Carriers For Drug Delivery Applications Research Articles

Elucidating the Drug Release from Metal-Organic Framework Nanocomposites via In Situ Synchrotron Microspectroscopy and Theoretical Modeling.

Nanocomposites comprising metal-organic frameworks (MOFs) embedded in a polymeric matrix are promising carriers for drug delivery applications. While understanding the chemical and physical transformations of MOFs during the release of confined drug molecules is challenging, this is central to devising better ways for controlled release of therapeutic agents. Herein, we demonstrate the efficacy of synchrotron microspectroscopy to track the in situ release of 5-fluorouracil (5-FU) anticancer drug molecules from a drug@MOF/polymer composite (5-FU@HKUST-1/polyurethane). Using experimental time-resolved infrared spectra jointly with newly developed density functional theory calculations, we reveal the detailed dynamics of vibrational motions underpinning the dissociation of 5-FU bound to the framework of HKUST-1 upon water exposure. We discover that HKUST-1 creates hydrophilic channels within the hydrophobic polyurethane matrix hence helping to tune drug release rate. The synergy between a hydrophilic MOF with a hydrophobic polymer can be harnessed to engineer a tunable nanocomposite that alleviates the unwanted burst effect commonly encountered in drug delivery.

The Engineering of Porous Silica and Hollow Silica Nanoparticles to Enhance Drug-loading Capacity

As a promising candidate for expanding the capacity of drug loading in silica nanoplatforms, hollow mesoporous silica nanoparticles (HMSNs) are gaining increasing attention. In this study, porous nanosilica (PNS) and HMSNs were prepared by the sol-gel method and template assisted method, then further used for Rhodamine (RhB) loading. To characterize the as-synthesized nanocarriers, a number of techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen absorption-desorption isotherms, dynamic light scattering (DLS), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR) were employed. The size of HMSN nanoparticles in aqueous solution averaged 134.0 ± 0.3 nm, which could be adjusted by minor changes during synthesis, whereas that of PNS nanoparticles was 63.4 ± 0.6 nm. In addition, the encapsulation of RhB into HMSN nanoparticles to form RhB-loaded nanocarriers (RhB/HMSN) was successful, achieving high loading efficiency (51.67% ± 0.11%). This was significantly higher than that of RhB-loaded PNS (RhB/PNS) (12.24% ± 0.24%). Similarly, RhB/HMSN also possessed a higher RhB loading content (10.44% ± 0.02%) compared to RhB/PNS (2.90% ± 0.05%). From those results, it is suggested that prepared HMSN nanocarriers may act as high-capacity carriers in drug delivery applications.

Non-antibacterial biogenic gold nanoparticles an ulterior drug carrier

Gold nanoparticles have been synthesized by use of different volumes of aqueous extract which has been prepared from woman’s tongue tree white flower. The gold nanoparticles and extract were tested for bactericidal qualities on B. subtilis, S. aureus, (Gram positive) and P. aeruginosa, E. coli, (Gram negative) in the concentration range of 0.5 mg ml−1 to 2.0 mg ml−1 using well diffusion. Antibacterial activity shown by all the gold nanoparticles against any of the four organisms was negligible, in spite of the fact that gold nanoparticles are conventionally known to show antibacterial properties. Lack of anti-bacterial properties of gold nanoparticles reported in this paper highlights its inert nature making it a promising alternative for its use in biomedical applications. Given that gold nanoparticles are most suited due to its targeted specificity as well as biocompatibility; these stable gold nanoparticles would be best suited as carriers for drug delivery applications.

Tunable morphology of lipid/chitosan particle assemblies

Lipid/chitosan (CS) particle assemblies have recently been developed as new promising carriers for drug delivery applications. The present work reports for the first time the formation of such assemblies by a simple spontaneous adsorption of lipid membranes onto the CS particle surfaces. As shown by dynamic light scattering (DLS) measurements, final non-aggregated assemblies with relatively satisfactory size distributions were obtained by using this process. Furthermore, a particular attention has been paid herein to the effect of the initial morphology of lipid membranes (i.e., vesicular or discoidal) on the resulting characteristics of assemblies. To this end, each one of these membranes was mixed with CS particles, and the obtained assemblies were observed by transmission electron microscopy (TEM). According to these observations, the vesicular lipid membranes seem to wrap mostly CS particles. In contrast, lipid discs are not reorganized onto the particle surface but would rather be stacked onto the CS particle.

