Poly(lactic-co-glycolic) Acid as a Slow-Release Drug-Carrying Matrix for Methotrexate Coated onto Intraocular Lenses to Conquer Posterior Capsule Opacification

Kassumeh, Stefan; Wertheimer, Christian; Studnitz, Annabel von; Hillenmayer, Anna; Priglinger, Claudia; Wolf, Armin; Mayer, Wolfgang J.; Teupser, Daniel; Holdt, Lesca M.; Priglinger, Siegfried; Eibl-Lindner, Kirsten

doi:10.1080/02713683.2018.1437455

Cited by 25 publications

(30 citation statements)

References 31 publications

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“…The advantage of nanoparticles over microspheres is that they can avoid the risk of migrating into the anterior chamber, and mitigate the risk of corneal or initial intraocular pressure (IOP) issues. Poly (lactic-co-glycolic acid) (PLGA) is composed of lactic acid and glycolic acid,19 and it is used in drug delivery systems due to its biodegradability and biocompatibility. Polyethylenimine (PEI) has been widely used in drug delivery systems due to it proton sponge effect 20,21.…”

Section: Introductionmentioning

confidence: 99%

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

Liu

Zhang

et al. 2019

IJN

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PurposeAge-related macular degeneration is a multifactorial disease involving inflammation and choroidal neovascularization. Vascular endothelial growth factor (VEGF) has been regarded as a potential therapeutic target to treat choroidal neovascularization. Dexamethasone can interfere with the expression or action of VEGF while bevacizumab targets and combines with VEGF. We propose electrostatically-conjugated bevacizumab-bearing dexamethasone-loaded poly (D,L-lactide-co-glycolide)/polyethylenimine nanoparticles (eBev-DPPNs) for angiogenic combination treatment of ocular diseases.MethodsWe prepared a novel nanoparticle composed of poly (D, L-lactide-co-glycolide) and polyethylenimine and loaded the nanoparticles with dexamethasone. Bevacizumab was adsorbed onto the surfaces of the nanoparticles by electrostatic interactions. The eBev-DPPNs were evaluated according to their size, polydispersity index, zeta potential, morphology, drug loading, release behavior, and stability. The structural stability of bevacizumab on the surface of the nanoparticles was also analyzed. Subsequently, angiogenesis was investigated in the presence of the eBev-DPPNs using cell apoptosis, wound healing, Transwell invasion, and tube formation assays on the human umbilical vein endothelial cells (HUVECs) in vitro and chick embryo chorioallantoic membrane assay in vivo. The eBev-DPPNs intravitreal injection was applied in the laser-induced rabbit choroidal neovascularization (CNV) model to confirm the role for potential intravitreal applications.ResultsThe eBev-DPPNs was about 200 nm in diameter, with a narrow diameter distribution, and the surface charge was neutral (0.85 ± 0.37mV), which made the eBev-DPPNs stable under physiological conditions. The apoptosis, migration, invasion, and tube formation assays showed that the eBev-DPPNs had a good anti-angiogenic effect on HUVECs. The eBev-DPPNs also provided a strong inhibitory effect on VEGF secretion from HUVECs. Moreover, in vivo chick embryo chorioallantoic membrane assay showed eBev-DPPNs greatly reduced the amount of blood vessels. The leakage area of CNV decreased in the eBev-DPPNs group on rabbit CNV model.ConclusionThe eBev-DPPNs are a promising novel anti-angiogenesis therapeutic for potential intravitreal applications such as age-related macular degeneration.

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Section: Introductionmentioning

confidence: 99%

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

Liu

Zhang

et al. 2019

IJN

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“…Current research aims at developing biodegradable implants that may deliver the necessary antibiotic and anti-inflammatory medication, and significant progress has already been demonstrated [30][31][32][33]. The modification of IOLs has been proven [21][22][23][24] to be a promising technique and this study provides a significant contribution to the literature.…”

Section: Discussionmentioning

confidence: 98%

Design and fabrication of drug‐eluting polymeric thin films for applications in ophthalmology

Lamprogiannis

Karamitsos

Karagkiozaki

et al. 2018

IET nanobiotechnol.

