Entrapment Of Molecules Research Articles

Electroless Functionalization of Silver Films by Its Molecular Doping.

We present a methodology which by far extends the potential applications of thin conductive silver films achieved by an electroless molecular doping process of the metal with any of the endless functional molecules that the large library of organic molecules offer. The resulting metallic films within which the molecule is entrapped--molecule@Ag--carry both the classical chemical and physical properties of silver films, as well as the function of the entrapped molecule. Raman measurements of the organic molecules from within the silver films provide the first spectroscopic observations from within silver, and clearly show that entrapment, a three-dimensional process, and adsorption, a two-dimensional process, on silver films are distinctly different processes. Three organic molecules, the cationic Neutral red, the anionic Congo red, and the antibacterial agent chlorhexidine digluconate (CH), were used to demonstrate the generality of this method for various types of molecules. We studied the sensitivity of the film conductivity to the type of the molecule entrapped within the film, to its concentration, and to temperature. Dual functionality was demonstrated with CH@Ag films, which are both conductive and have prolonged and high antibacterial activity, a combination of properties that has been unknown so far.

Cytotoxicity and sustained release of modified divinylsulfone from silk based 3D construct.

Monovinylsulfones have been extensively studied for its biological activities but modified divinylsulfones (mDVS2) were largely neglected due to the non-availability of appropriate synthetic routes. The present report describes the potential of a unique derivative of divinylsulfone as a remedial molecule. The mDVS2, available in reasonably large amount through an easy synthesis route, incites necrosis in invasive and non-invasive breast cancer cells in a time and concentration dependent manner. This molecule is further used to fabricate mDVS2 embedded silk based 3D scaffolds in order to achieve sustained release. The entrapped molecules retain their activity over time, as 100% cell death is observed within 7 days. The findings demonstrate the cytotoxic property of mDVS and highlight the importance of under utilized mDVSs as potential therapeutic agents.

Thiol-ene and photo-cleavage chemistry for controlled presentation of biomolecules in hydrogels

Hydrogels have emerged as promising scaffolds in regenerative medicine for the delivery of biomolecules to promote healing. However, increasing evidence suggests that the context that biomolecules are presented to cells (e.g., as soluble verses tethered signals) can influence their bioactivity. A common approach to deliver biomolecules in hydrogels involves physically entrapping them within the network, such that they diffuse out over time to the surrounding tissues. While simple and versatile, the release profiles in such system are highly dependent on the molecular weight of the entrapped molecule relative to the network structure, and it can be difficult to control the release of two different signals at independent rates. In some cases, supraphysiologically high loadings are used to achieve therapeutic local concentrations, but uncontrolled release can then cause deleterious off-target side effects. In vivo, many growth factors and cytokines are stored in the extracellular matrix (ECM) and released on demand as needed during development, growth, and wound healing. Thus, emerging strategies in biomaterial chemistry have focused on ways to tether or sequester biological signals and engineer these bioactive scaffolds to signal to delivered cells or endogenous cells. While many strategies exist to achieve tethering of peptides, protein, and small molecules, this review focuses on photochemical methods, and their usefulness as a mild reaction that proceeds with fast kinetics in aqueous solutions and at physiological conditions. Photo-click and photo-caging methods are particularly useful because one can direct light to specific regions of the hydrogel to achieve spatial patterning. Recent methods have even demonstrated reversible introduction of biomolecules to mimic the dynamic changes of native ECM, enabling researchers to explore how the spatial and dynamic context of biomolecular signals influences important cell functions. This review will highlight how two photochemical methods have led to important advances in the tissue regeneration community, namely the thiol-ene photo-click reaction for bioconjugation and photocleavage reactions that allow for the removal of protecting groups. Specific examples will be highlighted where these methodologies have been used to engineer hydrogels that control and direct cell function with the aim of inspiring their use in regenerative medicine.

