Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood–Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis
Abstract
1. Introduction
2. Results and Discussion
2.1. SLNs Characterization
2.2. Entrapment Efficiency and Drug Loading
2.3. Release of BXL from SLNs
2.4. Differential Scanning Calorimetry
2.4.1. SLNs and SLN-BXL Calorimetric Analysis
2.4.2. MLV-SLNs Interaction Analysis: Kinetics Studies
2.5. Cell Viability
2.6. Wound Healing Assay
2.7. Tube Formation
2.8. PGE2 Secretion in HBMEC Media
2.9. IL-8 Secretion in HBMEC Media
3. Materials and Methods
3.1. Materials
3.2. SLNs Preparation
3.3. SLNs Characterization
3.3.1. Particles Size, Polidispersity Index, and Zeta-Potential
3.3.2. Determination of the encapsulation efficiency and drug loading
3.4. Release of BXL from SLNs
3.5. Differential Scanning Calorimetry
3.5.1. SLNs and SLN-BXL Calorimetric Analyses
3.5.2. MLV-SLNs Interaction Analysis
3.6. Cell Cultures
3.7. Cell Viability
3.8. Wound Healing Assay
3.9. Tube Formation
3.10. Prostaglandin E2 (PGE2) Release
3.11. Interleukin-8 (IL-8) Release
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Pan, J.-Y.; Chen, S.-L.; Yang, M.-H.; Wu, J.; Sinkkonen, J.; Zou, K. An Update on Lignans: Natural Products and Synthesis. Nat. Prod. Rep. 2009, 26, 1251–1292. [Google Scholar] [CrossRef]
- Whiting, D.A. Ligans and Neolignans. Nat. Prod. Rep. 1985, 2, 191–211. [Google Scholar] [CrossRef]
- Di Micco, S.; Mazué, F.; Daquino, C.; Spatafora, C.; Delmas, D.; Latruffe, N.; Tringali, C.; Riccio, R.; Bifulco, G. Structural Basis for the Potential Antitumour Activity of DNA-Interacting Benzo[Kl]Xanthenelignans. Org. Biomol. Chem. 2011, 9, 701–710. [Google Scholar] [CrossRef]
- Yamauchi, S.; Ina, T.; Kirikihira, T.; Masuda, T. Synthesis and Antioxidant Activity of Oxygenated Furofuran Lignans. Biosci. Biotechnol. Biochem. 2004, 68, 183–192. [Google Scholar] [CrossRef]
- Lu, H.; Liu, G.-T. Anti-Oxidant Activity of Dibenzocyclooctene Lignans Isolated from Schisandraceae. Planta Med. 1992, 58, 311–313. [Google Scholar] [CrossRef]
- Kim, J.Y.; Lim, H.J.; Lee, D.Y.; Kim, J.S.; Kim, D.H.; Lee, H.J.; Kim, H.D.; Jeon, R.; Ryu, J.-H. In Vitro Anti-Inflammatory Activity of Lignans Isolated from Magnolia fargesii. Bioorg. Med. Chem. Lett. 2009, 19, 937–940. [Google Scholar] [CrossRef] [PubMed]
- Thompson, L.U.; Seidl, M.M.; Rickard, S.E.; Orcheson, L.J.; Fong, H.H.S. Antitumorigenic Effect of a Mammalian Lignan Precursor from Flaxseed. Nutr. Cancer 1996, 26, 159–165. [Google Scholar] [CrossRef]
- Charlton, J.L. Antiviral Activity of Lignans. J. Nat. Prod. 1998, 61, 1447–1451. [Google Scholar] [CrossRef] [PubMed]
- Gaafar, A.; Salama, Z.; Askar, M.S.; El-Hariri, D.M.; Bakry, B.A. In Vitro Antioxidant and Antimicrobial Activities of Lignan Flax Seed Extract (Linumusitatissimum, L.). Int. J. Pharm. Sci. Rev. Res. 2013, 23, 291–297. [Google Scholar]
- Ghisalberti, E.L. Cardiovascular Activity of Naturally Occurring Lignans. Phytomedicine 1997, 4, 151–166. [Google Scholar] [CrossRef]
- Daquino, C.; Rescifina, A.; Spatafora, C.; Tringali, C. Biomimetic Synthesis of Natural and “Unnatural” Lignans by Oxidative Coupling of Caffeic Esters. Eur. J. Org. Chem. 2009, 2009, 6289–6300. [Google Scholar] [CrossRef]
