“Design of Poly(ethylene glycol)-Polycaprolactone Diblock Micelles with RGD Targeting Ligands and Embedded Iron Oxide Nanoparticles for Thermally-activated Release”

2012 ◽  
Vol 1416 ◽  
Author(s):  
Christopher S. Brazel ◽  
James B. Bennett ◽  
Amanda L. Glover ◽  
Jacqueline A. Nikles ◽  
Maaike Everts ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Drug Release ◽  
Ethylene Glycol ◽  
Melting Transition ◽  
Release Mechanism ◽  
Poly Ethylene Glycol ◽  
Rgd Peptides ◽  
Thermally Activated ◽  
Poly Ethylene

ABSTRACTA thermally-activated micelle consisting of a crystallizable poly(caprolactone), PCL, core and a poly(ethylene glycol), PEG, corona was developed to contain magnetic nanoparticles and anti-cancer agent doxorubicin as well as display a targeting RGD peptide. This system has the potential to target cancer cells, deliver combination hyperthermia and chemotherapy, and offer magnetic resonance imaging contrast. The micelles self-assemble in aqueous solutions and form a crystalline core with a melting transition ranging from 40 to 50 °C, depending on the length of the PCL blocks, with dynamic light scattering showing micelle sizes typically ranging from 20 to 100 nm, depending on block lengths and added drug or nanoparticles. The micelles become unstable as they are heated above their melting point, creating a thermally-activated drug release mechanism. By adding magnetite (Fe3O4) nanoparticles into the PCL core, the micelles can be heated using an externally applied AC magnetic field to induce hyperthermia in combination with the thermally-activated drug release. The polymers and magnetic nanoparticles (MNPs) were synthesized and characterized in our laboratories. The melting transitions of the PCL micelle cores were investigated using microcalorimetry. The heating of nanoparticles and magnetomicelles was conducted using a custom-built hyperthermia coil capable of generating fields of several hundred Oersteds at frequencies ranging from 50 to 450 kHz. Heating of MNPs was maximized at high field intensities. RGD peptides were attached to the PEG corona using maleimide chemistry, and the ability of the RGD-derivatized micelles to target integrin-expressing cells was investigated using fluorescent dye PKH26 to identify the localization of micelles in cultured human kidney (293) cells in vitro. The crystallizable (and meltable) cores in these micelles were designed to overcome drug leakage common in liposome systems and release the drug on demand after a period of time for localization to integrin receptors.

scholarly journals Hydrogels Based on Poly(Ether-Ester)s as Highly Controlled 5-Fluorouracil Delivery Systems—Synthesis and Characterization

Materials ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 98
Author(s):  
Adam Kasiński ◽  
Monika Zielińska-Pisklak ◽  
Ewa Oledzka ◽  
Grzegorz Nałęcz-Jawecki ◽  
Agata Drobniewska ◽  
...  
Keyword(s):  
Drug Release ◽  
Ethylene Glycol ◽  
Gel Permeation Chromatography ◽  
Zero Order ◽  
Hexamethylene Diisocyanate ◽  
Release Mechanism ◽  
Poly Ethylene Glycol ◽  
First Order ◽  
Poly Ethylene

A novel and promising hydrogel drug delivery system (DDS) capable of releasing 5‑fluorouracil (5-FU) in a prolonged and controlled manner was obtained using ε‑caprolactone‑poly(ethylene glycol) (CL-PEG) or rac‑lactide-poly(ethylene glycol) (rac‑LA-PEG) copolymers. Copolymers were synthesized via the ring-opening polymerization (ROP) process of cyclic monomers, ε‑caprolactone (CL) or rac-lactide (rac-LA), in the presence of zirconium(IV) octoate (Zr(Oct)4) and poly(ethylene glycol) 200 (PEG 200) as catalyst and initiator, respectively. Obtained triblock copolymers were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques; the structure and tacticity of the macromolecules were determined. The relationship between the copolymer structure and the reaction conditions was evaluated. The optimal conditions were specified as 140 °C and 24 h. In the next step, CL-PEG and rac-LA-PEG copolymers were chemically crosslinked using hexamethylene diisocyanate (HDI). Selected hydrogels were subjected to in vitro antitumor drug release studies, and the release data were analyzed using zero-order, first-order, and Korsmeyer-Peppas mathematical models. Controlled and prolonged (up to 432 h) 5-FU release profiles were observed for all examined hydrogels with first-order or zero-order kinetics. The drug release mechanism was generally denoted as non-Fickian transport.

