Investigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics

We report the synthesis and characterization of a polymeric nanoparticle (NP) based on hyperbranched polyglycerol (HPG) containing a hydrophobic core and a hydrophilic shell, and assessed its suitability to be developed as a systemic anticancer drug carrier. HPG NP displayed low toxicity to primary cell cultures and were well-tolerated in mice after intravenous administration. When tested in mice tumor xenograft models, HPG NP accumulated significantly in the tumors with low accumulation in the liver and the spleen. In vitro studies demonstrated that HPG NP was capable of hydrophobically binding docetaxel and releasing it in a controlled manner. The HPG NP formulation of docetaxel conferred a preferential protective effect on primary non-cancerous cells while effectively killing cancer cells, indicating great potential for widening its therapeutic index. Taken together, these data indicate that HPG NP is a highly promising nanocarrier platform for systemic delivery of anticancer drugs.From the Clinical EditorThe use of polyethylene glycol on nano-carriers as "stealth" to deliver intravenous drugs is well known. Here, the authors developed polymeric nanoparticle (NP) with hyperbranched polyglycerol (HPG) and tested its efficacy in delivering docetaxel. The results showed that this formulation could preferentially killed cancer cells with a high therapeutic index. It seems that this platform could have a great potential in cancer therapy.

Graphical AbstractA 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.Figure optionsDownload high-quality image (155 K)Download as PowerPoint slide