- Basini, G.; Baioni, L.; Bussolati, S.; Grasselli, F.; Daquino, C.; Spatafora, C.; Tringali, C. Antiangiogenic Properties of an Unusual Benzo[k,l]Xanthene Lignan Derived from CAPE (Caffeic Acid Phenethyl Ester). Investig. New Drugs 2012, 30, 186–190. [Google Scholar] [CrossRef]
- Vijayakurup, V.; Carmela, S.; Carmelo, D.; Corrado, T.; Srinivas, P.; Gopala, S. Phenethyl Caffeate Benzo[Kl]Xanthene Lignan with DNA Interacting Properties Induces DNA Damage and Apoptosis in Colon Cancer Cells. Life Sci. 2012, 91, 1336–1344. [Google Scholar] [CrossRef]
- Capolupo, A.; Tosco, A.; Mozzicafreddo, M.; Tringali, C.; Cardullo, N.; Monti, M.C.; Casapullo, A. Proteasome as a New Target for Bio-Inspired Benzo[k,l]Xanthene Lignans. Chem.—Eur. J. 2017, 23, 8371–8374. [Google Scholar] [CrossRef]
- Genovese, C.; Pulvirenti, L.; Cardullo, N.; Muccilli, V.; Tempera, G.; Nicolosi, D.; Tringali, C. Bioinspired Benzoxanthene Lignans as a New Class of Antimycotic Agents: Synthesis and Candida spp. Growth Inhibition. Nat. Prod. Res. 2020, 34, 1653–1662. [Google Scholar] [CrossRef]
- Tumir, L.-M.; Zonjić, I.; Žuna, K.; Brkanac, S.R.; Jukić, M.; Huđek, A.; Durgo, K.; Crnolatac, I.; Glavaš-Obrovac, L.; Cardullo, N.; et al. Synthesis, DNA/RNA-Interaction and Biological Activity of Benzo[k,l]Xanthene Lignans. Bioorg. Chem. 2020, 104, 104190. [Google Scholar] [CrossRef]
- Spatafora, C.; Barresi, V.; Bhusainahalli, V.M.; Micco, S.D.; Musso, N.; Riccio, R.; Bifulco, G.; Condorelli, D.; Tringali, C. Bio-Inspired Benzo[k,l]Xanthene Lignans: Synthesis, DNA-Interaction and Antiproliferative Properties. Org. Biomol. Chem. 2014, 12, 2686–2701. [Google Scholar] [CrossRef]
- Üner, M.; Yener, G. Importance of Solid Lipid Nanoparticles (SLN) in Various Administration Routes and Future Perspectives. Int. J. Nanomed. 2007, 2, 289–300. [Google Scholar]
- Yuan, Y.; Sun, J.; Dong, Q.; Cui, M. Blood-Brain Barrier Endothelial Cells in Neurodegenerative Diseases: Signals from the “Barrier”. Front. Neurosci. 2023, 17, 1047778. [Google Scholar] [CrossRef]
- Zhao, Z.; Nelson, A.R.; Betsholtz, C.; Zlokovic, B.V. Establishment and Dysfunction of the Blood-Brain Barrier. Cell 2015, 163, 1064–1078. [Google Scholar] [CrossRef]
- Neuwelt, E.A.; Bauer, B.; Fahlke, C.; Fricker, G.; Iadecola, C.; Janigro, D.; Leybaert, L.; Molnár, Z.; O’Donnell, M.E.; Povlishock, J.T.; et al. Engaging Neuroscience to Advance Translational Research in Brain Barrier Biology. Nat. Rev. Neurosci. 2011, 12, 169–182. [Google Scholar] [CrossRef] [PubMed]
- Banks, W.A. The Blood-Brain Barrier as an Endocrine Tissue. Nat. Rev. Endocrinol. 2019, 15, 444–455. [Google Scholar] [CrossRef]
- Hanahan, D.; Folkman, J. Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis. Cell 1996, 86, 353–364. [Google Scholar] [CrossRef]
- Agnihotri, T.G.; Salave, S.; Shinde, T.; Srikanth, I.; Gyanani, V.; Haley, J.C.; Jain, A. Understanding the Role of Endothelial Cells in Brain Tumor Formation and Metastasis: A Proposition to Be Explored for Better Therapy. J. Natl. Cancer Cent. 2023, 3, 222–235. [Google Scholar] [CrossRef]
