Publications by authors named "Roberta Cassano"

53 Publications

Gel-Based Materials for Ophthalmic Drug Delivery.

Gels 2021 Aug 29;7(3). Epub 2021 Aug 29.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

The most common route of administration of ophthalmic drugs is the topical route because it is convenient, non-invasive, and accessible to all patients. Unfortunately, drugs administered topically are not able to reach effective concentrations. Moreover, their bioavailability must be improved to decrease the frequency of administrations and their side effects, and to increase their therapeutic efficiency. For this purpose, in recent decades, particular attention has been given to the possibility of developing prolonged-release forms that are able to increase the precorneal residence time and decrease the loss of the drug due to tearing. Among these forms, gel-based materials have been studied as an ideal delivery system because they are an extremely versatile class with numerous prospective applications in ophthalmology. These materials are used in gel eye drops, in situ gelling formulations, intravitreal injections, and therapeutic contact lenses. This review is intended to describe gel-based materials and their main applications in ophthalmology.
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http://dx.doi.org/10.3390/gels7030130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482217PMC
August 2021

Valorization of Tomato Waste as a Source of Carotenoids.

Molecules 2021 Aug 20;26(16). Epub 2021 Aug 20.

Department of Biochemical Sciences "A. Rossi-Fanelli", Sapienza University of Rome, Piazzale Aldo Moro, 00185 Rome, Italy.

Fast-accumulating scientific evidence from many studies has revealed that fruits and vegetables are the main source of bioactive compounds; in most cases, wastes and byproducts generated by the food processing industry present similar or a higher content of antioxidant compounds. In recent years, the ever-growing amount of agricultural and food wastes has raised serious concerns from an environmental point of view. Therefore, there is an increasing interest in finding new ways for their processing toward safely upgrading these wastes for recovering high-value-added products with a sustainable approach. Among food waste, the abundance of bioactive compounds in byproducts derived from tomato suggests possibility of utilizing them as a low-cost source of antioxidants as functional ingredients. This contribution gives an overview of latest studies on the extraction methods of carotenoids from tomato waste, along with an evaluation of their antioxidant activity, as well as their industrial applications.
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http://dx.doi.org/10.3390/molecules26165062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398759PMC
August 2021

Polymeric Biomaterials for the Treatment of Cardiac Post-Infarction Injuries.

Pharmaceutics 2021 Jul 7;13(7). Epub 2021 Jul 7.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy.

Cardiac regeneration aims to reconstruct the heart contractile mass, preventing the organ from a progressive functional deterioration, by delivering pro-regenerative cells, drugs, or growth factors to the site of injury. In recent years, scientific research focused the attention on tissue engineering for the regeneration of cardiac infarct tissue, and biomaterials able to anatomically and physiologically adapt to the heart muscle have been proposed as valuable tools for this purpose, providing the cells with the stimuli necessary to initiate a complete regenerative process. An ideal biomaterial for cardiac tissue regeneration should have a positive influence on the biomechanical, biochemical, and biological properties of tissues and cells; perfectly reflect the morphology and functionality of the native myocardium; and be mechanically stable, with a suitable thickness. Among others, engineered hydrogels, three-dimensional polymeric systems made from synthetic and natural biomaterials, have attracted much interest for cardiac post-infarction therapy. In addition, biocompatible nanosystems, and polymeric nanoparticles in particular, have been explored in preclinical studies as drug delivery and tissue engineering platforms for the treatment of cardiovascular diseases. This review focused on the most employed natural and synthetic biomaterials in cardiac regeneration, paying particular attention to the contribution of Italian research groups in this field, the fabrication techniques, and the current status of the clinical trials.
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http://dx.doi.org/10.3390/pharmaceutics13071038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309168PMC
July 2021

Characterization of a hyaluronic acid and folic acid-based hydrogel for cisplatin delivery: Antineoplastic effect in human ovarian cancer cells in vitro.

Int J Pharm 2021 Sep 27;606:120899. Epub 2021 Jul 27.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy.

We successfully prepared and characterized a hyaluronic acid- and folic acid-based hydrogel for the delivery of cisplatin (GEL-CIS) with the aim to induce specific and efficient incorporation of CIS into ovarian cancer (OC) cells, improve its antineoplastic effect and avoid CIS-resistance. The slow and controlled release of the drug from the polymeric network and its swelling degree at physiologic pH suggested its suitability for CIS delivery in OC. We compared here the effects of pure CIS to that of GEL-CIS on human OC cell lines, either wild type or CIS-resistant, in basal conditions and in the presence of macrophage-derived conditioned medium, mimicking the action of tumor-associated macrophages in vivo. GEL-CIS inhibited OC cell growth and migration more efficiently than pure CIS and modulated the expression of proteins involved in the Epithelial Mesenchymal Transition, a process playing a key role in OC metastatic spread and resistance to CIS.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120899DOI Listing
September 2021

Biomaterials for Drugs Nose-Brain Transport: A New Therapeutic Approach for Neurological Diseases.