Synthesis and characterization of diselenide crosslinked polymeric micelles via Diels–Alder click reaction

ABSTRACTA well-defined amphiphilic block copolymer, poly (ethylene oxide)-b-(poly (furfuryl methacrylate) (PEO-b-PFMA) was prepared by single electron transfer living radical polymerization using tris(dimethylamino)ethyl amine (Me6TREN) as a ligand. The block copolymer formed sub-100 nm micelles in water with PEO as a shell and PFMA as a core. Diels–Alder click type reaction was employed to form core-crosslinked micelles using a diselenide-containing crosslinker without any catalyst. The block copolymer and micelles were characterized by gel permeation chromatography, nuclear magnetic resonance, Fourier-transform infrared spectroscopy, dynamic light scattering analysis and transmission electron microscopy. The stability of core-crosslinked micelles under reductive-oxidative condition was also investigated. The diselenide crosslinked micelles displayed good stability against extensive dilution but decomposed under the presence of hydrogen peroxide or glutathione. The redox responsive core-crosslinked micelles can be a promising carrier for drug delivery applications.

Adsorption of 5-fluorouracil, hydroxyurea and mercaptopurine drugs on zeolitic imidazolate frameworks (ZIF-7, ZIF-8 and ZIF-9)

A series of bio-compatible zeolitic imidazolate frameworks (ZIF-7, ZIF-8 and ZIF-9) have been studied as potential carriers for drug delivery applications. Grand canonical Monte Carlo (GCMC) simulations were performed to study the adsorption of three anti-cancer drugs namely 5-Fluorouracil, Hydroxyurea and Mercaptopurine. Adsorption isotherms, snapshots and energy of adsorption were used to analyze the drug delivery process. Our GCMC simulations revealed the high capacities of studied ZIFs (0.65–0.68 g/g) for the adsorption of 5-Fluorouracil and Hydroxyurea. ZIF-8 showed high capacity (0.55 g/g) for the adsorption of Mercaptopurine, while the adsorption capacity of ZIF-7 and ZIF-9 for Mercaptopurine were moderate (about 0.36–0.44 g/g). The high heat of adsorption (115–133 kJ/mol for 5-Fluorouracil in ZIF-8 and 200–240 kJ/mol for Mercaptopurine in three ZIFs) also suggests a controlled release process. The analysis of snapshots and radial distribution functions (RDFs) showed that the adsorption of drugs occurred preferentially in the 6-membered pores of ZIFs.

Multivariate analysis for the optimization of polysaccharide-based nanoparticles prepared by self-assembly

Polysaccharide-based nanoparticles are promising carriers for drug delivery applications. The particle size influences the biodistribution of the nanoparticles; hence size distributions and polydispersity index (PDI) are critical characteristics. However, the preparation of stable particles with a low PDI is a challenging task and is usually based on empirical trials. In this study, we report the use of multivariate evaluation to optimize the formulation factors for the preparation of alginate-zinc nanoparticles by ionotropic gelation. The PDI was selected as the response variable. Particle size, size distributions, zeta potential and pH of the samples were also recorded. Two full factorial (mixed-level) designs were analyzed by partial least squares regression (PLS). In the first design, the influence of the polysaccharide and the crosslinker concentrations were studied. The results revealed that size distributions with a low PDI were obtained by using a low polysaccharide concentrations (0.03⿿0.05%) and a zinc concentration of 0.03% (w/w). However, a high polysaccharide concentration can be advantageous for drug delivery systems. Therefore, in the second design, a high alginate concentration was used (0.09%) and a reduction in the PDI was obtained by simultaneously increasing the ionic strength of the solvent and the zinc concentration. The multivariate analysis also revealed the interaction between the factors in terms of their effects on the PDI; hence, compared to traditional univariate analyses, the multivariate analysis allowed us to obtain a more complete understanding of the effects of the factors scrutinized. In addition, the results are considered useful in order to avoid extensive empirical tests for future formulation studies.

Formation and characterization of β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug.