P(VPBA-DMAEA) as a pH-sensitive nanovalve for mesoporous silica nanoparticles based controlled release

Abstract A pH-sensitive controlled release system was proposed in this work, which consists of mesoporous silica nanoparticles (MSNs) functionalized on the pore outlets with poly(4-vinylphenybronic acid-co-2-(dimethylamino)ethyl acrylate) [P(VPBA-DMAEA)]. Four kinds of P(VPBA-DMAEA)-gated MSNs were synthesized and applied for the pH-sensitive controlled release. The results showed that P(VPBA-DMAEA) can work as a pH-sensitive nanovalve. The release behavior of the hybrid nanoparticles could be adjusted by changing the mole ratio of VPBA and DMAEA. With the increasing of the mole ratio of VPBA, the leakage of the entrapped molecules in the pores of MSNs could be decreased at neutral and alkaline conditions. By altering the pH of buffer from 4.0 to 8.0, the valve could be switched “on” and “off” reversibly. In addition, cells viability results indicated that these P(VPBA-DMAEA)-gated MSNs had good biocompatibility. We believe that these MSNs based pH-sensitive controlled release system will provide a promising nanodevice for sited release of drug delivery.

Enhanced anticancer potency using an acid-responsive ZnO-incorporated liposomal drug-delivery system.

The development of stimuli-responsive nanocarriers is becoming important in chemotherapy. Liposomes, with an appropriate triggering mechanism, can efficiently deliver their encapsulated cargo in a controlled manner. We explored the use of acid-sensitive zinc oxide nanoparticles (ZNPs) as modulators of the responsive properties of liposomes. Nanocomplexes formed by the incorporation of ZNPs in liposomes (ZNP-liposomes) were designed to demonstrate the pH-responsive release of a drug (daunorubicin) without premature drug leakage and with the maintenance of the relevant therapeutic concentrations. The nanocomplexes were spherical in shape with a narrow size distribution and showed a high drug-encapsulating efficiency. Under acidic conditions, the ZNP-liposome nanocomplexes released the loaded drug more rapidly than bare liposomes. Using flow cytometry, confocal microscopy and an MTT assay, we demonstrated that these nanocomplexes were readily taken up by cancer cells, resulting in significantly enhanced cytotoxicity. On exposure to the acidic conditions inside cancer cells, the ZNPs rapidly decomposed, releasing the entrapped drug molecules from the ZNP-liposome nanocomplexes, producing widespread cytotoxic effects. The incorporated ZNPs were multimodal in that they not only resulted in a pH-responsive drug-delivery system, but they also had a synergistic chemo-photodynamic anticancer action. This design provides a significant step towards the development of multimodal liposome structures.

Experimental and first-principles investigation of the adsorption and entrapping of guanine with SiO2 clusters of sol-gel silicate material for understanding DNA photodamage.

We report a first principles density functional theoretical (DFT) investigation of guanine (G) adsorption onto SiO2 clusters, viz., Si2O4, Si3O6, Si4O8 and Si5O10 in terms of geometry, binding energy (EB), binding site, energy gap (Eg), and electronic and spectral properties. Guanine entrapped within a Si9O18 cluster was also studied in terms of geometry, energy gap (Eg), electronic and spectral properties. We observed that the most stable forms of the cluster were Si5O10 and Si9O18. Guanine adsorbed onto SiO2 (G-SiO2) and guanine entrapped within SiO2 (GE-SiO2) were analyzed by the B3LYP/LanL2DZ method. The HOMO-LUMO energies illustrate that charge transfer from ligand to metal (L → M) occurs in G-SiO2 clusters as guanine to SiO2. The composite of guanine with nanostructured silica material was prepared by simple precipitation and chemical sol-gel processes. The prepared G-SiO2 and GE-SiO2 composites were characterized by FT-IR and FE-SEM with EDX analysis. The resulting experimental evidence is included for better understanding the guanine adsorption and entrapment. The adsorption and entrapping of G-SiO2 and GE-SiO2 was also confirmed by UV-vis spectroscopy. Experimental results are compared with the DFT results. Furthermore, the sol-gel silicate material used to protect the DNA base (guanine) from UVA-irradiation has been highlighted.