Materials (Basel) 2021 Apr 6;14(7). Epub 2021 Apr 6.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

In the last years, neurological diseases have resulted in a global health issue, representing the first cause of disability worldwide. Current therapeutic approaches against neurological disorders include oral, topical, or intravenous administration of drugs and more invasive techniques such as surgery and brain implants. Unfortunately, at present, there are no fully effective treatments against neurodegenerative diseases, because they are not associated with a regeneration of the neural tissue but rather act on slowing the neurodegenerative process. The main limitation of central nervous system therapeutics is related to their delivery to the nervous system in therapeutic quantities due to the presence of the blood-brain barrier. In this regard, recently, the intranasal route has emerged as a promising administration site for central nervous system therapeutics since it provides a direct connection to the central nervous system, avoiding the passage through the blood-brain barrier, consequently increasing drug cerebral bioavailability. This review provides an overview of the nose-to-brain route: first, we summarize the anatomy of this route, focusing on the neural mechanisms responsible for the delivery of central nervous system therapeutics to the brain, and then we discuss the recent advances made on the design of intranasal drug delivery systems of central nervous system therapeutics to the brain, focusing in particular on stimuli-responsive hydrogels.
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http://dx.doi.org/10.3390/ma14071802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038678PMC
April 2021

Chitosan Membranes Filled with Cyclosporine A as Possible Devices for Local Administration of Drugs in the Treatment of Breast Cancer.

Molecules 2021 Mar 26;26(7). Epub 2021 Mar 26.

Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

The aim of this work is the design, preparation and characterization of membranes based on cyclosporine A (CsA) and chitosan carboxylate (CC) to be used as an implantable subcutaneous medical device for a prolonged therapeutic effect in the treatment of breast cancer. The choice to use CsA is due to literature data that have demonstrated its possible antitumor activity on different types of neoplastic cells. To this end, CsA was bound to CC through an amidation reaction to obtain a prodrug to be dispersed in a chitosan-based polymeric membrane. The reaction intermediates and the final product were characterized by Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (H-NMR). Membranes were analyzed by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The data obtained showed the effective formation of the amide bond between CsA and CC and the complete dispersion of CsA inside the polymeric membrane. Furthermore, preliminary tests, conducted on MDA-MB-231, a type of breast cancer cell line, have shown a high reduction in the proliferation of cancer cells. These results indicate the possibility of using the obtained membranes as an interesting strategy for the release of cyclosporin-A in breast cancer patients.
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http://dx.doi.org/10.3390/molecules26071889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036521PMC
March 2021

Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia.

Pharmaceutics 2021 Mar 12;13(3). Epub 2021 Mar 12.

Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.

Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia. Therefore, the aim of this study was to engineer a nanotechnology delivery system based on solid lipid nanoparticles loaded with bergamot essential oil (BEO) and devised in the pharmaceutical form of an odorless cream (NanoBEO) to confirm its analgesic efficacy for further development and application to control agitation in dementia. BEO has proven strong antinociceptive and anti-allodynic properties and, in its bergapten-free form, it is completely devoid of phototoxicity. NanoBEO has been studied in vivo confirming the previously reported analgesic activity of BEO to which is now added its anti-itching properties. Due to the nanotechnology delivery system, the stability of titrated BEO components is guaranteed. Finally, the latter invention, currently under patent consideration, is smell-devoid allowing efficacy and safety to be established in double-blind clinical trials; until now the latter studies have been impeded in aromatherapy by the strong odor of essential oils. A clinical trial NCT04321889 has been designed to provide information about the efficacy and safety of NanoBEO on agitation and pain in patients suffering from severe dementia.
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http://dx.doi.org/10.3390/pharmaceutics13030379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999378PMC
March 2021

Nose-to-brain delivery: A comparative study between carboxymethyl chitosan based conjugates of dopamine.

Int J Pharm 2021 Apr 4;599:120453. Epub 2021 Mar 4.

Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.

Herein, the synthesis of a novel polymeric conjugate N,O-CMCS-Dopamine (DA) based on an amide linkage is reported. The performances of this conjugate were compared with those of an analogous N,O-CMCS-DA ester conjugate previously studied (Cassano et al., 2020) to gain insight into their potential utility for Parkinson's disease treatment. The new amide conjugate was synthesized by standard carbodiimide coupling procedure and characterized by FT-IR, H NMR spectroscopies and thermal analysis (Differential Scanning Calorimetry). In vitro mucoadhesive studies in simulated nasal fluid (SNF) evidenced high adhesive effect of both ester and amide conjugates. Results demonstrated that the amide conjugate exerted an important role to prevent DA spontaneous autoxidation both under stressed conditions and physiological mimicking ones. MTT test indicated cytocompatibility of the amide conjugate with Olfactory Ensheating Cells (OECs), which were shown by cytofluorimetry to internalize efficiently the conjugate. Overall, among the two conjugates herein studied, the N,O-CMCS-DA amide conjugate seems a promising candidate for improving the delivery of DA by nose-to-brain administration.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120453DOI Listing
April 2021

Recent Advances in Nanotechnology for the Treatment of Melanoma.

