Doxorubicin-galactomannan nanoconjugates for potential cancer treatment.

In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.

Reversible Thermo-Optical Response Nanocomposites Based on RAFT Symmetric Triblock Copolymers (ABA) of Acrylamide and N-Isopropylacrylamide and Gold Nanoparticles.

The development of composite materials with thermo-optical properties based on smart polymeric systems and nanostructures have been extensively studied. Due to the fact of its ability to self-assemble into a structure that generates a significant change in the refractive index, one of most attractive thermo-responsive polymers is poly(N-isopropylacrylamide) (PNIPAM), as well as its derivatives such as multiblock copolymers. In this work, symmetric triblock copolymers of polyacrylamide (PAM) and PNIPAM (PAMx-b-PNIPAMy-b-PAMx) with different block lengths were prepared by reversible addition-fragmentation chain-transfer polymerization (RAFT). The ABA sequence of these triblock copolymers was obtained in only two steps using a symmetrical trithiocarbonate as a transfer agent. The copolymers were combined with gold nanoparticles (AuNPs) to prepare nanocomposite materials with tunable optical properties. The results show that copolymers behave differently in solution due to the fact of variations in their composition. Therefore, they have a different impact on the nanoparticle formation process. Likewise, as expected, an increase in the length of the PNIPAM block promotes a better thermo-optical response.

Poly(N-isopropylacrylamide)/galactomannan from Delonix regia seed thermal responsive graft copolymer via Schiff base reaction.

Aminated poly(N-isopropylacrylamide) (PNIPAm-NH2) was grafted onto oxidized galactomannan polysaccharide extracted from Delonix regia (OXGM) via Schiff base reaction by a simple, rapid synthetic route, deprived of the use of organic solvents. Grafting was confirmed by FTIR and 1H NMR and the self-organizing ability of the obtained nanoparticle copolymers was investigated by dynamic light scattering (DLS). The minimum concentration required for self-organization (CAC) at 25 °C was higher than at 50 °C. Lower critical solution temperature (LCST) was in the range 34-40 °C, depending on both inserted PNIPAm-NH2 molar mass and on the presence of reduced imine bond. Synthesized copolymers are promising candidates for drug delivery as they show good cell viability, particle size around 250 nm and transition temperature closer to that of human body. Reaction success points out to the possibility of use free aldehyde groups of oxidized polysaccharide, not used in the copolymerization, to form a pro-drug with substances that possess NH2 groups in their structure, such as doxorubicin.

Small interfering RNA for cancer treatment: overcoming hurdles in delivery.

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

Synthesis of a Smart Conductive Block Copolymer Responsive to Heat and Near Infrared Light.

A method for the synthesis of a linear block copolymer (PNIPAM-b-PANI), containing a thermoresponsive block (poly(N-isopropylacrylamide), PNIPAM) and a Near Infrared (NIR) light-absorbing block (polyaniline, PANI), is reported. The synthetic approach involves a two-step successive polymerization reaction. First, the radical polymerization of NIPAM is done using 4-aminothiophenol as a chain transfer agent for the obtention of thermosensitive block terminated with an aniline (ANI) moiety. Second, the oxidative polymerization of ANI is initiated in ANI moiety of thermosensitive block to grow the second conductive PANI block. 1H nuclear magnetic resonance (NMR) and FT-IR spectroscopy shows the characteristics peaks of both polymeric blocks revealing the successful copolymerization process. Static Light Scattering (SLS) and UV-Visible combined measurements allowed the determination of the Mw for PNIPAM-b-PANI macromolecule: 5.5 × 105 g mol-1. The resulting copolymer is soluble in water (8.3 g L-1) and in non-aqueous solvents, such as ethanol, formic acid, acetonitrile, and others. Both polymer blocks chains show the properties of the polymer chains. The block copolymer shows a lower critical solution temperature (LCST) at the same temperature (32-34 °C) than PNIPAM, while the copolymer shows pH dependent UV-vis-NIR absorption similar to PANI. The PNIPAM block suffers a coil to globule transition upon NIR light irradiation (785 nm, 100 mW), as shown by turbidimetry and Atomic Force Microscopy (AFM), due to local heating (more than 9 °C in 12 min) induced by the NIR absorption at the PANI block. Furthermore, the electrical conductivity of PNIPAM-b-PANI thin films is demonstrated (resistivity of 5.3 × 10-4 Ω-1 cm-1), indicating that the PANI block is present in its conductive form.

Electrochemical preparation and characterization of PNIPAM-HAp scaffolds for bone tissue engineering.

In the last decade, a variety of methods for fabrication of three-dimensional biomimetic scaffolds based on hydrogels have been developed for tissue engineering. However, many methods require the use of catalysts which compromises the biocompatibility of the scaffolds. The electrochemical polymerization (ECP) of acrylic monomers has received an increased attention in recent years due to its versatility in the production of highly biocompatible coatings for the electrodes used in medical devices. The main aim of this work was the use of ECP as scaffold fabrication technique to produce highly porous poly(N-isopropylacrylamide) (PNIPAM)/hydroxyapatite (HAp) composite for bone tissue regeneration. The prepared PNIPAM-HAp porous scaffolds were characterized by SEM, FTIR, water swelling, porosity measurements and X-ray diffraction (XRD) techniques. FTIR indicates that ECP promotes a successful conversion of NIPAM to PNIPAM. The water swelling and porosity were shown to be controlled by the HAp content in PNIPAM-HAp scaffolds. The PNIPAM-HAp scaffolds exhibited no cytotoxicity to MG63 cells, showing that ECP are potentially useful for the production of PNIPAM-HAp scaffolds. To address the osteomyelitis, a significant complication in orthopedic surgeries, PNIPAM-HAp scaffolds were loaded with the antibiotic oxacillin. The oxacillin release and the bacterial killing activity of the released oxacillin from PNIPAM-HAp against S. aureus and P. aeruginosa were demonstrated. These observations demonstrate that ECP are promising technique for the production of non-toxic, biocompatible PNIPAM-HAp scaffolds for tissue engineering.

Starch and chitosan oligosaccharides as interpenetrating phases in poly(N-isopropylacrylamide) injectable gels.

Thermosensitive interpenetrating gels were prepared by physically blending poly(N-isopropylacrylamide) (PNIPA) as the matrix and the following polysaccharides as interpenetrating phases: chitosan oligosaccharides (identified as QNAD and QNED) and soluble starch (STARCH). The molecular weight of the dispersed phase, the free water/bound water ratio and the thermosensitivity (transition temperature: LCST) of the gels were determined. It was found that these gels are pseudoplastic and that their viscosity depends on the molecular weight of the dispersed phase. LCST transition occurred around 35-37°C. The morphology of the porosity of the freeze-dried samples was studied by Scanning Electron Microscopy (SEM). An in vitro test of cell hemolysis on blood agar showed that these gels are noncytotoxic. According to the results obtained, these interpenetrating gels show characteristics of an injectable material, and have a transition LCST at body temperature, which reinforces their potential to be used in the surgical field and as scaffolds for tissue engineering.