Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Nanoparticle Synthesis
2.3. Physicochemical Characterization
2.3.1. Dynamic Laser Scattering
2.3.2. Zeta Potential
2.3.3. Morphological Analysis
2.3.4. Encapsulation Efficiency
2.3.5. Stability Study
2.4. Cell Culture
2.5. Fluorescence Microscopic Analysis and Immunofluorescence
2.6. Cell Viability Assay
2.7. Flow Cytometry Analysis
2.8. Statistical Analysis
3. Results
3.1. Generation and Characterization of Solid Lipid Nanoparticles Containing a Gel Core
3.2. Evaluation of SLN.05 and SLN.06 Toxicity to ARPE-19 and 661W Retinal Cell Lines
3.3. SLN.05 and SLN.06 Internalization by Retinal Cell Lines
3.4. Encapsulated Cargo Release Inside the Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Lechner, J.; O’Leary, O.E.; Stitt, A.W. The pathology associated with diabetic retinopathy. Vision Res. 2017, 139, 7–14. [Google Scholar] [CrossRef]
- Mitchell, P.; Liew, G.; Gopinath, B.; Wong, T.Y. Age-related macular degeneration. Lancet 2018, 392, 1147–1159. [Google Scholar] [CrossRef]
- Swaroop, A.; Sieving, P.A. The golden era of ocular disease gene discovery: Race to the finish. Clin. Genet. 2013, 84, 99–101. [Google Scholar] [CrossRef] [Green Version]
- Chakravarthy, U.; Biundo, E.; Saka, R.O.; Fasser, C.; Bourne, R.; Little, J.A. The Economic Impact of Blindness in Europe. Ophthalmic Epidemiol. 2017, 24, 239–247. [Google Scholar] [CrossRef] [Green Version]
- Gallego, I.; Villate-Beitia, I.; Martínez-Navarrete, G.; Menéndez, M.; López-Méndez, T.; Soto-Sánchez, C.; Zárate, J.; Puras, G.; Fernández, E.; Pedraz, J.L. Non-viral vectors based on cationic niosomes and minicircle DNA technology enhance gene delivery efficiency for biomedical applications in retinal disorders. Nanomed. Nanotechnol. Biol. Med. 2019, 17, 308–318. [Google Scholar] [CrossRef]
- Tolone, A.; Belhadj, S.; Rentsch, A.; Schwede, F.; Paquet-Durand, F. The cGMP pathway and inherited photoreceptor degeneration: Targets, compounds, and biomarkers. Genes 2019, 10, 453. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Q.; Li, X.; Zhao, C. Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules. Front. Bioeng. Biotechnol. 2020, 8, 437. [Google Scholar] [CrossRef] [PubMed]
- Himawan, E.; Ekström, P.; Buzgo, M.; Gaillard, P.; Stefánsson, E.; Marigo, V.; Loftsson, T.; Paquet-Durand, F. Drug delivery to retinal photoreceptors. Drug Discov. Today 2019, 24, 1637–1643. [Google Scholar] [CrossRef]
- Gorantla, S.; Rapalli, V.K.; Waghule, T.; Singh, P.P.; Dubey, S.K.; Saha, R.N.; Singhvi, G. Nanocarriers for ocular drug delivery: Current status and translational opportunity. RSC Adv. 2020, 10, 27835–27855. [Google Scholar] [CrossRef]
- Peeters, L.; Sanders, N.N.; Braeckmans, K.; Boussery, K.; Van de Voorde, J.; De Smedt, S.C.; Demeester, J. Vitreous: A Barrier to Nonviral Ocular Gene Therapy. Investig. Opthalmol. Vis. Sci. 2005, 46, 3553. [Google Scholar] [CrossRef] [PubMed]
- Xu, Q.; Boylan, N.J.; Suk, J.S.; Wang, Y.Y.; Nance, E.A.; Yang, J.C.; McDonnell, P.J.; Cone, R.A.; Duh, E.J.; Hanes, J. Nanoparticle diffusion in, and microrheology of, the bovine vitreous ex vivo. J. Control. Release 2013, 167, 76–84. [Google Scholar] [CrossRef] [Green Version]
- Tavakoli, S.; Kari, O.K.; Turunen, T.; Lajunen, T.; Schmitt, M.; Lehtinen, J.; Tasaka, F.; Parkkila, P.; Ndika, J.; Viitala, T.; et al. Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations. Mol. Pharm. 2021, 18, 699–713. [Google Scholar] [CrossRef]
- del Amo, E.M.; Rimpelä, A.K.; Heikkinen, E.; Kari, O.K.; Ramsay, E.; Lajunen, T.; Schmitt, M.; Pelkonen, L.; Bhattacharya, M.; Richardson, D.; et al. Pharmacokinetic aspects of retinal drug delivery. Prog. Retin. Eye Res. 2017, 57, 134–185. [Google Scholar] [CrossRef] [PubMed]
