Resveratrol and oxyresveratrol are natural polyphenolic stilbenes with several important pharmacological activities. However, low solubility and aqueous instability are the major limitations in their drug delivery applications. In the present work, we demonstrated the encapsulation of resveratrol and oxyresveratrol with nanosponge to improve solubility and stability. Several characterization techniques were used to confirm the encapsulation of both drug molecules within the nanosponges. The high encapsulation efficiency of resveratrol (77.73%) and oxyresveratrol (80.33%) was achieved within the nanosponges. Transmission electron microscopy suggested uniform spherical size particles of resveratrol and oxyresveratrol loaded nanosponges. Compared to free drugs, better protection against UV degradation was observed for resveratrol-loaded nanosponge (2-fold) and oxyresveratrol-loaded nanosponge (3-fold). Moreover, a higher solubilization of resveratrol- and oxyresveratrol-loaded nanosponges lead to a better antioxidant activity compared to drug molecules alone. Cytotoxicity studies against DU-145 prostate cancer cell lines further suggested improved activity of both resveratrol and oxyresveratrol-loaded nanosponges without any significant toxicity of blank nanosponges.

Abstract:The incidence of heart failure (HF) is increasing worldwide and myocardial infarction (MI), which follows ischemia and reperfusion (I/R), is often at the basis of HF development. Nanocarriers are interesting particles for their potential application in cardiovascular disease. Impaired drug delivery in ischemic disease is challenging. Cyclodextrin nanosponges (NS) can be considered innovative tools for improving oxygen delivery in a controlled manner. This study has developed new α-cyclodextrin-based formulations as oxygen nanocarriers such as native α-cyclodextrin (α-CD), branched α-cyclodextrin polymer (α-CD POLY), and α-cyclodextrin nanosponges (α-CD NS). The three different α-CD-based formulations were tested at 0.2, 2, and 20 µg/mL to ascertain their capability to reduce cell mortality during hypoxia and reoxygenation (H/R) in vitro protocols. H9c2, a cardiomyoblast cell line, was exposed to normoxia (20% oxygen) or hypoxia (5% CO 2 and 95% N 2 ). The different formulations, applied before hypoxia, induced a significant reduction in cell mortality (in a range of 15% to 30%) when compared to samples devoid of oxygen. Moreover, their application at the beginning of reoxygenation induced a considerable reduction in cell death (12% to 20%). α-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for future medical application of polymer systems for MI treatment.

Smart drug delivery systems are required for the site-specific drug targeting to enhance the therapeutic efficiency of a drug. Resveratrol (RV) is a polyphenolic compound with anti-cancer activity. However, its poor aqueous solubility and non-selectivity are the major challenges for its employment in cancer therapy. In this work, we present the synthesis of RV-loaded glutathione responsive cyclodextrin nanosponges (RV-GSH-NSs) to improve the therapeutic efficiency and selective delivery of RV. The drug loading and encapsulation efficiency were 16.12% and 80.64%, respectively. The in vitro release profile confirmed that RV release was enhanced in response to external glutathione (GSH). Nude NSs were not toxic per se to human fibroblasts when administered for up to 72 h at the highest dose. Cell internalization studies confirmed that RV-GSH-NSs were preferentially up-taken by tumor cells compared to non-tumorigenic cells. Accordingly, RV showed selective toxicity to cancer cells compared to normal cells. GSH depletion by buthionine sulfoximine, a potent inhibitor of its synthesis, reflected in a significant decrease of the NSs accumulation, and consequently resulted in a drastic reduction of RV-mediated toxic effects in cancer cells. These findings demonstrate that GSH- responsive NSs represent an effective delivery system for targeting cancer cells by harnessing the differential tumor characteristics in terms of redox status in parallel with the limitation of side effects toward normal cells.

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The aqueous solubility of KYNA was increased by encapsulation with β-CDNS2. • The molar ratio of CDI to β-CD affected the solubilization efficiency of nanosponges. • Higher antioxidant activity of KYNA loaded NS was achieved compared to plain KYNA. • Cell viability study showed that NS was nontoxic to SHSY-5Y human neuroblastoma cell lines. • The particle size and zeta potential of KYNA loaded NS and blank NS remained unchanged on storage.