- Lakka, S.S.; Rao, J.S. Antiangiogenic Therapy in Brain Tumors. Expert Rev. Neurother. 2008, 8, 1457–1473. [Google Scholar] [CrossRef] [PubMed]
- Reinders, M.E.J.; Sho, M.; Izawa, A.; Wang, P.; Mukhopadhyay, D.; Koss, K.E.; Geehan, C.S.; Luster, A.D.; Sayegh, M.H.; Briscoe, D.M. Proinflammatory Functions of Vascular Endothelial Growth Factor in Alloimmunity. J. Clin. Investig. 2003, 112, 1655–1665. [Google Scholar] [CrossRef] [PubMed]
- Anfuso, C.D.; Motta, C.; Giurdanella, G.; Arena, V.; Alberghina, M.; Lupo, G. Endothelial PKCα-MAPK/ERK-Phospholipase A2 Pathway Activation as a Response of Glioma in a Triple Culture Model. A New Role for Pericytes? Biochimie 2014, 99, 77–87. [Google Scholar] [CrossRef]
- Aguilar-Cazares, D.; Chavez-Dominguez, R.; Carlos-Reyes, A.; Lopez-Camarillo, C.; Hernadez de la Cruz, O.N.; Lopez-Gonzalez, J.S. Contribution of Angiogenesis to Inflammation and Cancer. Front. Oncol. 2019, 9, 1399. [Google Scholar] [CrossRef] [PubMed]
- Rao, R.; Redha, R.; Macias-Perez, I.; Su, Y.; Hao, C.; Zent, R.; Breyer, M.D.; Pozzi, A. Prostaglandin E2-EP4 Receptor Promotes Endothelial Cell Migration via ERK Activation and Angiogenesis in Vivo. J. Biol. Chem. 2007, 282, 16959–16968. [Google Scholar] [CrossRef]
- Allaj, V.; Guo, C.; Nie, D. Non-Steroid Anti-Inflammatory Drugs, Prostaglandins, and Cancer. Cell Biosci. 2013, 3, 8. [Google Scholar] [CrossRef]
- Giurdanella, G.; Lupo, G.; Gennuso, F.; Conti, F.; Furno, D.L.; Mannino, G.; Anfuso, C.D.; Drago, F.; Salomone, S.; Bucolo, C. Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy. Int. J. Mol. Sci. 2020, 21, 7528. [Google Scholar] [CrossRef] [PubMed]
- Giurdanella, G.; Lazzara, F.; Caporarello, N.; Lupo, G.; Anfuso, C.D.; Eandi, C.M.; Leggio, G.M.; Drago, F.; Bucolo, C.; Salomone, S. Sulodexide Prevents Activation of the PLA2/COX-2/VEGF Inflammatory Pathway in Human Retinal Endothelial Cells by Blocking the Effect of AGE/RAGE. Biochem. Pharmacol. 2017, 142, 145–154. [Google Scholar] [CrossRef]
- Yu, H.; Huang, X.; Ma, Y.; Gao, M.; Wang, O.; Gao, T.; Shen, Y.; Liu, X. Interleukin-8 Regulates Endothelial Permeability by down-Regulation of Tight Junction but Not Dependent on Integrins Induced Focal Adhesions. Int. J. Biol. Sci. 2013, 9, 966–979. [Google Scholar] [CrossRef] [PubMed]
- Ning, Y.; Manegold, P.C.; Hong, Y.K.; Zhang, W.; Pohl, A.; Lurje, G.; Winder, T.; Yang, D.; LaBonte, M.J.; Wilson, P.M.; et al. Interleukin-8 Is Associated with Proliferation, Migration, Angiogenesis and Chemosensitivity in Vitro and in Vivo in Colon Cancer Cell Line Models. Int. J. Cancer 2011, 128, 2038–2049. [Google Scholar] [CrossRef] [PubMed]
- Potta, S.G.; Minemi, S.; Nukala, R.K.; Peinado, C.; Lamprou, D.A.; Urquhart, A.; Douroumis, D. Preparation and Characterization of Ibuprofen Solid Lipid Nanoparticles with Enhanced Solubility. J. Microencapsul. 2011, 28, 74–81. [Google Scholar] [CrossRef] [PubMed]
- Mura, P.; Maestrelli, F.; D’Ambrosio, M.; Luceri, C.; Cirri, M. Evaluation and Comparison of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Vectors to Develop Hydrochlorothiazide Effective and Safe Pediatric Oral Liquid Formulations. Pharmaceutics 2021, 13, 437. [Google Scholar] [CrossRef] [PubMed]
