Hydrolytic degradation of star-shaped poly(ε-caprolactone)s with different number of arms and their cytotoxic effects

Abstract

Star-shaped polymers of biodegradable aliphatic polyester, poly( ε-caprolactone), PCL, with different number of arms (three, four, and six) were synthesized by ring-opening polymerization initiated by multifunctional alcohols used as cores. As potential biomaterials, synthesized star-shaped poly( ε-caprolactone)s, sPCL, were thoroughly characterized in terms of their degradation under different pH conditions and in respect to their cytotoxicity. The in vitro degradation was performed in phosphate buffer (pH 7.4) and hydrochloric acid solution (pH 1.0) over 5 weeks. Degradation of sPCL films was followed by the weight loss measurements, GPC, FTIR, and AFM analysis. While the most of the samples were stable against the abiotic hydrolysis at pH 7.4 after 5 weeks of degradation, degradation was significantly accelerated in the acidic medium. Degradation rate of polymer films was affected by the polymer architecture and molecular weight. The molecular weight profiles during the degradation revealed random chain scission of the ester bonds indicating bulk degradation mechanism of hydrolysis at pH 7.4, while acidic hydrolysis proceeded through the bulk degradation associated with surface erosion, confirmed by AFM. The in vitro toxicity tests, cytotoxicity applying normal human fibroblasts (MRC5) and embryotoxicity assessment (using zebra fish model, Danio rerio), suggested those polymeric materials as suitable for biomedical application.

Moldable plastics (polycaprolactone) can be acutely toxic to developing zebrafish and activate nuclear receptors in mammalian cells

“…License: CC BY 4.0 developing zebrafish embryos and found no observable effect on mortality; however, this waterborne exposure was conducted at a concentration of 0.2 mg/mL, well below the concentration that acute toxicity was observed by us (150 times less than the LC50). 114 Comparatively, in the same study, in vitro cytotoxicity at 10 mg/mL cell culture medium was observed. 114 Recent work has suggested that PCL oligomers can improve the biocompatibility of PCL materials.…”

“…In contrast, in vivo biomedical studies have implanted or injected engineered PCL biomaterials into developed (adult) mammals. 81,[104][105][106][107][108][109][110][111] Additionally, few studies have investigated the zebrafish response to PCL, 88,[112][113][114] and those that have primarily focused on small particles, not macroscopic items, as in our study. One study previously investigated the toxicity of finely ground PCL particles to https://doi.org/10.26434/chemrxiv-2024-qzzm4 ORCID: https://orcid.org/0000-0002-6104-8310 Content not peer-reviewed by ChemRxiv.…”

Star-shaped poly(ε-caprolactones) with well-defined architecture as potential drug carriers

“…They were synthesized by ring-opening polymerization (ROP) of ε-CL in bulk, initiated with hydroxyl groups of multifunctional alcohols and catalyzed using Sn(Oct) 2 , as previously reported. 22 Variation in the number of arms was achieved using multifunctional alcohol, such as trimethylolpropane (TMP), ditrimethylolpropane (diTMP), penthaerytritol (PERT) and dipentaerytritol (diPERT), while the PCL arms' length was fixed (5000 g/mol). Dichloromethane (Fischer Chemicals) and chloroform (Sigma Aldrich) were used without further purification.…”

“…[18][19][20][21] In our previous study, the synthesis and characterization of star-shaped poly-(ε-caprolactone)s, with a different number of arms (three, four and six) with similar molecular weight was reported. 22 However, the studies focused on the ibuprofen loaded microspheres prepared from star-shaped PCL with different number of arms and arms' length as polymer matrix, and drug release profiles of such systems, have been very limited. Therefore, this study was related to the use of star-shaped PCL polyesters with well-defined structure as a novel drug carrier.…”

Synthesis, physicochemical, and antimicrobial characteristics of novel poly(urethane-siloxane) network/silver ferrite nanocomposites

“…Cytotoxicity of materials was measured using the standard MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide) assay [57] on MRC5 cells (supplied by ATCC) with appropriate controls and in triplicate, an indirect approach suitable for materials testing [58,59]. Absorbances were read at 540 nm as previously described [59], and the morphology of MRC5 cells was studied by 100 9 magnification light microscopy (DM IL LED Inverted Microscope, Leica Microsystems, Wetzlar, Germany) [60].…”