Mohsen Adeli

Novel linear–globular thermoreversible hydrogel ABA type copolymers from dendritic citric acid as the A blocks and poly(ethyleneglycol) as the B block

Abstract The syntheses of novel linear–dendritic thermoreversible hydrogel copolymers were achieved via two procedures. In the first procedure synthesis of linear–dendritic copolymers carried out through an esterification step using thionylchloride and pyridine. In the second procedure linear–dendritic copolymers were prepared using dicyclohexylcarbodiimide and pyridine. The citric acid as the monomer unit was used for the preparation of ester-linked fragments. Diacid poly(ethyleneglycol) was chlorinated and diacyl halide poly(ethyleneglycol) prepared and used as the core. The formation of water soluble inclusion complexes with a variety of small size guest molecules is also described. Moreover, the thermoreversible behavior of the prepared hydrogels of both citric acid–poly(ethyleneglycol)–citric acid (CA–PEG–CA) triblock copolymers and the complexes derived from CA–PEG–CA triblock copolymers with various drugs have been investigated. The structure definition and analysis of the new resulted triblock copolymers and their complexes were carried out using NMR, optical microscopy, viscosimetry, FT–IR and UV–VIS spectrometry methods.

Multi-walled carbon nanotubes with immobilised cobalt nanoparticle for modification of glassy carbon electrode: Application to sensitive voltammetric determination of thioridazine

Multi-walled carbon nanotubes (MWCNTs) were immobilised with cobalt nanoparticles and analyzed by transmission electron microscopy. This modification procedure substantially improved colloidal dispersion of the immobilised MWCNTs in water and organic solvents, yielding uniform and stable thin films for modification of the glassy carbon electrode surface. The modified electrode showed an efficient catalytic role for the electrochemical oxidation of thioridazine (TR), leading to remarkable decrease in its oxidation overpotential of approximately 100 mV and enhancement of the kinetics of the electrode reaction, which can be confirmed by increasing in the peak current and sharpness of the peak. A remarkable enhancement in microscopic area of the electrode together with the catalytic role of the composite modifier resulted in a considerable increase of the peak current (approximately 55 times), and negative shift in the oxidation potential of TR. The effect of the thickness of the modifier on the GCE surface was optimized by monitoring its cyclic voltammetric responses toward TR. The mechanism of the electrocatalytic process on the surface of the modified electrode was analyzed by obtaining the cyclic voltammograms at various potential sweep rates and pHs of the buffer solutions. Differential pulse voltammetry was applied as a very sensitive analytical method for the determination of sub-micromolar amounts of TR. A linear dynamic range of 5.0 x 10(-7) to 1.0 x 10(-4)M with a detection limit of 5.0 x 10(-8)M TR was obtained. The prepared modified electrode shows several advantages such as simple preparation method, high stability and uniformity in the composite film, high sensitivity, and excellent catalytic activity in physiological conditions, long-term stability and remarkable voltammetric reproducibility. These excellent properties make the prepared sensor suitable for analysis in pharmaceutical and clinical preparations. The modified electrode was successfully applied for the accurate determination of minor amounts of TR in pharmaceutical and clinical preparations.

Increased paclitaxel cytotoxicity against cancer cell lines using a novel functionalized carbon nanotube

Potential applications of carbon nanotubes have attracted many researchers in the field of drug delivery systems. In this study, multiwalled carbon nanotubes (MWNTs) were first functionalized using hyperbranched poly citric acid (PCA) to improve their hydrophilicity and functionality. Then, paclitaxel (PTX), a potent anticancer agent, was conjugated to the carboxyl functional groups of poly citric acid via a cleavable ester bond to obtain a MWNT-g-PCA-PTX conjugate. Drug content of the conjugate was about 38% (w/w). The particle size of MWNT-g-PCA and MWNT-g-PCA-PTX was approximately 125 and 200 nm, respectively. Atomic force microscopy and transmission electron microscopy images showed a curved shape for MWNT-g-PCA and MWNT-g-PCA-PTX, which was in contrast with the straight or linear conformation expected from carbon nanotubes. It seems that the high hydrophilicity of poly citric acid and high hydrophobicity of MWNTs led to conformational changes from a linear state to a curved state. Paclitaxel can be released from the MWNT-g-PCA-PTX conjugates faster at pH 6.8 and 5.0 than at pH 7.4, which was suitable for the release of the drug in tumor tissues and tumor cells. In vitro cytotoxicity studies were evaluated in the A549 and SKOV3 cell lines. MWNT-g-PCA had an insignificant cytotoxic effect on both cell lines. MWNT-g-PCA-PTX had more of a cytotoxic effect than the free drug over a shorter incubation time (eg, 24 hours versus 48 hours), which suggests improved cell penetration of MWNT-g-PCA-PTX. Therefore, paclitaxel conjugated to MWNT-g-PCA is promising for cancer therapeutics.