- Biswas, A.K.; Islam, M.R.; Choudhury, Z.S.; Mostafa, A.; Kadir, M.F. Nanotechnology Based Approaches in Cancer Therapeutics. Adv. Nat. Sci. Nanosci. Nanotechnol. 2014, 5, 043001. [Google Scholar] [CrossRef]
- Sharma, A.K.; Sahoo, P.K.; Majumdar, D.K.; Sharma, N.; Sharma, R.K.; Kumar, A. Fabrication and Evaluation of Lipid Nanoparticulates for Ocular Delivery of a COX-2 Inhibitor. Drug Deliv. 2016, 23, 3364–3373. [Google Scholar] [CrossRef]
- Bharti, S.; Roy, R. Quantitative 1H NMR Spectroscopy. TrAC Trends Anal. Chem. 2012, 35, 5–26. [Google Scholar] [CrossRef]
- Torrisi, C.; Cardullo, N.; Russo, S.; La Mantia, A.; Acquaviva, R.; Muccilli, V.; Castelli, F.; Sarpietro, M.G. Benzo[k,l]Xanthene Lignan-Loaded Solid Lipid Nanoparticles for Topical Application: A Preliminary Study. Molecules 2022, 27, 5887. [Google Scholar] [CrossRef]
- Takajo, Y.; Matsuki, H.; Matsubara, H.; Tsuchiya, K.; Aratono, M.; Yamanaka, M. Structural and Morphological Transition of Long-Chain Phospholipid Vesicles Induced by Mixing with Short-Chain Phospholipid. Colloids Surf. B Biointerfaces 2010, 76, 571–576. [Google Scholar] [CrossRef] [PubMed]
- Kendig, E.L.; Le, H.H.; Belcher, S.M. Defining Hormesis: Evaluation of a Complex Concentration Response Phenomenon. Int. J. Toxicol. 2010, 29, 235–246. [Google Scholar] [CrossRef] [PubMed]
- Sahebnasagh, A.; Eghbali, S.; Saghafi, F.; Sureda, A.; Avan, R. Neurohormetic Phytochemicals in the Pathogenesis of Neurodegenerative Diseases. Immun. Ageing 2022, 19, 36. [Google Scholar] [CrossRef]
- Zhang, C.; Li, C.; Chen, S.; Li, Z.; Ma, L.; Jia, X.; Wang, K.; Bao, J.; Liang, Y.; Chen, M.; et al. Hormetic Effect of Panaxatriol Saponins Confers Neuroprotection in PC12 Cells and Zebrafish through PI3K/AKT/mTOR and AMPK/SIRT1/FOXO3 Pathways. Sci. Rep. 2017, 7, 41082. [Google Scholar] [CrossRef]
- Lee, H.-W.; Shin, J.H.; Simons, M. Flow Goes Forward and Cells Step Backward: Endothelial Migration. Exp. Mol. Med. 2022, 54, 711–719. [Google Scholar] [CrossRef]
- Kalluri, R. Basement Membranes: Structure, Assembly and Role in Tumour Angiogenesis. Nat. Rev. Cancer 2003, 3, 422–433. [Google Scholar] [CrossRef]
- Folkman, J.; D’Amore, P.A. Blood Vessel Formation: What Is Its Molecular Basis? Cell 1996, 87, 1153–1155. [Google Scholar] [CrossRef] [PubMed]
- Bao, P.; Kodra, A.; Tomic-Canic, M.; Golinko, M.S.; Ehrlich, H.P.; Brem, H. The Role of Vascular Endothelial Growth Factor in Wound Healing. J. Surg. Res. 2009, 153, 347–358. [Google Scholar] [CrossRef]
- Liakouli, V.; Cipriani, P.; Di Benedetto, P.; Ruscitti, P.; Carubbi, F.; Berardicurti, O.; Panzera, N.; Giacomelli, R. The Role of Extracellular Matrix Components in Angiogenesis and Fibrosis: Possible Implication for Systemic Sclerosis. Mod. Rheumatol. 2018, 28, 922–932. [Google Scholar] [CrossRef]
- Gonzalez-Avila, G.; Sommer, B.; Mendoza-Posada, D.A.; Ramos, C.; Garcia-Hernandez, A.A.; Falfan-Valencia, R. Matrix Metalloproteinases Participation in the Metastatic Process and Their Diagnostic and Therapeutic Applications in Cancer. Crit. Rev. Oncol. Hematol. 2019, 137, 57–83. [Google Scholar] [CrossRef]
- Olgierd, B.; Kamila, Ż.; Anna, B.; Emilia, M. The Pluripotent Activities of Caffeic Acid Phenethyl Ester. Molecules 2021, 26, 1335. [Google Scholar] [CrossRef] [PubMed]