In this work, β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated iron oxide nanoparticles (Fe3O4-β-CD-PEG-PEI) were developed as drug carriers for drug delivery applications. The 5- Fluorouracil (5-FU) was chosen as model drug molecule. The developed nanoparticles (Fe3O4-β-CD-PEG-PEI) were characterized by various techniques such as Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The average particles size range of 5-FU loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles were from 151 to 300nm and zeta potential value of nanoparticles were from -43mV to -20mV as measured using Malvern Zetasizer. Finally, encapsulation efficiency (EE), loading capacity (LC) and in-vitro drug release performance of 5-FU drug loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles was evaluated by UV-vis spectroscopy. In-vitro cytotoxicity tests investigated by MTT assay indicate that 5-FU loaded Fe3O4-β-CD-PEG-PEI nanoparticles were toxic to cancer cells and non-toxic to normal cells. The in-vitro release behavior of 5-FU from drug (5-FU) loaded Fe3O4-β-CD-PEG-PEI composite at different pH values and temperature was studied. It was found that 5-FU was released faster in pH 6.8 than in the acidic mediums (pH 1.2), and the released quantity was higher. Therefore, the newly prepared Fe3O4-β-CD-PEG-PEI carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy.

Colloidal and spherical mesoporous silica particles: synthesis and new technologies for delivery applications

Continuous research in prominent fields such as biotechnology, biomedicine and nanopharmaceutics has brought the development of a widespread class of materials, and studies for mesoporous materials have been exponentially growing lately. The purpose of this review is to provide a useful guide for different materials, methods and configurations that have been reported in the last 5 years for the synthesis of spherical mesoporous silica particles (MSP), in the colloidal size range (1–1000 nm). MSP exhibit several limitations that must be overcome in order to enable their medical and clinical use. Surface modification of these particles will allow getting new promising characteristics of these materials, including better drug release control and biocompatibility improvement. These modified MSP could be potentially used in many biomedical applications, especially for drug delivery systems. Emphasis is made on the pore size, diameter and shape of the final particles since these parameters will establish key characteristics, i.e., drug delivery profile, loading capacity and efficiency. Spreading the use of mesoporous silica particles in biomedicine is possible by the improvement of its inner characteristics through surface modification. This may be done by chemical functionalization or by coating with macromolecular layers or brushes, thus creating novel responsive core–shell hybrid composites to be used as carriers for drug delivery applications.

A DFT study of 5-fluorouracil adsorption on the pure and doped BN nanotubes

The electronic and adsorption properties of the pristine, Al-, Ga-, and Ge-doped BN nanotubes interacted with 5-fluorouracil molecule (5-FU) were theoretically investigated in the gas phase using the B3LYP density functional theory (DFT) calculations. It was found that the adsorption behavior of 5FU molecule on the pristine (8, 0) and (5, 5) BNNTs are electrostatic in nature. In contrast, the 5FU molecule (O-side) implies strong adsorption on the metal-doped BNNTs. Our results indicate that the Ga-doped presents high sensitivity and strong adsorption with the 5-FU molecule than the Al- and Ge-doped BNNTs. Therefore, it can be introduced as a carrier for drug delivery applications.

Nanoparticle stability in biologically relevant media: influence of polymer architecture.

We have contrasted the behavior of nanoparticles formed by the self-assembly of polymers based on poly(ethylene glycol) (PEG) and poly(D,L-lactide), with linear, linear-dendritic and bottle-brush architectures in biologically relevant media. Polymer PEG content ranged between 14% and 46% w/w, and self-assembly was triggered by a rapid and large change in solvent quality inside a four-stream vortex mixer. We examined nanoparticle interaction with human serum albumin (HSA), and solute release in the presence of fetal bovine serum. Dynamic light scattering data showed that PEG surface brushes of all nanoparticles provided effective steric stabilization, thus limiting their interaction with human serum albumin. Calorimetric experiments revealed that nanoparticle-HSA interaction was relatively weak and enthalpically driven, whereas dynamic light scattering results of incubated nanoparticles showed the absence of larger aggregates for most of the polymers examined. Solute core partitioning was examined by the loss of Forster resonance energy transfer (FRET) from a core-loaded donor-acceptor pair. The rate and magnitude of FRET efficiency loss was strongly dependent on the polymer architecture, and was found to be lowest for the bottle-brush, attributed to its covalent nature. Collectively, these findings are expected to impact the molecular design of increasingly stable polymeric carriers for drug delivery applications.

