Emergent Strategies for Natural Products Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 41332

Special Issue Editors

Department of Chemistry “Ugo Schiff”, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy
Interests: natural products; drug delivery systems; nanocarriers; topical administration; oral administration; brain delivery
Special Issues, Collections and Topics in MDPI journals
Department of Chemistry, University of Florence, Florence, Italy
Interests: natural products; nanocarriers; stealth and cationic liposomes; microemulsions; nanoemulsions; oral administration

Special Issue Information

Dear Colleagues,

Natural products have a wide range of applications with a profound impact in the medical and healthcare fields. In the last decade, numerous delivery systems based on natural products have been developed to optimise their biopharmaceutical properties, to achieve desirable target characteristics, to reduce doses and side effects, and even to achieve therapeutic levels of drugs over an extended period.

This is generally related to the scarce water solubility, low lipophilicity and inappropriate molecular size of natural compounds, which undergo structural instability in a biological milieu, rapid clearance and a high metabolic rate. Additionally, some molecules are destroyed in gastric juice or suffer a massive pre-systemic metabolism in the liver when administered orally, limiting their clinical use. Reduced bioavailability can be also linked to drug distribution/accumulation in non-targeted tissues and organs that increase the side effects, lowering the therapeutic efficacy and patient compliance. Delivery systems represent favourable tools to increase the bioavailability and activities of natural products.

Dr. Anna Rita Bilia
Dr. Maria Camilla Bergonzi
Dr. Vieri Piazzini
Guest Editors

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Keywords

  • Natural products
  • Delivery systems
  • Nanocarriers
  • Microcarriers
  • Polymeric carriers
  • Lipid carriers
  • Bioavailability
  • Stability
  • Solubility

Published Papers (11 papers)

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Editorial

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4 pages, 176 KiB  
Editorial
Emergent Strategies for Natural Products Delivery
by Anna Rita Bilia, Vieri Piazzini and Maria Camilla Bergonzi
Pharmaceutics 2020, 12(12), 1179; https://doi.org/10.3390/pharmaceutics12121179 - 03 Dec 2020
Viewed by 1091
Abstract
Natural products have a wide range of applications with a profound impact in the medical and healthcare fields [...] Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)

