# β-Cyclodextrin Inclusion Complexes of Curcumin and Synthetic Analogues in PVA/Carrageenan Hydrogels: A Platform for Sustained Release and Microbial Control

## TL;DR

This study creates hydrogel films with curcumin and its analogue to provide long-term drug release and fight bacterial infections like bacterial vaginosis.

## Contribution

A novel carrageenan-based hydrogel platform with β-CD inclusion complexes for sustained release and antimicrobial action against Gardnerella vaginalis.

## Key findings

- Hydrogels with β-CD inclusion complexes showed sustained release of curcumin (76.49%) and CN56 (56.02%) over 36 hours.
- Complex-loaded films exhibited improved surface uniformity and significantly greater fluid uptake (1080% for CN56 after 45 min).
- Curcumin and CN56 demonstrated strong antimicrobial activity against Gardnerella vaginalis with low cytotoxicity.

## Abstract

This study describes the development of β-cyclodextrin (β-CD) inclusion complexes of curcumin (CUR) and a synthetic curcuminoid analogue (CN56), which were incorporated into poly(vinyl alcohol)/κ-carrageenan hydrogel films to create a multifunctional system capable of sustained drug release and effective antimicrobial action. Carrageenan was extracted from Gigartina skottsbergii, and hydrogels were prepared using a freeze–thaw crosslinking method. The inclusion complexes were formed at a 1:6 molar ratio, achieving loading efficiencies of 75.62% for CUR and 79.00% for CN56. FTIR confirmed molecular interactions between the complexes and the polymeric matrix, accompanied by reduced crystallinity and increased amorphous character. Thermogravimetric analysis revealed enhanced thermal stability, with degradation onset temperatures above 239 °C, while DSC analysis indicated irreversible amorphization after the first heating cycle. SEM analysis showed improved surface uniformity in complex-loaded films compared with those containing free compounds. Swelling experiments demonstrated significantly greater fluid uptake in complex-loaded hydrogels, particularly for CN56 (1080% after 45 min). Controlled release studies revealed sustained drug release profiles, with 76.49% of CUR and 56.02% of CN56 released over 36 h, following Fickian diffusion mechanisms. In vitro antimicrobial assays confirmed marked activity of CUR and CN56 against Gardnerella vaginalis, a key pathogen associated with bacterial vaginosis. Biocompatibility tests, including hemolysis and MTT reduction assays, indicated low cytotoxicity and satisfactory hemocompatibility. Rheological analysis further demonstrated increased viscosity and potential mucoadhesive behavior. Collectively, these findings highlight the potential of carrageenan-based PVA hydrogels as innovative pharmaceutical platforms for the prevention and treatment of recurrent bacterial vaginosis, offering a promising alternative to conventional therapies.