Hydrophilic Molecules Research Articles

Fabrication of novel PHB-liposome nanoparticles and study of their toxicity in vitro

Liposomes represent a tool used in cosmetics and for drug delivery due to their small size, biocompatibility, and ability to house both hydrophobic and hydrophilic molecules. However, under storage, there is a tendency for liposomes to release encapsulated components. In order to enhance their stability, combination with biodegradable polymers may be a promising option. Bacterial polymer poly(3-hydroxybutyrate) (PHB) is one such material that may contribute liposome structure, as it is also biocompatible and biodegradable and promotes controlled release of active agents in the skin. Nanoparticles consisting of PHB and phospholipids can be very attractive as biomaterials for application in cosmetics. In this work, novel combined PHB-liposome nanoparticles were synthesized and characterized, and their biocompatability with mammalian cells was assessed in vitro. Incorporation of PHB into liposome particles led to preservation of small size (123.8 ± 0.9 nm; evaluated by DLS) and colloidal stability of particles for 2 months in water environment. Cytotoxicity studies using MTT test with two different skin keratinocytes cell lines (HEK and HaCaT) showed significant dose-dependent differences in cell viability after exposure to liposome and PHB liposome particles in vitro. However, these PHB-liposomes were not found toxic both for HEK and HaCaT cells. Regarding to natural UV-scattering effect of PHB, we suggest that newly fabricated combined liposome-PHB particles could exhibit added value as carriers of active substances for topical applications. However, further study is necessary in order to reveal interactions between this new type of particle and human cells.

Gallic Acid-Loaded Zein Nanoparticles by Electrospraying Process.

Currently, electrospraying is a novel process for obtaining the nanoparticles from biopolymers. Zein nanoparticles have been obtained by this method and used to protect both hydrophilic and hydrophobic antioxidant molecules from environmental factors. The objective of this work was to prepare and characterize gallic acid-loaded zein nanoparticles obtained by the electrospraying process to provide protection to gallic acid from environmental factors. Thus, it was related to the concentration of gallic acid in physicochemical and rheological properties of the electrosprayed solution, and also to equipment parameters, such as voltage, flow rate, and distance of the collector in morphology, and particle size. The physicochemical properties showed a relationship in the formation of a Taylor cone, in which at a low concentration of gallic acid (1% w/v), low viscosity (0.00464 ± 0.00001 Pa·s), and density (0.886 ± 0.00002 g/cm3 ), as well as high electrical conductivity (369 ± 4.3 µs/cm), forms a stable cone-jet mode. The rheological properties and the Power Law model of the gallic acid-zein electrosprayed solution demonstrated Newtonian behavior (n = 1). The morphology and size of the particle were dependent on the concentration of gallic acid. Electrosprayed parameters with high voltage (15 kV), low flow rate (0.1 mL/hr), and short distance (10 cm) exhibited a smaller diameter and spherical morphology. FT-IR showed interaction in the gallic acid-loaded zein nanoparticle by hydrogen bonds. Therefore, the electrospraying process is a feasible technique for obtaining gallic acid-loaded zein nanoparticles and providing potential protection to gallic acid from environmental factors.

Hybrid polymeric microspheres for enhancing the encapsulation of phenylethyl resorcinol

Phenylethyl resorcinol (PR) has been known to allow the whitening effect by inhibiting formation of tyrosinase. PR has solubility of 4.05 ± 0.02 mg/g for water and log P of 3.017, proposed an amphiphilic substance. Hybrid PLGA microspheres with oil (HPMSs) have been used to improve encapsulation efficiency (EE) of hydrophilic molecules and control the release of them. The solubility (618.3 ± 22.29 mg/g) of PR was the highest in CapryolTM 90. The formulations (F6 and F`6) were selected after evaluation with EE and the released % (w/w) at 8 h. HPMSs showed 40% (w/w) increase of EE compared to that in CPMSs. Retention study on rat skin at 12 h resulted in that PR of HPMSs was remained more than that of CPMSs in dermal layer forming the melanin. HPMSs showed 1.4-fold increase of tyrosinase inhibition significantly in melanoma cells than that of the PR solution at 24 h.

