated.

Curcumin Encapsulated Casein Nanoparticles: Enhanced Bioavailability and Anticancer Efficacy.

The poor water solubility and bioactivity of drugs can be potentially improved by using suitable nanocarriers. Herein, an economically viable methodology is developed for encapsulation of hydrophobic anticancer agent, curcumin in casein nanoparticles (CasNPs). The successful encapsulation of curcumin was evident from the structural, thermal and spectroscopic analysis of curcumin encapsulated CasNPs (Cur-CasNPs). The CasNPs and Cur-CasNPs samples were lyophilized for their long-term stability and lyophilized powders are found to be stable for more than 6 months at 4-8 °C. From DLS studies, it has been observed that the variation in average size of drug formulations before and after reconstitution were less than 5%. Further, it shows good water-dispersibility, enhanced bioavailability and pH dependent charge conversal feature. Cur-CasNPs showed pH dependent release characteristics with higher at mild acidic environment and enhanced toxicity towards cancer cells (MCF-7) as compared to normal cells (CHO). Moreover, the CasNPs are non-toxic in nature and the developed nanoformulation of drug exhibits substantial cellular internalization and enhanced toxicity towards MCF-7 cells over pure drug, indicating their potential applications.

Immobilization of protein on Fe3O4 nanoparticles for magnetic hyperthermia application.

We report a facile approach for the preparation of protein conjugated glutaric acid functionalized Fe3O4 magnetic nanoparticles (Pro-Glu-MNPs), having improved colloidal stability and heating efficacy. The Pro-Glu-MNPs were prepared by covalent conjugation of BSA protein onto the surface of glutaric acid functionalized Fe3O4 magnetic nanoparticles (Glu-MNPs) obtained through thermal decomposition. XRD and TEM analyses confirmed the formation of crystalline Fe3O4 nanoparticles of average size ~5 nm, whereas the conjugation of BSA protein to them was evident from XPS, FTIR, TGA, DLS and zeta-potential measurements. These Pro-Glu-MNPs showed good colloidal stability in different media (water, phosphate buffer saline, cell culture medium) and exhibited room temperature superparamagnetism with good magnetic field responsivity towards the external magnet. The induction heating studies revealed that the heating efficacy of these Pro-Glu-MNPs was strongly reliant on the particle concentration and their stabilizing media. In addition, they showed enhanced heating efficacy over Glu-MNPs as surface passivation by protein offers colloidal stability to them as well as prevents their aggregation under AC magnetic field. Further, Pro-Glu-MNPs are biocompatible towards normal cells and showed substantial cellular internalization in cancerous cells, suggesting their potential application in hyperthermia therapy.

Glutamic acid-coated Fe3O4 nanoparticles for tumor-targeted imaging and therapeutics.

We have developed surface functionalised Fe3O4 magnetic nanoparticles (MNPs) based system that can be used for tumor-targeted multimodal therapies and MR imaging. Biocompatible, non-essential amino acid (glutamic acid) was introduced onto the surface of Fe3O4 MNPs to provide functional sites for binding of chemotherapeutic drugs. These glutamic acid-coated Fe3O4 MNPs (GAMNPs) exhibit good water-dispersibility, magnetic responsivity and pH dependent charge conversal feature. The magnetic core as well as organic shell of GAMNPs was characterized by XRD, TEM, DLS, FTIR, PPMS and UV-visible spectroscopy and zeta-potential analyzer etc. The broad spectrum anticancer drugs, doxorubicin hydrochloride (DOX) and methotrexate (MTX) were electrostatically and covalently conjugated to the surface of GAMNPs, respectively for combination chemotherapy. These dual drugs loaded system (DOX-MTX-GAMNPs) shows pH dependent release behaviour of both the drugs and enhanced toxicity towards breast cancer cell line (MCF-7) as compared to their individual treatment. Fluorescence microscopy and flow cytometric analyses confirmed the successful uptake of drug loaded system into MCF-7 cell lines. Further MTX being analogue of folic acid, its co-delivery with DOX would help in internalization of both the drugs into MCF-7 cells. These GAMNPs also show good heating efficiency under AC magnetic field (Intrinsic loss power, ILP = 0.95 and 0.73 and 0.48 nHm2/Kg at Fe concentration of 0.5, 1 and 2 mg/ml, respectively) and transverse relaxivity (r2 = 152 mM-1 s-1) indicating their potential capability for hyperthermia therapy and MRI tracking. Furthermore, it has been observed that the combination of chemotherapeutic drugs and hyperthermia leads to an enhancement of cytotoxicity in MCF-7 cells.

