TROTTA Francesco - Rif. Prog. n.303-1 - POR-FESR 2014/2020 INCOMERA - “Approaching CKD with Nanosponges”

In the last two decades, by virtue of their biocompatibility and versatility, cyclodextrin based nanosponges were found to be an efficient, safe, cheap nanocarrier for a great deal of drugs. One recent EU commission report focused on the use of cyclodextrin nanosponges as a promising innovative system for drug delivery. They can be used as excipients in preparing tablets, capsules, pellets, granules, suspensions, solid dispersions, or topical dosage forms or as new nanotechnological, multifunctional carriers. Nanosponges have the capacity to incorporate drugs within their structure, either as inclusion complexes or as non inclusion complexes. There are far more interaction sites available for incorporation within a nanosponge structure than in -cyclodextrin molecules, and they also show different mesh polarities (hydrophobic cyclodextrin cavities surrounded by hydrophilic nanochannels of the polymeric network) thereby enabling significant interactions between molecules with different lipophilicities and structures. The ability of cyclodextrin nanosponges to encapsulate drugshas been studied in depth for both hydrophilic and lipophilic molecules, including dexamethasone, flurbiprofen, doxorubicin, itraconazole, resveratrol, paclitaxel, 5-fluorouracil and tamoxifen, and many others. GSH bio-responsive nanosponges were recently reported. Unito team has a well recognized leadership on the chemistry of nanosponges ad documented by dozen of articles, patents and reviews. However, cyclodextrins generally have low inclusion constants and are not useful to adsorb organic molecules and cations. Better results were achieved by using cross-linked cyclodextrin polymers but these latter found applications only in decontamination processes. The aim of this project is to use safe fashion made nanosponges to selectively remove from gastric fluid unwanted toxic molecule such as indole in order to slow the progression of CKD. Molecular imprinted technique will be also used. Using the nanosponges for the adsorbtion of organic toxic molecules the main scope of the project is to develop a new way of approaching the chronical kidney disease in alternative to the dyalisis like a less invasive therapeutic metod. Sequestring these molecule, the workload for the kidney is reduced, through a minor reduction of the glomerular filtration rate, ensuring a better quality of life for the CKD affected patient, a reduction in pain and a probable reduction of cardiovascular associated risks. Also the frequency of dyalisis process could be reduced in that way contributing to the improvement of the quality of life.