To develop silk fibroin nanoparticles (SFNs) for prolonged drug delivery to the ocular surface.
Methods:
SFNs were prepared using nanoprecipitation, coated with chitosan (CS; positively charged), and stabilized with polyethylene glycol 400. Their morphology, particle size distribution, and surface charge were analyzed using dynamic light scattering. Fourier transform infrared (FTIR) spectroscopy assessed the intermolecular interactions between CS and silk fibroin. The entrapment efficiencies (EE) for sodium fluorescein (NaF) and Nile Red (NR), which served as hydrophilic and hydrophobic drug surrogates, respectively, were determined. The mucoadhesiveness of SFNs was examined ex vivo with freshly isolated porcine eyes. Cellular uptake and cytotoxicity were evaluated in a human corneal epithelium cell line (HCEC).
Results:
SFNs were spherical, measuring 198.47 ± 35.54 nm in diameter, and had a surface charge of 38.33 ± 0.67 mV. The coating of CS on SFNs resulted in a peak shift in the amide group in the FTIR spectrum. The maximum EEs for NaF and NR in SFNs were approximately 95% and 67%, respectively. SFNs exhibited prolonged mucoadhesion on corneas for over 240 min and were rapidly endocytosed by HCEC in less than 30 min without inducing cytotoxicity.
Conclusion:
The properties of SFNs are suitable for delivering drugs to the ocular surface.
Get full access to this article
View all access options for this article.
References
1.
ChaiyasanW, PraputbutS, KompellaUB, et al.Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea. Colloids Surf B Biointerfaces, 2017; 149:288–296; doi: 10.1016/j.colsurfb.2016.10.032
2.
ChaiyasanW, SrinivasSP, TiyaboonchaiW. Mucoadhesive chitosan-dextran sulfate nanoparticles for sustained drug delivery to the ocular surface. J Ocul Pharmacol Ther, 2013; 29(2):200–207; doi: 10.1089/jop.2012.0193
3.
GaudanaR, AnanthulaHK, ParenkyA, et al.Ocular drug delivery. Aaps J, 2010; 12(3):348–360; doi: 10.1208/s12248-010-9183-3
4.
SilvaMM, CaladoR, MartoJ, et al.Chitosan nanoparticles as a mucoadhesive drug delivery system for ocular administration. Mar Drugs, 2017; 15(12):370; doi: 10.3390/md15120370
5.
JeevanandamJ, BarhoumA, ChanYS, et al.Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations. Beilstein J Nanotechnol, 2018; 9:1050–1074; doi: 10.3762/bjnano.9.98
6.
LynchC, KondiahPPD, ChoonaraYE, et al.Advances in biodegradable nano-sized polymer-based ocular drug delivery. Polymers (Basel), 2019; 11(8):1371; doi: 10.3390/polym11081371
7.
JurczykK, JurczykMU. 7 - Nanostructured surfaces in biomaterials. In: Nanobiomaterials. (NarayanR. ed.) Woodhead Publishing: 2018; pp. 179–195. doi:10.1016/B978-0-08-100716-7.00008-8
8.
UeharaN, YoshidaO. Release of Nile red from thermoresponsive gold nanocomposites by heating a solution and the addition of glutathione. Anal Sci, 2012; 28(12):1125–1132; doi: 10.2116/analsci.28.1125
9.
CorriasF, SchlichM, SinicoC, et al.Nile red nanosuspensions as investigative model to study the follicular targeting of drug nanocrystals. Int J Pharm, 2017; 524(1–2):1–8; doi: 10.1016/j.ijpharm.2017.03.042
10.
BiancoA, CarenaL, PeitsaroN, et al.Rapid detection of nanoplastics and small microplastics by Nile-Red staining and flow cytometry. Environ Chem Lett, 2023; 21(2):647–653; doi: 10.1007/s10311-022-01545-3
11.
ChomchalaoP, NimtrakulP, PhamDT, et al.Development of amphotericin B-loaded fibroin nanoparticles: A novel approach for topical ocular application. J Mater Sci, 2020; 55(12):5268–5279; doi: 10.1007/s10853-020-04350-x
12.
ToropainenE, Fraser-MillerSJ, NovakovicD, et al.Biopharmaceutics of topical ophthalmic suspensions: Importance of viscosity and particle size in ocular absorption of indomethacin. Pharmaceutics, 2021; 13(4):452; doi: 10.3390/pharmaceutics13040452
13.