Poly(citric acid)-block-poly(ethylene glycol) copolymers—new biocompatible hybrid materials for nanomedicine

Linear-dendritic ABA triblock copolymers containing poly(ethylene glycol) (PEG) as B block and hyperbranched poly(citric acid) (PCA) as A blocks were synthesized through polycondensation. The molecular self-assembly of synthesized PCA-PEG-PCA copolymers in water led to formation of nanoparticles and fibers in different sizes and shapes depending on the time and size of PCA blocks. Ten days after dissolving PCA-PEG-PCA copolymers in water, the size of fibers had reached several millimeters. Mixing a water solution of fluorescein as a small guest molecule and PCA-PEG-PCA copolymers led to the encapsulation of fluorescein by products of molecular self-assembly. To investigate their potential application in nanomedicine and to understand the limitations and capabilities of these materials as nanoexcipients in biological systems, different types of short-term in vitro cytotoxicity experiments on the HT1080 cell line (human fibrosarcoma) and hemocompatibility tests were performed. From the clinical editor: This manuscript investigates the potentials of linear-dendritic ABA triblock copolymers containing poly(ethylene glycol) (PEG) as B block and hyperbranched poly(citric acid) (PCA) as A blocks for future applications in nanomedicine.

Fabrication of a modified electrode based on Fe3O4NPs/MWCNT nanocomposite: Application to simultaneous determination of guanine and adenine in DNA

Multi-walled carbon nanotubes decorated with Fe(3)O(4) nanoparticles (Fe(3)O(4)NPs/MWCNT) were prepared and used to construct a novel biosensor for the simultaneous detection of adenine and guanine. The direct electro-oxidation of adenine and guanine on the modified electrode were investigated by linear sweep voltammetry. The results indicate a remarkable increase in the oxidation peak currents together with negative shift in the oxidation peak potentials for both adenine and guanine, in comparison to the bare glassy carbon electrode (GCE). The surface morphology and nature of the composite film deposited on GCE were characterized by transmission electron microscopy, atomic force microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. The Fe(3)O(4)NPs/MWCNT based electrochemical biosensor exhibits linear ranges of 0.01-10 μM and 0.05-8 μM with detection limits of 1 nM and 5 nM for adenine and guanine, respectively. The proposed method was successfully applied for a highly sensitive simultaneous determination of trace amounts of adenine and guanine in DNA of fish sperm samples with satisfactory results. The experimental detection limit was found to be equal to 3 ng mL(-1) DNA. The value of (G+C)/(A+T) in DNA was calculated to be 0.81. The fabricated electrode showed excellent reproducibility, repeatability and stability.

Anticancer drug delivery systems based on noncovalent interactions between carbon nanotubes and linear–dendritic copolymers

Hybrid nanomaterial-based drug delivery systems (HNDDSs) consisting of carbon nanotubes and linear–dendritic copolymers linked to anticancer drugs were synthesized and characterized. Polycitric acid–polyethylene glycol–polycitric acid (PCA–PEG–PCA) linear–dendritic copolymers were used to solubilize and functionalize multi-walled carbon nanotubes (MWCNTs) by noncovalent interactions. There are two key features of HNDDSs: (a) functionalized MWCNTs as a biocompatible platform for the delivery of therapeutic agents and diagnostics, (b) PCA–PEG–PCA linear–dendritic copolymers as water soluble, biocompatible and highly functional hybrid materials with a linear PEG block and two dendritic PCA blocks that improve the solubility and functionality of MWCNTs respectively. In this work, cisplatin (cis-diamminedichloroplatinum (CDDP)—a platinum-based chemotherapy drug) was conjugated to the carboxyl functional groups of the dendritic blocks of PCA–PEG–PCA linear–dendritic copolymers and then the prodrugs interacted with the MWCNTs noncovalently and HNDDSs were obtained. To prove the efficacy of the synthesized HNDDSs, they were subjected to endocytosis and released CDDP molecules inside murine colon adenocarcinoma tumor C26 cancer cells. Then it was proved that HNDDSs are able to kill cancer cells effectively. Release of the anticancer drug from HNDDSs was also investigated.