Research

Jump to: Editorial

21 pages, 3649 KiB  
Article
Exploiting Lipid and Polymer Nanocarriers to Improve the Anticancer Sonodynamic Activity of Chlorophyll
by Federica Bosca, Federica Foglietta, Alberto Gimenez, Roberto Canaparo, Giovanni Durando, Ilaria Andreana, Alessandro Barge, Elena Peira, Silvia Arpicco, Loredana Serpe and Barbara Stella
Pharmaceutics 2020, 12(7), 605; https://doi.org/10.3390/pharmaceutics12070605 - 30 Jun 2020
Cited by 7 | Viewed by 2744
Abstract
Sonodynamic therapy is an emerging approach that uses low-intensity ultrasound to activate a sonosensitizer agent triggering its cytotoxicity for selective cancer cell killing. Several molecules have been proposed as sonosensitizer agents, but most of these, as chlorophyll, are strongly hydrophobic with a low [...] Read more.
Sonodynamic therapy is an emerging approach that uses low-intensity ultrasound to activate a sonosensitizer agent triggering its cytotoxicity for selective cancer cell killing. Several molecules have been proposed as sonosensitizer agents, but most of these, as chlorophyll, are strongly hydrophobic with a low selectivity towards cancer tissues. Nanocarriers can help to deliver more efficiently the sonosensitizer agents in the target tumor site, increasing at the same time their sonodynamic effect, since nanosystems act as cavitation nuclei. Herein, we propose the incorporation of unmodified plant-extracted chlorophyll into nanocarriers with different composition and structure (i.e., liposomes, solid lipid nanoparticles and poly(lactic-co-glycolic acid) nanoparticles) to obtain aqueous formulations of this natural pigment. The nanocarriers have been deeply characterized and then incubated with human prostatic cancer cells (PC-3) and spheroids (DU-145) to assess the influence of the different formulations on the chlorophyll sonodynamic effect. The highest sonodynamic cytotoxicity was obtained with chlorophyll loaded into poly(lactic-co-glycolic acid) nanoparticles, showing promising results for future clinical investigations on sonodynamic therapy. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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28 pages, 9953 KiB  
Article
Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles
by Khaled AbouAitah, Agata Stefanek, Iman M. Higazy, Magdalena Janczewska, Anna Swiderska-Sroda, Agnieszka Chodara, Jacek Wojnarowicz, Urszula Szałaj, Samar A. Shahein, Ahmed M. Aboul-Enein, Faten Abou-Elella, Stanislaw Gierlotka, Tomasz Ciach and Witold Lojkowski
Pharmaceutics 2020, 12(1), 70; https://doi.org/10.3390/pharmaceutics12010070 - 16 Jan 2020
Cited by 30 | Viewed by 5740
Abstract
Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with [...] Read more.
Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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20 pages, 1637 KiB  
Article
Satureja montana L. Essential Oils: Chemical Profiles/Phytochemical Screening, Antimicrobial Activity and O/W NanoEmulsion Formulations
by Alessandro Maccelli, Luca Vitanza, Anna Imbriano, Caterina Fraschetti, Antonello Filippi, Paola Goldoni, Linda Maurizi, Maria Grazia Ammendolia, Maria Elisa Crestoni, Simonetta Fornarini, Luigi Menghini, Maria Carafa, Carlotta Marianecci, Catia Longhi and Federica Rinaldi
Pharmaceutics 2020, 12(1), 7; https://doi.org/10.3390/pharmaceutics12010007 - 19 Dec 2019
Cited by 40 | Viewed by 4709
Abstract
Chemical fingerprints of four different Satureja montana L. essential oils (SEOs) were assayed by an untargeted metabolomics approach based on Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) coupled with either electrospray ionization or atmospheric pressure chemical ionization ion sources. Analysis and relative [...] Read more.
Chemical fingerprints of four different Satureja montana L. essential oils (SEOs) were assayed by an untargeted metabolomics approach based on Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) coupled with either electrospray ionization or atmospheric pressure chemical ionization ion sources. Analysis and relative quantification of the non-polar volatile fraction were conducted by gas chromatography (GC) coupled to MS. FT-ICR MS confirmed significant differences in the polar metabolite composition, while GC-MS analyses confirmed slight fluctuations in the relative amount of major terpenes and terpenoids, known to play a key role in antimicrobial mechanisms. Oil in eater (O/W) nanoemulsions (NEs) composed by SEOs and Tween 20 or Tween 80 were prepared and analyzed in terms of hydrodynamic diameter, ζ-potential and polydispersity index. The results confirm the formation of stable NEs homogeneous in size. Minimum inhibitory and minimum bactericidal concentrations of SEOs were determined towards Gram-positive (Listeria monocytogenes, Staphylococcus aureus, Staphylococcus haemolyticus) and Gram-negative clinical isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens). Commercial SEO showed strongest antibacterial activity, while SEO 3 was found to be the most active among the lab made extractions. MIC and MBC values ranged from 0.39 to 6.25 mg·mL−1. Furthermore, a SEO structured in NEs formulation was able to preserve and improve antimicrobial activity. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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13 pages, 1860 KiB  