Plant Aquaporins: Diversity, Evolution and Biotechnological Applications.

The plasma membrane forms a permeable barrier that separates the cytoplasm from the external environment, defining the physical and chemical limits in each cell in all organisms. The movement of molecules and ions into and out of cells is controlled by the plasma membrane as a critical process for cell stability and survival, maintaining essential differences between the composition of the extracellular fluid and the cytosol. In this process aquaporins (AQPs) figure as important actors, comprising highly conserved membrane proteins that carry water, glycerol and other hydrophilic molecules through biomembranes, including the cell wall and membranes of cytoplasmic organelles. While mammals have 15 types of AQPs described so far (displaying 18 paralogs), a single plant species can present more than 120 isoforms, providing transport of different types of solutes. Such aquaporins may be present in the whole plant or can be associated with different tissues or situations, including biotic and especially abiotic stresses, such as drought, salinity or tolerance to soils rich in heavy metals, for instance. The present review addresses several aspects of plant aquaporins, from their structure, classification, and function, to in silico methodologies for their analysis and identification in transcriptomes and genomes. Aspects of evolution and diversification of AQPs (with a focus on plants) are approached for the first time with the aid of the LCA (Last Common Ancestor) analysis. Finally, the main practical applications involving the use of AQPs are discussed, including patents and future perspectives involving this important protein family.

Lipid Headgroup Charge and Acyl Chain Composition Modulate Closure of Bacterial β-Barrel Channels.

The outer membrane of Gram-negative bacteria contains β-barrel proteins that form high-conducting ion channels providing a path for hydrophilic molecules, including antibiotics. Traditionally, these proteins have been considered to exist only in an open state so that regulation of outer membrane permeability was accomplished via protein expression. However, electrophysiological recordings show that β-barrel channels respond to transmembrane voltages by characteristically switching from a high-conducting, open state, to a so-called ‘closed’ state, with reduced permeability and possibly exclusion of large metabolites. Here, we use the bacterial porin OmpF from E. coli as a model system to gain insight on the control of outer membrane permeability by bacterial porins through the modulation of their open state. Using planar bilayer electrophysiology, we perform an extensive study of the role of membrane lipids in the OmpF channel closure by voltage. We pay attention not only to the effects of charges in the hydrophilic lipid heads but also to the contribution of the hydrophobic tails in the lipid-protein interactions. Our results show that gating kinetics is governed by lipid characteristics so that each stage of a sequential closure is different from the previous one, probably because of intra- or intermonomeric rearrangements.

Interaction of Mixing Water with Superlasticizers and Hyperplasticizers Additives in Concrete Mixture

The article deals with the mechanism of interaction of super-plasticizers and hyper-plasticizers additives with mixing water, the formation of micelles and organized water. The interaction of mixing water and additives with Portland cement particles, surface tension, specific surface of bindings and their significance in setting and hardening processes are considered. It is shown that a local effect plays a decisive role in micro-heterogeneous organized media associated with the dissolution of hydrophilic and hydrophobic molecules in the volume of the micellar system or the receptor molecule cavity. In this case, the change of dissolved substances properties is due to the change of the medium state only in the microenvironment, and not in the whole solvent - water. The surface energy of the dispersed material and the degree of dispersion are very important for the concrete technology. All dispersed materials of the system are unstable. The aggregation of powder particles of building materials spontaneously takes place in highly dispersed powders and if such powders get pressure, it is possible to get a hard and strong material without water and additives.

