Cyclodextrin-based functional polymeric systems for pharmaceutical and environmental applications

Hydrophobic molecules present a significant challenge in both biomedical and environmental contexts. In the pharmaceutical sector, poor solubility limits their transport, absorption, and bioavailability, thereby compromising therapeutic efficacy. Environmentally, these molecules tend to persist and bioaccumulate, posing risks to ecosystems and human health. A promising strategy to address these issues involves cyclodextrins (CDs), cyclic oligosaccharides derived from the enzymatic degradation of starch. The primary natural CDs (α, β, and γ) consist of 6, 7, and 8 glucose units, respectively, and possess a truncated cone structure with a hydrophobic internal cavity and hydrophilic outer surface. This unique architecture enables the formation of host–guest inclusion complexes with hydrophobic molecules, improving their aqueous solubility. However, natural CDs face limitations, including restricted solubility, low encapsulation efficiency, and relatively unstable complexes due to weak interactions. To overcome these hurdles, the numerous hydroxyl groups on the CD exterior can be chemically functionalized to tailor physicochemical properties for specific applications. Furthermore, functionalized CDs can serve as building blocks for complex architectures, such as CDs-grafted polymers. These systems combine the molecular recognition of CDs with the structural stability and versatility of polymers, resulting in advanced materials suitable for diverse biotechnological applications. In this study, β- and γ-CDs were functionalized with maleic anhydride (β- and γ-CDM) or succinic anhydride (β- and γ-CDS). These macrocycles were selected for the cost-effectiveness of β-CD and the larger cavity size of γ-CD. Characterization via FT-IR, 1H-NMR, and DSC revealed degrees of substitution ranging from 15% (γ-CDM) to 40% (β-CDS). The inclusion capacity of both native and functionalized CDs was evaluated using curcumin, a highly hydrophobic polyphenol, as a model guest. The investigation transitioned from solution-phase analysis (solubility, stoichiometry, and stability) to the preparation of the solid-state complexes. The functionalized derivatives exhibited superior performance: solubility increased up to 100-fold for γCDS compared to free curcumin, alongside significantly enhanced encapsulation efficiency. Moreover, while preserving antioxidant activity, the functionalized complexes showed markedly improved antibacterial properties, with significantly lower Minimum Inhibitory Concentration (MIC) values than free curcumin. Subsequently, the functionalized CDs were grafted onto chitosan, a biocompatible and biodegradable polysaccharide widely used in drug delivery and environmental remediation. This combination yielded porous matrices, which were tested for curcumin encapsulation and delivery. The CD-modified chitosan systems demonstrated superior performance compared to native chitosan, showing higher encapsulation efficiency and more effective release profiles at both physiological and acidic pH, with γCD systems yielding the most promising results. Furthermore, these matrices exhibited enhanced antibacterial properties. Finally, to demonstrate the versatility of these matrices, they were evaluated as adsorbents for pesticide removal from aqueous solutions, showing significant potential for water remediation applications.