PhamDT, TiyaboonchaiW. Fibroin nanoparticles: A promising drug delivery system. Drug Deliv, 2020; 27(1):431–448; doi: 10.1080/10717544.2020.1736208
14.
LammelA, HuX, ParkS-H, et al.Controlling silk fibroin particle features for drug delivery. Biomaterials, 2010; 31(16):4583–4591; doi: 10.1016/j.biomaterials.2010.02.024
15.
RahmaniH, FattahiA, SadrjavadiK, et al.Preparation and characterization of silk fibroin nanoparticles as a potential drug delivery system for 5-Fluorouracil. Adv Pharm Bull, 2019; 9(4):601–608; doi: 10.15171/apb.2019.069
16.
MoinA, WaniSUD, OsmaniRA, et al.Formulation, characterization, and cellular toxicity assessment of tamoxifen-loaded silk fibroin nanoparticles in breast cancer. Drug Deliv, 2021; 28(1):1626–1636; doi: 10.1080/10717544.2021.1958106
17.
Sánchez-LópezE, EgeaMA, CanoA, et al.PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen-in vitro, ex vivo and in vivo characterization. Colloids Surf B Biointerfaces, 2016; 145:241–250; doi: 10.1016/j.colsurfb.2016.04.054
18.
ShiL, ZhangJ, ZhaoM, et al.Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery. Nanoscale, 2021; 13(24):10748–10764; doi: 10.1039/D1NR02065J
19.
ChomchalaoP, SaelimN, LamlertthonS, et al.Mucoadhesive hybrid system of silk fibroin nanoparticles and thermosensitive in situ hydrogel for Amphotericin B Delivery: A potential option for fungal keratitis treatment. Polymers (Basel), 2024; 16(1):148; doi: 10.3390/polym16010148
20.
CarissimiG, BaronioCM, MontalbánMG, et al.On the secondary structure of silk fibroin nanoparticles obtained using ionic liquids: An infrared spectroscopy study. Polymers (Basel), 2020; 12(6):1294; doi: 10.3390/polym12061294
21.
WuP, LiuQ, WangQ, et al.Novel silk fibroin nanoparticles incorporated silk fibroin hydrogel for inhibition of cancer stem cells and tumor growth. Int J Nanomedicine, 2018; 13:5405–5418; doi: 10.2147/ijn.S166104
22.
PramonoE, UtomoSB, WulandariV, et al.The effect of polyethylene glycol on shellac stability. IOP Conf Ser: Mater Sci Eng, 2016; 107(1):012066; doi: 10.1088/1757-899X/107/1/012066
23.
ChaiyasanW, SrinivasSP, TiyaboonchaiW. Crosslinked chitosan-dextran sulfate nanoparticle for improved topical ocular drug delivery. Mol Vis, 2015; 21:1224–1234.
24.
AminMK, BoatengJS. Enhancing stability and mucoadhesive properties of chitosan nanoparticles by surface modification with sodium alginate and polyethylene glycol for potential oral mucosa vaccine delivery. Mar Drugs, 2022; 20(3):156; doi: 10.3390/md20030156
25.
Caballero-FloránIH, CortésH, Borbolla-JiménezFV, et al.PEG 400:Trehalose coating enhances curcumin-loaded PLGA nanoparticle internalization in neuronal cells. Pharmaceutics, 2023; 15(6):1594; doi: 10.3390/pharmaceutics15061594
26.
YangP, DongY, HuangD, et al.Silk fibroin nanoparticles for enhanced bio-macromolecule delivery to the retina. Pharm Dev Technol, 2019; 24(5):575–583; doi: 10.1080/10837450.2018.1545236
27.
DongY, DongP, HuangD, et al.Fabrication and characterization of silk fibroin-coated liposomes for ocular drug delivery. Eur J Pharm Biopharm, 2015; 91:82–90; doi: 10.1016/j.ejpb.2015.01.018
28.
DasS, MitraS, KhuranaSMP, et al.Nanomaterials for biomedical applications. Frontiers in Life Science, 2013; 7(3–4):90–98; doi: 10.1080/21553769.2013.869510
29.
MagdalenaJ-S, EwaM. General cytotoxicity and its application in nanomaterial analysis. In: Cytotoxicity. (Tülay AşkinÇ. ed.) IntechOpen: Rijeka; 2017; p. 11; doi: 10.5772/intechopen.72578