Article
Sulforaphane-Loaded Ultradeformable Vesicles as A Potential Natural Nanomedicine for the Treatment of Skin Cancer Diseases
by Maria Chiara Cristiano, Francesca Froiio, Roberta Spaccapelo, Antonia Mancuso, Steven P. Nisticò, Betty P. Udongo, Massimo Fresta and Donatella Paolino
Pharmaceutics 2020, 12(1), 6; https://doi.org/10.3390/pharmaceutics12010006 - 19 Dec 2019
Cited by 66 | Viewed by 4432
Abstract
Sulforaphane is a multi-action drug and its anticancer activity is the reason for the continuous growth of attention being paid to this drug. Sulforaphane shows an in vitro antiproliferative activity against melanoma and other skin cancer diseases. Unfortunately, this natural compound cannot be [...] Read more.
Sulforaphane is a multi-action drug and its anticancer activity is the reason for the continuous growth of attention being paid to this drug. Sulforaphane shows an in vitro antiproliferative activity against melanoma and other skin cancer diseases. Unfortunately, this natural compound cannot be applied in free form on the skin due to its poor percutaneous permeation determined by its physico-chemical characteristics. The aim of this investigation was to evaluate ethosomes® and transfersomes® as ultradeformable vesicular carriers for the percutaneous delivery of sulforaphane to be used for the treatment of skin cancer diseases. The physico-chemical features of the ultradeformable vesicles were evaluated. Namely, ethosomes® and transfersomes® had mean sizes <400 nm and a polydispersity index close to 0. The stability studies demonstrated that the most suitable ultradeformable vesicles to be used as topical carriers of sulforaphane were ethosomes® made up of ethanol 40% (w/v) and phospholipon 90G 2% (w/v). In particular, in vitro studies of percutaneous permeation through human stratum corneum and epidermis membranes showed an increase of the percutaneous permeation of sulforaphane. The antiproliferative activity of sulforaphane-loaded ethosomes® was tested on SK-MEL 28 and improved anticancer activity was observed in comparison with the free drug. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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22 pages, 3233 KiB  
Article
Development and Percutaneous Permeation Study of Escinosomes, Escin-Based Nanovesicles Loaded with Berberine Chloride
by Giulia Vanti, Daniele Bani, Maria Cristina Salvatici, Maria Camilla Bergonzi and Anna Rita Bilia
Pharmaceutics 2019, 11(12), 682; https://doi.org/10.3390/pharmaceutics11120682 - 15 Dec 2019
Cited by 23 | Viewed by 3242
Abstract
Escin is a natural saponin, clinically used for the anti-edematous and anti-inflammatory effects. The aim of the study was to explore the possibility of converting escin into vesicle bilayer-forming component. The hyaluronidase inhibition activity of escin was evaluated after its formulation in escinosomes. [...] Read more.
Escin is a natural saponin, clinically used for the anti-edematous and anti-inflammatory effects. The aim of the study was to explore the possibility of converting escin into vesicle bilayer-forming component. The hyaluronidase inhibition activity of escin was evaluated after its formulation in escinosomes. Berberine chloride, a natural quaternary isoquinoline alkaloid isolated from several medicinal plants that is traditionally used for various skin conditions was loaded in the vesicles. The developed nanovesicles were characterized in terms of diameter, polydispersity, ζ-potential, deformability, recovery, encapsulation efficiency, stability, and release kinetics. Nanovesicle permeation properties through artificial membranes and rabbit ear skin were investigated using skin-PAMPATM and Franz cells were also evaluated. Escinosomes, made of phosphatidylcholine and escin, were loaded with berberine chloride. These nanovesicles displayed the best characteristics for skin application, particularly optimal polydispersity (0.17) and deformability, high negative ζ-potential value, great encapsulation efficiency (about 67%), high stability, and the best release properties of berberine chloride (about 75% after 24 h). In conclusion, escinosomes seem to be new vesicular carriers, capable to maintain escin properties such as hyaluronidase inhibition activity, and able to load other active molecules such as berberine chloride, in order to enhance or expand the activity of the loaded drug. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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15 pages, 2925 KiB  
