Carboxymethyl chitosan‐montmorillonite nanoparticles for controlled delivery of isoniazid: evaluation of the effect of the glutaraldehyde and montmorillonite

Chitosan, a natural biopolymer, is used for drug delivery application. But its potential application is limited by its low solubility in aqueous media. The present study was designed to prepare carboxymethyl chitosan (CMC), a water soluble derivative of chitosan, and evaluate the prospective of crosslinked CMC‐Montmorillonite (MMT) nanoparticles for controlled delivery of isoniazid. The nanoparticles were characterized by Fourier Transmission Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and Transmission emission microscopy (TEM). The effects of MMT and glutaraldehyde on nanoparticles were assessed with regard to encapsulation efficiency, percentage swelling degree, and cumulative release. Percentage swelling degree and cumulative release were studied in pH medium 1.2 and 7.4 for 6 h. The cumulative release was studied by UV‐visible spectrophotometer. Cell viability study was performed by MTT assay analysis. FTIR and NMR study indicated the successful preparation of CMC. FTIR study confirmed the interaction of MMT with CMC. The exfoliation of MMT layers and molecular level dispersion of isoniazid in CMC was examined by XRD and TEM. SEM study showed that the surface of the CMC‐MMT nanoparticles was smooth compared with those of CMC nanoparticles. Swelling and release of isoniazid from the nanoparticles increased with the decrease in the MMT and glutaraldehyde content. The percentage swelling degree and cumulative release was more in pH 1.2. Cell viability study revealed that CMC was not cytotoxic, and the nanoparticles containing MMT was less cytotoxic than those of MMT free nanoparticles. CMC‐MMT nanoparticles can be exploited as potential drug carrier for controlled release applications. Copyright © 2014 John Wiley & Sons, Ltd.     

Dual‐Pore Mesoporous Carbon@Silica Composite Core–Shell Nanospheres for Multidrug Delivery

Monodispersed mesoporous phenolic polymer nanospheres with uniform diameters were prepared and used as the core for the further growth of core–shell mesoporous nanorattles. The hierarchical mesoporous nanospheres have a uniform diameter of 200 nm and dual‐ordered mesopores of 3.1 and 5.8 nm. The hierarchical mesostructure and amphiphilicity of the hydrophobic carbon cores and hydrophilic silica shells lead to distinct benefits in multidrug combination therapy with cisplatin and paclitaxel for the treatment of human ovarian cancer, even drug‐resistant strains.     

Development of Multinuclear Polymeric Nanoparticles as Robust Protein Nanocarriers

One limitation of current biodegradable polymeric nanoparticles is their inability to effectively encapsulate and sustainably release proteins while maintaining protein bioactivity. Here we report the engineering of PLGA–polycation nanoparticles with a core–shell structure that act as a robust vector for the encapsulation and delivery of proteins and peptides. The optimized nanoparticles can load high amounts of proteins (>20 % of nanoparticles by weight) in aqueous solution without organic solvents through electrostatic interactions by simple mixing, thereby forming nanospheres in seconds with diameters <200 nm. The relationship between nanosphere size, surface charge, PLGA–polycation composition, and protein loading is also investigated. The stable nanosphere complexes contain multiple PLGA–polycation nanoparticles, surrounded by large amounts of protein. This study highlights a novel strategy for the delivery of proteins and other relevant molecules.     

Supramolecular Interactions of Nonsteroidal Anti‐inflammatory Drug in Nanochannels of Molecular Containers: A Spectroscopic,Thermogravimetric and Microscopic Investigation

Supramolecular host–guest complexation between the nonsteroidal anti‐inflammatory drug indomethacin (IMC) and molecular containers were investigated. The weakly fluorescent drug molecule becomes highly fluorescent on complexation with different molecular containers, and time‐resolved fluorescence emission spectroscopy reveals that the lifetime components of IMC significantly increase in the presence of molecular containers, compared with the lifetimes in neat water. The respective solid host–guest complexes were synthesised and characterised by Fourier transform infrared and ¹H nuclear magnetic resonance spectroscopic analysis. Microscopy techniques were used to analyse modifications of the surface morphology, owing to the formation of supramolecular complexes. The effect of the molecular container on the optical properties of IMC has also been investigated to determine the effect of nanochannels of different size and structure.     

