Physicochemical properties of structured phosphatidylcholine in drug carrier lipid emulsions for drug delivery systems

Drug carrier emulsions were prepared with structured phosphatidylcholine (PC-LM) which has both a long hydrocarbon chain and a medium hydrocarbon chain, and the characteristics of PC-LM as an emulsifier were investigated by measuring the creaming ratio, the surface tension of the emulsion system, and the mean particle size and zeta potential of the oil droplets in emulsions. The emulsion prepared with PC-LM as an emulsifier kept the condition and the ratio of separation was lower than those with purified egg yolk lecithin (PEL). The mean particle size of the emulsion prepared with PC-LM was smaller than that with PEL when using only sonication, approximately 250 nm. When using a high-pressure homogenizer after sonication, the mean emulsion size with PC-LM was also smaller than with PEL, approximately 150 nm. The surface tension of the various emulsions and the zeta potential of the emulsion droplets were measured to investigate the stability of the systems. In emulsions with PC-LM or PEL, the surface tension as an index of stability increased as the pressure of the homogenizer increased. Moreover, the zeta potential of the emulsion droplets prepared with PC-LM also increased with an increase in pressure of the homogenizer. As a result, it was found that the drug carrier emulsion prepared with PC-LM had significant advantages in terms of stability and mean diameter. We considered it could be used for the preparations of nanoparticle dispersion systems in drug delivery systems.     

Interaction between glycophorin and phospholipids in recombined systems.

Both the MN-glycoprotein from human erythrocytes and the hydrophobic fragment from the protein isolated with trypsin treatment, T(is), have been recombined with egg phosphatidylcholine in bilayers at various phospholipid/protein ratios. In order to investigate the effect of the protein on the phospholipid headgroups, 31P nuclear magnetic resonance spectra were obtained with the MN-glycoprotein recombined with egg phosphatidylcholine, which revealed two classes of phospholipid environments, one immobilized and one not immobilized. Electron spin resonance (ESR) of fatty acid methyl ester spin labels provided supporting evidence. Computer analysis of the ESR spectra indicate that 4-5 moles of phospholipid are immobilized per mole of protein over a wide range of lipid-to-protein ratios. The immobilization of the phospholipids appears mediated by both the polar headgroups and the hydrocarbon tails of the phospholipid.     

A modified method for no carrier added radioiodination of L-tyrosine via chloramine-T as an oxidizing agent

A modified method for the preparation of L-[^131/123I] iodotyrosine as a brain imaging agent is described. The method is based on direct electrophilic radioiodination of L-tyrosine with NaI [^131/123I] using chloramine-T (CAT) and 0.001 g KI as a carrier at pH 7.0. The product was purified by reverse phase high performance liquid chromatography (HPLC). A high radiochemical yield up to 85% of L-[^131/123I] iodotyrosine has been achieved with radiochemical purity of greater than 97%. The relation between the pKa of L-tyrosine and pH of the reaction medium was calculated in order to correlate the radiochemical yield of L-[^131/123I] iodotyrosine and the state of the three ionizable groups of L-tyrosine. Also, the influence of the reaction conditions on the radiochemical yield of L-[^131/123I] iodotyrosine was investigated.     

Properties of various phospholipid mixtures as emulsifiers or dispersing agents in nanoparticle drug carrier preparations

The characteristics of mixed phospholipids were examined when used as dispersing agents and emulsifiers. Synthesized phospholipids were mixed to investigate the potential effects of different hydrophilic or lipophilic groups on emulsification and dispersion. To examine the effects of the hydrophilic polar head group on the dispersing or emulsifying potency of phospholipids, l--phosphatidylcholine dimyristoyl (DMPC) and l--phosphatidylethanolamine dimyristoyl (DMPE) were mixed in various ratios. Moreover, all combinations of two kinds of phosphatidylcholines (PCs) out of l--phosphatidylcholine dilauroyl (DLPC), DMPC, l--phosphatidylcholine dipalmitoyl (DPPC) and l--phosphatidylcholine distearoyl (DSPC) were tested (50:50, w/w) to examine the effects of the hydrophobic carbon chains on the dispersing or emulsifying potency of phospholipids. Mean diameters of vesicles and O/W emulsions prepared by sonication were measured. Vesicles prepared with DMPC–DMPE mixtures gave larger particle sizes than those of DMPC alone. Particle sizes of vesicles prepared with a mixture of two kinds of PCs increased when adding a PC with a longer carbon chain, while particle sizes in a mixture with a PC having a shorter carbon chain was comparable to those in pure PC. In vesicles that were generated by hydration of phospholipids and had a bilayer form, the physical form of the phospholipids consisting of bilayers was thought to be an important factor influencing particle sizes. Among the emulsions, DMPC–DMPE mixtures gave a similar droplet size to DMPC alone. Droplet size in emulsions prepared with a mixture of two kinds of PCs had a strong positive correlation with the total number of carbons, which corresponds to hydrophilic–lipophilic balance (HLB). In O/W emulsions, in which phospholipids were absorbed at water–oil interfaces and which have a single layer form, HLB was thought to be a major factor in the determination of particle size; likewise with non-ionic emulsifiers.     