Article
Comparison of Chitosan Nanoparticles and Soluplus Micelles to Optimize the Bioactivity of Posidonia oceanica Extract on Human Neuroblastoma Cell Migration
by Vieri Piazzini, Marzia Vasarri, Donatella Degl’Innocenti, Asia Guastini, Emanuela Barletta, Maria Cristina Salvatici and Maria Camilla Bergonzi
Pharmaceutics 2019, 11(12), 655; https://doi.org/10.3390/pharmaceutics11120655 - 06 Dec 2019
Cited by 23 | Viewed by 3203
Abstract
Posidonia oceanica (L.) Delile is a marine plant endemic of Mediterranean Sea endowed with interesting bioactivities. The hydroalcholic extract of P. oceanica leaves (POE), rich in polyphenols and carbohydrates, has been shown to inhibit human cancer cell migration. Neuroblastoma is a common childhood [...] Read more.
Posidonia oceanica (L.) Delile is a marine plant endemic of Mediterranean Sea endowed with interesting bioactivities. The hydroalcholic extract of P. oceanica leaves (POE), rich in polyphenols and carbohydrates, has been shown to inhibit human cancer cell migration. Neuroblastoma is a common childhood extracranial solid tumor with high rate of invasiveness. Novel therapeutics loaded into nanocarriers may be used to target the migratory and metastatic ability of neuroblastoma. Our goal was to improve both the aqueous solubility of POE and its inhibitory effect on cancer cell migration. Methods: Chitosan nanoparticles (NP) and Soluplus polymeric micelles (PM) loaded with POE have been developed. Nanoformulations were chemically and physically defined and characterized. In vitro release studies were also performed. Finally, the inhibitory effect of both nanoformulations was tested on SH-SY5Y cell migration by wound healing assay and compared to that of unformulated POE. Results: Both nanoformulations showed excellent physical and chemical stability during storage, and enhanced the solubility of POE. PM-POE improved the inhibitory effect of POE on cell migration probably due to the high encapsulation efficiency and the prolonged release of the extract. Conclusions: For the first time, a phytocomplex of marine origin, i.e., P. oceanica extract, has enhanced in terms of acqueous solubility and bioactivity once encapsulated inside nanomicelles. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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17 pages, 4698 KiB  
Article
Anti-Inflammatory Effect of Cherry Extract Loaded in Polymeric Nanoparticles: Relevance of Particle Internalization in Endothelial Cells
by Denise Beconcini, Francesca Felice, Ylenia Zambito, Angela Fabiano, Anna Maria Piras, Maria Helena Macedo, Bruno Sarmento and Rossella Di Stefano
Pharmaceutics 2019, 11(10), 500; https://doi.org/10.3390/pharmaceutics11100500 - 29 Sep 2019
Cited by 21 | Viewed by 4412
Abstract
This study aimed at evaluating the anti-inflammatory effect of natural cherry extract (CE), either free or encapsulated in nanoparticles (NPs) based on chitosan derivatives (Ch-der) or poly(lactic-co-glycolic acid) (PLGA), on human umbilical vein endothelial cells (HUVEC). CE from Prunus avium L. [...] Read more.
This study aimed at evaluating the anti-inflammatory effect of natural cherry extract (CE), either free or encapsulated in nanoparticles (NPs) based on chitosan derivatives (Ch-der) or poly(lactic-co-glycolic acid) (PLGA), on human umbilical vein endothelial cells (HUVEC). CE from Prunus avium L. was characterized for total polyphenols, flavonoids, and anthocyanins content. CE and CE-loaded NP cytotoxicity and protective effect on lipopolysaccharide (LPS)-stressed HUVEC were tested by water-soluble tetrazolium salt (WST-1) assay. Pro- and anti-inflammatory cytokines (TNF-α, IL-6, IL-10, and PGE2) released by HUVEC were quantified by enzyme-linked immunosorbent assay (ELISA). All NP types were internalized into HUVEC after 2 h incubation and promoted the anti-inflammatory effect of free CE at the concentration of 2 µg gallic acid equivalents (GAE)/mL. CE-loaded Ch-der NPs showed the highest in vitro uptake and anti-inflammatory activity, blunting the secretion of IL-6, TNF-α, and PGE2 cytokines. Moreover, all NPs reduced the production of nitric oxide and NLRP3 inflammasome, and had a stronger anti-inflammatory effect than the major corticosteroid dexamethasone. In particular, the results demonstrate that natural CE protects endothelial cells from inflammatory stress when encapsulated in NPs based on quaternary ammonium chitosan. The CE beneficial effects were directly related with in vitro internalization of CE-loaded NPs. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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17 pages, 3278 KiB  
Article
Manufacturing Different Types of Solid Dispersions of BCS Class IV Polyphenol (Daidzein) by Spray Drying: Formulation and Bioavailability
by Gean Pier Panizzon, Fernanda Giacomini Bueno, Tânia Ueda-Nakamura, Celso Vataru Nakamura and Benedito Prado Dias Filho
