Biodegradable Dendritic Polyglycerol Sulfate for the Delivery and Tumor Accumulation of Cytostatic Anticancer Drugs

Abstract

Targeted delivery and extended blood circulation of anticancer drugs have been the challenges for decreasing the adverse side effects and improving the therapeutic efficiency in cancer chemotherapy. Herein, we present a drug delivery system (DDS) based on biodegradable dendritic polyglycerol sulfatebearing poly(caprolactone) (dPGS-PCL) chains, which has been synthesized on 20 g scale using a straightforward two-step protocol. In vivo fluorescence imaging demonstrated a significant accumulation of the DDS in the tumor environment. Sunitinib, an anticancer drug, was loaded into the DDS and the drug-induced toxicity was investigated in vitro and in vivo. The drug encapsulated in dPGS-PCL and the free drug showed similar toxicities in A431 and HT-29 cells, and the cellular uptake was comparable. The straightforward and large-scale synthesis, the organic solvent-free drug-loading approach, together with the tumor targetability of the biodegradable dendritic polyglycerols, render this copolymer a promising candidate for targeted cancer nanomedicine drug delivery systems.

Polyglycerols as Multi-Functional Platforms: Synthesis and Biomedical Applications

“…Figure 6 shows some of the strategies to obtain degradable HPG. Cherri et al, proved the scalability and reproducibility of the sulfated HPGs bearing bio-degradable caprolactone segments system with controlled molecular weights (20-60 kDa) in two-step synthesis [50]. The system showed the ability to encapsulate the hydrophobic tyrosine kinase inhibitor chemotherapeutical drug sunitinib [50].…”

“…Cherri et al, proved the scalability and reproducibility of the sulfated HPGs bearing bio-degradable caprolactone segments system with controlled molecular weights (20-60 kDa) in two-step synthesis [50]. The system showed the ability to encapsulate the hydrophobic tyrosine kinase inhibitor chemotherapeutical drug sunitinib [50]. The drug delivery system was able to release its guest molecule under acidic and enzymatic conditions, accumulate in the tumor site, and perform better than the free sunitinib in vivo [50].…”

“…The system showed the ability to encapsulate the hydrophobic tyrosine kinase inhibitor chemotherapeutical drug sunitinib [50]. The drug delivery system was able to release its guest molecule under acidic and enzymatic conditions, accumulate in the tumor site, and perform better than the free sunitinib in vivo [50]. Another system developed by Zabihi et al, followed a similar strategy to synthesize poly(glycidol-lactide) up to 43 kDa [51].…”

Chemical Approaches to Synthetic Drug Delivery Systems for Systemic Applications

“…The system was proven to increase the solubility of sunitinib, a multi‐targeted receptor tyrosine kinase inhibitor that was approved by the FDA for the treatment of renal cell carcinoma and Imatinib‐resistant gastrointestinal stromal tumors. This unimolecular system showed superior performance when tested in mice against an A431 tumor xenograft model [134, 135] …”

Chemische Ansätze für synthetische Wirkstofftransportsysteme für systemische Anwendungen

“…Die biologische Abbaubarkeit beruht auf den Caprolacton-Einheiten, die in das Polymergrundgerüst der hyperverzweigten Struktur integriert sind. [134] Die katalysierte Synthese wurde im 100-Gramm-Maßstab durchgeführt. Das System erhöhte nachweislich die Löslichkeit von Sunitinib, einem multizentrischen Rezeptor-Tyrosinkinase-Inhibitor, der von der FDA für die Behandlung von Nierenzellkarzinomen und Imatinib-resistenten gastrointestinalen Stromatumoren zugelassen wurde.…”