Molecules 2021 Feb 3;26(4). Epub 2021 Feb 3.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed.
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http://dx.doi.org/10.3390/molecules26040785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913377PMC
February 2021

Nano- and Micro-Technologies Applied to Food Nutritional Ingredients.

Curr Drug Deliv 2021 ;18(6):670-678

Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy.

New technologies are currently investigated to improve the quality of foods by enhancing their nutritional value, freshness, safety, and shelf-life, as well as by improving their tastes, flavors and textures. Moreover, new technological approaches are being explored, in this field, to address nutritional and metabolism-related diseases (i.e., obesity, diabetes, cardiovascular diseases), to improve targeted nutrition, in particular for specific lifestyles and elderly population, and to maintain the sustainability of food production. A number of new processes and materials, derived from micro- and nano-technology, have been used to provide answers to many of these needs and offer the possibility to control and manipulate properties of foods and their ingredients at the molecular level. The present review focuses on the importance of micro- and nano-technology in the food and nutritional sector and, in particular, provides an overview of the micro- and nano-materials used for the administration of nutritional constituents essential to maintain and improve health, as well as to prevent the development and complications of diseases.
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http://dx.doi.org/10.2174/1567201817999201125205025DOI Listing
January 2021

Synthesis and characterization of novel chitosan-dopamine or chitosan-tyrosine conjugates for potential nose-to-brain delivery.

Int J Pharm 2020 Nov 30;589:119829. Epub 2020 Aug 30.

Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.

This work aims to the synthesis of novel carboxylated chitosan-dopamine (DA) and -tyrosine (Tyr) conjugates as systems for improving the brain delivery of the neurotransmitter DA following nasal administration. For this purpose, ester or amide conjugates were synthesized by N,N-dicyclohexylcarbodiimide (DCC) mediated coupling reactions between the appropriate N-tert-butyloxycarbonyl (Boc) protected starting polymers N,O-carboxymethyl chitosan and 6-carboxy chitosan and DA or O-tert-Butyl-L-tyrosine-tert-butyl ester hydrochloride. The resulting conjugates were characterized by FT-IR and H- and C NMR spectroscopies and their in vitro mucoadhesive properties in simulated nasal fluid (SNF), toxicity and uptake from Olfactory Ensheathing Cells (OECs) were assessed. Results demonstrated that N,O-carboxymethyl chitosan-DA conjugate was the most mucoadhesive polymer in the series examined and, together with the 6-carboxy chitosan-DA-conjugate were able to release the neurotransmitter in SNF. The MTT assay showed that the starting polymers as well as all the prepared conjugates in OECs resulted not toxic at any concentration tested. Likewise, the three synthesized conjugates were not cytotoxic as well. Cytofluorimetric analysis revealed that the N,O-carboxymethyl chitosan DA conjugate was internalized by OECs in a superior manner at 24 h as compared with the starting polymer. Overall, the N,O-CMCS-DA conjugate seems promising for improving the delivery of DA by nose-to-brain administration.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119829DOI Listing
November 2020

Viscosified Solid Lipidic Nanoparticles Based on Naringenin and Linolenic Acid for the Release of Cyclosporine A on the Skin.

Molecules 2020 Aug 2;25(15). Epub 2020 Aug 2.

Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.

Psoriasis is one of the most common human skin disorders. Although its pathogenesis is complex and not completely know, the hyperactivation of the immune system seem to have a key role. In this regard, among the most effective systemic therapeutics used in psoriasis, we find cyclosporine, an immunosuppressive medication. However, one of the major problems associated with the use of cyclosporine is the occurrence of systemic side effects such as nephrotoxicity, hypertension, etc. The present work fits in this context and its aim is the design of suitable platforms for cyclosporine topical release in psoriasis treatment. The main objective is to achieve local administration of cyclosporine in order to reduce its systemic absorption and, consequently, its side effects. In order to improve dermal penetration, solid lipid nanoparticles (SLNs) are used as carriers, due to their lipophilicity and occlusive properties, and naringenin and linolenic acid are chosen, due to their properties, as starting materials for SLNs design. In order to have dermatological formulations and further modulate drug release, SLNs are incorporated in several topical vehicles obtaining gels with different degree of lipophilicity. Potential applications for psoriasis treatment were evaluated by considering the encapsulation efficiency, release profiles, in vitro skin permeation, and anti-inflammatory effects.
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http://dx.doi.org/10.3390/molecules25153535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435943PMC
August 2020

Special Issue on Designing Hydrogels for Controlled Drug Delivery: Guest Editors' Introduction.

