Toolbox of Biodegradable Dendritic (Poly glycerol sulfate)–SS-poly(ester) Micelles for Cancer Treatment: Stability, Drug Release, and Tumor Targeting

Abstract

In this paper, we present well-defined dPGS-SS-PCL/PLGA/PLA micellar systems demonstrating excellent capabilities as a drug delivery platform in light of high stability and precise in vitro and in vivo drug release combined with active targetability to tumors. These six amphiphilic block copolymers were each targeted in two different molecular weights (8 or 16 kDa) and characterized using 1H NMR, gel permeation chromatography (GPC), and elemental analysis. The block copolymer micelles showed monodispersed size distributions of 81–187 nm, strong negative charges between −52 and −41 mV, and low critical micelle concentrations (CMCs) of up to 1.13–3.58 mg/L (134–527 nM). The serum stability was determined as 94% after 24 h. The drug-loading efficiency for Sunitinib ranges from 38 to 83% (8–17 wt %). The release was selectively triggered by glutathione (GSH) and lipase, reaching 85% after 5 days, while only 20% leaching was observed under physiological conditions. Both the in vitro and in vivo studies showed sustained release of Sunitinib over 1 week. CCK-8 assays on HeLa lines demonstrated the high cell compatibility (1 mg/mL, 94% cell viability, 48 h) and the high cancer cell toxicity of Sunitinib-loaded micelles (IC50 2.5 μg/mL). By in vivo fluorescence imaging studies on HT-29 tumor-bearing mice, the targetability of dPGS7.8-SS-PCL7.8 enabled substantial accumulation in tumor tissue compared to nonsulfated dPG3.9-SS-PCL7.8. As a proof of concept, Sunitinib-loaded dPGS-SS-poly­(ester) micelles improved the antitumor efficacy of the chemotherapeutic. A tenfold lower dosage of loaded Sunitinib led to an even higher tumor growth inhibition compared to the free drug, as demonstrated in a HeLa human cervical tumor-bearing mice model. No toxicity for the organism was observed, confirming the good biocompatibility of the system.

Polyglycerols as Multi-Functional Platforms: Synthesis and Biomedical Applications

“…When tested on MCF-7 human mammary carcinoma mice models, the micelles induced complete tumor suppression and improved the survival rate [60]. Later, Braatz et al, assembled a toolbox of the same micellar system that contained various polyesters as the hydrophobic segment as well as two different molecular weights of the sulfated HPG hydrophilic segment [61]. The study also included determining the critical micelle concentration (CMC), testing the stability, drug release, and tumor targeting of the system when encapsulated with sunitinib [61].…”

“…Later, Braatz et al, assembled a toolbox of the same micellar system that contained various polyesters as the hydrophobic segment as well as two different molecular weights of the sulfated HPG hydrophilic segment [61]. The study also included determining the critical micelle concentration (CMC), testing the stability, drug release, and tumor targeting of the system when encapsulated with sunitinib [61]. When the loaded micelles were injected into an HeLa human cervical tumorbearing mice model, a ten-fold lower dose of the micelle in comparison to the free drug was able to improve the antitumor efficacy of the API [61].…”

“…The study also included determining the critical micelle concentration (CMC), testing the stability, drug release, and tumor targeting of the system when encapsulated with sunitinib [61]. When the loaded micelles were injected into an HeLa human cervical tumorbearing mice model, a ten-fold lower dose of the micelle in comparison to the free drug was able to improve the antitumor efficacy of the API [61].…”

Bovine Serum Albumin Interaction with Polyanionic and Polycationic Brushes: The Case Theoretical Study

“…Second, colloidal polyelectrolyte brushes, microgels, or micelles with polyelectrolyte coronae are actively explored for biomedical applications such as drug and gene delivery, inhibition of viral infection, etc. [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

Dendritic polyglycerolsulfate-SS-poly(ester amide) micelles for the systemic delivery of docetaxel: pushing the limits of stability through the insertion of π–π interactions

“…13 Recently, biodegradable micelles based on dendritic polyglycerolsulfate (dPGS) demonstrated their high therapeutic potential in vivo with selective accumulation in tumor tissue showing no toxicity to the organisms. 14,15 However, remaining is the central question of whether the stability of this system can be further increased to boost its therapeutic potential.…”