Posted by This study investigates the PEG‑β‑CD polymer, a water‑soluble polyethylene glycol–β‑cyclodextrin cross‑linked carrier, as a potential alternative to conventional oestradiol formulations for menopause therapy. Its submicron structure may reduce side effects and improve patient tolerability. Cytotoxicity studies in RAW 264.7 macrophages and NIH/3T3 fibroblasts showed minimal toxicity up to 10% (w/w), consistent with the known biocompatibility of cyclodextrin‑based systems. The absence of harmful effects in immune and subcutaneous‑relevant cells suggests low risk of inflammatory activation.
Phase‑solubility analysis demonstrated that the polymer significantly increases oestradiol solubility through a dual mechanism involving β‑CD cavity inclusion and diffusion into the polymer’s 3D network. The AL‑type profile and 1.5‑fold solubility enhancement highlight its potential for improving bioavailability. DLS measurements confirmed complex formation, with particle size increasing from 49.76 nm to 270.70 nm, typical of submicron delivery systems that support stability and controlled release. FTIR spectra further verified non‑covalent drug entrapment.
Immunological assessments showed no significant changes in MHC‑II expression or cytokine production, indicating strong immunocompatibility. This aligns with the mild immunomodulatory behaviour reported for cyclodextrin derivatives. In vivo safety was supported by the Galleria mellonella model, which showed no toxicity across tested doses.
Pharmacokinetic profiles after intramuscular administration to rats resembled those of established oestradiol esters, with an early peak followed by a gradual decline over 7–10 days. Overall, the oestradiol–cyclodextrin polymer complex enhances solubility, forms stable nanoscale assemblies, and demonstrates favourable safety and pharmacokinetic characteristics, supporting its potential as a better‑tolerated alternative to oil‑based oestradiol esters.
Révész, R., Mengenli, A. D., Dossi, E., Alsheikh, R., Nemes, D., Ujhelyi, Z., Pető, Á., Rusznyák, Á., Sipos, É., Gyöngyösi, A., Lekli, I., Bácskay, I., Fenyvesi, F., & Haimhoffer, Á. (2026). Cyclodextrin Polymer Complexation Improves the Tolerability of Parenteral Oestradiol. Pharmaceutics, 18(2), 247. https://doi.org/10.3390/pharmaceutics18020247