High antimicrobial photodynamic activity of photosensitizer encapsulated dual-functional metallocatanionic vesicles against drug-resistant bacteria S. aureus.

Developments in the field of photodynamic therapy (PDT) are being made by investigating appropriate photosensitizers (PSs) and enhancing the penetration effect of light by developing new nano-carriers. So, to boost the PDT effect, in the present work, new metallocatanionic vesicles were fabricated by a convenient, efficient, green and inexpensive method to encapsulate PSs and evaluate their antimicrobial PDT against the drug-resistant bacterium Staphylococcus aureus. They were prepared from a combination of a double-chained copper-based cationic metallosurfactant (CuCPCII) and an anionic surfactant sodium bis(2-ethylhexyl)sulfosuccinate (Aerosol OT or AOT). The surface charge, structure and ability to encapsulate oppositely charged photosensitizers are some crucial factors that need to be controlled for their effective utilization in PDT. In this approach, two of the fractions, one each from a cationic rich and anionic rich side, were selected to encapsulate cationic (methylene blue; MB) and anionic (rose bengal (RB)) PSs after characterization by SAXS, AFM, FESEM, DLS, and zeta-potential, and conductivity measurements. Afterwards, PDT was performed on S. aureus (a multidrug-resistant bacterium) by the colony forming unit (CFU) method using PS encapsulated metallocatanionic vesicles that demonstrated high bactericidal activity by using visible light (532 nm) and facilitated the generation of singlet oxygen. The singlet oxygen generation capability of both the PSs was enhanced under irradiation when encapsulated in metallocatanionic vesicles because the presence of metal accelerated the intersystem crossing of triplet oxygen to singlet oxygen. Furthermore, these studies reveal that the metallocatanionic vesicles have dual functionality i.e. encapsulate PSs and even show dark toxicity against S. aureus. To study the killing of S. aureus, bacterial DNA was extracted and its interactions and conformational changes in the presence of metallocatanionic vesicles were analyzed via., UV-Visible, and circular dichroism (CD) spectroscopy. Comet assay (single-cell gel-electrophoresis) demonstrated the DNA damage after PDT treatment in an individual cell. The bacterial DNA damage was more with the metallosurfactant rich 70 : 30 fraction than with the 30 : 70 fraction, in combination with RB under irradiation. This work provides a new metal hybrid smart material that possesses dual functionality and is prepared by an easy, economical and feasible procedure which resulted in enhanced PDT against a drug-resistant bacterium, thus, providing an alternative for antibacterial therapy.

Development of surface functionalized hydroxyapatite nanoparticles for enhanced specificity towards tumor cells.