Pharmaceutics 2019, 11(10), 492; https://doi.org/10.3390/pharmaceutics11100492 - 25 Sep 2019
Cited by 16 | Viewed by 3171
Abstract
Daidzein (DZ) is a polyphenolic compound belonging to Biopharmaceutical Classification System class IV, which shows that it may have limited therapeutic effects due to its low solubility and poor bioavailability. This study aimed to obtain high-purity DZ and prepare and characterize different types [...] Read more.
Daidzein (DZ) is a polyphenolic compound belonging to Biopharmaceutical Classification System class IV, which shows that it may have limited therapeutic effects due to its low solubility and poor bioavailability. This study aimed to obtain high-purity DZ and prepare and characterize different types of solid dispersions (SDs) in order to enhance aqueous solubility and bioavailability. Excipients were investigated in order to manufacture different types of solid dispersions (SDs). Second-generation solid dispersions (SG), third-generation solid dispersions (TG), and second- and third-generation pH-modulated solid dispersions (SD and TG pHM-SD) were produced via spray drying. The SDs were characterized and tested for in vitro DZ release and oral bioavailability. SDs have shown increased aqueous solubility and in vitro release rate. Solid-state characterization showed that DZ was in an amorphous state in most of the formulations. The enhanced aqueous solubility of TG-pHM SD was reflected by an increase in oral bioavailability, which significantly increased the maximum plasma concentration approximately 20-fold and decreased the time to reach the maximum plasma concentration. The production of pHM SDs that contain DZ via spray drying is a simple and effective approach for oral drug delivery, which has the potential to greatly reduce the dose and enhance therapeutics effects. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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15 pages, 4425 KiB  
Article
Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc
by Moira Loepfe, Anja Duss, Katerina-Alexandra Zafeiropoulou, Oddny Björgvinsdóttir, Matteo D’Este, David Eglin, Giuseppino Fortunato, Juergen Klasen, Stephen J. Ferguson, Karin Wuertz-Kozak and Olga Krupkova
Pharmaceutics 2019, 11(9), 435; https://doi.org/10.3390/pharmaceutics11090435 - 01 Sep 2019
Cited by 13 | Viewed by 2949
Abstract
Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study [...] Read more.
Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER™ technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use. Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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19 pages, 5192 KiB  
Article
Functional Role of VCAM-1 Targeted Flavonoid-Loaded Lipid Nanoemulsions in Reducing Endothelium Inflammation
by Elena Valeria Fuior, Mariana Deleanu, Cristina Ana Constantinescu, Daniela Rebleanu, Geanina Voicu, Maya Simionescu and Manuela Calin
Pharmaceutics 2019, 11(8), 391; https://doi.org/10.3390/pharmaceutics11080391 - 03 Aug 2019
Cited by 21 | Viewed by 4818
Abstract
Citrus flavonoids have well-documented protective effects on cardiovascular system, but the poor water solubility and reduced bioavailability restrict their therapeutic use. We aimed to overcome these limitations and encapsulated naringenin and hesperetin into lipid nanoemulsions (LNs), targeted to vascular cell adhesion molecule-1 (VCAM-1), [...] Read more.
Citrus flavonoids have well-documented protective effects on cardiovascular system, but the poor water solubility and reduced bioavailability restrict their therapeutic use. We aimed to overcome these limitations and encapsulated naringenin and hesperetin into lipid nanoemulsions (LNs), targeted to vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated endothelial cells (ECs). LNs were characterized by a hydrodynamic size of ~200 nm, negative zeta potential, an encapsulation efficiency of flavonoids higher than 80%, good in vitro stability and steady release of the cargo. The LNs were neither cytotoxic to human ECs line EA.hy926, nor provoked in vitro lysis of murine erithrocytes. Then, we tested whether these nanoformulations reduce tumor necrosis factor-alpha (TNF-α) induced EC-activation. We found that flavonoid-loaded LNs, either non-targeted or targeted to the endothelium, were taken up by the EA.hy926 cells in a dose-dependent manner, but dependent on TNF-α only in the case of endothelium-targeted LNs. Moreover, these nanoparticles inhibited both the adhesion and transmigration of THP-1 monocytes on/through activated ECs, by mechanisms involving a reduced expression of the pro-inflammatory chemokine monocyte chemotactic protein 1 (MCP-1) and diminished nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Full article
(This article belongs to the Special Issue Emergent Strategies for Natural Products Delivery)
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