A novel biocompatible drug carrier for oral delivery and controlled release of antibiotic drug: loading and release of clarithromycin as an antibiotic drug model

In this work, a novel biocompatible carrier was designed by modification of nanoporous carbon material and synthesized by hydrothermal condensation of d-Fructose, as the carbon source, in the presence of Pluronic^® F127, as the surfactant. The prepared material is completely biocompatible and suitable for oral drug delivery. As this nanoporous carbon has surface decorated hydroxyl groups, they are able to react with 3-aminopropyltriethoxysilane agent and produce amino-functionalized nanoporous carbon. The synthesis of amine-modified carbon nanoporous material was confirmed by X-ray powder diffraction, IR spectroscopy, elemental analysis, thermal analysis and nitrogen adsorption analysis. Clarithromycin as an active drug molecule with carbonyl and hydroxyl functional groups in chemical structure was chosen as the drug model and stored in pores of the amine-modified nanoporous carbon. Release of clarithromycin from modified nanoporous carbon was investigated in mouth and stomach pH values. The results showed that this drug carrier can transfer the drug up to stomach without any leak or release. The release time was investigated, and the results showed that the carrier is also successful for the controlled-release delivery.     

Synthesis of an esterase‐sensitive degradable polyester as facile drug carrier for cancer therapy

Polyethylene glycol (PEG) is widely used as a carrier to improve the pharmaceutical properties of drugs with low molecular weight. However, PEG has few functional groups (usually two) for drug conjugation and the resulting low drug content (1–2%) has hampered its clinical applications. For this study, we synthesized biodegradable poly(ethylene glycol‐co‐anhydride). This polyester‐based polymer possesses multiple carboxylic acid groups that can be used as facile drug carriers. Two anticancer drugs, camptothecin (CPT) and doxorubicin (DOX) were loaded into the carrier and their releasing properties and in vitro anticancer activities were studied. The polymer–drug conjugates exhibited esterase‐promoted degradation and drug release. Their cytotoxicity against the human ovarian cancer cell line SKOV‐3 was comparable to unconjugated drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 507–515     

Periodic mesoporous organosilicas with co-existence of diurea and sulfanilamide as an effective drug delivery carrier

In this article we report the synthesis of new periodic mesoporous organosilicas (PMOs) with the co-existence of diurea and sulfanilamide-bridged organosilica that are potentially useful for controlled drug release system. The materials possess hexagonal pores with a high degree of uniformity and show long-range order as confirmed by the measurements of small-angle X-ray scattering (SAXS), N₂ adsorption isotherms, and transmission electron microscopy(TEM). FT-IR and solid state ²⁹Si MAS and ¹³C CP MAS NMR spectroscopic analyses proved that the bridging groups in the framework are not cleaved and covalently attached in the walls of the PMOs. It was found that the organic functionality could be introduced in a maximum of 10 mol% with respect to the total silicon content and be thermally stable up to 230 °C. The synthesized materials were shown to be particularly suitable for adsorption and desorption of hydrophilic/hydrophobic drugs from a phosphate buffer solution at pH 7.4.     