Nanoparticles coupled with targeting moieties have attracted a great deal of attention for cancer therapy since they can facilitate site-specific delivery of drug and significantly limit the side effects of systemic chemotherapy. In this study, our aim is to develop surface functionalized hydroxyapatite nanoparticles, which could provide binding sites for a cancer cell targeting ligand, folic acid (FA) as well as an anticancer drug, doxorubicin hydrochloride (DOX). In order to attain dual functionalities, hydroxyapatite nanoparticles were functionalized with gelatin molecules. Gelatin, being a protein has both carboxyl and amine moieties, which makes it suitable for binding of DOX and FA. FA was chemically conjugated to the nanoparticles through an EDCNHS coupling reaction. The formation of single-phase hydroxyapatite nanostructure was ascertained by X-ray diffraction studies and the presence of organic moieties on the surface of nanoparticles was evident from Fourier transform infrared spectroscopy, thermogravimetric analysis and U.V.-visible spectroscopy. The FA-conjugated nanoparticles (FA-Gel-HANPs) showed high affinity towards DOX and pH-responsive sustained release of drug with higher release rate under acidic pH conditions, desired for cancer therapy. The FA-Gel-HANPs showed negligible cytotoxicity towards different cell lines (HepG2, WEHI-164, KB, WI-26 VA4 and WRL-68). However, DOX loaded nanoparticles (DOX-FA-Gel-HANPs) exhibited significant toxicity towards these cells, which was however highest in folate receptor (FR)-overexpressing, KB cells. These results were correlated with enhanced cellular uptake of DOX-FA-Gel-HANPs in KB cells in comparison to FR-deficient, WRL-68 cells studied by confocal laser scanning microscopy and flow cytometry. Moreover, cell cycle analysis in KB cells, showed higher sub-G1 population, indicating apoptosis as one of the cell death mechanisms. Overall, this study suggests that DOX-FA-Gel-HANPs could serve as a promising tumor-targeted drug delivery system.

The burden of trauma presenting to the government referral hospital in Freetown, Sierra Leone: An observational study.

INTRODUCTION: Trauma accounts for a significant proportion of the global burden of disease, with highest mortality rates seen in Africa. This epidemic is predicted to increase with urbanisation and an aim of the Sustainable Development Goals is to reduce deaths and trauma caused by road accidents. Data available on urban trauma in Sierra Leone is limited. METHODS: We conducted a retrospective observational study of trauma and injury related presentations to the emergency centre (EC) of Connaught Hospital, the principal adult tertiary referral centre in Freetown, Sierra Leone between January and March 2016. Patient demographics are described with mechanism of injury. Additional data on length of stay and surgical procedures were recorded for admissions to the trauma ward. RESULTS: During the 3-month period, a total of 340 patients with injury presented to the EC, accounting for 11.6% of total attendances and 68% of adult surgical admissions. The majority were male (66%) and mean age was 26 years (IQR 15-40). The proportion of trauma presentations were higher in the evening and at weekends and 41% of patients were triaged as emergency or very urgent cases. Road traffic accidents were the most frequent cause of injury (55%) followed by falls (17%) and assaults (14%). Burns were more common in children. Head and lower limbs were the most commonly injured body parts and a minority of patients underwent surgical procedures. Median length of stay for adult patients was 4.5 days (IQR 2-11) and 7 days (IQR 4-14) for children. DISCUSSION: Injury accounts for a high burden of disease at Connaught Hospital and consumes a significant proportion of EC and hospital resources. Efforts should be directed towards strengthening the pre-hospital and emergency trauma systems with accurate, formal data collection as well as targeting injury prevention initiatives and improving road safety to reduce morbidity and mortality.

Synthesis, thermal and surface activity of cationic single chain metal hybrid surfactants and their interaction with microbes and proteins.

A series of water-soluble metal functionalized surfactants have been prepared using commercially available surfactant cetyl pyridinium chloride and transition metal salts. These complexes were characterized in the solid state by elemental analysis, FTIR, 1H NMR and thermogravimetric analysis. The interfacial surface activity and aggregation behaviour of the metallosurfactants were analysed through conductivity, surface tension and small angle neutron scattering measurements. Our results show that the presence of metal ions as co-ions along with counter ions favours micellization at a low critical micellization concentration (CMC). Small angle neutron scattering revealed that the metallomicelles are of a prolate ellipsoidal shape and exhibit strong counterion binding. This article further describes the interaction of the metallosurfactants with transport protein Bovine Serum Albumin (BSA) using different spectroscopic techniques. A spectroscopic study was used to study the binding, interaction and quenching mechanism of BSA with the metallosurfactants. Gel electrophoresis (SDS-PAGE) and circular dichroism (CD) investigated the structural and conformational changes produced in BSA due to the metallosurfactants. The results indicate that there is an alteration in the secondary structure of BSA due to the electrostatic interaction between positive head groups and metal co-ions of the metallosurfactants and negatively charged amino acids of BSA. As the concentration increases, the α-helicity of BSA decreases and all the three studied metallosurfactants gave comparable results. Finally, the in vitro cytotoxicity and antimicrobial activity of the metallosurfactants were evaluated against erythrocytes and microorganisms, which showed prominent effects related to the presence of a metal ion in metallomicelles of the hybrid surfactants.