Pharmaceutics 2020 Jan 10;12(1). Epub 2020 Jan 10.

Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.

Hydrogels have received growing attention in recent years as materials for drug delivery systems (DDS), because they are biocompatible and nontoxic [...].
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http://dx.doi.org/10.3390/pharmaceutics12010057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023385PMC
January 2020

Gelatin and Glycerine-Based Bioadhesive Vaginal Hydrogel.

Curr Drug Deliv 2020 ;17(4):303-311

Department of Pharmacy, Health and Nutritional Sciences, Università della Calabria, Arcavacata di Rende, Cosenza, Italy.

Aim: The work's aim was the preparation and characterization of a hydrogel based on gelatin and glycerine, useful for site-specific release of benzydamine, an anti-inflammatory drug, able to attenuate the inflammatory process typical of the vaginal infection.

Objective: The obtained hydrogel has been characterized by Electronic Scanning Microscopy (SEM) and Differential Scanning Calorimetry (DSC). In addition, due to the precursor properties, the hydrogel exhibits a relevant mucoadhesive activity.

Methods: The swelling degree was evaluated at two different pHs and at defined time intervals. In particular, phosphate buffers were used at pH 6.6, in order to mimic the typical conditions of infectious diseases at the vaginal level, particularly for HIV-seropositive pregnant women, and pH 4.6, to simulate the physiological environment.

Results: The obtained results revealed that the hydrogel swells up well at both pHs.

Conclusion: Release studies conducted at both pathological and physiological pHs have shown that benzydamine is released at the level of the vaginal mucosa in a slow and gradual manner. These data support the hypothesis of the hydrogel use for the site-specific release of benzydamine in the vaginal mucosa.
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http://dx.doi.org/10.2174/1567201817666200129130031DOI Listing
May 2021

L. and (L.) Scop.: Phytochemical Content and In Vitro Antioxidant and Anti-Inflammatory Potential.

Plants (Basel) 2019 Nov 15;8(11). Epub 2019 Nov 15.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.

Spontaneous edible plants have an old history of use in popular traditions all around the world, and the rediscovery of these species could also be useful for the search of new drugs. L. (Amaranthaceae) and (L.) Scop. (Brassicaceae) are two annual plants traditionally used both as food and herbal remedies against inflammatory disorders. In this work, the potential anti-inflammatory and anti-arthritic activities of these plant species have been investigated, together with their antioxidant potential. The phytochemical composition was assessed as well by means of gas chromatography coupled to mass spectrometry (GC-MS) and high performance thin layer chromatography (HPTLC). The antioxidant properties were assessed using the DPPH and β-carotene bleaching test. The ability of extracts to protect against lipid peroxidation was also examined in rat-liver microsomal membranes. All the samples showed a preservation of antioxidant activity up to 60 min. A significant inhibitory activity on the production of the pro-inflammatory mediator nitric oxide was induced in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells by the dichloromethane fraction of extract, with an IC value equal to 81.7 ± 0.9 μg/mL. The same sample showed also a concentration-dependent anti-denaturation effect on heat-treated bovine serum albumin (IC = 975.6 ± 5.5 μg/mL), even if the best in vitro anti-arthritic activity was observed for the dichloromethane fraction of extract, with an IC value of 680.9 ± 13.2 μg/mL.
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http://dx.doi.org/10.3390/plants8110505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918386PMC
November 2019

Strategies for Hyaluronic Acid-Based Hydrogel Design in Drug Delivery.

Pharmaceutics 2019 Aug 12;11(8). Epub 2019 Aug 12.

Department of Pharmacy, Health and Nutritional Science, University of Calabria, Arcavacata, 87036 Rende, Italy.

Hyaluronic acid (HA) is a natural, linear, endogenous polysaccharide that plays important physiological and biological roles in the human body. Nowadays, among biopolymers, HA is emerging as an appealing starting material for hydrogels design due to its biocompatibility, native biofunctionality, biodegradability, non-immunogenicity, and versatility. Since HA is not able to form gels alone, chemical modifications, covalent crosslinking, and gelling agents are always needed in order to obtain HA-based hydrogels. Therefore, in the last decade, different strategies for the design of physical and chemical HA hydrogels have been developed, such as click chemistry reactions, enzymatic and disulfide crosslinking, supramolecular assembly via inclusion complexation, and so on. HA-based hydrogels turn out to be versatile platforms, ranging from static to smart and stimuli-responsive systems, and for these reasons, they are widely investigated for biomedical applications like drug delivery, tissue engineering, regenerative medicine, cell therapy, and diagnostics. Furthermore, the overexpression of HA receptors on various tumor cells makes these platforms promising drug delivery systems for targeted cancer therapy. The aim of the present review is to highlight and discuss recent advances made in the last years on the design of chemical and physical HA-based hydrogels and their application for biomedical purposes, in particular, drug delivery. Notable attention is given to HA hydrogel-based drug delivery systems for targeted therapy of cancer and osteoarthritis.
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http://dx.doi.org/10.3390/pharmaceutics11080407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722772PMC
August 2019

Green Synthesis of Privileged Benzimidazole Scaffolds Using Active Deep Eutectic Solvent.