Characterization of Biocompatible Nanoparticles for Biophysical and Biomedical Applications

Reverse micelles are soft nanoparticles created when amphiphilic molecules surround small volumes of water in a bulk nonpolar solvent. Typically these mixtures spontaneously organize into roughly spherical complexes. RM particles are quite stable, and can be used to encapsulate small hydrophilic molecules. Under optimal conditions, they can also be used to encapsulate macromolecules without perturbing their structures. Recently, a mixture composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamine-N-oxide (LDAO) has been shown to encapsulated a wide array of proteins and nucleic acids. In addition to its versatility, this mixture also has the benefit of biocompatibility. The Nucci lab is exploring the utility of this mixture for a variety of biomedical and nanotechnology applications. The purpose of the present study is to thoroughly characterize the shape and dispersity of 10MAG/LDAO RMs in the presence and absence of macromolecular cargo. Dynamic light scattering is a primary tool for this endeavor and is augmented by electron microscopy and nuclear magnetic resonance. This characterization informs further application of this mixture as a biotechnological development platform.

Cholesterol re-organisation and lipid de-packing by arginine-rich cell penetrating peptides: Role in membrane translocation.

Cell penetrating peptides (CPPs) are able to transport hydrophilic molecules inside cells. To reach the cytosol, the peptide associated with a cargo must cross the plasma or the endosomal membrane. Different molecular mechanisms for peptide internalisation into cells have been proposed and it is becoming clear that the cellular internalisation mechanisms are different depending on the peptide sequence and structure and the target membrane. Herein, the penetration of three peptides into large unilamellar vesicles were studied: the homeodomain derived 16-residues penetratin, nona-arginine (R9), and a small peptide containing 6 arginine and 3 tryptophan residues (RW9). The membrane models were composed of phospholipids from natural sources containing different molecular species. We observed that among the three peptides, only the amphipathic peptide RW9 was able to cross the membrane vesicles in the liquid disordered state. The changes in the distribution of the previously characterized cholesterol-pyrene probe show that cholesterol-pyrene molecules dissociate from clusters upon membrane interaction with the three peptides and that the cholesterol environment becomes more disordered in the presence of RW9. Finally, we studied the effect of the peptides on lipid ordering on giant plasma membrane vesicles. The amphipathic peptides RW9 and its longer homologue RW16 induced lipid de-packing in plasma membrane vesicles. Overall, the data suggest that a disordered membrane favours the translocation of RW9, that the membrane cholesterol is redistributed during peptide interaction, and that the peptide amphipathic character is important to increase membrane fluidity and peptide membrane translocation.

Cationic Niosomes as Non-Viral Vehicles for Nucleic Acids: Challenges and Opportunities in Gene Delivery.

Cationic niosomes have become important non-viral vehicles for transporting a good number of small drug molecules and macromolecules. Growing interest shown by these colloidal nanoparticles in therapy is determined by their structural similarities to liposomes. Cationic niosomes are usually obtained from the self-assembly of non-ionic surfactant molecules. This process can be governed not only by the nature of such surfactants but also by others factors like the presence of additives, formulation preparation and properties of the encapsulated hydrophobic or hydrophilic molecules. This review is aimed at providing recent information for using cationic niosomes for gene delivery purposes with particular emphasis on improving the transportation of antisense oligonucleotides (ASOs), small interference RNAs (siRNAs), aptamers and plasmids (pDNA).

Immobilization of tungsten chelate complexes on functionalized mesoporous silica SBA-15 as heterogeneous catalysts for oxidation of cyclopentene

An efficient hybrid mesoporous heterogeneous catalyst system was synthesized via covalently grafting tungsten chelate complex W-N,N (N,N = (3-triethoxysilylpropyl) [3-(2-pyridyl)-1-pyrazolyl] acetamide, N,N-chelating ligand) in organic moieties (diphenyldichlorosilane, DPHS)-functionalized mesoporous silica SBA-15 or pure SBA-15. Characterization of synthesized materials via N2 sorption, XRD, TEM, UV–Vis DRS, 29Si MAS NMR, element analysis, and FT-IR indicated that W-N,N was successfully anchored and highly dispersed in the mesochannels of SBA-15 and the mesostructure of SBA-15 was maintained during the grafting course. The synthesized hybrid catalysts were highly active and authentically heterogeneous in triphasic oxidation reaction of cyclopentene (CPE) with H2O2. W,N-N immobilized on functionalized SBA-15 with DPHS moieties (W-N,N-DPHS-SBA-15) showed better catalytic properties (activity and stability) than its unmodified counterpart W-N,N-SBA-15 catalyst. Besides, possible catalytic reaction route for CPE oxidation with H2O2 over W-N,N-DPHS-SBA-15 catalyst was proposed. The amphiphilic mesochannels of W-N,N-DPHS-SBA-15 provided suitable accommodation for both hydrophilic H2O2 and hydrophobic CPE molecules and acted as nanoreactors for CPE/H2O2/solid triphase reaction.