Intimate-partner violence and reproductive decision-making by women attending Victorian Maternal- and Child-Health services: a cross-sectional study.

The reproductive years are a critical period where women experience greater risk of intimate-partner violence (IPV). Most studies investigating the association between IPV and reproductive health have been completed in low- and middle-income countries. This study aimed to examine the relationship between IPV and women's reproductive decision-making in Victoria, Australia. We analysed secondary data from a cluster-randomised trial of IPV screening that surveyed new mothers attending Maternal- and Child-Health centres in Melbourne. Survey measures included the experience of partner abuse in the past 12 months using the Composite Abuse Scale and four reproductive decision-making indicators. Results showed that IPV affects reproductive decision-making among postpartum women. Women who reported abuse were less likely to plan for a baby (adjusted Odds Ratio 0.48, 95% CI: 0.31-0.75) than were non-abused women, significantly more likely to have partners make decisions for them about contraception (Risk ratio (RR) 4.09, 95% CI: 1.31-12.75), and whether and when to have a baby (RR 12.35, 95% CI: 4.46-34.16), than they were to make decisions jointly. Pregnant and postpartum women need to be screened for partner violence that compromises women's decision-making power regarding their reproductive rights.

Cationic double chained metallosurfactants: synthesis, aggregation, cytotoxicity, antimicrobial activity and their impact on the structure of bovine serum albumin.

Bovine serum albumin (BSA) is one of the most copious and significant blood proteins with dynamic structure. The understanding of the structural functionality of BSA and its interaction with metal ions is desired for various biological functions. Herein, three different metallosurfactants containing different transition metals and the same hydrophobic tail were engaged to investigate the structural transition of BSA. The metallosurfactants have been prepared by a combination of metal ions (M = Fe, Co and Ni) with cetylpyridinium chloride surfactant via the ligand insertion method and were characterized by elemental, FTIR, 1H-NMR, and thermogravimetric analysis (TGA). The obtained results reveal that insertion of a metal ion perturbs the aggregation behavior of the surfactant. Incorporation of a metal-ion has been found to decrease the CMC value of the surfactant, which has been supported by conductivity, surface tension and small angle X-ray scattering (SAXS). These metallosurfactants were employed to study the interaction and binding mechanism of BSA under physiological conditions. SDS-PAGE analysis points out a weak effect of metallosurfactants on the primary structure of BSA, whereas CD spectra implied a significant change in secondary structure with the decreased α-helical content of BSA. Fluorescence spectroscopy indicates the effect of metallosurfactants on the tertiary structure of BSA, whereas absorption spectra demonstrated static quenching with a blue shift in the presence of metallosurfactants. Moreover, unfolding of BSA in the presence of metallosurfactants has also been confirmed by SAXS studies. The overall results indicate that insertion of the metal ion into the framework of the surfactant structure enhances its protein binding/folding/unfolding abilities, which would be helpful in clinical as well as in life sciences.

Investigating the structural integrity of Bovine serum albumin in presence of newly synthesized metallosurfactants.