Molecules 2019 Aug 8;24(16). Epub 2019 Aug 8.

Department of Health Sciences, Magna Græcia University, Viale Europa, 88100 Germaneto CZ, Italy.

The exploitation and use of alternative synthetic methods, in the face of classical procedures that do not conform to the ethics of green chemistry, represent an ever-present problem in the pharmaceutical industry. The procedures for the synthesis of benzimidazoles have become a focus in synthetic organic chemistry, as they are building blocks of strong interest for the development of compounds with pharmacological activity. Various benzimidazole derivatives exhibit important activities such as antimicrobial, antiviral, anti-inflammatory, and analgesic activities, and some of the already synthesized compounds have found very strong applications in medicine praxis. Here we report a selective and sustainable method for the synthesis of 1,2-disubstituted or 2-substituted benzimidazoles, starting from -phenylenediamine in the presence of different aldehydes. The use of deep eutectic solvent (DES), both as reaction medium and reagent without any external solvent, provides advantages in terms of yields as well as in the work up procedure of the reaction.
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http://dx.doi.org/10.3390/molecules24162885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719900PMC
August 2019

Anti-Irritant and Anti-Inflammatory Effects of DHA Encapsulated in Resveratrol-Based Solid Lipid Nanoparticles in Human Keratinocytes.

Nutrients 2019 Jun 21;11(6). Epub 2019 Jun 21.

Institute of General Pathology, Università Cattolica del Sacro Cuore, Largo F. Vito, 00168 Roma, Italy.

We recently found that the dietary long chain omega-3 polyunsaturated fatty acid (LC-ω-3 PUFA), docosahexaenoic acid (DHA), showed enhanced antineoplastic activity against colon cancer cells if encapsulated in resveratrol-based solid lipid nanoparticles (RV-SLNs). In the present study, we investigated whether the DHA enclosed in RV-SLNs (DHA-RV-SLNs) could have the potential of attenuating irritation and inflammation caused by environmental factors at the skin level. To this aim, we used two keratinocyte lines (HaCaT and NCTC 2544 cells) and exposed them to the cytotoxic action of the surfactant, sodium dodecyl sulfate (SDS), as an in vitro model of irritation, or to the pro-inflammatory activity of the cytokine TNF-α. We found that DHA enclosed in RV-SLNs significantly enhanced its ability to contrast the cytotoxic effect of SDS and to inhibit the SDS- and TNF-α-induced production of the inflammatory cytokines IL-1β, IL-6, and 1 MCP-1, in the two keratinocyte cell lines, as well as the NLRP3 inflammasome activation. Moreover, it more efficiently reduced the upsurge of reactive oxygen species (ROS) levels obtained in the presence of a pro-oxidant (HO). Overall, our findings suggest the possibility that a sustained dietary supplementation with DHA-RV-SLNs could efficiently protect skin from the pro-irritant and pro-inflammatory activity of environmental attacks.
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http://dx.doi.org/10.3390/nu11061400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627705PMC
June 2019

Nanomedicine-based formulations containing ω-3 polyunsaturated fatty acids: potential application in cardiovascular and neoplastic diseases.

Int J Nanomedicine 2019 23;14:2809-2828. Epub 2019 Apr 23.

Institute of General Pathology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy,

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are dietary factors involved in the prevention of cardiovascular, inflammatory, and neoplastic diseases. A multidisciplinary approach - based on recent findings in nutritional science, lipid biochemistry, biotechnology, and biology of inflammation and cancer - has been recently employed to develop ω-3 PUFA-containing nanoformulations with an aim to protect these fatty acids from degradation, increase their bioavailability and delivery to target tissues, and, thus, enhance their bioactivity. In some cases, these nanoformulations were designed to administer ω-3 PUFAs in combination with other nutraceuticals or conventional/innovative drugs. The aim of this strategy was to increase the activities of the compounds contained in the nanoformulation and to reduce the adverse effects often induced by drugs. We herein analyze the results of papers evaluating the potential use of ω-3 PUFA-containing nanomaterials in fighting cardiovascular diseases and cancer. Future directions in this field of research are also provided.
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http://dx.doi.org/10.2147/IJN.S197499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488162PMC
July 2019

Harnessing Stem Cells and Neurotrophic Factors with Novel Technologies in the Treatment of Parkinson's Disease.

