Research Article Enhanced Bioactivity of Pomegranate Peel Extract following Controlled Release from CaCO 3 Nanocrystals Francesca Baldassarre , 1,2 Viviana Vergaro , 2 Federica De Castro , 1 Francesca Biondo , 1,2 Gian Paolo Suranna , 2,3 Paride Papadia , 1 Francesco P. Fanizzi , 1 Domenico Rongai , 4 and Giuseppe Ciccarella 1,2 1 Department of Biological and Environmental Sciences, UdR INSTM of Lecce University of Salento, Via Monteroni, 73100 Lecce, Italy 2 Institute of Nanotechnology, CNR NANOTEC, Consiglio Nazionale Delle Ricerche, Via Monteroni, 73100 Lecce, Italy 3 Department of Civil,Environmental,Land,Building Engineering and Chemistry (DICATECh), Politecnico di Bari, Via Orabona 4, Bari 70125, Italy 4 CREA-IT PE-Research Centre for Engineering and Agro-Food Processing, Via Lombardia, Pescara, Italy Correspondence should be addressed to Francesca Baldassarre; francesca.baldassarre@unisalento.it and Giuseppe Ciccarella; giuseppe.ciccarella@unisalento.it Received 26 October 2021; Accepted 24 December 2021; Published 12 February 2022 Academic Editor: Domenico Osella Copyright©2022FrancescaBaldassarreetal.isisanopenaccessarticledistributedundertheCreativeCommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pomegranate peel extract is rich of interesting bioactive chemicals, principally phenolic compounds, which have shown anti- microbial, anticancer, and antioxidative properties. e aim of this work was to improve extract’ bioactivity through the ad- sorption on calcium carbonate nanocrystals. Nanocrystals revealed as efficient tools for extract adsorption reaching 50% of loading efficiency. Controlled release of the contained metabolites under acidic pH has been found, as it was confirmed by quantitative assay and qualitative study through NMR analysis. Specific functionality of inorganic nanocarriers could be also tuned by biopolymeric coating. e resulting coated nanoformulations showed a great antimicrobial activity against B. cinerea funguspreventingstrawberriesdiseasebetterthanacommercialfungicide.Furthermore,nanoformulationsdemonstratedagood antiproliferative activity in neuroblastoma and breast cancer cells carrying out a higher cytotoxic effect respect to free extract, confirmingacrucialroleofnanocarriers.Finally,pomegranatepeelextractshowedaveryhighradicalscavengingability,equalto ascorbicacid.Antioxidantactivity,measuredalsoinintracellularenvironment,highlightedaprotectiveactionofextract-adsorbed nanocrystals twice than free extract, providing a possible application for new nutraceutical formulations. 1.Introduction Punica granatum isoneofthefruitsthatmostattractedthe interest of researchers for its high potential use in medicine andfoodindustry[1–3].Itisrichinseveralmetaboliteswith antimicrobial, anticancer, antiobesity, antidiabetic, anti- ulcerogenic,andantihypertensiveproprieties[4].eabove beneficialpropertiesarenotonlylimitedtotheediblepartof fruit but also nonedible fractions (i.e., peel, seeds, flowers, bark, buds, and leaves) contain these compounds, and they comeinhugequantitiesasby-productsinpomegranatejuice processingindustries,constitutingagreatbioresource[5–7]. In particular, the peels represent about 50% of total fruit weight and are most often discarded as waste without any valorisation [8]. Interestingly, pomegranate peel extract contains the highest concentration of phytochemicals, principally phenolic compounds family, such as tannins, ellagitannins, and anthocyanins, including ellagic acid and punicalagin[9,10].esebioactiveingredientshaveproven antimicrobial propriety toward many pathogens and anti- proliferativeactivityfordifferentcelllines[11–13].Recently, phenols from hydromethanol pomegranate (Punica gran- atum L.) peel extract have showed interesting anti- hyperglycemic, antihyperlipidemic, and antioxidant Hindawi Bioinorganic Chemistry and Applications Volume 2022, Article ID 6341298, 16 pages https://doi.org/10.1155/2022/6341298