Bovine Serum Albumin is major transport protein and is often used as a drug carrier in body organs. Knowledge of its binding with metallosurfactant can significantly influence the biodistribution of metallodrugs. Current work demonstrated a facile method to prepare four different double chained metallosurfactants containing Fe, Co, Ni and Cu as part of their counter ion. The as-synthesized metallosurfactants were characterized using FTIR, AAS, TGA and XRD in solid form. The aggregation of these metallosurfactants in aqueous medium was investigated through conductivity, surface tension and SAXS. Further, we have investigated their binding with BSA through different analytical methods The effect of concentration of metallosurfactants on the primary and secondary structure of BSA was further examined by SDS-PAGE and Circular dichroism, respetively. It is found that at premicellar concentration, the primary structure of BSA was not affected but the secondary structure i.e. α-helical structure of BSA was altered as shown by circular dichroism. Interestingly, post micellar concentration of metallosurfactants shows the pronounced effect on the primary and secondary structure of BSA. SAXS study also supports the fact of unfolding of protein and its wrapping around the micelles. Zeta potential describes the electrical charge and stability of the protein in the presence of different concentration of metallosurfactant. Along with, it was found that presence of protein delays the aggregation behavior of metallosurfactant, as a sign of binding of BSA with metallosurfactant.

Interaction of Tyrosine Analogues with Quaternary Ammonium Head Groups at the Micelle/Water Interface and Contrasting Effect of Molecular Folding on the Hydrophobic Outcome and End-Cap Geometry.

The surface property of the cationic micelles of cetyltrimethylammonium bromide (CTAB) in an aqueous medium is highly modified in the presence of tyrosineoctyl ester (TYOE) and tyrosinedodecyl ester (TYDE), the models for aromatic amino acid side chains of transmembrane proteins. While the synergistic interaction between the quaternary ammonium head group of CTAB and the π-electron cloud of aromatic amino acid ester is influenced by the relative orientation and the unusual molecular geometry of the latter, this eventually triggers a morphology transition of the spherical micelle to cylindrical/wormlike micelles and imparts a strong viscoelasticity in the medium. Physical characteristics of the elongated micelles have been investigated by high resolution transmission electron microscopy (HRTEM) and the small angle neutron scattering (SANS) technique; the complex fluidic nature of the system is investigated by a dynamic rheological measurement. The intermolecular interactions have been recognized via 1H NMR and 2D nuclear Overhauser effect spectroscopy (NOESY), and the unambiguous geometry of the end-caps of the rods has been ascertained for the first time. While the interplay between lipids and transmembrane proteins is thought to be crucial in controlling the membrane shape of the cells during many vital events such as cellular fission, fusion, and virus entry, the observed tuning of the micellar surface curvature via the cation-π interaction involving tyrosine analogues is thought provoking and opens up an avenue for new physical chemistry research on a vital biological phenomena.

pH sensitive surfactant-stabilized Fe3O4 magnetic nanocarriers for dual drug delivery.

Highly water-dispersible surfactant-stabilized Fe3O4 magnetic nanocarriers (SMNCs) were prepared by self-assembly of anionic surfactant, sodium dodecyl sulphate (SDS) on hydrophobic (oleic acid coated) nanoparticles and their biomedical applications were investigated. These nanocarriers have an average size of about 10nm and possess tunable surface charge properties. The formation of an organic coating of SDS was evident from infrared spectroscopy, dynamic light scattering, zeta-potential and thermogravimetric measurements. These nanocarriers were used for loading of both hydrophilic and hydrophobic anticancer agents such as doxorubicin hydrochloride (DOX) and curcumin (CUR), respectively. DOX was conjugated onto the surface of nanocarriers through electrostatic interaction, whereas CUR was encapsulated into the hydrophobic interlayer between oleic acid and SDS. The toxicity and cellular internalization of drug loaded nanocarriers were investigated against WEHI-164 cancer cell line. Specifically, the drug loading, pH sensitive drug release and cellular internalization studies suggested that these nanocarriers are suitable for dual drug delivery. Furthermore, they show good heating ability under AC magnetic field, thus can be used as effective heating source for hyperthermia treatment of cancer.