Curr Stem Cell Res Ther 2019 ;14(7):549-569

Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons, oxidative stress and neuroinflammation. The classical therapeutic approach with L-DOPA is not able to control motor symptoms in the long term, thus new disease-modifying or neuroprotective treatments are urgently required in order to match such yet unmet clinical needs. Success in cell-based therapy has been accomplished at a clinical level with human fetal mesencephalic tissue, but ethical issues and a shortage of organs clearly underline the need for novel sources of dopaminergic neurons. Mesenchymal stem cells (MSCs) can be obtained from different adult and fetal tissues that are normally discarded as waste, including adipose tissue, placenta, umbilical cord, and dental tissues. Their neuroregenerative, anti-inflammatory and immunomodulatory properties are mainly mediated by the secretion of an array of bioactive molecules and are heightened when MSCs form tri-dimensional structures called spheroids. Not only can MSCs spontaneously produce neurotrophic factors (NFs) but they can be engineered to synthetize and secrete them in vivo. The aim of this review is to provide a picture of results gained with MSC secretome and spheroids in PD, as well as the possibility of harnessing MSC-based therapy with the use of nano- and micro-structured materials for NF delivery.
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http://dx.doi.org/10.2174/1574888X14666190301150210DOI Listing
April 2020

Xanthan gum-based materials for omega-3 PUFA delivery: Preparation, characterization and antineoplastic activity evaluation.

Carbohydr Polym 2019 Mar 2;208:431-440. Epub 2019 Jan 2.

Institute of General Pathology, Università Cattolica del Sacro Cuore, Roma, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

Xanthan gum-based microspheres and hydrogels, useful for targeted colorectal release of omega-3 polyunsaturated fatty acids (PUFAs), were successfully prepared and characterized. In particular, the microsphere size, as well as the high hydrogel swelling degree at pH 7.4, and the omega-3 PUFA loading efficiency of both the materials suggested their suitability for colorectal delivery. Moreover, the antioxidant efficiency of the xanthan gum based materials suggests their ability to protect the omega-PUFA cargo. We demonstrated that α-linolenic acid (ALA 18:3ω-3) carried by the materials increased significantly its ability to reduce colorectal cancer cell growth in vitro. On the contrary, docosahexaenoic acid (DHA, 22:6ω-3) enclosed in the hydrogel formulation did not enhance its already high anti-neoplastic potential. The improved anti-neoplastic efficacy of ALA enclosed in both the xanthan gum-based formulations further supports the hypothesis of a potential use of this omega-3 PUFA as a suitable and more sustainable alternative to the fish-derived DHA.
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http://dx.doi.org/10.1016/j.carbpol.2019.01.001DOI Listing
March 2019

Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles: Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro.

Int J Mol Sci 2018 Feb 16;19(2). Epub 2018 Feb 16.

Department of Pharmacy, Health and Nutritional Sciences, Università della Calabria, Via Pietro Bucci, 87036 Arcavacata di Rende, Cosenza, Italy.

New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC), one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA). These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN) having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.
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http://dx.doi.org/10.3390/ijms19020586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855808PMC
February 2018

Hemostatic gauze based on chitosan and hydroquinone: preparation, characterization and blood coagulation evaluation.

J Mater Sci Mater Med 2017 Nov 7;28(12):190. Epub 2017 Nov 7.

Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Arcavacata di Rende, Cosenza, 87036, Italy.

This work concerns on the preparation and performance evaluation of a new chitosan hydroquinone based gauze for hemostatic use. Chitosan and hydroquinone were firstly connected by etherification and then linked to the pre-carboxylate gauze. The functionalized material and the chitosan-hydroquinone ether were characterized by Fourier Transform Infrared (FT-IR) Spectroscopy and Differential Scanning Calorimetry (DSC). FT-IR results showed that an esterification occurred on carboxylic group of the gauze. The gauze functionalization degree was also evaluated by volumetric analysis. The ether hydroquinone content was obtained by the Folin test. Moreover, the linkage between hydroquinone and chitosan was confirmed by nuclear magnetic resonance (NMR). The hemostatic activity of functionalized gauze was evaluated by dynamic blood clotting assays. The obtained results showed that the prepared material can shorten the blood clotting time and induce the adhesion and activation of platelets. Finally, swelling characteristic of the new gauze was evaluated to confirm its high capacity to absorb the blood.
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http://dx.doi.org/10.1007/s10856-017-6000-xDOI Listing
November 2017

α-Tocopheryl linolenate solid lipid nanoparticles for the encapsulation, protection, and release of the omega-3 polyunsaturated fatty acid: in vitro anti-melanoma activity evaluation.

Colloids Surf B Biointerfaces 2017 Mar 10;151:128-133. Epub 2016 Dec 10.

