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In this article, we used monolayer two dimensional (2D) and 3D multicellular spheroid models to improve our understanding of the gene delivery process of a new modified cationic hyper-branched cyclodextrin-based polymer (Ppoly)-loaded plasmid encoding Enhanced Green Fluorescent Protein (EGFP). A comparison between the cytotoxicity effect and transfection efficiency of the plasmid DNA (pDNA)-loaded Ppoly system in 2D and 3D spheroid cells determined that the transfection efficiency and cytotoxicity of Ppoly–pDNA nanocomplexes were lower in 3D spheroids than in 2D monolayer cells. Furthermore, histopathology visualization of Ppoly–pDNA complex cellular uptake in 3D spheroids demonstrated that Ppoly penetrated into the inner layers. This study indicated that the Ppoly, as a non-viral gene delivery system in complex with pDNA, is hemocompatible, non-toxic, high in encapsulation efficiency, and has good transfection efficiency in both 2D and 3D cell cultures compared to free pDNA and lipofectamine (as the control).

This study aimed to design and fabricate novel hydroxypropyl-β-cyclodextrin-based hypercrosslinked polymers, called nanosponges, as carriers for anticancer hydrophobic agents and compare them with host–guest complexes of hydroxypropyl-β-cyclodextrin, a remarkable solubilizer, to investigate their application in improving the pharmaceutical properties of the flavonoid naringenin, a model hydrophobic nutraceutical with versatile anticancer effects. For this purpose, three new nanosponges, crosslinked with pyromellitic dianhydride, citric acid, and carbonyldiimidazole, were fabricated. The carbonate nanosponge synthesized by carbonyldiimidazole presented the highest naringenin loading capacity (≈19.42%) and exerted significantly higher antiproliferative effects against MCF-7 cancer cells compared to free naringenin. Additionally, this carbonate nanosponge formed a stable nanosuspension, providing several advantages over the naringenin/hydroxypropyl-β-cyclodextrin host–guest complex, including an increase of about 3.62-fold in the loading capacity percentage, sustained released pattern (versus the burst pattern of host–guest complex), and up to an 8.3-fold increase in antiproliferative effects against MCF-7 cancer cells. Both naringenin-loaded carriers were less toxic to L929 murine fibroblast normal cells than MCF-7 cancer cells. These findings suggest that hydroxypropyl-β-cyclodextrin-based carbonate nanosponges could be a good candidate as a drug delivery system with potential applications in cancer treatment.

At present, antibiotic resistance is considered a real problem. Therefore, for decades scientists have been looking for novel strategies to treat bacterial infections. Nisin Z, an antimicrobial peptide (AMP), can be considered an option, but its usage is mainly limited by the poor stability and short duration of its antimicrobial activity. In this context, cyclodextrin (CD)-based nanosponges (NSs), synthesized using carbonyldiimidazole (CDI) and pyromellitic dianhydride (PMDA), were chosen for nisin Z loading. To determine the minimum inhibitory of nisin Z loaded on CD-NS formulations, agar well diffusion plates were used. Then, the bactericide concentrations of nisin Z loaded on CD-NS formulations were determined against Gram-positive (Staphylococcus aureus) and -negative (Escherichia coli) bacteria, using microdilution brain heart infusion (BHI) and tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The minimum and bactericide inhibitory values of the nisin complex with NSs were potentially decreased against both bacteria, compared with the nisin-free sample, while the nisin complex with β-CD showed lower antibacterial activity. The antimicrobial effect was also demonstrated by free NSs. Furthermore, the total viable counts (TVCs) antibacterial experiment indicated that the combination of nisin Z in both PMDA and CDI β-CD-based NSs, especially CDI, can provide a better conservative effect on cooked chicken meat. Generally, the present study outcomes suggest that the cross-linked β-CD-based NSs can present their own antimicrobial potency or serve as promising carriers to deliver and enhance the antibacterial action of nisin Z.

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.

Imiquimod (IMQ) is an immune response modifier clinically used for the treatment of various topical diseases. However, its poor aqueous solubility and skin penetration capability make the topical delivery of IMQ a challenging task. This work aims at developing a nanomedicine-based topical formulation, carrying IMQ to control the scarring process for the treatment of aberrant wounds. For this purpose, IMQ was loaded in β-cyclodextrin-based nanosponges and dispersed in a hydrogel suitable for dermal application. The formulation was characterized in vitro and compared with IMQ inclusion complexes, with (2-hydroxy)propyl β-cyclodextrin(HPβCD) and carboxymethyl β-cyclodextrin (CMβCD) showing enhanced penetration properties. The hydrogel containing IMQ-loaded nanosponges could act as a drug reservoir and guarantee the sustained release of IMQ through the skin. A greater inhibitory effect on fibroblast proliferation was observed for IMQ loaded in nanosponges compared to the other formulations.

Babchi (Psoralea corylifolia) oil is an important essential oil used in several traditional medicines to cure various disorders. This phytotherapeutic agent possesses a number of pharmacological activities including antibacterial, antifungal, antioxidant, anti-inflammatory, immunomodulatory, and antitumor factors. However, volatile nature, poor stability, and solubility of babchi oil (BO) restrict its pharmaceutical applications. Therefore, the aim of the present work was to encapsulate this oil in β-cyclodextrin nanosponges (NS) in order to overcome the above limitations. To fabricate nanosponges, β-cyclodextrin was cross-linked with diphenyl carbonate in different molar ratios viz. 1:2, 1:4, 1:6, 1:8, and 1:10. The blank nanosponges were loaded with BO using the freeze-drying method. The particle size of the BO loaded nanosponges was found to lie between 200 and 500 nm with low polydispersity index. Furthermore, the zeta potential, the Fourier transform infrared spectroscopy, X-ray diffraction, thermal analysis, and electron microscopy were carried out for characterization of BO nanosponges. Results obtained from spectral analysis ascertained the formation of inclusion complexes. Additionally, solubilisation efficiency of BO was checked in distilled water and found enhanced by 4.95 times with optimized β-cyclodextrin nanosponges. The cytotoxicity study was carried out by the MTT assay using HaCaT cell lines. A significant improvement in photo-stability of essential oil was also observed by inclusion innanosponges. Lastly, the optimized formulation was tested for antibacterial activity using Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Therefore, encapsulation of BO in nanosponges resulted in efficacious carrier system in terms of solubility, photo-stability, and safety of this oil along with handling benefits.