Kinetics of Antimicrobial Drug Ion Transfer at a Water/Oil Interface Studied by Nanopipet Voltammetry.

Effective delivery and accumulation of antimicrobial agents into the microbial organism is essential for the treatment of bacterial infections. Transports of hydrophilic drug molecules, however, encounter a robust barrier of hydrophobic double membrane cell envelope, thus, leading to drug-resistance in Gram-negative bacteria. Accordingly, a deeper understanding about a transit of charged molecules through a bacterial membrane is needed to remediate the antibacterial resistance. Herein, we apply a steady-state voltammetry using nanopipet-supported interfaces between two immiscible electrolyte solutions (ITIES) to quantitatively study transport-kinetics of antimicrobial drug ions (quinolones and sulfonamides) at a water/oil interface. Importantly, ITIES can mimic a cellular membrane system, thus, being employed as insightful surrogates for the kinetic study of drug entry through bacterial cytoplasmic membranes. This approach enables us to voltammetrically and amperometrically detect redox-inactive drug ions as pristine under physiological conditions. Considerably slow kinetics of drug-ion transports are successfully measured by nanopipet voltammetry and theoretically analyzed. This analysis reveals that the drug-ion transport is ∼3 orders of magnitude slower than tetrabutylammonium ion transport. In addition, the extreme hydrophilicity of drug ions in comparison to ClO4- is quantitatively assessed from half-wave potentials of obtained voltammograms. The high hydrophilicity exclusively attributed to localized negative charges on carboxylate or amide group of deprotonated quinolone or sulfonamide, respectively, may play a dominant role in sluggish kinetics due to the increase in energy barriers upon interfacial ion transfer. Notably, this study using nanopipet voltammetry provides physicochemical insights on the correlation between structural properties of pristine drug ions and their transfer kinetics at a water/oil interface in lieu of biological membranes.

Non-spherical polymersomes: formation and characterization.

Polymersomes are self-assembled hollow membrane sacs that are not only able to encapsulate hydrophobic and/or hydrophilic molecules, but also possess exceptional chemical and physical stability, structural versatility, and surface modifiability. For the above reasons, polymersomes have in recent years emerged as a powerful tool for a wide range of applications in the fields of biomimicry and drug delivery. The full potential of polymersomes, however, has yet to be harnessed due to a lack of appreciation of existing shape control methods. This very much contrasts the field of inorganic nanoparticle synthesis where non-spherical hollow metal nanoparticles are routinely prepared and used. Here, we summarize recent efforts over the past decade to study the morphological transformation of conventionally spherical polymersomes into non-spherical polymersomes.

Magneto-Responsive Hydrogels: Preparation, Characterization, Biotechnological and Environmental Applications

Hydrogels are hydrophilic three-dimensional networks able to hold large amount of water and hydrophilic molecules. Magneto-responsive hydrogels comprise of magnetic nanoparticles dispersed in polymeric networks that can be manipulated under external magnetic field. This review aims at (i) giving a brief overview on the evolution of hydrogels until the design and development of magnetic hydrogels; (ii) describing the types of hydrogels and the basic concepts about superparamagnetic iron oxide nanoparticles, as well as the preparation and characterization of magneto-responsive hydrogels; (iii) displaying the relevant applications of magneto-responsive hydrogels for drug delivery, regenerative medicine of tissues, cancer therapy and environmental issues and (iv) highlighting the challenges and future trends of magneto-responsive hydrogels for 3D and 4D printing.