A possible anticancer drug delivery system based on carbon nanotube–dendrimer hybrid nanomaterials

Iron oxide nanoparticles, γ-Fe2O3NP, were deposited onto the surface of multi-walled carbon nanotubes and CNT/γ-Fe2O3NP hybrid nanomaterials were obtained. Then linear-dendritic ABA type block copolymers consisting of polyethylene glycol as B block and poly(citric acid) as A block, PCA–PEG–PCA, were synthesized and cisplatin (cis-diamminedichloroplatinum (CDDP)—a platinum-based chemotherapy drug) was conjugated with their carboxyl functional groups and CDDP/PCA–PEG–PCA anticancer prodrugs were prepared. Noncovalent interactions between CDDP/PCA–PEG–PCA anticancer prodrugs and CNT/γ-Fe2O3NP hybrid nanomaterials led to CDDP/PCA–PEG–PCA/CNT/γ-Fe2O3NP drug delivery systems. There are several key features of these hybrid drug delivery systems: (i) their ability to cross cell membranes and also high surface area per unit weight for high drug loading assigned to CNTs, (ii) high functionality, water solubility and biocompatibility assigned to PCA–PEG–PCA linear-dendritic copolymers and (iii) targeting tumors using a magnetic field assigned to γ-Fe2O3 nanoparticles. The efficacy of drug delivery systems for killing the cancer cells and targeting the drugs towards tumors was investigated.

Polyamidoamine and polyglycerol; their linear, dendritic and linear–dendritic architectures as anticancer drug delivery systems

Despite extensive investigations in the field of cancer diagnosis and therapy in recent decades, cancer is still the major cause of morbidity and mortality all over the world. Recently, with the advancement of nanotechnology, the design and preparation of efficient nano-sized structures with the potential for diagnosis and treatment of cancer have been proposed. Among the different types of nano-sized materials, biocompatible polymers seem to be innovative tools with huge potential for cancer treatment. Advances in polymer chemistry and the application of various organic reactions have enabled the design and tailoring of multifunctional polymeric platforms with controllable architectures, with the ability to carry anticancer drugs, labelling probes and targeting agents simultaneously. This review covers the latest advances in the conjugation of the most studied chemotherapeutics (such as doxorubicin, paclitaxel, methotrexate, fluorouracil and cisplatin) to common dendritic polymers, including polyamidoamine dendrimers and hyperbranched polyglycerols (PGs) and their linear analogues, producing fatal weapons against tumors, with a focus on their cytotoxicity, biodistribution and biodegradability.

Supramolecular anticancer drug delivery systems based on linear–dendritic copolymers

Current cancer chemotherapy often suffers severe side-effects of the administered cancer drugs on the normal tissues. In addition, poor bioavailability, due to the low water solubility of the anticancer drugs, limits their applications in chemotherapy. New delivery technologies could help overcome this challenge by improving the water solubility and achieving the targeted delivery of the anticancer drugs. Linear–dendritic hybrid nanomaterials, which combine the highly branched architectures and multifunctionality of dendrimers with the processability of traditional linear–linear block copolymers, have been introduced as ideal carriers in anticancer drug delivery applications. This review presents recent advances in the investigational aspects of linear–dendritic copolymers to be applied as anticancer drug delivery vehicles. We highlight the structures, synthesis of linear–dendritic block copolymers, interaction mechanisms between linear–dendritic copolymers and anticancer drug molecules, and findings on their drug release behavior and anticancer efficacies in vitro and in vivo.

Design and synthesis of novel polyglycerol hybrid nanomaterials for potential applications in drug delivery systems.

The synthesis of a new drug delivery system based on hybrid nanomaterials containing a β-CD core and hyperbranched PG is described. Conjugating PG branches onto β-CD not only increases its water solubility but also affects its host/guest properties deeply. It can form molecular inclusion complexes with small hydrophobic guest molecules such as ferrocene or FITC with reasonable release. In addition, the achievable payloads are significantly higher as for carriers such as hyperbranched PGs. Short-term in vitro cytotoxicity and hemocompatibility tests on L929 cell lines show that the hybrid nanomaterial is highly biocompatible. Due to their outstanding properties, β-CD-g-PG hybrid nanomaterials are introduced as promising materials for nanomedicine, e.g., for drug delivery issues.