Nanosponges are solid cross-linked polymeric nano-sized porous structures. This broad concept involves, among others, metal organic frameworks and hydrogels. The focus of this manuscript is on cyclodextrin-based nanosponges. Cyclodextrins are cyclic oligomers of glucose derived from starch. The combined external hydrophilicity with the internal hydrophobic surface constitute a unique “microenvironment”, that confers cyclodextrins the peculiar ability to form inclusion host‒guest complexes with many hydrophobic substances. These complexes may impart beneficial modifications of the properties of guest molecules such as solubility enhancement and stabilization of labile guests. These properties complemented with the possibility of using different crosslinkers and high polymeric surface, make these sponges highly suitable for a large range of applications. Despite that, in the last 2 decades, cyclodextrin-based nanosponges have been developed for pharmaceutical and biomedical applications, taking advantage of the nontoxicity of cyclodextrins towards humans. This paper provides a critical and timely compilation of the contributions involving cyclodextrins nanosponges for those areas, but also paves the way for other important applications, including water and soil remediation and catalysis. Graphical Abstract

/pdf/cyclodextrin-based-nanosponges-overview-and-opportunities-1gymkxh1.pdf

Cyclodextrin-Based Nanosponges: Overview and Opportunities

Cyclodextrin polymers and cyclodextrin-based nanosponges have been widely investigated for increasing drug bioavailability. This study examined curcumin’s complexation stability and solubilization with β-cyclodextrin and β-cyclodextrin-based nanosponge. Nanosponges were prepared through the cross-linking of β-cyclodextrin with different molar ratios of diphenyl carbonate. Phase solubility experiments were conducted to evaluate the formed complexes and evaluate the potential of using β-cyclodextrin and nanosponge in pharmaceutical formulations. Furthermore, physicochemical characterizations of the prepared complexes included PXRD, FTIR, NMR, and DSC. In addition, in vitro release studies were performed for the prepared formulations. The formation of β-cyclodextrin complexes enhanced curcumin solubility up to 2.34-fold compared to the inherent solubility, compared to a 2.95-fold increment in curcumin solubility when loaded in β-cyclodextrin-based nanosponges. Interestingly, the stability constant for curcumin nanosponges was (4972.90 M−1), which was ten times higher than that for the β-cyclodextrin complex, where the value was 487.34 M−1. The study results indicated a decrease in the complexation efficiency and solubilization effect with the increased cross-linker amount. This study’s findings showed the potential of using cyclodextrin-based nanosponge and the importance of studying the effect of cross-linking density for the preparation of β-cyclodextrin-based nanosponges to be used for pharmaceutical formulations.

Evaluation and Characterization of Curcumin-β-Cyclodextrin and Cyclodextrin-Based Nanosponge Inclusion Complexation

Many active pharmaceutical ingredients show low oral bioavailability due to factors such as poor solubility and physical and chemical instability. The formation of inclusion complexes with cyclodextrins, as well as cyclodextrin-based polymers, nanosponges, and nanofibers, is a valuable tool to improve the oral bioavailability of many drugs. The microencapsulation process modifies key properties of the included drugs including volatility, dissolution rate, bioavailability, and bioactivity. In this context, we present relevant examples of the stabilization of labile drugs through the encapsulation in cyclodextrins. The formation of inclusion complexes with drugs belonging to class IV in the biopharmaceutical classification system as an effective solution to increase their bioavailability is also discussed. The stabilization and improvement in nutraceuticals used as food supplements, which often have low intestinal absorption due to their poor solubility, is also considered. Cyclodextrin-based nanofibers, which are polymer-free and can be generated using environmentally friendly technologies, lead to dramatic bioavailability enhancements. The synthesis of chemically modified cyclodextrins, polymers, and nanosponges based on cyclodextrins is discussed. Analytical techniques that allow the characterization and verification of the formation of true inclusion complexes are also considered, taking into account the differences in the procedures for the formation of inclusion complexes in solution and in the solid state.