Aggregation and Rheological Behavior of the Lavender Oil-Pluronic P123 Microemulsions in Water-Ethanol Mixed Solvents.

The effect of lavender oil on aggregation characteristics of P123 in aqueous-ethanolic solutions is investigated systematically by DLS, SANS, and rheology. The solubilization capacity of the P123 based formulations toward Lavender oil increased by increasing P123 concentration. The study unveiled the importance of the short chain alcohol-ethanol, as solubilization enhancer. The apparent hydrodynamic radius (Rh) increased significantly with an increase in lavender oil concentration up to maximum oil solubilization capacity of the copolymer at a particular ethanol concentration. DLS measurements on 5, 10, and 15 wt% P123 in the presence of 25% ethanol revealed the presence of large-sized micellar clusters in addition to the oil swollen micelles. The core size (RC), radius of hard sphere (RHS), and aggregation number (N) obtained from SANS profiles showed considerable enhancement with the addition of lavender oil confirming penetration of oil inside the copolymer. Rheological studies showed that viscosity also increased significantly with the addition of lavender oil near the maximum loading limit of the P123 concentration. Quite interestingly, the sol-gel transition temperature displayed a strong dependence on both P123 as well as oil concentration and decreased almost linearly by increasing oil concentration. This study demonstrates the use of a biocompatible and temperature sensitive self-assembled P123 based formulation for lavender oil solubilization that can be beneficial in the cosmetic industry wherein controlled release of fragrances and so forth is demanded.

Fabrication of metalosomes (metal containing cationic liposomes) using single chain surfactants as a precursor via formation of inorganic organic hybrids.

Among the self-assembled forms of surfactants, vesicles/liposomes are a highly promising and interesting feature of surfactants, which are usually formed from water insoluble surfactants. Herein, we demonstrate the formation of liposomes from single-chain cationic surfactants with the help of metals as a part of the counter ion, and these metal embedded liposomes are termed as metalosomes. It is a noteworthy advancement in the area of self-assembled molecular structures since we report the preparation of metal embedded liposomes (metalosomes) from a water soluble single chain cationic surfactant, which is otherwise a property or an arrangement made by double tailed surfactants, or more precisely lipids that are poorly water soluble. We can use this method for various cationic surfactants and metal combinations and the studies are still in process. However, this preliminary report on manganese-based surfactants depicts the successful formation of cationic metalosomes (with/without cholesterol), and the formation, structure and size has been verified using TEM, FE-SEM, DLS XRD and SAXS. The comparison of metalosomes with reverse vesicles in different solvents further gave an insight of microstructure and solvent environment effects on the self-assembly of metallosurfactants. In addition, we have also evaluated the encapsulation ability of metalosomes for fluorescein dye. High encapsulation efficiency of Mn-somes makes them promising candidates for several applications, particularly because of its water solubility.

PEG coated vesicles from mixtures of Pluronic P123 and l-α-phosphatidylcholine: structure, rheology and curcumin encapsulation.

PEG coated vesicles are important vehicles for the passive targeting of anticancer drugs. With a view to prepare PEG decorated vesicles using co-assembly of block copolymers and lipids, here we investigated the microstructure of aggregates formed in mixtures comprising lipids (l-α-phosphatidylcholine) and block copolymers (Pluronic P123), in the polymer rich regime. DLS and SANS studies show that the structure of the aggregates can be tuned from micelles to rod-like micelles or vesicles by changing the lipid to polymer composition. Rheological studies on gels formed by mixtures of polymer and lipid suggest incorporation of the lipid into the polymer matrix. The encapsulation efficiencies of polymer incorporated liposomes for curcumin and doxorubicin hydrochloride (DOX) are evaluated at different drug to carrier ratios. The pH dependent sustained release of both the drugs from the PEGylated liposomes suggests their application in the development of cost effective formulations for anticancer drug delivery.