- Apaolaza, P.S.; del Pozo-Rodríguez, A.; Solinís, M.A.; Rodríguez, J.M.; Friedrich, U.; Torrecilla, J.; Weber, B.H.F.; Rodríguez-Gascón, A. Structural recovery of the retina in a retinoschisin-deficient mouse after gene replacement therapy by solid lipid nanoparticles. Biomaterials 2016, 90, 40–49. [Google Scholar] [CrossRef] [PubMed]
- Bisht, R.; Mandal, A.; Jaiswal, J.K.; Rupenthal, I.D. Nanocarrier mediated retinal drug delivery: Overcoming ocular barriers to treat posterior eye diseases. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2018, 10, e1473. [Google Scholar] [CrossRef]
- Zariwala, M.G.; Bendre, H.; Markiv, A.; Farnaud, S.; Renshaw, D.; Taylor, K.M.G.; Somavarapu, S. Hydrophobically modified chitosan nanoliposomes for intestinal drug delivery. Int. J. Nanomed. 2018, 13, 5837–5848. [Google Scholar] [CrossRef] [Green Version]
- Khalkhali, M.; Mohammadinejad, S.; Khoeini, F.; Rostamizadeh, K. Vesicle-like structure of lipid-based nanoparticles as drug delivery system revealed by molecular dynamics simulations. Int. J. Pharm. 2019, 559, 173–181. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Severino, P.; Pinho, S.C.; Souto, E.B.; Santana, M.H.A. Polymorphism, Crystallinity and hydrophilic–lipophilic balance of stearic acid and stearic acid–capric/caprylic triglyceride matrices for production of stable nanoparticles. Colloids Surf B Biointerfaces 2011, 86, 125–130. [Google Scholar] [CrossRef]
- Yang, R.; Gao, R.C.; Cai, C.F.; Xu, H.; Li, F.; He, H.B.; Tang, X. Preparation of gel-core-solid lipid nanoparticle: A novel way to improve the encapsulation of protein and peptide. Chem. Pharm. Bull. 2010, 58, 1195–1202. [Google Scholar] [CrossRef] [Green Version]
- Chen, C.; Zhu, X.; Dou, Y.; Xu, J.; Zhang, J.; Fan, T.; Du, J.; Liu, K.; Deng, Y.; Zhao, L.; et al. Exendin-4 loaded nanoparticles with a lipid shell and aqueous core containing micelles for enhanced intestinal absorption. J. Biomed. Nanotechnol. 2015, 11, 865–876. [Google Scholar] [CrossRef]
- Xu, Y.; Zheng, Y.; Wu, L.; Zhu, X.; Zhang, Z.; Huang, Y. Novel Solid Lipid Nanoparticle with Endosomal Escape Function for Oral Delivery of Insulin. ACS Appl. Mater. Interfaces 2018, 10, 9315–9324. [Google Scholar] [CrossRef] [PubMed]
- Martens, T.F.; Remaut, K.; Demeester, J.; De Smedt, S.C.; Braeckmans, K. Intracellular delivery of nanomaterials: How to catch endosomal escape in the act. Nano Today 2014, 9, 344–364. [Google Scholar] [CrossRef] [Green Version]
- Dunn, K.C.; Aotaki-Keen, A.E.; Putkey, F.R.; Hjelmeland, L.M. ARPE-19, A Human Retinal Pigment Epithelial Cell Line with Differentiated Properties. Exp. Eye Res. 1996, 62, 155–170. [Google Scholar] [CrossRef] [PubMed]
- Tan, E.; Ding, X.-Q.; Saadi, A.; Agarwal, N.; Naash, M.I.; Al-Ubaidi, M.R. Expression of Cone-Photoreceptor–Specific Antigens in a Cell Line Derived from Retinal Tumors in Transgenic Mice. Investig. Opthalmol. Vis. Sci. 2004, 45, 764. [Google Scholar] [CrossRef] [Green Version]
- Huang, L.; Kutluer, M.; Adani, E.; Comitato, A.; Marigo, V. New In Vitro Cellular Model for Molecular Studies of Retinitis Pigmentosa. Int. J. Mol. Sci. 2021, 22, 6440. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.; Fan, T.; Jin, Y.; Zhou, Z.; Yang, Y.; Zhu, X.; Zhang, Z.R.; Zhang, Q.; Huang, Y. Orally delivered salmon calcitonin-loaded solid lipid nanoparticles prepared by micelle-double emulsion method via the combined use of different solid lipids. Nanomedicine 2013, 8, 1085–1100. [Google Scholar] [CrossRef]
- Vighi, E.; Trifunovic, D.; Veiga-Crespo, P.; Rentsch, A.; Hoffmann, D.; Sahaboglu, A.; Strasser, T.; Kulkarni, M.; Bertolotti, E.; Van Den Heuvel, A.; et al. Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration. Proc. Natl. Acad. Sci. USA 2018, 115, E2997–E3006. [Google Scholar] [CrossRef] [Green Version]