- Carpentier, G.; Berndt, S.; Ferratge, S.; Rasband, W.; Cuendet, M.; Uzan, G.; Albanese, P. Angiogenesis Analyzer for ImageJ—A Comparative Morphometric Analysis of “Endothelial Tube Formation Assay” and “Fibrin Bead Assay”. Sci. Rep. 2020, 10, 11568. [Google Scholar] [CrossRef] [PubMed]
- Gately, S. The Contributions of Cyclooxygenase-2 to Tumor Angiogenesis. Cancer Metastasis Rev. 2000, 19, 19–27. [Google Scholar] [CrossRef] [PubMed]
- Kamiyama, M.; Pozzi, A.; Yang, L.; DeBusk, L.M.; Breyer, R.M.; Lin, P.C. EP2, a Receptor for PGE2, Regulates Tumor Angiogenesis through Direct Effects on Endothelial Cell Motility and Survival. Oncogene 2006, 25, 7019–7028. [Google Scholar] [CrossRef] [PubMed]
- Amano, H.; Hayashi, I.; Endo, H.; Kitasato, H.; Yamashina, S.; Maruyama, T.; Kobayashi, M.; Satoh, K.; Narita, M.; Sugimoto, Y.; et al. Host Prostaglandin E2-EP3 Signaling Regulates Tumor-Associated Angiogenesis and Tumor Growth. J. Exp. Med. 2003, 197, 221–232. [Google Scholar] [CrossRef] [PubMed]
- Lupo, G.; Motta, C.; Salmeri, M.; Spina-Purrello, V.; Alberghina, M.; Anfuso, C.D. An in Vitro Retinoblastoma Human Triple Culture Model of Angiogenesis: A Modulatory Effect of TGF-β. Cancer Lett. 2014, 354, 181–188. [Google Scholar] [CrossRef] [PubMed]
- Tamura, K.; Sakurai, T.; Kogo, H. Relationship between Prostaglandin E2 and Vascular Endothelial Growth Factor (VEGF) in Angiogenesis in Human Vascular Endothelial Cells. Vasc. Pharmacol. 2006, 44, 411–416. [Google Scholar] [CrossRef] [PubMed]
- Uspenskaya, Y.A.; Morgun, A.V.; Osipova, E.D.; Pozhilenkova, E.A.; Salmina, A.B. Mechanisms of Cerebral Angiogenesis in Health and Brain Pathology. Neurosci. Behav. Phys. 2022, 52, 453–461. [Google Scholar] [CrossRef]
- Dudley, A.C.; Griffioen, A.W. Pathological Angiogenesis: Mechanisms and Therapeutic Strategies. Angiogenesis 2023, 26, 313–347. [Google Scholar] [CrossRef]
- Li, L.; Sun, W.; Wu, T.; Lu, R.; Shi, B. Caffeic Acid Phenethyl Ester Attenuates Lipopolysaccharide-Stimulated Proinflammatory Responses in Human Gingival Fibroblasts via NF-κB and PI3K/Akt Signaling Pathway. Eur. J. Pharmacol. 2017, 794, 61–68. [Google Scholar] [CrossRef]
- Doiron, J.A.; Leblanc, L.M.; Hébert, M.J.G.; Levesque, N.A.; Paré, A.F.; Jean-François, J.; Cormier, M.; Surette, M.E.; Touaibia, M. Structure–Activity Relationship of Caffeic Acid Phenethyl Ester Analogs as New 5-Lipoxygenase Inhibitors. Chem. Biol. Drug Des. 2017, 89, 514–528. [Google Scholar] [CrossRef]
- Dinc, E.; Ayaz, L.; Kurt, A.H. Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells. Curr. Eye Res. 2017, 42, 1659–1666. [Google Scholar] [CrossRef]
- Nasution, R.A.; Islam, A.A.; Hatta, M.; Prihantono; Massi, M.N.; Warsinggih; Kaelan, C.; Bahar, B.; Nasution, K.I.; Wangi, H.; et al. Effectiveness of CAPE in Reducing Vascular Permeability after Brain Injury. Med. Clín. Práct. 2021, 4, 100229. [Google Scholar] [CrossRef]
- Chung, T.-W.; Kim, S.-J.; Choi, H.-J.; Kwak, C.-H.; Song, K.-H.; Suh, S.-J.; Kim, K.-J.; Ha, K.-T.; Park, Y.-G.; Chang, Y.-C.; et al. CAPE Suppresses VEGFR-2 Activation, and Tumor Neovascularization and Growth. J. Mol. Med. 2013, 91, 271–282. [Google Scholar] [CrossRef] [PubMed]