scholarly journals Polypeptides Micelles Composed of Methoxy-Poly(Ethylene Glycol)-Poly(l-Glutamic Acid)-Poly(l-Phenylalanine) Triblock Polymer for Sustained Drug Delivery

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 230 ◽  
Author(s):  
Xingzheng Liu ◽  
Rongrong Fan ◽  
Boting Lu ◽  
Yuan Le
Keyword(s):  
Drug Release ◽  
Ethylene Glycol ◽  
Glutamic Acid ◽  
Drug Carrier ◽  
Drug Loading ◽  
Poly Ethylene Glycol ◽  
Sustained Drug Release ◽  
Poly Ethylene ◽  
Triblock Polymers

Methoxy-poly(ethylene glycol)-poly(l-glutamic acid)-poly(l-phenylalanine) triblock polymers with different architecture were synthesized as drug carrier to obtain sustained and controlled release by tuning the composition. These triblock polymers were prepared by ring opening polymerization and poly(ethylene glycol) was used as an initiator. Polymerization was confirmed by 1H NMR, FT-IR and gel penetration chromatography. The polymers can self-assemble to form micelles in aqueous medium and their critical micelle concentrations values were examined. The micelles were spherical shape with size of 50–100 nm and especially can arranged in a regular manner. Sorafenib was selected as the model drug and the drug loading performance was dependent on the composition of the block copolymer. In vitro drug release indicated that the polymers can realize controlled and sustained drug release. Furthermore, in vitro cytotoxicity assay showed that the polymers were biocompatible and the drug-loaded micelles can increase toxicity towards tumor cells. Confocal fluorescence microscopy assays illustrated that the micelles can be uptaken quickly and release drug persistently to inhibit tumor cell growth.

scholarly journals Amphiphilic Block Copolymer Microspheres Derived from Castor Oil, Poly(ε-carpolactone), and Poly(ethylene glycol): Preparation, Characterization and Application in Naltrexone Drug Delivery

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1996 ◽  
Author(s):  
Maria Nerantzaki ◽  
Eirini Skoufa ◽  
Kyriakos-Vasileios Adam ◽  
Stavroula Nanaki ◽  
Apostolos Avgeropoulos ◽  
...  
Keyword(s):  
Drug Release ◽  
Ethylene Glycol ◽  
Castor Oil ◽  
In Vitro Dissolution ◽  
Release Mechanism ◽  
Release Kinetic ◽  
Burst Release ◽  
Poly Ethylene Glycol ◽  
Long Term Treatment ◽  
Poly Ethylene

In the present study, the newly synthesized castor oil-derived thioether-containing ω-hydroxyacid (TEHA) block copolymers with polycaprolactone (TEHA-b-PCL), with methoxypoly(ethylene glycol) (mPEG), (TEHA-b-mPEG) and with poly(ethylene glycol) (PEG) (TEHA-b-PEG-b-TEHA), were investigated as polymeric carriers for fabrication of naltrexone (NLX)-loaded microspheres by the single emulsion solvent evaporation technique. These microspheres are appropriate for the long-term treatment of opioid/alcohol dependence. Physical properties of the obtained microspheres were characterized in terms of size, morphology, drug loading capacity, and drug release. A scanning electron microscopy study revealed that the desired NLX-loaded uniform microspheres with a mean particle size of 5–10 µm were obtained in all cases. The maximum percentage encapsulation efficiency was found to be about 25.9% for the microspheres obtained from the TEHA-b-PEG-b-TEHA copolymer. Differential scanning calorimetry and X-ray diffractometry analysis confirmed the drug entrapment within microspheres in the amorphous state. In vitro dissolution studies revealed that all NLX-loaded formulations had a similar drug release profile: An initial burst release after 24 h, followed by a sustained and slower drug release for up to 50 days. The analysis of the release kinetic data, which were fitted into the Korsmeyer–Peppas release model, indicated that diffusion is the main release mechanism of NLX from TEHA-b-PCL and TEHA-b-mPEG microspheres, while microspheres obtained from TEHA-b-PEG-b-TEHA exhibited a drug release closer to an erosion process.

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