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Preparation and Mechanical Properties of …

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28/07/2015 · The dispersion polymerization of L ..

In the field of nanomedicine, the global trend over the past few years has been toward the design of highly sophisticated drug delivery systems with active targeting and/or imaging capabilities, as well as responsiveness to various stimuli to increase their therapeutic efficacy. However, providing sophistication generally increases complexity that could be detrimental in regards to potential pharmaceutical development. An emerging concept to design efficient yet simple drug delivery systems, termed the “drug-initiated” method, consists of growing short polymer chains from drugs in a controlled fashion to yield well-defined drug–polymer prodrugs. These materials are obtained in a reduced amount of synthetic steps and can be self-assembled into polymer prodrug nanoparticles, be incorporated into lipid nanocarriers or be used as water-soluble polymer prodrugs. This Perspective article will capture the recent achievements from the “drug-initiated” method and highlight the great biomedical potential of these materials.

and n-butanol as an initiator in ..

The dispersion polymerization of L-lactide(LA) /ε-caprolactone(CL) with stannous octoate (Sn(Oct)2) as a catalyst and n-butanol as an initiator in supercritical carbon dioxide (ScCO2) was studied. The effects of operating parameters, such as pressure, temperature, stirring rate and monomer rate of LA/CL, on the characteristics of L-lactide and ε- caprolactone copolymer (PCLA) were investigated. The experimental results show that the pressure has the greatest effect on the morphology of the copolymer, and the temperature is the most decisive factor in the conversion ratio of the monomer. The changes of the conversion rate of the monomer were observed when the temperature risen from 90 to 110 °C. At the pressure of 18 MPa, the best morphology of the product can be got. Under the optimum reaction condition, PCLA with various ratio of LA/CL were obtained. Finally, fine powder particles of L-lactide and ε-caprolactone copolymer (PCLA) with high molecular weight were obtained.

polymerization of ε-caprolactone in supercritical carbon dioxide.

Synthesis of Stereoregular Cyclic Poly ..

Currently, most star-shaped polymers in use are of three or four arms (). However, the more arms the star-shaped polymer has, the more sites can be modified and the higher encapsulation efficiency it will have. In our study, we designed and synthesized a series of six-arm star-shaped PLGAs. Moreover, the methodology of orthogonal testing, which is based on orthogonality, was adopted to study multiple factors and levels in the experiment. To test part of the representative level combination chosen from a comprehensive selection and to reduce the workload, an orthogonal experiment was designed to find the optimal conditions for preparing paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs). Following this, the obtained NPs were characterized and compared with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs) in human aortic vascular smooth-muscle cells (T/G HA-VSMCs; American Type Culture Collection, Manassas, VA, USA).

Poly(lactic-co-glycolic acid) (PLGA) is one of the commonly used drug-carrier matrices approved by the US Food and Drug Administration, and is widely used in biomedical applications due to its good biocompatibility and biodegradability., Several decades of biomaterials research have led to a progressively heightened interest in the use of PLGA-based nanoparticles (NPs) for drug delivery. For PLGA-based NPs, commercially available PLGA with a linear structure is widely accepted and used as a carrier matrix. However, much attention was initially focused on the modification of linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-NPs) to effectively meet a variety of requirements in drug delivery along with the need for treatment. For example, Subramanian et al modified the existing terminal carboxylic acid groups on the surface of PLGA NPs with p-aminobenzyl diethylenetriamine pentaacetic acid for enhanced availability of functional groups to make them suitable for technetium-99 m complexation. In this way, they improved both the radiolabeling yield and the biological efficacy of the NPs. Mittal et al optimized estradiol-loaded PLGA nanoparticulate formulations by varying the molecular weight and copolymer composition of PLGA, which resulted in the improved oral bioavailability and sustained release of estradiol. In another study, Stanwick et al designed a composite drug-delivery system comprised of neurotrophin-3 encapsulated in PLGA NPs dispersed in an injectable hydrogel to achieve sustained local delivery.

Synthesis of Stereoregular Cyclic Poly(lactide)s via “Thiol−Ene ..

Polylactide-Based Paclitaxel ..

A new series of six-arm star-shaped poly(lactic-co-glycolic acid) (6-s-PLGA) was synthesized by ring-opening polymerization. The structure and properties of the 6-s-PLGA were characterized by carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, gel permeation chromatography, and differential scanning calorimetry. Then, paclitaxel-loaded six-arm star-shaped poly(lactic-co-glycolic acid) nanoparticles (6-s-PLGA-PTX-NPs) were prepared under the conditions optimized by the orthogonal testing. High-performance liquid chromatography was used to analyze the nanoparticles’ encapsulation efficiency and drug-loading capacity, dynamic light scattering was used to determine their size and size distribution, and transmission electron microscopy was used to evaluate their morphology. The release performance of the 6-s-PLGA-PTX-NPs in vitro and the cytostatic effect of 6-s-PLGA-PTX-NPs were investigated in comparison with paclitaxel-loaded linear poly(lactic-co-glycolic acid) nanoparticles (L-PLGA-PTX-NPs).

The results of carbon-13 nuclear magnetic resonance spectroscopy and infrared spectroscopy suggest that the polymerization was successfully initiated by inositol and confirm the structure of 6-s-PLGA. The molecular weights of a series of 6-s-PLGAs had a ratio corresponding to the molar ratio of raw materials to initiator. Differential scanning calorimetry revealed that the 6-s-PLGA had a low glass transition temperature of 40°C–50°C. The 6-s-PLGA-PTX-NPs were monodispersed with an average diameter of 240.4±6.9 nm in water, which was further confirmed by transmission electron microscopy. The encapsulation efficiency of the 6-s-PLGA-PTX-NPs was higher than that of the L-PLGA-PTX-NPs. In terms of the in vitro release of nanoparticles, paclitaxel (PTX) was released more slowly and more steadily from 6-s-PLGA than from linear poly(lactic-co-glycolic acid). In the cytostatic study, the 6-s-PLGA-PTX-NPs and L-PLGA-PTX-NPs were found to have a similar antiproliferative effect, which indicates durable efficacy due to the slower release of the PTX when loaded in 6-s-PLGA.

biodistribution and anti-tumor effect of paclitaxel ..
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Synthesis of telechelic polylactide and ..

Figure 4. Use of metal alkoxides (MORs) as initiators for the synthesis of polylactide (PLA) by ring-opening polymerization (ROP) via a coordination–insertion mechanism. M = metal; L = ligand; OR = hydroxyl-containing molecule.

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