University of Calabria/Department of Pharmacy, Health and Nutritional Sciences, Via Pietro Bucci, 87036, Arcavacata di Rende (CS), Italy. Electronic address:

The main target of this study was the preparation, characterization and antioxidant activity evaluation of α-tocopheryl linolenate based solid lipid nanoparticles (SLNs-TL), able to incorporate omega-3 α-linolenic acid, useful for the treatment of melanoma, a type of skin cancer. In particular, α-linolenic acid was successfully derivatized with α-tocopherol and the obtained compound was characterized by Fourier transform infrared (FT-IR) and by H NMR to confirm the ester linkage. Both the empty SLNs-TL that SLNs-TL-LIN, containing omega-3-linolenic acid, were prepared through the technique of the microemulsion. The nanoparticles were characterized for entrapment efficiency, size and shape. Their antioxidant activity was investigated in rat liver microsomal membranes in inhibiting the lipid peroxidation induced by tert-butyl hydroperoxide (tert-BOOH), which endogenously produces alkoxyl radicals by Fenton reactions. The obtained results indicate that the α-tocopherol, linked by ester bond to α-linolenic acid, maintains an excellent antioxidant activity. The encapsulation efficiency was equal to 77% and the polydispersity index 0.198 indicating a good dimensional distribution. Furthermore, the nanoparticles were tested in vitro for their cytotoxic activity against human melanoma cancer cell line C32. Both empty SLNs-TL and loaded SLNs-TL-LIN showed a high biological activity, being more effective than α-linolenic acid and α-tocopherol. The results indicated that these nanoparticles could provide the delivery and the protection of unstable molecules, such as α-linolenic acid, from degradation induced by mechanisms of oxidative stress.
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http://dx.doi.org/10.1016/j.colsurfb.2016.11.043DOI Listing
March 2017

Role of β-catenin signaling in the anti-invasive effect of the omega-3 fatty acid DHA in human melanoma cells.

J Dermatol Sci 2016 Nov 23;84(2):149-159. Epub 2016 Jun 23.

Institute of General Pathology, Università Cattolica del S. Cuore, Rome, Italy; Research Center for Biotechnology Applied to Cosmetology, Università Cattolica del S. Cuore, Rome, Italy. Electronic address:

Background: We previously found that docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid present at high level in fatty fish, inhibited cell growth and induced differentiation of melanoma cells in vitro by increasing nuclear β-catenin content. An anti-neoplastic role of nuclear β-catenin was suggested in melanoma, and related to the presence in the melanocyte lineage of the microphtalmia transcription factor (MITF), which interferes with the transcription of β-catenin/TCF/LEF pro-invasive target genes.

Objective: In the present work we investigated if DHA could inhibit the invasive potential of melanoma cells, and if this effect could be related to DHA-induced alterations of the Wnt/β-catenin signaling, including changes in MITF expression.

Methods: WM115 and WM266-4 human melanoma, and B16-F10 murine melanoma cell lines were used. Cell invasion was evaluated by Wound Healing and Matrigel transwell assays. Protein expression was analyzed by Western Blotting and β-catenin phosphorylation by immunoprecipitation. The role of MITF in the anti-invasive effect of DHA was analyzed by siRNA gene silencing.

Results: We found that DHA inhibited anchorage-independent cell growth, reduced their migration/invasion in vitro and down-regulated several Matrix Metalloproteinases (MMP: MMP-2, MT1-MMP and MMP-13), known to be involved in melanoma invasion. We related these effects to the β-catenin increased nuclear expression and PKA-dependent phosphorylation, as well as to the increased expression of MITF.

Conclusion: The data obtained further support the potential role of dietary DHA as suppressor of melanoma progression to invasive malignancy through its ability to enhance MITF expression and PKA-dependent nuclear β-catenin phosphorylation.
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http://dx.doi.org/10.1016/j.jdermsci.2016.06.010DOI Listing
November 2016

Solid lipid nanoparticles for antifungal drugs delivery for topical applications.

Ther Deliv 2016 09;7(9):639-47

Department of Pharmacy, Health & Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.

Systemic and local infections caused by fungi, in particular those concerning the skin and nails, are increasing. Various drugs are used for mycoses treatment such as amphotericin B, nystatin and ketoconazole, fluconazole, itraconazole and fluconazole, among others. Unfortunately, many of these antifungal agents can cause side effects such as allergic and severe skin reaction. With the aim to reduce these side effects and maximize the antifungal drug activity, various drug-delivery systems have been formulated and been investigated in the last few years. In this context, solid lipid nanoparticles are attracting great attention. The aim of this review is to highlight the role of solid lipid nanoparticles as carriers of antifungal drugs for topical applications.
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http://dx.doi.org/10.4155/tde-2016-0040DOI Listing
September 2016

Novel microspheres based on triterpene saponins from the roots of Physospermum verticillatum (Waldst & Kit) (Apiaceae) for the improvement of gemcitabine release.

J Pharm Pharmacol 2016 Feb 1;68(2):275-81. Epub 2016 Feb 1.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, Cosenza, Italy.