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To study the development, characterisation, and drug release of one-and two-layered thin films based on organic polymers [poly(D,L-lactide-co-glycolide) lactide:glycolide (65:35), poly(D,L-lactide-co-glycolide) lactide:glycolide (75:25), and polycaprolactone] and dexamethasone. To examine their applicability for intraocular lenses (IOLs) and function in intraocular drug delivery systems. Four series of thin films, single and double-layer, were prepared by the spin-coating method on a silicon substrate. The films were studied using atomic force microscopy and spectroscopic ellipsometry. The release rate of dexamethasone was studied for a period of ten weeks. Series A and C demonstrated the formation of large dexamethasone aggregates. The monolayer films of series C and D formed pores, in agreement with previous findings. The spectroscopic ellipsometry study demonstrated that the samples were transparent. The drug release study demonstrated that dexamethasone was released during the first 6 weeks at a desirable rate. The films exhibited properties suitable for use in intraocular drug delivery systems. The single-layer thin films demonstrated a sufficient encapsulation of dexamethasone and appropriate release of the therapeutic substance. Further studies are necessary to investigate the possibility of developing the films directly on the surface of the IOL.

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“…The implantation of an IOL is an essential stage of cataract surgery, not only because it restores the visual acuity, but also because it corrects pre-existing refractive errors with the favourable visual outcome [23]. 'Dropless' cataract surgery [24] and the modification of IOLs [15][16][17][18] are nowadays on the epicentre of research in ophthalmology. Previous biomedical applications of PLGA-PCL films proven their biocompatibility and their good degradation rate [25].…”

Section: Discussionmentioning

confidence: 99%

Design, characterisation and drug release study of polymeric, drug‐eluting single layer thin films on the surface of intraocular lenses

Karamitsos

Lamprogiannis

Karagkiozaki

et al. 2020

IET nanobiotechnol.

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To design, develop and study a novel drug delivery system for intraocular applications. The spin coating technique was applied to develop a polymeric, drug-eluting thin film consisting of a blend of organic polymers [poly (D, L lactide coglycolide) lactide: glycolide 75: 25, PLGA and polycaprolactone, PCL] and dexamethasone on the surface of intraocular lenses (IOLs). The initial durability of the IOLs during spinning was assessed. Information about the structural and optical properties of the modified IOLs was extracted using atomic force microscopy, scanning electron microscopy and spectroscopic ellipsometry. A drug release study was conducted for 8 weeks. The IOLs were durable in spinning speeds higher than the ones used to develop thin films. Single-layer thin films were successfully developed on the optics and the haptics of the lenses. The films formed nanopores with encapsulated aggregates of dexamethasone. The spectroscopic ellipsometry showed an acceptable optical transparency of the lenses regardless of the deposition of the drug-eluting films on their surface. The drug release study demonstrated gradual dexamethasone release over the selected period. In conclusion, the novel drug-eluting IOL system exhibited desired properties regarding its transparency and drug release rate. Further research is necessary to assess their suitability as an intraocular drug delivery system.

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Poly(lactic-co-glycolic) Acid as a Slow-Release Drug-Carrying Matrix for Methotrexate Coated onto Intraocular Lenses to Conquer Posterior Capsule Opacification

Abstract: In view of the strong inhibition of PCO in vitro with the lack of toxic effects on a corneal cell line, MTX encapsulating microspheres seem to be a promising method for modifying IOL.

Cited by 25 publications

References 31 publications

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

<p>Anti-Angiogenic Activity Of Bevacizumab-Bearing Dexamethasone-Loaded PLGA Nanoparticles For Potential Intravitreal Applications</p>

Design and fabrication of drug‐eluting polymeric thin films for applications in ophthalmology

Design, characterisation and drug release study of polymeric, drug‐eluting single layer thin films on the surface of intraocular lenses

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