Original ArticleInvestigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics
Graphical Abstract
A hyperbranched polyglycerol-based nanoparticle (HPG NP) containing a hydrophobic core and a PEGylated shell was evaluated for its safety and biodistribution in tumor-bearing mice. This nanoparticle accumulated at significant level in the tumors and was well-tolerated in vitro and in vivo. The nanoparticle formulation of docetaxel (DTX) was found to confer a preferential protective effect on normal cells while killing cancer cells. The results of the study indicate that this nanoparticle is a potential carrier for systemic anticancer drug delivery.
Section snippets
Materials and methods
All the reagents and chemicals were purchased from Sigma-Aldrich, Canada (Oakville, Ontario) and used without further purification unless mentioned. Glycidol was purified by distillation under reduced pressure before use and stored over molecular sieves at 4 °C. Octyl/decyl glycidyl ether (ODGE) was purified by distillation under reduced pressure. Tritiated methyl iodide was purchased from ARC Radiochemical (St. Louis. MO) as solution in toluene and was used directly after dilution in
Synthesis and characterization of HPG NP
HPG NP used in the present study was synthesized by the anionic ring opening polymerization of glycidol with epoxide-containing co-monomers by a two-step procedure. In the first step, a mixture of glycidol and octadecyl glycidyl ether (ODGE) was polymerized using trimethylol propane (TMP) as the initiator at 95 °C. In the second step, polymerization was continued in the same sample pot by the addition of α-epoxy-ω-methoxy polyethylene glycol (mPEG400-epoxide) to afford the HPG NP with
Discussion
Biocompatibility is a major consideration for developing drug carriers for parenteral administrations. For instance, early promises of developing dendrimers into nanocarriers were hindered by high levels of cytotoxicity27 until modifications of dendrimers were introduced to lessen their adverse effects.28 The results of our in vitro and in vivo studies suggest that HPG NP (HPG-C10-PEG) is biocompatible. It exhibited much lower cytotoxicity (IC50 of 0.6-1.2 mg/mL) when compared with G7 dendrimers
Acknowledgment
Support from Dr. Donald E. Brooks is gratefully acknowledged. The wonderful technical support from the staff at Investigation Drug Program and Animal Resources Centre at the BC Cancer Research Centre were much appreciated, and from Mr. Aarman Rahim. We also thank free.clipartof.com and cliparts.co for making the clip arts of the mouse and the syringe available for the composition of the graphical abstract.
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2017, European Polymer JournalCitation Excerpt :We attempted to reveal how the immobilized state on gold surface of the sensor or on surface of PLGA nanoparticles influences the mechanism of affinity of the amphiphilic polymers to lipid layers. The hyperbranched polyglycerol (HbPG) as another promising polymer type has been examined and offered recently for biomedical purposes due to its stability, biocompatibility, tuneable properties and structural variability [36–38]. Although, the biocompatibility and hemocompatibility of HbPG are proven and its several bioconjugates were prepared, the interaction with membrane lipid layer has not been studied yet.
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The authors have no conflict of interest to disclose.
The authors would like to acknowledge the start-up funds for MKK from the BC Cancer Agency and the University of British Columbia. This work is also partially funded by Pancreatic Cancer Canada. JNK acknowledges Michael Smith Foundation for Health Research Career Award and funding support from CIHR and NSERC.
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Equal contribution.