Cytotoxicity of a Unimolecular Polymeric Micelle and Its Degradation Products

Abstract

The cytotoxicity of a unimolecular polymeric micelle (1) and its degradation products was assessed by cell proliferation and viability with L929 mouse areolar/adipose fibroblasts. Polymer 1 and poly(ethylene glycol) (PEG) were diluted to concentrations from 10(-4) to 10(-6) M in culture media, whereas the degradation products were diluted to concentrations (10(-4) to 10(-6) M) that would theoretically occur upon degradation of polymer 1. The polymer degradation products that were evaluated included mucic acid, hexanoic acid, 1,1,1-tris(4-hydroxyphenyl)ethane (THPE),2,3,4,5-tetrakis-hexanoyloxy-hexanedioic acid or MA(hex), Core(hex), and PEG5, which is PEG of molecular weight 5000. Cells exposed to polymer 1 proliferated at the same rate as cells grown in polymer-free or PEG5-containing solutions up to 36 h. In both the polymer 1 and PEG5 solutions, cytotoxicity was not observed at any concentration (up to 10(-4) M) as indicated by cell attachment, growth, and morphology. Fibroblasts exposed to the degradation products fared as well as fibroblasts in contact with polymer 1 and PEG5, except for cells exposed to the highest concentration (10(-4) M) of THPE.

Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery

“…In general, for polymeric micelles, stability and particle size are important properties that influence in vivo performance. Stable and smaller particle sizes (<200 nm) will ensure lowered level of reticuloendothelial system (RES) uptake, minimal renal excretion, as well as their ability to take advantage of the enhanced permeability and retention effect for passive tumor-targeting [24]. These two factors will directly affect the biodistribution and circulation time of polymeric micelles.…”

Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells

“…34 All the micelles exhibited similar slightly negative surface charge at pH 7.4, indicating a good steric protection. The nearly net surface charge of the micelles was able to prevent the recognition of opsonin, leading to a prolonged in vivo circulation and subsequent passive or active targeting.…”

Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release

“…The size of the micelles is an important parameter for drug delivery, which influences the in vivo performance. Small sizes (< 200 nm) of micelles are beneficial to maintain low level of reticuloendothelial system (RES) uptake, minimal renal excretion, strong EPR effect for passive tumor-targeting [46]. The characteristic size and morphology of H40-star-PLA-SS-PEG micelles were determined by DLS and TEM.…”