- Abdel-Malak, N.A.; Srikant, C.B.; Kristof, A.S.; Magder, S.A.; Di Battista, J.A.; Hussain, S.N.A. Angiopoietin-1 Promotes Endothelial Cell Proliferation and Migration through AP-1-Dependent Autocrine Production of Interleukin-8. Blood 2008, 111, 4145–4154. [Google Scholar] [CrossRef] [PubMed]
- Lee, T.-H.; Avraham, H.; Lee, S.-H.; Avraham, S. Vascular Endothelial Growth Factor Modulates Neutrophil Transendothelial Migration via Up-Regulation of Interleukin-8 in Human Brain Microvascular Endothelial Cells. J. Biol. Chem. 2002, 277, 10445–10451. [Google Scholar] [CrossRef]
- Giurdanella, G.; Motta, C.; Muriana, S.; Arena, V.; Anfuso, C.D.; Lupo, G.; Alberghina, M. Cytosolic and Calcium-Independent Phospholipase A2 Mediate Glioma-Enhanced Proangiogenic Activity of Brain Endothelial Cells. Microvasc. Res. 2011, 81, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Yoshida, S.; Ono, M.; Shono, T.; Izumi, H.; Ishibashi, T.; Suzuki, H.; Kuwano, M. Involvement of Interleukin-8, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor in Tumor Necrosis Factor Alpha-Dependent Angiogenesis. Mol. Cell Biol. 1997, 17, 4015–4023. [Google Scholar] [CrossRef]
- Muñoz, C.; Pascual-Salcedo, D.; Castellanos, M.C.; Alfranca, A.; Aragonés, J.; Vara, A.; Redondo, J.M.; de Landázuri, M.O. Pyrrolidine Dithiocarbamate Inhibits the Production of Interleukin-6, Interleukin-8, and Granulocyte-Macrophage Colony-Stimulating Factor by Human Endothelial Cells in Response to Inflammatory Mediators: Modulation of NF-Kappa B and AP-1 Transcription Factors Activity. Blood 1996, 88, 3482–3490. [Google Scholar]
- Zhang, X.-M.; Patel, A.B.; de Graaf, R.A.; Behar, K.L. Determination of Liposomal Encapsulation Efficiency Using Proton NMR Spectroscopy. Chem. Phys. Lipids 2004, 127, 113–120. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Greco, G.; Agafonova, A.; Cosentino, A.; Cardullo, N.; Muccilli, V.; Puglia, C.; Anfuso, C.D.; Sarpietro, M.G.; Lupo, G. Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood–Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis. Molecules 2024, 29, 3103. https://doi.org/10.3390/molecules29133103
Greco G, Agafonova A, Cosentino A, Cardullo N, Muccilli V, Puglia C, Anfuso CD, Sarpietro MG, Lupo G. Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood–Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis. Molecules. 2024; 29(13):3103. https://doi.org/10.3390/molecules29133103
Chicago/Turabian StyleGreco, Giuliana, Aleksandra Agafonova, Alessia Cosentino, Nunzio Cardullo, Vera Muccilli, Carmelo Puglia, Carmelina Daniela Anfuso, Maria Grazia Sarpietro, and Gabriella Lupo. 2024. "Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood–Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis" Molecules 29, no. 13: 3103. https://doi.org/10.3390/molecules29133103
APA StyleGreco, G., Agafonova, A., Cosentino, A., Cardullo, N., Muccilli, V., Puglia, C., Anfuso, C. D., Sarpietro, M. G., & Lupo, G. (2024). Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood–Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis. Molecules, 29(13), 3103. https://doi.org/10.3390/molecules29133103