Thermoresponsive polymeric gel as a medium for examining interactions between dsDNA and an anticancer drug

A piece of dry N-isopropylacrylamide polymer was soaked in phosphate buffer to obtain a hydrogel which was then employed in the examination of interactions between an anticancer drug C-1311 (5-diethylaminoethyl-amino-8-hydroxyimidazoacridinone) and dsDNA. dsDNA was introduced into the polymer at the polymerization stage. The drug was added to the buffer. Using the volume phase transition of the gel at 40 °C, the unbound drug could be determined in the solution released during the transition, which made the calculations more reliable. The interaction parameters were calculated using the McGhee and von Hippel model. It appeared that in the gel medium, the interaction between the drug and dsDNA is spatially limited, since the number of binding units of the polymer chain occupied by one drug molecule was found to be one, while it was two in the regular buffer solution. Figure   The two authors Agata Kowalczyk and Anna M. Nowicka contributed equally to this work.     

Chitosan-coated hemoglobin microcapsules for use in an electrochemical sensor and as a carrier for oxygen

The article describes the preparation of chitosan-coated hemoglobin (Hb-CS) microcapsules by (a) preparing a CaCO₃ precipitate containing Hb, (b) crosslinking Hb with glutaraldehye, (c) coating the particles with chitosan, and (d) preparing Hb-CS microcapsules by removing the CaCO₃ template with a solution of disodium EDTA. The morphology and electrochemical properties of the Hb-CS microcapsules were investigated by scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. An oxygen sensor was obtained by immobilizing the Hb-CS microcapsules on the surface of a glassy carbon electrode (GCE) first modified with gold nanoparticles. The application of Hb-CS microcapsules facilitates electron transfer on the surface of GCE and warrants the integrity and biological activity of Hb. The oxygen sensor, operated best at a working voltage of ?0.335  V (vs. SCE), displays a low limit of detection (30 nM). The Hb-CS microcapsules also are shown to release loaded oxygen to an anaerobic aqueous environment within 300 min.

Open image in new window

Graphical abstract The hemoglobin-chitosan microcapsule shows an excellent ability of electrocatalysis and carrying of oxygen.

     

Boron nitride nanocluster as a carrier for lomustine anticancer drug delivery: DFT and thermodynamics studies

Monatshefte für Chemie - Chemical Monthly - Previous reports were shown that boron nitride nanostructures can be biocompatible and nontoxic. Therefore, interaction of lomustine as an...     

Synthesis and characterization of a starch‐modified hydrogel as potential carrier for drug delivery system

Synthesis and characterization of a new hydrogel were carried out using a chemically modified starch (starch‐M) consisting of coupling C?C bounds coming from glycidil methacrylate (GMA) onto the polysaccharide structure. ¹³C NMR, ¹H NMR, and FT‐IR spectroscopies were used to confirm the incorporation of such groups onto the starch‐M. The hydrogel was prepared by a crosslinking polymerization of starch‐M using sodium persulfate as an initiating agent. The starch‐M hydrogel shows morphology clearly different from that of the raw starch film due to the presence of voids on its surface. The swelling process of the starch‐M hydrogel was not significantly affected by changes on the temperature or on pH of the surrounding liquid, indicating the such behavior can be then understood by a diffusional process, resulting from its physical–chemical interactions with the solvent. The values of the diffusional exponent n were on the order of 0.45–0.49 for the range of pHs investigated, demonstrating that the water transport mechanism of starch‐M hydrogel is more dependent on Fickian diffusion, that is, controlled by water diffusion. Such starch‐M hydrogel is a promising candidate to be used in transporting and in preserving acid‐responsive drugs, such as corticoids, for the treatment of colon‐specific diseases, for example, Crohn's disease. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2567–2574, 2008     

Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent

Trypanosoma brucei is a parasite that causes African sleeping sickness in humans and nagana in livestock and is transmitted by the tsetse fly. There is an urgent need for the development of new drugs against African trypanosomiasis due to the lack of vaccines and effective drugs. Orlistat (also called tetrahydrolipstatin or THL) is an FDA-approved antiobesity drug targeting primarily the pancreatic and gastric lipases within the gastrointestinal tract. It shows potential activities against tumors, mycobacteria, and parasites. Herein, we report the synthesis and evaluation of an expanded set of orlistat-like compounds, some of which showed highly potent trypanocidal activities in both the bloodstream form (BSF) and the procyclic form (PCF) of T. brucei. Subsequent in situ parasite-based proteome profiling was carried out to elucidate potential cellular targets of the drug in both forms. Some newly identified targets were further validated by the labeling of recombinantly expressed enzymes in Escherichia coli lysates. Bioimaging experiments with a selected compound were carried out to study the cellular uptake of the drug in T. brucei. Results indicated that orlistat is much more efficiently taken up by the BSF than the PCF of T. brucei and has clear effects on the morphology of mitochondria, glycosomes, and the endoplasmic reticulum in both BSF and PCF cells. These results support specific effects of orlistat on these organelles and correlate well with our in situ proteome profiling. Given the economic challenges of de novo drug development for neglected diseases, we hope that our findings will stimulate further research towards the conversion of orlistat-like compounds into new trypanocidal drugs.     

