Dasatinib loaded nanostructured lipid carriers for effective treatment of corneal neovascularization

Li, Qingqing; Zhang, Peipei; Mo, Fei; Si, Peiru; Kang, Xin; Wang, Menghan; Zhang, Jiye

doi:10.1039/d0bm01599g

Cited by 17 publications

(7 citation statements)

References 37 publications

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“…When developing ophthalmic drug delivery systems, eye safety has always been a major issue. Studies have shown that rabbits are more sensitive to eye irritants than humans; thus, the safety to human eyes can be estimated based on the results of animal experiments ((a) Li et al., 2021 ). Next, the Draize irritation test scoring standard was used to evaluate the irritation caused by SRB-NLC eye drops in rabbit eyes.…”

Section: Discussionmentioning

confidence: 99%

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Sorafenib-loaded nanostructured lipid carriers for topical ocular therapy of corneal neovascularization: development, in-vitro and in vivo study

Luo

Yang

et al. 2022

Drug Delivery

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Sorafenib (SRB), a multikinase inhibitor, is effective in reducing experimental corneal neovascularization (CNV) after oral administration; however, its therapeutic use in ocular surface disorders is restricted due to poor solubility and limited bioavailability. This study aimed to develop and optimize SRB-loaded nanostructured lipid carriers (SRB-NLCs) for topical ocular delivery by a central composite design response surface methodology (CCD-RSM). It was spherical and uniform in morphology with an average particle size of 111.87 ± 0.93 nm and a narrow size distribution. The in vitro drug release from the released SRB-NLC formulation was well fitted to Korsmeyer Peppas release kinetics. The cell counting kit-8 (CCK-8) cell viability assay demonstrated that SRB-NLC was not obviously cytotoxic to human corneal epithelial cells (HCECs). An in vivo ocular irritation test showed that SRB-NLC was well tolerated by rabbit eyes. Ocular pharmacokinetics revealed 6.79-fold and 1.24-fold increase in the area under concentration-time curves (AUC 0-12h ) over 12 h in rabbit cornea and conjunctiva, respectively, treated with one dose of SRB-NLC compared with those treated with SRB suspension. Moreover, SRB-NLC (0.05% SRB) and dexamethasone (0.025%) similarly suppressed corneal neovascularization in mice. In conclusion, the optimized SRB-NLC formulation demonstrated excellent physicochemical properties and good tolerance, sustained release, and enhanced ocular bioavailability. It is safe and potentially effective for the treatment of corneal neovascularization.

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Section: Discussionmentioning

confidence: 99%

“…In addition to drug selection, the drug delivery challenges for eye diseases should also be considered ((a) Li et al., 2021 ). Drug molecules that have a good effect in vitro may be ineffective in vivo due to inefficiency and insufficiency after topical administration.…”

Section: Introductionmentioning

confidence: 99%

Sorafenib-loaded nanostructured lipid carriers for topical ocular therapy of corneal neovascularization: development, in-vitro and in vivo study

Luo

Yang

et al. 2022

Drug Delivery

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“…The particle size of the shikonin-loaded MPEG-PCL micelles was in good accordance with that of the drug-loaded MPEG-PCL micelles reported previously. 30 Typically, micelle sizes is proportional to the block length. Drug-loaded nanoparticles with a relatively small size (20–200 nm) can accumulate in pathological regions such as sites of inflammation and tumors via enhanced permeability and retention effect.…”

Section: Discussionmentioning

confidence: 99%

“…The drug loading and encapsulation efficiency were calculated with the following equations: [30][31][32] Drug loading ð%Þ ¼ Amount of drug in micelles Total amount of micelles � 100…”

Section: Drug Loading and Encapsulation Efficiencymentioning

confidence: 99%

Combined Shikonin-Loaded MPEG-PCL Micelles Inhibits Effective Transition of Endothelial-to-Mesenchymal Cells

Li¹,

Shang²,

Li³

et al. 2022

IJN

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Introduction Shikonin is well known for its anti-inflammatory activity in cardiovascular diseases. However, the application of shikonin is limited by its low water solubility and poor bioavailability. Methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) (MPEG-PCL) is considered a promising delivery system for hydrophobic drugs. Therefore, in this study, we prepared shikonin-loaded MPEG-PCL micelles and investigated their effect on endothelial-to-mesenchymal transition (EndMT) induced by inflammatory cytokines. Methods Shikonin was encapsulated in MPEG-PCL micelles using an anti-solvent method and the physiochemical characteristics of the micelles (particle size, zeta potential, morphology, critical micelle concentration (CMC), drug loading and encapsulation efficiency) were investigated. Cellular uptake of micelles in human umbilical vein endothelial cells (HUVECs) was evaluated using fluorescence microscopy. In vitro EndMT inhibition was explored in HUVECs by quantitative real-time PCR analysis. Results The average particle size of shikonin-loaded MPEG-PCL micelles was 54.57±0.13 nm and 60 nm determined by dynamic light scattering and transmission electron microscopy, respectively. The zeta potential was −6.23±0.02 mV. The CMC of the micelles was 6.31×10 −7 mol/L. The drug loading and encapsulation efficiency were 0.88±0.08% and 43.08±3.77%, respectively. The MPEG-PCL micelles significantly improved the cellular uptake of cargo with low water solubility. Real-time PCR analysis showed that co-treatment with TNF-α and IL-1β successfully induced EndMT in HUVECs, whereas this process was significantly inhibited by shikonin and shikonin-loaded MPEG-PCL micelles, with greater inhibition mediated by the shikonin-loaded MPEG-PCL micelles. Conclusion Shikonin-loaded MPEG-PCL micelles significantly improved the EndMT-inhibiting effect of the free shikonin. MPEG-PCL is suitable for use more generally as a lipophilic drug carrier.

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“… [ 305 ] NLC Glyceryl monostearate, lipoplysaccharides Dasatinib Observed sustained release, reduced ocular toxicity, and facilitated penetration into cornea via topical administration with effective inhibition of CNV. [ 306 ] Dendrimer Lecithin Anti-VEGF Plus Oligonucleotide 1 Topical delivery of dendrimers plus ODN-1 to the eyes of rats and inhibited laser-induced CNV for up to 6 months. [ 307 ] Niosomes DOTAP, squalene, Polysorbate 80 pDNA Persistent protein expression after transfection intravitreally for at least 1 month after injection.…”

Section: Formulation Approachesmentioning

confidence: 99%

Ocular Delivery of Therapeutic Proteins: A Review

2023

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Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed.

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Dasatinib loaded nanostructured lipid carriers for effective treatment of corneal neovascularization

Abstract: Corneal neovasularization (CNV) is one of the most important causes of visual impairment worldwide. Dasatinib, a poorly water-soluble tyrosine kinase inhibitor with dual Src family kinase and platelet derived growth...

Cited by 17 publications

References 37 publications

Sorafenib-loaded nanostructured lipid carriers for topical ocular therapy of corneal neovascularization: development, in-vitro and in vivo study

Sorafenib-loaded nanostructured lipid carriers for topical ocular therapy of corneal neovascularization: development, in-vitro and in vivo study

Combined Shikonin-Loaded MPEG-PCL Micelles Inhibits Effective Transition of Endothelial-to-Mesenchymal Cells

Ocular Delivery of Therapeutic Proteins: A Review

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