- Firdessa, R.; Oelschlaeger, T.A.; Moll, H. Identification of multiple cellular uptake pathways of polystyrene nanoparticles and factors affecting the uptake: Relevance for drug delivery systems. Eur. J. Cell Biol. 2014, 93, 323–337. [Google Scholar] [CrossRef]
- Yang, S.T.; Zaitseva, E.; Chernomordik, L.V.; Melikov, K. Cell-penetrating peptide induces leaky fusion of liposomes containing late endosome-specific anionic lipid. Biophys. J. 2010, 99, 2525–2533. [Google Scholar] [CrossRef] [Green Version]
- Foroozandeh, P.; Aziz, A.A. Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Res. Lett. 2018, 13, 339. [Google Scholar] [CrossRef]
- Kong, B.; Seog, J.H.; Graham, L.M.; Lee, S.B. Experimental considerations on the cytotoxicity of nanoparticles. Nanomedicine 2011, 6, 929–941. [Google Scholar] [CrossRef] [Green Version]
- He, C.; Hu, Y.; Yin, L.; Tang, C.; Yin, C. Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 2010, 31, 3657–3666. [Google Scholar] [CrossRef]
- Kumari, S.; MG, S.; Mayor, S. Endocytosis unplugged: Multiple ways to enter the cell. Cell Res. 2010, 20, 256–275. [Google Scholar] [CrossRef] [Green Version]
- Bertolotti, E.; Neri, A.; Camparini, M.; Macaluso, C.; Marigo, V. Stem cells as source for retinal pigment epithelium transplantation. Prog. Retin. Eye Res. 2014, 42, 130–144. [Google Scholar] [CrossRef] [PubMed]
- Behzadi, S.; Serpooshan, V.; Tao, W.; Hamaly, M.A.; Alkawareek, M.Y.; Dreaden, E.C.; Brown, D.; Alkilany, A.M.; Farokhzad, O.C.; Mahmoudi, M. Cellular uptake of nanoparticles: Journey inside the cell. Chem. Soc. Rev. 2017, 46, 4218–4244. [Google Scholar] [CrossRef] [PubMed]
- Palocci, C.; Valletta, A.; Chronopoulou, L.; Donati, L.; Bramosanti, M.; Brasili, E.; Baldan, B.; Pasqua, G. Endocytic pathways involved in PLGA nanoparticle uptake by grapevine cells and role of cell wall and membrane in size selection. Plant Cell Rep. 2017, 36, 1917–1928. [Google Scholar] [CrossRef] [PubMed]
- Arana, L.; Bayón-Cordero, L.; Sarasola, L.; Berasategi, M.; Ruiz, S.; Alkorta, I. Solid Lipid Nanoparticles Surface Modification Modulates Cell Internalization and Improves Chemotoxic Treatment in an Oral Carcinoma Cell Line. Nanomaterials 2019, 9, 464. [Google Scholar] [CrossRef] [Green Version]
- Belhadj, S.; Tolone, A.; Christensen, G.; Das, S.; Chen, Y.; Paquet-Durand, F. Long-Term, Serum-Free Cultivation of Organotypic Mouse Retina Explants with Intact Retinal Pigment Epithelium. J. Vis. Exp. 2020, 165, e61868. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 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
Huang, L.; Himawan, E.; Belhadj, S.; Pérez García, R.O.; Paquet Durand, F.; Schipper, N.; Buzgo, M.; Simaite, A.; Marigo, V. Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles. Pharmaceutics 2022, 14, 74. https://doi.org/10.3390/pharmaceutics14010074
Huang L, Himawan E, Belhadj S, Pérez García RO, Paquet Durand F, Schipper N, Buzgo M, Simaite A, Marigo V. Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles. Pharmaceutics. 2022; 14(1):74. https://doi.org/10.3390/pharmaceutics14010074
Chicago/Turabian StyleHuang, Li, Erico Himawan, Soumaya Belhadj, Raúl Oswaldo Pérez García, François Paquet Durand, Nicolaas Schipper, Matej Buzgo, Aiva Simaite, and Valeria Marigo. 2022. "Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles" Pharmaceutics 14, no. 1: 74. https://doi.org/10.3390/pharmaceutics14010074
APA StyleHuang, L., Himawan, E., Belhadj, S., Pérez García, R. O., Paquet Durand, F., Schipper, N., Buzgo, M., Simaite, A., & Marigo, V. (2022). Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles. Pharmaceutics, 14(1), 74. https://doi.org/10.3390/pharmaceutics14010074