Alginate/sodium caseinate aqueous-core capsules: A pH-responsive matrix

HypothesisAlginate capsules have several applications. Their functionality depends considerably on their permeability, chemical and mechanical stability. Consequently, the creation of composite system by addition of further components is expected to control mechanical and release properties of alginate capsules. ExperimentsAlginate and alginate–sodium caseinate composite liquid-core capsules were prepared by a simple extrusion. The influence of the preparation pH and sodium caseinate concentration on capsules physico-chemical properties was investigated. FindingsResults showed that sodium caseinate influenced significantly capsules properties. As regards to the membrane mechanical stability, composite capsules prepared at pH below the isoelectric point of sodium caseinate exhibited the highest surface Young’s modulus, increasing with protein content, explained by potential electrostatic interactions between sodium caseinate amino-groups and alginate carboxylic group. The kinetic of cochineal red A release changed significantly for composite capsules and showed a pH-responsive release.Sodium caseinate-dye mixture studied by absorbance and fluorescence spectroscopy confirmed complex formation at pH 2 by electrostatic interactions between sodium caseinate tryptophan residues and cochineal red sulfonate-groups. Consequently, the release mechanism was explained by membrane adsorption process.This global approach is useful to control release mechanism from macro and micro-capsules by incorporating guest molecules which can interact with the entrapped molecule under specific conditions.

Microfluidic conceived pH sensitive core–shell particles for dual drug delivery

In current study, we report on the synthesis of core–shell microparticles for dual drug delivery by means of a two co-axial microfluidic device and online UV assisted free radical polymerization. Before developing pH-sensitive particles, ketoprofen loaded poly(methyl acrylate) core–ranitidine HCl loaded poly(acrylamide) shell particles were produced. Influence of inner and outer phases flow rates on particle size, shape, core diameter, shell thickness, and drug release properties was studied. All the particles were monodispersed with coefficient of variation below 5%. Furthermore, their diameter ranged from 100 to 151μm by increasing continuous (Qc) to middle (Qm) phase flow rate ratio (Qc/Qm). Core diameter varied from 58 to 115μm by decreasing middle (Qm) to inner (Qi) phase flow rate ratio (Qm/Qi) at constant continuous phase flow rate as confirmed by SEM images. It was observed that an optimum concentration of acrylamide (30wt%) and an appropriate combination of surfactants were necessary to get core–shell particles otherwise Janus structure was obtained. FTIR confirmed the complete polymerization of core and shell phases. MTT assay showed variation in viability of cells under non-contact and contact conditions with less cytotoxicity for the former. Under non-contact conditions LD50 was 3.1mg/mL. Release studies in USP phosphate buffer solution showed simultaneously release of ketoprofen and ranitidine HCl for non pH-sensitive particles. However, release rates of ranitidine HCl and ketoprofen were higher at low and high pH respectively. To develop pH-sensitive particles for colon targeting, the previous shell phase was admixed with few weight percentage of pH sensitive carboxyethyl acrylate monomer. Core and shell contained the same hydrophobic and hydrophilic model drugs as in previous case. The pH-sensitive shell prevented the release of the two entrapped molecules at low pH while increasing significantly their release rate at higher pH with a maximum discharge at colonic pH of 7.4.

Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release

Polyamidic nanofibrous membranes containing gated silica mesoporous particles, acting as carriers, are described as novel hybrid composite materials for encapsulation and on-command delivery of garlic extracts. The carrier system consists of MCM-41 solids functionalized in the outer surface, with linear polyamines (solid P1) and with hydrolyzed starch (solid P2), both acting as molecular gates. Those particles were adsorbed on electospun nylon-6 nanofibrous membranes yielding to composite materials M1 and M2. FE-SEM analysis confirmed the presence of particles incorporated on the nylon nanofibers. The release of the entrapped molecules (garlic extract) from the P1, P2, M1, and M2 materials was evaluated using cyclic voltammetry measurements. Electrochemical studies showed that at acidic pH P1 and M1 were unable to release their entrapped cargo (closed gate), whereas at neutral pH both materials release their loading (open gate). Dealing with P2 and M2 materials, in the absence of pancreatin a negligible release is observed (closed gate), whereas in the presence of enzyme the load is freely to diffuse to the solution. These newly developed composite nanomaterials, provide a homogeneous easy-to-handle system with controlled delivery and bioactive-protective features, having potential applications on pharmacology, medical and engineering fields.