Advances in hydrophilic nanomaterials for glycoproteomics.

Owing to the formidable challenge posed by microheterogeneities in glycosylation sites, macroheterogeneity of the modification number of glycans, and low abundance and ionization efficiency of glycosylation, the crucial premise for conducting in-depth profiling of the glycoproteome is to develop highly efficient technology for separation and enrichment. The appearance of hydrophilic interaction chromatography (HILIC) has considerably accelerated the progress in glycoproteomics. In particular, additional hydrophilic nanomaterials have been developed for glycoproteomics research in the recent years. In this review, we mainly summarize the recent progresses made in the design and synthesis of different hydrophilic nanomaterials, as well as their applications in glycoproteomics, according to the classification of the main hydrophilic functional molecules on the surface. Further, we briefly illustrate the potential retention mechanism of the HILIC mode and discuss the limits and barriers of hydrophilic nanomaterials in glycoproteomics, as well as propose their possible development trends in the future.

A toxicity profile of the Pheroid® technology in rodents

The Pheroid® drug delivery system is now on the threshold of progressing into human clinical trials for various patented pharmaceutical applications and a systematic investigation of its toxicological properties in vitro and in vivo is thus a priority. Colloidal dispersions (nano- and microemulsions) demonstrate the ability to be adapted to accommodate either lipophilic, hydrophilic or amphiphilic drug molecules. The colloidal dispersions investigated during this evaluation has a general size of 200 nm - 2 μm, a zeta-potential of -25 mV and the main ingredient was ethyl esters of essential fatty acids. The Ames mutagenicity assay was performed on selected Salmonella thyphimurium strains TA98, TA100 and TA102. The Ames assay included S9 metabolic activation and no mutagenicity was present during the assay. The effect of acute and subchronic administration on a biological system was investigated in two species of rodent (BALB/c mice and Sprague-Dawley rats). Observations focused on the physical condition, blood biochemical analysis and the haematological profiles. Gross necropsy was performed on all the test animals. Organ weights followed by histopathology of selected organ tissues were recorded. During the acute evaluation animals showed tolerance of the maximum prescribed dose of 2000 mg/kg (according to OECD guidelines) in two rodent species after intravenous administration (absolute bioavaibility). The oral formulation was tolerated without incidents in both acute and subchronic studies. Although valuable baseline safety data was obtained regarding the Pheroid® system, future studies with the entrapped active pharmaceutical ingredients is necessary to provide a definitive safety profile.

STING activation in cancer immunotherapy.

Cancer immunotherapy modulates and leverages the host immune system to treat cancer. The past decade has witnessed historical advancement of cancer immunotherapy. A myriad of approaches have been explored to elicit or augment anticancer innate immunity and/or adaptive immunity. Recently, activation of stimulator of interferon (IFN) genes (STING), an intracellular receptor residing in the endoplasmic reticulum, has shown great potential to enhance antitumor immunity through the induction of a variety of pro-inflammatory cytokines and chemokines, including type I IFNs. A number of natural and synthetic STING agonists have been discovered or developed, and tested in preclinical models and in the clinic for the immunotherapy of diseases such as cancer and infectious diseases. Cyclic dinucleotides (CDNs), such as cyclic dimeric guanosine monophosphate (c-di-GMP), cyclic dimeric adenosine monophosphate (c-di-AMP), and cyclic GMP-AMP (cGAMP), are a class of STING agonists that can elicit immune responses. However, natural CDNs are hydrophilic small molecules with negative charges and are susceptible to enzymatic degradation, leading to low bioavailability in target tissues yet unwanted toxicities and narrow therapeutic windows. Drug delivery systems, coupled with nucleic acid chemistry, have been exploited to address these challenges. Here, we will discuss the underlying immunological mechanisms and approaches to STING activation, with a focus on the delivery of STING agonists, for cancer immunotherapy.

