Tuesday, April 25, 2017

mPEG-PCL, mPEG-PLA, and mPEG-PLGA from PolySciTech used in design of theranostic stealth nanocarriers as part of drug-delivery research


One promising area of research in cancer therapy is the development of theranostics. This area of research focuses on simultaneous application of both a therapeutic agent (typically a chemotherapeutic agent such as paclitaxel) and a diagnostic agent (typically a contrast agent or fluorescent dye which renders the tumor ‘visible’). This research requires highly advanced delivery systems which can ensure that the tumor receives a suitable quantity of both agents such that it becomes visible to a surgeon as well as receives an effective dose of the therapeutic agent. In a fundamental sense, this requires well-designed nanocarriers with high loading efficiency (large doses of each agent) and which are highly stable in the bloodstream. Recently, researchers at Wroclaw University (Poland) utilized a series of PolySciTech (www.polyscitech.com) polymers including mPEG-PCL (PolyVivo Cat# AK128), mPEG-PLA (PolyVivo Cat# AK056), and mPEG-PLGA (PolyVivo Cat# AK037) to systematically generate a series of test-loaded nanoparticles containing model DNA and fluorescent dye Thiazole Orange. The researchers systematically investigated all steps involved in nanoparticle formation and tested the particles for their stability, loading capacity, and other parameters relevant to their clinical usage. This research holds promise for the development of highly advanced nanocarriers to assist in theranostic treatments of a wide variety of cancers. Read more:  Bazylińska, Urszula. "Rationally designed double emulsion process for co-encapsulation of hybrid cargo in stealth nanocarriers." Colloids and Surfaces A: Physicochemical and Engineering Aspects (2017). http://www.sciencedirect.com/science/article/pii/S092777571730359X
“Abstract: Double emulsion process has become highly promising for development of PEG-ylated nanocarriers (NCs) with co-encapsulated hybrid model agents, i.e, hydrophilic deoxyribonucleic acid (DNA) and hydrophobic Thiazole Orange (TO) dye, in the double compartment structure to protect them from the environmental conditions and to investigate different parameters affecting the size, charge and morphology as well as colloidal and biological stability of the final theranostic nanosystems. Different stabilizing agents including surfactants: Cremophor A25, Cremophor RH 40, Poloxamer 407, di-C12DMAB as well as polymers: PEG-PDLLA, PEG-PLGA, PEG-PCL, were screened to choose suitable ones for this approach. The average size of the synthesized NCs measured by dynamic light scattering (DLS) remained < 200 nm. The encapsulation efficiency of the hybrid cargo was confirmed by UV-Vis spectroscopy. Morphology and shape of the loaded nanocontainers were investigated by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Time-depended colloidal stability studies with DLS and ζ-potential followed by turbidimetric technique allow to select only the long-term nanosystems to final investigation the “stealth” properties of the fabricated PEGylated NCs. Highlights: Double emulsion process has become easy-scalable synthetic approach to develop “stealth” nanocarriers (NCs) successful in DNA and TO co-encapsulation. PEG-PDLLA, PEG-PLGA, PEG-PCL acted as pre-approved biocompatible components of the NCs polymer shell.The optimized encapsulation process resulted in NCs with diameter < 200 nm, narrow size distribution and nearly neutral surface. DLS, ζ-potential and backscattering studies confirmed a long-term NCs stability, indicating their potential as theranostic biocompatible agents. The biological stability exposed the PEG-ylated NCs ability to overcome various specific barriers to efficient drug and gene delivery. Keywords: w/o/w emulsions; PEG-ylated polyesters; DNA; Thiazole Orange; colloidal stability. Fabrication method: Polymeric nanocarriers stabilized by PEG-PLGA, PEG-PCL, PEG-PDLLA and non-ionic or cationic surfactants for co-encapsulation of therapeutic (model DNA in the initial concentration of 0.1 mg/ml) and diagnostic agent (TO in the initial concentration of 0.2 mg/ml) were prepared by modified double emulsion (w/o/w) evaporation process without any pH adjustment [8]. Generally, aqueous internal phase (with DNA) was emulsified for 5 min in dichloromethane (containing TO, PEG-ylated polymer in concentration of 5 mg/ml and di-C12DMAB) in the ratio 1:4 using a homogenizer with 25,000 rpm. This primary nanoemulsion was poured into 1% hydrophilic surfactant solution (Cremophor A25, Cremophor RH 40 or Poloxamer 407) aqueous solution stirring in a homogenizer for 10 min (25,000 rpm) and immersed in an ice water bath to create the water-in-oil-in-water (w/o/w) emulsion. The organic solvent was then evaporated under reduced pressure in a rotary evaporator (Ika RV 10 digital) and polymeric nanocarriers loaded by the hybrid cargo were collected overnight.”
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