Molecular targeting of neuroblastoma with a novel p16INK4a transporter system

Potential molecular targets in neuroblastoma include ALK mutations, p16 deletion and CDK2A mutations; however, targeted therapeutics have not been developed for these factors. We developed Wr-T, a new system for intracellular peptide and protein delivery with a 30-residue sequence that mediates molecule entrapment and intracellular permeability. Wr-T was used to introduce the p16INK4a functional peptide to restore the tumor suppressor function of p16INK4a. Introduction of Wr-T into rats with subcutaneous grafts of neuroblastoma produced an astonishing 75.6% tumor suppression (p<0.0005). Thus, the p16INK4a functional peptide can be introduced in low doses and, because it exists invivo, it should produce fewer side-effects than standard chemotherapy. We suggest this system could be used for molecular-targeted peptides other than p16INK4a and should be pursued for further development.

The Amine Content of PEGylated Chitosan Bombyx mori Nanoparticles Acts as a Trigger for Protein Delivery

In modern medicine, effective protein therapy is a major challenge to which a significant contribution can be expected from nanoscience through the development of novel delivery systems. Here we present the effect of the amine content of nanoparticles based on PEGylated chitosan Bombyx mori (PEG-O-ChsBm) copolymers on the entrapment of molecules in a search for highly efficient nanocarriers. PEG-O-ChsBm copolymers were synthesized with amine contents from 1.12% to 0.70%, and nanoparticles were generated by self-assembly in dilute aqueous solutions. These nanoparticles successfully entrapped molecules with a wide range of sizes, the efficiency of which was dependent on their amine contents. While hydrophobic molecules were entrapped with high efficiency in all types of nanoparticle, hydrophilic molecules were entrapped only in those with low amine content. Bovine serum albumin, selected as a model protein, was entrapped in nanoparticles and efficiently released in acidic conditions. The triggered entrapment of molecules in PEG-O-ChsBm nanoparticles by selection of the appropriate amine content represents a straightforward way to modulate their delivery by fine changes in the properties of nanocarriers.

Porous Hybrids: MOF Nano‐Vesicles and Toroids: Self‐Assembled Porous Soft‐Hybrids for Light Harvesting (Adv. Funct. Mater. 45/2013)

Nature employs light-harvesting complexes for efficient migration of photons to the reaction centre for the conversion of solar energy to chemical energy. Mimicking this natural process of energy transfer in a synthetic light-harvesting system is demonstrated by V. M. Suresh, S. J. George, and T. K. Maji in a functional nanoscale soft-porous luminescent metal–organic framework. On page 5585, coordination-directed self-assembly of a chromophoric organic linker results in ordered metal-organic vesicular and toroid nanostructures that act as a light-harvesting scaffold for noncovalently entrapped dye molecules.

Degradation Properties and pH-responsive Guest-release of Cyclophanes Having Four Ester Side Chains with Terminal Choline Residues

Abstract Water-soluble cationic cyclophane 1 having four ester side chains with terminal choline residues was synthesized as a pH-responsive degradable host. Alkaline hydrolysis of the ester bonds of 1 gave the corresponding tetraanionic cyclophane 2, which exhibited guest-binding affinities that led to release of the entrapped anionic guest molecules into the bulk aqueous phase.