Triggered Liposomal Release through a Synthetic Phosphatidylcholine Analogue Bearing a Photocleavable Moiety Embedded within the sn‐2 Acyl Chain

Liposomes represent promising carriers for drug delivery applications. To maximize this potential, there has been significant interest in developing liposomal systems encapsulating molecular cargo that are highly stable until their contents are released remotely in a controlled manner. Herein, we describe the design, synthesis, and analysis of a photocleavable analogue of the ubiquitous lipid phosphoatidylcholine (PC) for the development of highly stable and controllable photodisruptable membranes. Our strategy was to develop a lipid that closely mimics the structure of PC to optimize favorable properties including biocompatibility and stability of subsequent liposomes when mixed with lipids possessing a broad range of physicochemical properties. Thus, NB-PC was designed, which contains a photocleavable 2-nitrobenzyl group embedded within the acyl chain at the sn-2 position. Following the synthesis of NB-PC, liposome disruption efficacy was evaluated through photolysis studies involving the detection of nile red release. Studies performed using a range of liposomes with different percentages of NB-PC, PC, phosphatidylethanolamine (PE), cholesterol, and polyethylene glycol-PE (PEG-PE) demonstrated minimal background release in controls, release efficacies that correlate directly with the amount of NB-PC incorporation, and that release is only minimally impacted by the inclusion of the lipids PE and cholesterol that possess disparate properties. These results demonstrate that the NB-PC system is a highly stable, flexible, and tunable system for photoinitiated release from liposomal systems.

Polyester Dendrimers: Smart Carriers for Drug Delivery

Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug delivery applications have been surveyed. Both covalent and non-covalent incorporation of drugs are discussed.

Screening of bio-compatible metal-organic frameworks as potential drug carriers using Monte Carlo simulations.

A series of bio-compatible metal-organic frameworks (MOFs) have been studied as potential carriers for drug delivery applications. Grand canonical Monte Carlo (GCMC) simulations were performed to study the adsorption of the model drug ibuprofen. Simulations were first validated with available experimental data for ibuprofen adsorption and release in MIL-53, MIL-100 and MIL-101. In the second stage, the study was extended to three additional MOFs with interesting properties in terms of bio-compatibility and porosity: CDMOF-1, based on edible precursors; MOF-74 containing a highly biocompatible metal (Mg); and BioMOF-100, a mesoporous MOF with extremely high pore volume. By comparing with experimental data, we show how GCMC simulation is able to predict the macroscopic performance of new porous MOFs in drug delivery applications, providing useful molecular-level insights and giving thermodynamic and structural details of the process. Adsorption isotherms, snapshots, energy of adsorption and radial distribution functions were used to analyse the drug delivery process.

Chemical robotics — chemotactic drug carriers

Abstract In this review we show and describe a concept of designing autonomously moving artificial cells (chemical robots) carrying drugs and having tactic behavior based on artificial chemotaxis. Such systems could help to provide new and more efficient drug delivery applications. Chemical robot can be constructed based on the self-organization — natural “bottom-up” way — of fatty acid or lipid molecules into ordered nano- or micrometer size objects that have the ability to move and respond to environmental stimuli. The idea of using tactic carriers in drug delivery applications can be justified by the fact that cancer sites in the living body have different physiological characters (lower pH and higher resting temperature) compared to normal cells. The proposed “bottom-up” design method for self-propelled objects at small scales for targeted drug delivery applications could realize the original designation of nanoscience proposed 50 years ago by Richard Feynman.

Amphiphilic Copolymers having Saturated and Unsaturated Aliphatic Side Chains as Nano Carriers for Drug Delivery Applications

Nano-particles with controllable particle size and shape are of great interest in biomedical applications (1). From the standpoint of drug carrier design with wide applicability to a variety of hydrophobic drugs, an effective strategy would be to prepare a simple copolymer having the property to form stable polymeric micelles which can entrap hydrophobic drugs in the core (2). In this study, we have attached saturated and unsaturated long chain acid chlorides to the copolymer of PEG and dimethyl-5-aminoisophthalate via an amide linkage in order to make the copolymers amphiphilic. Further, bioactive compounds like β-carotene, which has considerable double bond unsaturation and curcumin, which has considerable aromatic unsaturation, were encapsulated in these amphiphilic copolymers which successfully demonstrated their drug loading ability.

α-Fe-incorporated nanoporous carbon with magnetic properties

A kind of magnetic nanoporous carbon (MNC) has been synthesized through nanocasting strategy by using ordered mesoporous silica as a hard template and sugar as a carbon source. Small angle X-ray diffraction measurements show that MNC basically resembles the pore symmetry of the template, namely, two-dimensional (2D) hexagonal mesostructure with P6mm space group. Results also indicate that, the introduced iron precursor, Fe(NO 3) 3·9H 2O, was decomposed and in-situ confined within the carbon framework, being present in a form of α-Fe nanoparticles, which results in superparamagnetic property and good separability of MNC. As evidenced by desorption kinetic studies, MNC is a very promising carrier for drug delivery applications.