Exploiting Supramolecular Synthons in Designing Gelators Derived from Multiple Drugs

A simple strategy for designing salt‐based supramolecular gelators comprised of various nonsteroidal anti‐inflammatory drugs (NSAIDs) and amantadine (AMN) (an antiviral drug) has been demonstrated using a supramolecular synthon approach. Single‐crystal and powder X‐ray diffraction established the existence of the well‐studied gel‐forming 1D supramolecular synthon, namely, primary ammonium monocarboxylate (PAM) synthon in all the salts. Remarkably five out of six salts were found to be capable of gelling methyl salicylate (MS)—an important ingredient in commercially available topical gels; one such selected biocompatible salt displayed an anti‐inflammatory response in prostaglandin E₂ (PGE₂) assay, thereby indicating their plausible biomedical applications.     

Upconverting Nanoparticles with a Mesoporous TiO2 Shell for Near‐Infrared‐Triggered Drug Delivery and Synergistic Targeted Cancer Therapy

Malignant tumors remain a major health burden throughout the world and effective therapeutic strategies are urgently needed. Herein, we report the synthesis of upconverting nanoparticles with a mesoporous TiO₂ (mTiO₂) shell for near‐infrared (NIR)‐triggered drug delivery and synergistic targeted cancer therapy. The NaGdF₄:Yb,Tm could convert NIR light to UV light, which activated the mTiO₂ to produce reactive oxygen species for photodynamic therapy (PDT). Due to the large surface area and porous structure, the mTiO₂ shell endowed the nanoplatform with another functionality of anticancer drug loading for chemotherapy. The hyaluronic acid modified on the surface not only promised controlled drug release but also conferred targeted ability of the system toward cluster determinant 44 overexpressed cancer cells. More importantly, cytotoxicity experiments demonstrated that combined therapy mediated the highest rate of death of breast carcinoma cells compared with that of single chemotherapy or PDT.     

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.     

Multifunctional 8‐Hydroxyquinoline‐Appended Cyclodextrins as New Inhibitors of Metal‐Induced Protein Aggregation

Mounting evidence suggests a pivotal role of metal imbalances in protein misfolding and amyloid diseases. As such, metal ions represent a promising therapeutic target. In this context, the synthesis of chelators that also contain complementary functionalities to combat the multifactorial nature of neurodegenerative diseases is a highly topical issue. We report two new 8‐hydroxyquinoline‐appended cyclodextrins and highlight their multifunctional properties, including their Cu^II and Zn^II binding abilities, and capacity to act as antioxidants and metal‐induced antiaggregants. In particular, the latter property has been applied in the development of an effective assay that exploits the formation of amyloid fibrils when β‐lactoglobulin A is heated in the presence of metal ions.     

Enhanced Salt Tolerance of Polyurethane Based Multilayer Films

In our previous study, polyurethane (PU) based multilayer films assembled with weak polyelectrolytes exhibited controllable loading and release properties, but would be decomposed in high salt solution. Herein, a strong polyelectrolyte, poly(styrene sulfonic acid) sodium (PSS), was introduced to fabricate multilayer films. The salt tolerance of the film was investigated by evaluating the loading and release profiles towards model drug in salt solution with different concentrations. Results showed that the release behavior of the film, as well as its loading capacity, can be tuned by varying the salt concentrations. And the film showed a good salt tolerance that can remain integrity even after 6 cycles of drug loading and release in 600 mmol·L^?1 NaCl solution. It showed that the salt tolerance of PU based films can be greatly improved through assembling with strong polyelectrolyte.     

Ketoprofen enantioseparation with a Cinchona alkaloid based stationary phase: Enantiorecognition mechanism and release studies

With the present contribution, we demonstrate that the baseline separation of ketoprofen enantiomers can be successfully achieved (α = 1.09; R_S = 1.60) in the reversed‐phase mode of elution with a commercially available anion‐exchange‐based chiral stationary phase, incorporating the quinine 2,6‐diisopropylphenyl carbamate derivative as the enantioresolving unit. Focused modification of the eluent composition indicated a stereoselective role of hydrophobic and π–π interactions between the selector and selectand units, besides the prime ionic intermolecular interaction. The mechanistic hypotheses based on the chromatographic data were confirmed by in silico molecular dynamic simulations, which allowed us to establish the network of selector–selectand interactions underlying the stereorecognition process at a molecular level. The validated method was successfully used to evaluate the drug content and release profile of ketoprofen‐loaded polymeric film, showing drug homogeneous distribution into the film and no preferential interactions between the polymer and one of the enantiomers, with the racemate released at each time point.