Non-covalent hydrogels of cyclodextrins and poloxamines for the controlled release of proteins

Different types of gels were prepared by combining poloxamines (Tetronic), i.e. poly(ethylene oxide)/poly(propylene oxide) (PEO/PPO) octablock star copolymers, and cyclodextrins (CD). Two different poloxamines with the same molecular weight (ca. 7000) but different molecular architectures were used. For each of their four diblock arms, direct Tetronic 904 presents PEO outer blocks while in reverse Tetronic 90R4 the hydrophilic PEO blocks are the inner ones. These gels were prepared by combining α-CD and poloxamine aqueous solutions. The physicochemical properties of these systems depend on several factors such as the structure of the block copolymers and the Tetronic/α-CD ratio. These gels were characterized using differential scanning calorimetry (DSC), viscometry and X-ray diffraction measurements. The 90R4 gels present a consistency that makes them suitable for sustained drug delivery. The resulting gels were easily eroded: these complexes were dismantled when placed in a large amount of water, so controlled release of entrapped large molecules such as proteins (Bovine Serum Albumin, BSA) is feasible and can be tuned by varying the copolymer/CD ratio.

Hydrolytic Conversion of a Metal–Organic Polyhedron into a Metal–Organic Framework

Twist and release: The metal-organic polyhedron 1 synthesized from 5-(prop-2-ynyloxy)isophthalic acid and Cu(NO3 )2 ⋅ 3 H2 O has a hydrophobic outer surface and a hydrophilic inner core. In an aqueous medium, the resulting polarity gradient led to the transformation of 1 into the 2D metal-organic framework 2. This unique phenomenon enabled the gradual release of entrapped drug molecules.

Protamine‐Capped Mesoporous Silica Nanoparticles for Biologically Triggered Drug Release

The fabrication of a mesoporous silica nanoparticle (MSN)−protamine hybrid system (MSN−PRM) is reported that selectively releases drugs in the presence of specific enzyme triggers present in the proximity of cancer cells. The enzyme trigger involved is a protease called trypsin, which is overexpressed in certain specific pathological conditions, such as inflammation and cancer. Overexpression of trypsin is known to be associated with invasion, metastasis, and growth in several cancers, such as leukemia, colon cancer, and colorectal cancer. The current system (MSN–PRM) consists of an MSN support in which mesopores are capped with an FDA‐approved peptide drug protamine, which effectively blocks the outward diffusion of the drug molecules from the mesopores of the MSNs. On exposure to the enzyme trigger, the protamine cap disintegrates, opening up the molecular gates and releasing the entrapped drug molecules. The system exhibits minimal premature release in the absence of the trigger and selectively releases the encapsulated drugs in the presence of the proteases secreted by colorectal cancer cells. The ability of the MSN–PRM particles to deliver anticancer drugs to colorectal cancer cells has also been demonstrated. The hydrophobic drug is released into cancer cells subsequent to disintegration of the protamine cap, resulting in cell death. Drug‐induced cell death in colorectal cancer cells is significantly enhanced when the hydrophobic drug that is known to degrade in aqueous environments is encapsulated in the MSN–PRM system in comparison to the free drug (P &lt; 0.05). The system, which shows good biocompatibility and selective drug release, is a promising platform for cancer specific drug delivery.

Effect of Freeze-Thawing Study on Curcumin Liposome for Obtaining Better Freeze-Dried Product

Liposomes are widely used in the pharmaceutical, biopharmaceutical, cosmetic, and nutraceutical sectors as an efficacious drug-delivery system for improving the bioavailability and protection of the entrapped drug molecule. The present study evaluates freeze-thaw as a simple approach for screening the most appropriate lyoprotectant. The freeze-thaw study is based on the principle that an excipient, which protects liposomes during the first step of freezing, is likely to be an effective lyoprotectant. Curcumin liposomes with high entrapment efficiency were prepared using a lipid film hydration technique. The freeze-thawing study was carried out using various lyoprotectants such as sucrose, mannitol, lactose, dextrose, and maltose. Sucrose showed minimal particle size change with better cryoprotection after the freeze-thaw study. The internal and external addition of sucrose during formulation has shown significant effects on the retention of particle size and curcumin content during the freeze-thawing and drying studies, respectively. Scanning electron microscopy revealed round vesicles with a size ∼131 nm, which correlated well with zeta sizer particle size measurements. Infrared spectra and X-ray diffraction suggested interaction between the sugar and the liposomes and amorphization of the final freeze-dried product. The good correlation between freeze thawing and freeze drying suggests the freeze-thaw study as a simple and quick approach for screening optimal cryoprotectant for freeze drying.