Cyclodextrin Inclusion Complexes for Improved Drug Bioavailability and Activity: Synthetic and Analytical Aspects

Nanosponges with three-dimensional (3D) porous structures, narrow size distribution, and high entrapment efficiency are widely engineered for cancer therapy and drug delivery purposes. They protect the molecular agents from degradation and help to improve the solubility of lipophilic therapeutic agents/drugs with targeted delivery options in addition to being magnetized to attain suitable magnetic features. Nanosponge-based delivery systems have been applied for cancer therapy with high specificity, biocompatibility, degradability, and prolonged release behavior. In this context, the drug loading within nanosponges is influenced by the crystallization degree. Notably, 3D printing technologies can be applied for the development of novel nanosponge-based systems for biomedical applications. The impacts of polymers, cross-linkers, type of drugs, temperature, loading and mechanism of drug release, fabrication methods, and substitution degree ought to be analytically evaluated. Eco-friendly techniques for the manufacturing of nanosponges still need to be uncovered in addition to the existing methods, such as solvent techniques, ultrasound-assisted preparation, melting strategies, and emulsion solvent diffusion methods. Herein, the recent advancements associated with the drug delivery and cancer therapy potential of nanosponges (chiefly, cyclodextrin-based, DNAzyme, and ethylcellulose nanosponges) are deliberated, focusing on the important challenges and future perspectives.

https://www.mdpi.com/2079-4991/12/14/2440/pdf?version=1658209506

Nanosponges for Drug Delivery and Cancer Therapy: Recent Advances

Nutraceuticals are bioactive or chemical compounds acclaimed for their valuable biological activities and health-promoting effects. The global community is faced with many health concerns such as cancers, cardiovascular and neurodegenerative diseases, diabetes, arthritis, osteoporosis, etc. The effect of nutraceuticals is similar to pharmaceuticals, even though the term nutraceutical has no regulatory definition. The usage of nutraceuticals, to prevent and treat the aforementioned diseases, is limited by several features such as poor water solubility, low bioavailability, low stability, low permeability, low efficacy, etc. These downsides can be overcome by the application of the field of nanotechnology manipulating the properties and structures of materials at the nanometer scale. In this review, the linear and cyclic dextrin, formed during the enzymatic degradation of starch, are highlighted as highly promising nanomaterials- based drug delivery systems. The modified cyclic dextrin, cyclodextrin (CD)-based nanosponges (NSs), are well-known delivery systems of several nutraceuticals such as quercetin, curcumin, resveratrol, thyme essential oil, melatonin, and appear as a more advanced drug delivery system than modified linear dextrin. CD-based NSs prolong and control the nutraceuticals release, and display higher biocompatibility, stability, and solubility of poorly water-soluble nutraceuticals than the CD-inclusion complexes, or uncomplexed nutraceuticals. In addition, the well-explored CD-based NSs pathways, as drug delivery systems, are described. Although important progress is made in drug delivery, all the findings will serve as a source for the use of CD-based nanosystems for nutraceutical delivery. To sum up, our review introduces the extensive literature about the nutraceutical concepts, synthesis, characterization, and applications of the CD-based nano delivery systems that will further contribute to the nutraceutical delivery with more potent nanosystems based on linear dextrins.

/pdf/nutraceutical-concepts-and-dextrin-based-delivery-systems-2zdc08rf.pdf

Nutraceutical Concepts and Dextrin-Based Delivery Systems

Drugs are widely used as therapeutic agents; however, they may present some limitations To overcome some of the therapeutic disadvantages of drugs, the use of β-cyclodextrin-based nanosponges (βCDNS) constitutes a promising strategy βCDNS are matrices that contain multiple hydrophobic cavities, increasing the loading capacity, association, and stability of the included drugs On the other hand, gold nanoparticles (AuNPs) are also used as therapeutic and diagnostic agents due to their unique properties and high chemical reactivity In this work, we developed a new nanomaterial based on βCDNS and two therapeutic agents, drugs and AuNPs First, the drugs phenylethylamine (PhEA) and 2-amino-4-(4-chlorophenyl)-thiazole (AT) were loaded on βCDNS Later, the βCDNS-drug supramolecular complexes were functionalized with AuNPs, forming the βCDNS-PhEA-AuNP and βCDNS-AT-AuNP systems The success of the formation of βCDNS and the loading of PhEA, AT, and AuNPs was demonstrated using different characterization techniques The loading capacities of PhEA and AT in βCDNS were 90% and 150%, respectively, which is eight times higher than that with native βCD The functional groups SH and NH2 of the drugs remained exposed and allowed the stabilization of the AuNPs, 85% of which were immobilized These unique systems can be versatile materials with an efficient loading capacity for potential applications in the transport of therapeutic agents

https://www.mdpi.com/1999-4923/13/4/513/pdf

β-Cyclodextrin-Based Nanosponges Functionalized with Drugs and Gold Nanoparticles.

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β-Cyclodextrin-Based Nanosponges Functionalized with Drugs and Gold Nanoparticles.