PEGylated Oleic Acid-Lecithin Liposomes (POLL) for anticancer drug delivery

Cancer is a major health issue, conferring to more than 14.5 million deaths worldwide. Liposomes, self-assembly amphiphilic bilayer molecules, served as excellent alternative vehicles due to their ability to encapsulate both hydrophobic and hydrophilic anticancer drugs. Conventional liposomes, comprised mainly phospholipids are cost-ineffective, unstable, and easily degraded by the external environment. In this study, we introduced PEGylated oleic acid-lecithin liposomes constructed by using C-18 monounsaturated fatty acids (oleic acid) and soy lecithin, in the presence of DOPEPEG2000 in pH7.4, above their glass transition temperature, Tg, by employing the simple thin layer lipid hydration method. FTIR spectrum of oleic acid, soy lecithin, and DOPEPEG2000 was studied. The average particle size without further mechanical interference was 1102.3 nm while the zeta potential value was -18 mV, which is compatible with the zeta potential of the red blood cell. The polydispersity index (PDI) was reduced by 46.2% with the incorporation of the DOPEPEG2000. The morphological study using OPM showed the presence of spherical shape liposomes that exhibit the birefringence effect under the light field and Maltese cross under the dark field. Encapsulation of folinic acid, methotrexate, doxorubicin, or irinotecan resulted in greater than 75% encapsulation efficiency (EE). Half-maximal inhibitory concentration, IC50, was significantly reduced in POLL as compared to free anticancer drugs. Our data demonstrate POLL may be a promising alternative vehicle to deliver various anticancer drugs to targeted tumour sites

Fabrication of Ordered Uniform Porous Carbon Material and Its Application in Gas Separation

The main purpose of this work is to fabricate ordered uniform porous carbons and to test their usage in gas separation. The concerned problem statement includes irregular pores size distribution which will result poor selectivity during gas separation process. Therefore, the existence of ordered uniform network in porous carbon is important to overcome the poor selectivity issue. Porous carbons are remarkable due to the excellent absorption capability in their volume and surface. Ordered uniform porous carbons could be formed by template synthesis. Different template materials used for the template synthesis process will produce dissimilar porous carbons properties in term of specific surface area, pore diameter and pores distribution. The scope of study for this work concentrates on two main issues. First issue is the effect of template material's properties to the porous carbons fabrication. While another one involved application of the fabricated porous carbons in gas separation. The methodology of this work starts with preparation of carbon precursor. To be more specified, the preparation of carbon precursor includes synthesis of inorganic template and impregnate of the template with organic template. The impregnation of the templates means the precursor is polymerized. Subsequently, the carbon precursor would undergo carbonization process. The organic material is carbonized. The final stage of porous carbons fabrication is etching process. Through this process, the inorganic template is removed. Properties of the porous carbon are determined through characterization process using equipments such as X-ray diffraction (XRD) and Scanning Electron Micrograph (SEM). The application of fabricated porous carbons in this work could be proven by carbon dioxide, C02 gas separation using permeation cell

Synthesis and characterization of acylated low molecular weight chitosan and acylated low molecular weight phthaloyl chitosan

Oral drug delivery is one of the most convenient routes due to its painless administration and high patient compliance. However, oral administration is becoming more difficult to be conducted due to its poor water solubility, poor dissolution rate, and low oral bioavailability in the gastrointestinal tract. Herein, we develop a strategy to produce a chemically modified chitosan using depolymerization and introducing hydrophobic groups onto the chitosan backbone through acylation. By modifying the structure of chitosan, we aim to overcome limitations of drug delivery before and after the oral administration. The successful acylation of protected (using phthalic anhydride) chitosan and unprotected (without phthalic anhydride) chitosan was proved by Fourier transform infrared (FTIR). FTIR was conducted not only to characterize the functional group changes but also to find quantization of degree of acylation (DA) and the degree of substitution (DS) of chitosan before and after acylation. The particle size of chitosan was found ranges from 300-500 nm with zeta potential value shifted from -50 mV to a more positive value as acid anhydrides concentration increased. The Field Emission Scanning Electron Microscopy (FESEM) images showed the low molecular weight of chitosan and acylated chitosan nanoparticle possess non-spherical form with hollow structure. In addition, the size obtained was in accordance with the size measured by particle size. Hydrophobically modified chitosan has been successfully synthesized via acylation on both primary hydroxyl and amine groups on the backbone of chitosan. This chemically modified chitosan can enhance drug solubilization as well as improving biocompatibility and degradability

Preparation and characterization of PEGylated C18 fatty acids/Anti-SNAP25 antibody-targeted Liposomes

Background: Unsaturated C18 fatty acids, such as oleic acid (L1), linoleic acid (L2), and linolenic acid (L3), are a good choice of lipids to prepare liposomes. They are inexpensive, biocompatible, nontoxic, and readily available compared with phospholipids. Moreover, cis-double bonds of unsaturated fatty acids prevent the packing of molecules which increases membrane fluidity in liposomes making them a good choice of starting materials to prepare liposomes. Objective: Unsaturated C18 fatty acid liposomes, as well as their PEGylated and nonPEGylated antibody-targeted liposomes, were prepared and characterized. Method: The particle size and zeta potential of the prepared liposomes (1 mM, pH = 7.4) for 28 and 14 days, respectively, were monitored and characterized. Membrane-bound antibodies Anti-SNAP25 (AS25) and DOPE PEG2000 (DP) were conjugated to pure C18 fatty acid liposomes to achieve stable fatty acid formulations. Results: The mean particle sizes of pure L1, L2, and L3 liposome solutions were 125, 129, and 122 nm respectively, while their polydispersity index values were 0.28, 0.21, and 0.40 respectively. A large negative zeta potential value of 45 mV was observed due to anionic carboxylate head-group of pure liposomes. The incorporation of AS25 into L1/DP, L2/DP, and L3/DP liposome solutions stabilized their mean particle size and zeta potential measurements over 28 and 14 days, respectively. Conclusion: L1/DP/AS25 was found to be the most stable PEGylated antibody-targeted liposome system because its particle size remained between 90 and 125 nm in 28 days. Transmission electron microscopy observations also supported the incorporation of AS25 and DP on the membrane surface as predicted

Preparation and characterization of chitosan-coated oleic acid liposomes for intravenous delivery

Liposome has been studied as a potential carrier for targeting and controlled drug delivery. However, poor stability remains a challenge because it can lead to drug leakage from the vesicles thus reduce the effectiveness towards the target cell. For this aim, the present study incorporated the low molecular weight chitosan (LMWC) into the oleic acid liposome to maintain the stability and prolong the lifetime in the blood circulation. The thin-film hydration method was employed to prepare the oleic acid liposomes prior to coating them with LMWC. The stability of the liposomes was determined by the measurement of particle size and zeta potential for 28 days. The morphology of the liposome was confirmed by observing the shape under transmission electron microscopy (TEM) and it showed almost spherical in shape. The average particle size increased to 201.23 nm and -51.4 mV when 5 mg of LMWC was added to the oleic acid liposome. The increase of particle size and zeta potential of LMWC-coated liposome indicated that polymer-liposome interaction had changed the stability of liposome thus this invention could be useful for delivering active ingredients through intravenous delivery

Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies

Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (~70 nm) imaging of cells and mammalian tissues on conventional microscopes.United States. National Institutes of Health (1R01GM104948)United States. National Institutes of Health (1DP1NS087724)United States. National Institutes of Health ( NIH 1R01EY023173)United States. National Institutes of Health (1U01MH106011

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01