Interaction between oxidized polyaniline and oppositely charged amphiphilic assemblies in an aqueous/organic biphasic system

Amphiphilic assemblies (AAs) are known to interact with polyelectrolytes in such a manner that the dynamic AAs retain their structural features, but the polyelectrolytes undergo conformational changes. This article reports that a charge bearing, rigid, water insoluble and oxidized conjugated polymer, polyaniline, can withstand such conformational changes and at the same time force the AAs to disassemble. An interfacial setup, comprising of an aqueous/organic interface, was utilized to study the disassembly process and the subsequent phase transfer phenomenon of the in situ synthesized polymer. It has further been demonstrated that the phase transfer occurred only when the concentration of the amphiphile was at and above its critical aggregation concentration. Moreover, fine dispersions of polyaniline were obtained initially in the aqueous phase and later in the organic phase. These fine dispersions suggest possibilities for better processing of this otherwise “difficult to process” polymer. The disassembly phenomenon was followed by changes in fluorescence emission and UV–vis absorption spectra of an entrapped probe molecule, recorded before and after the interaction. Changes in particle size upon disassembly were studied by dynamic light scattering. Dispersions of the polymer in the two phases were realized from transmission electron micrographs and UV–vis absorption spectra of the dispersed polymer.

Near‐Infrared‐Controlled, Targeted Hydrophobic Drug‐Delivery System for Synergistic Cancer Therapy

Hydrophobicity has been an obstacle that hinders the use of many anticancer drugs. A critical challenge for cancer therapy concerns the limited availability of effective biocompatible delivery systems for most hydrophobic therapeutic anticancer drugs. In this study, we have developed a targeted near-infrared (NIR)-regulated hydrophobic drug-delivery platform based on gold nanorods incorporated within a mesoporous silica framework (AuMPs). Upon application of NIR light, the photothermal effect of the gold nanorods leads to a rapid rise in the local temperature, thus resulting in the release of the entrapped drug molecules. By integrating chemotherapy and photothermotherapy into one system, we have studied the therapeutic effects of camptothecin-loaded AuMP-polyethylene glycol-folic acid nanocarrier. Results revealed a synergistic effect in vitro and in vivo, which would make it possible to enhance the therapeutic effect of hydrophobic drugs and decrease drug side effects. Studies have shown the feasibility of using this nanocarrier as a targeted and noninvasive remote-controlled hydrophobic drug-delivery system with high spatial/temperal resolution. Owing to these advantages, we envision that this NIR-controlled, targeted drug-delivery method would promote the development of high-performance hydrophobic anticancer drug-delivery system in future clinical applications.

Photodynamic therapeutic effect of indocyanine green entrapped in polymeric nanoparticles and their anti-EGFR-conjugate in skin cancer in CD1 mice

Indocyanine green (ICG) is a promising photosensitive agent for photodynamic therapy (PDT) of tumors. Encapsulating ICG dye in polymeric nanoparticles based on PEBBLE technology forming (ICG-PEBBLE) could improve the aqueous stability of the entrapped ICG molecules. The study objective is to investigate the PDT effect of free ICG-PEBBLE and its Anti-EGFR conjugate. Skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) followed by a PDT protocol for four weeks. PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR decreased skin tumor sizes. Our findings revealed that the inflammatory mediators tumor necrosis factor (TNF-α), nitric oxide (NO), cycloxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the angiogenic mediator vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) were decreased, while apoptosis, caspase-3 and histone acetylation were induced in tumor bearing groups after PDT using both of ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR. The present study indicated the effectiveness of PDT using ICG-PEBBLE or ICG-PEBBLE-Anti-EGFR as an inhibitor modality for tumor size, apoptosis, angiogenesis and tumor inflammation. The conjugating of ICG-PEBBLE to anti-EGFR was found to be more effective in inhibiting VEGF and in increasing caspase-3 compared to free ICG-PEBBLE, but there were no other preferential PDT efficacy.