Objectives: This study concerns the preparation and characterization of microspheres based on a mixture of triterpene saponins, from Physospermum verticillatum (Waldst & Kit), as a carrier for the specific release of gemcitabine.

Methods: Triterpene saponins were derivatized with acrylic acid. The obtained polymerizable product was characterized by Fourier transform infrared to confirm the ester linkage. Then, spherical microparticles were prepared by suspension radical copolymerization and impregnated with gemcitabine.

Key Findings: Microspheres exhibited a mean diameter of 2.7 μ. The swelling studies showed that particles swell most at pH 6.2, typical of the tumour pathology, than at pH 7.4, miming physiological conditions. The microspheres were loaded with gemcitabine (LE 72.2%). Their release profile showed an initial dot of around 24% and a further release for 24 h.

Conclusions: This carrier could be potentially release the drug in the lung, as a function of different pHs between tumour cells and healthy, reducing the systemic drug toxicity, allowing the reduction of the doses number, increasing the drug half-life and eliminating the problems related to the fast clearance of gemcitabine administration.
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http://dx.doi.org/10.1111/jphp.12509DOI Listing
February 2016

A new pro-prodrug aminoacid-based for trans-ferulic Acid and silybin intestinal release.

J Funct Biomater 2014 Jul 24;5(3):99-110. Epub 2014 Jul 24.

Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, 87036 Arcavacata di Rende Cosenza, Italy.

The aim of this work was the preparation and characterization of a pro-prodrug able to simultaneously transport silybin, a drug possessing various pharmacological effects, and trans-ferulic acid, a known antioxidant. More specifically, l-phenylalanine-N-(4-hydroxy-3-methoxy-phenyl) prop-2-en-O-(2R,3R)-3,5,7-trihydroxy-2-((2R,3R)-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-2,3-dihydro-benzo-(1,4)-dioxin-6-yl)croman-4-one was synthesized by using the aminoacid l-phenylalanine (l-Phe) as carrier. Indeed, l-Phe is characterized by an intrinsic chemical reactivity due to the presence of an amino group, placed on the chiral center, and of a carboxylic group. The synthesis has been characterized first by adding silybin by means of carboxylic group and then, with the aim to confer antioxidant properties to this new carrier, by linking trans-ferulic acid to l-Phe via amino group. The so obtained derivative was then characterized by FT-IR, and 1H-NMR spectroscopies. Furthermore, its ability to inhibit lipid peroxidation induced by tert-butyl hydroperoxide in rat liver microsomes, was evaluated. The 1,1-diphenyl-2-picrylhydrazyl radical-scavenging effect, was also assessed. The release of silybin and trans-ferulic acid was determined in simulated gastric and intestinal fluids over the time. The results showed that the covalent bond between both (i) silybin; or (ii) trans-ferulic acid and the amino acid was degraded by enzymatic reactions. In addition, the pro-prodrug, showed strong antioxidant and scavenger activities. Due to these properties, this new pro-prodrug could be applied for the treatment of intestinal pathologies and it might improve the therapeutic potential of silybin which is strongly limited by its low solubility.
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http://dx.doi.org/10.3390/jfb5030099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192607PMC
July 2014

Preparation, characterization and in vitro activities evaluation of solid lipid nanoparticles based on PEG-40 stearate for antifungal drugs vaginal delivery.

Drug Deliv 2016 9;23(3):1047-56. Epub 2014 Jul 9.

a Department of Pharmaceutical Sciences , University of Calabria , Arcavacata di Rende , Cosenza , Italy and.

The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans.
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http://dx.doi.org/10.3109/10717544.2014.932862DOI Listing
November 2016

Anticancer activity of a hydrogel containing folic acid towards MCF-7 and MDA-MB-231 cells.

Anticancer Res 2013 Nov;33(11):4847-54

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Edificio Polifunzionale, Via Pietro Bucci, 87036 Arcavacata di Rende, Cosenza, Italy.

Aim: The aim of the present study was to prepare a hydrogel, based on ellagic acid and glycine, embedded with folic acid, as a subcutaneous implant for the treatment of breast cancer. The function of folic acid is to selectively and actively target tumor cells which are well-known to overexpress folic acid receptors on their surface.

Materials And Methods: A pro-drug based on L-glycine and ellagic acid, was functionalized with a polymerizable group and loaded with folic acid to make it more natural, non-toxic, compatible and specific for the site of action. Cytotoxicity against MCF-7 cells was also evaluated. Release studies of folic acid were conducted on aliquots of hydrogel at different pH (6.2 and 7.4) and time-points (1, 6, 12 and 24 h) using a shaking water bath at 37°C (body temperature).

Results: Our results show that folic acid release by the hydrogel is characterized by a slow kinetic release, especially at pH 6.2. Moreover, it was evidenced that the exposure of human breast cancer cells to ellagic acid-based hydrogel containing folic acid significantly reduced cell viability.
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November 2013
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