Ligand-directed nanobialys as theranostic agent for drug delivery and manganese-based magnetic resonance imaging of vascular targets

Although gadolinium has been the dominant paramagnetic metal for MR paramagnetic contrast agents, the recent association of this lanthanide with nephrogenic systemic fibrosis, an untreatable disease, has spawned renewed interest in alternative metals for MR molecular imaging. We have developed a self-assembled, manganese(III)-labeled nanobialys (1), a toroidal-shaped MR theranostic nanoparticle. In this report, Mn(III) nanobialys are characterized as MR molecular imaging agents for targeted detection of fibrin, a major biochemical feature of thrombus. A complementary ability of nanobialys to incorporate chemotherapeutic compounds with greater than 98% efficiency and to retain more than 80% of these drugs after infinite sink dissolution, point to the theranostic potential of this platform technology.     

Detailed Evidence for an Unparalleled Interaction Mode between Calmodulin and Orai Proteins

Calmodulin (CaM) binds most of its targets by wrapping around an amphipathic α‐helix. The N‐terminus of Orai proteins contains a conserved CaM‐binding segment but the binding mechanism has been only partially characterized. Here, microscale thermophoresis (MST), surface plasmon resonance (SPR), and atomic force microscopy (AFM) were employed to study the binding equilibria, the kinetics, and the single‐molecule interaction forces involved in the binding of CaM to the conserved helical segments of Orai1 and Orai3. The results consistently indicated stepwise binding of two separate target peptides to the two lobes of CaM. An unparalleled high affinity was found when two Orai peptides were dimerized or immobilized at high lateral density, thereby mimicking the close proximity of the N‐termini in native Orai oligomers. The analogous experiments with smooth muscle myosin light chain kinase (smMLCK) showed only the expected 1:1 binding, confirming the validity of our methods.     

A new crown ether as vesicular carrier for 5-fluoruracil: synthesis, characterization and drug delivery evaluation

Niosomes have shown promise as cheap and chemically stable drug delivery systems. In this paper a novel crown ether amphiphile, 1,16-hexadecanoyl-bis-(2-aminomethyl)-18-crown-6 (Bola A-16), has been synthesized with the aim of developing a long time stable controlled release system. Niosomes have been prepared with different molar ratios of amphiphile and cholesterol and their morphological properties have been determined by quasi-elastic light scattering and transmission electron microscopy. The composition of niosomes affects the entrapment efficiency and the release rate of 5-fluorouracil, a well-known antineoplastic molecule. In addition, other two known azacrown ether amphiphiles (4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecanedioc acid diamide (Bola D-16) and ,ω-(4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecane (Bola C-16), have been synthesized and the obtained vesicles have been characterized for comparison. Furthermore, the release profile of 5-fluorouracil in vitro, from these niosomes, has been studied over a period of 6 h in order to simulate a hematic adsorption.     

Potentiometric determination of free acidity and uranium in uranyl nitrate solutions using sulfate as complexing agent

In this paper free acid and uranium present together in the range of 0.05–3.0 meq and 20–250 mg, respectively, have been determined by potentiometric titration, using Na₂SO₄ and (NH₄)₂SO₄ complexants and NaOH and Na₂CO₃ as titrants. The results are presented as percentage recovery of free acidity and uranium over the range studied. It has been shown that percentage recovery of free acidity suggests a bias which varied from –5% to +74% at different free acidity and uranium concentrations for the Na₂SO₄–NaOH, Na₂SO₄–Na₂CO₃ and (NH₄)₂SO₄–NaOH complexant — titrant combinations. The percentage recovery of uranium always showed a positive bias which could be up to +8% for extreme free acidity — uranium ratios in the case of Na₂SO₄–Na₂CO₃ complexant — titrant combination. For the other Na₂SO₄–NaOH and (NH₄)₂SO₄–NaOH complexant — titrant combinations a positive bias of up to only +4% has been noticed.