Fractional laser-assisted topical delivery of bleomycin quantified by LC-MS and visualized by MALDI mass spectrometry imaging

Bleomycin exhibits antiproliferative effects desirable for use in dermato-oncology but topical use is limited by its 1415 Da molar mass. Ablative fractional laser (AFL)-assisted drug delivery has been shown to enhance drug uptake in skin. The aim of this study was with AFL to deliver bleomycin into skin, quantify uptake, and visualize biodistribution with mass spectrometry. In a Franz diffusion cell study, pig skin samples (n = 66) were treated with AFL (λ = 10,600 nm), 5% density, and 0, 5, 20, or 80 mJ/microbeam (mb) pulse energies before exposure to bleomycin for 0.5, 4, or 24 h. Bleomycin was quantified in biopsy cryosections at depths of 100, 500, and 1500 µm using high-performance liquid chromatography-mass spectrometry (LC-MS), and drug biodistribution was visualized for 80 mJ/mb samples by matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The pulse energies 5, 20, and 80 mJ/mb resulted in microscopic ablation zones (MAZs) reaching superficial, mid, and deep dermis respectively. Bleomycin was successfully delivered into the skin and deeper MAZs and longer exposure time resulted in higher skin concentrations. After 24 h, AFL exposure resulted in significant amounts of bleomycin throughout all skin layers (≥510 µg/cm3, p ≤ .002). In comparison, concentrations in intact skin exposed to bleomycin remained below limit of quantification. MALDI-MSI supported the quantitative LC-MS results by visualizing bleomycin biodistribution and revealing high uptake around MAZs with delivery into surrounding skin tissue. In conclusion, topical drug delivery of the large and hydrophilic molecule bleomycin is feasible, promising, and should be explored in an in vivo setting.

Chapter 12 - Central taste anatomy and physiology

The gustatory system contributes to the flavor of foods and beverages and communicates information about nutrients and poisons. This system has evolved to detect and ultimately respond to hydrophilic molecules dissolved in saliva. Taste receptor cells, located in taste buds and distributed throughout the oral cavity, activate nerve afferents that project to the brainstem. From here, information propagates to thalamic, subcortical, and cortical areas, where it is integrated with information from other sensory systems and with homeostatic, visceral, and affective processes. There is considerable divergence, as well as convergence, of information between multiple regions of the central nervous system that interact with the taste pathways, with reciprocal connections occurring between the involved regions. These widespread interactions among multiple systems are crucial for the perception of food. For example, memory, hunger, satiety, and visceral changes can directly affect and can be affected by the experience of tasting. In this chapter, we review the literature on the central processing of taste with a specific focus on the anatomic and physiologic responses of single neurons. Emphasis is placed on how information is distributed along multiple systems with the goal of better understanding how the rich and complex sensations associated with flavor emerge from large-scale, systems-wide, interactions.

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers.

Hydrophobic ion pairing has emerged as a method to modulate the solubility of charged hydrophilic molecules ranging in class from small molecules to large enzymes. Charged hydrophilic molecules are ionically paired with oppositely-charged molecules that include hydrophobic moieties; the resulting uncharged complex is water-insoluble and will precipitate in aqueous media. Here we review one of the most prominent applications of hydrophobic ion pairing: efficient encapsulation of charged hydrophilic molecules into nano-scale delivery vehicles – nanoparticles or nanocarriers. Hydrophobic complexes are formed and then encapsulated using techniques developed for poorly-water-soluble therapeutics. With this approach, researchers have reported encapsulation efficiencies up to 100% and drug loadings up to 30%. This review covers the fundamentals of hydrophobic ion pairing, including nomenclature, drug eligibility for the technique, commonly-used counterions, and drug release of encapsulated ion paired complexes. We then focus on nanoformulation techniques used in concert with hydrophobic ion pairing and note strengths and weaknesses specific to each. The penultimate section bridges hydrophobic ion pairing with the related fields of polyelectrolyte coacervation and polyelectrolyte-surfactant complexation. We then discuss the state of the art and anticipated future challenges. The review ends with comprehensive tables of reported hydrophobic ion pairing and encapsulation from the literature.

Effect of binder and load solubility properties on HPMC granules produced by wet granulation process

Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.