Preparation and In Vitro/In Vivo Evaluation of Cyclosporin A-Loaded Nanodecorated Ocular Implants for Subconjunctival Application

Pehlivan, Sibel Bozdağ; Yavuz, Burçin; Çalamak, Semih; Ulubayram, Kezban; Kaffashi, Abbas; Vural, İmran; Çakmak, Hasan Basri; Durgun, Meltem Ezgi; Denkbaş, Emir Baki; Ünlü, Nurşen

doi:10.1002/jps.24385

Cited by 42 publications

(23 citation statements)

References 27 publications

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“…Parallel copper electrodes in 1.8 cm distance from each other were used as a collector. In order to obtain PU nanofibers with aligned and smooth morphology, we optimized the electrospinning parameters such as polymer concentration, the distance between needle and collector, applied voltage and flow rate . Electrospinning solution was prepared by dissolving PU in tetrahidrofurano/dimethylformamide (60:40 [v/v]) solvent mixture and making 8% (w/v) concentration of PU.…”

Section: Methodsmentioning

confidence: 99%

“…In order to obtain PU nanofibers with aligned and smooth morphology, we optimized the electrospinning parameters such as polymer concentration, the distance between needle and collector, applied voltage and flow rate. [22][23][24][25][26][27] Electrospinning solution was prepared by dissolving PU in tetrahidrofurano/dimethylformamide (60:40 [v/v]) solvent mixture and making 8% (w/v) concentration of PU. Polymer solutions were placed in a glass syringe (5 mL) bearing metallic capillary (0.41 mm i.d.)…”

Section: Preparation Of Aligned Pu Nanofiber Scaffoldsmentioning

confidence: 99%

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Gold nano‐decorated aligned polyurethane nanofibers for enhancement of neurite outgrowth and elongation

Demir

Shahbazi

Çalamak

et al. 2018

J Biomedical Materials Res

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Neurite outgrowth and elongation of neural cells is the most important subject that is considered in nerve tissue engineering. In this regard, aligned nanofibers have taken much attention in terms of providing guidance for newly outgrown neurites. The main objective of this study was to fabricate aligned polyurethane nanofibers by electrospinning process and decorate them with gold nanoparticles to further investigate the synergistic effects of nanotopography, biological nerve growth factor (NGF) and electrical stimulations on neurite outgrowth and elongation of pheochromocytoma (PC-12) model cells. In this regard, smooth and uniform aligned polyurethane nanofibers with the average diameter of 519 ± 56 nm were fabricated and decorated with the gold nanoparticles with the average diameter of ∼50 nm. PC-12 cells were cultured on the various nanofiber surfaces inside the bio-mimetic bioreactor system and exposed either to NGF alone or combination of NGF and electrical stimulation. It was found that 50 ng/mL NGF concentration is an optimal value for the stimulation of neurite outgrowth. After 4 days of culture under 100 mV, 10 ms electrical stimulation in 1 h/day period it was found that the gold nanoparticle decorated aligned polyurethane nanofibers increased the neurite outgrowth and elongation more with the combinational NGF and electrical stimulation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1604-1613, 2018.

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Section: Methodsmentioning

confidence: 99%

Section: Preparation Of Aligned Pu Nanofiber Scaffoldsmentioning

confidence: 99%

Gold nano‐decorated aligned polyurethane nanofibers for enhancement of neurite outgrowth and elongation

Demir

Shahbazi

Çalamak

et al. 2018

J Biomedical Materials Res

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“…Another cyclosporine A implant study for LX201 employed subconjunctival implantation that would not affect neovascularization following keratoplasty (Bock et al 2014). It was also reported that cyclosporine A-loaded PLGA nanoparticles and poly[e-caprolactone] (PCL) subconjunctival implants were prepared for dry eye syndrome treatment, and they were able to extend the drug release up to 2 months and provided faster healing in dry eye-induced mice (Pehlivan et al 2015). Pfizer Inc. collaborated on a PLGA subconjunctival insert for sustained-release latanoprost for glaucoma treatment; however, the phase I/IIa (NCT01180062) study was terminated due to inadequate supply of inserts.…”

Section: Ocular Inserts and Implants For Anterior Segment Diseasesmentioning

confidence: 99%

“…In a recent study, PAMAM dendrimers with anionic and cationic charges were investigated for retinal dexamethasone delivery via topical and subconjunctival applications. It was reported that these systems were able to improve corneal and scleral permeability and provide higher ocular bioavailability; however, drug loading in these systems was limited (Yavuz et al 2015). PAMAM-triamcinolone acetonide conjugates with 21% drug loading were also prepared, and cell culture studies indicated increased anti-inflammatory activity of triamcinolone acetonide (Kambhampati et al 2015).…”

Section: Colloidal Dosage Forms For Posterior Segment Drug Deliverymentioning

confidence: 99%

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

Narayanan

Kuppermann

2016

Handbook of Experimental Pharmacology

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“…In this study, CsA nanoparticles-loaded extended release biodegradable implant and fiber implant formulations have been developed and two formulations were selected for in vivo applications based on in vitro characterization and in vitro release studies which were reported previously (Pehlivan et al, 2015). Selected formulations were implanted subconjunctivally to DES-induced mice model to evaluate the tissue CsA distribution following implantation and efficacy of the formulations.…”

Section: Introductionmentioning

confidence: 99%

In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano-decorated subconjunctival implants

et al. 2016

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Biodegradable implants are promising drug delivery systems for sustained release ocular drug delivery with the benefits such as minimum systemic side effects, constant drug concentration at the target site and getting cleared without surgical removal. Dry eye syndrome (DES) is a common disease characterized with the changes in ocular epithelia surface and results in inflammatory reaction that might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is frequently employed for the treatment of DES and it needs to be applied several times a day in tear drops form. The aim of this study was to evaluate in vivo behavior and efficacy of the developed nano-decorated subconjunctival implant systems for sustained release CsA delivery. Biodegradable Poly-ɛ-caprolactone (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co-glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve sustained release. Two of the formulations PCL-PLGA-NP-F and PCL-PCL-NP-I were selected for in vivo evaluation based on their in vitro characteristics determined in our previous study. In this study, formulations were implanted to Swiss Albino mice with induced dry eye syndrome to investigate the ocular distribution of CsA following subconjunctival implantation and to evaluate the efficacy. Tissue distribution study indicated that CsA was present in ocular tissues such as cornea, sclera and lens even 90 days after the application and blood CsA levels were found lower than ocular tissues. Efficacy studies also showed that application of CsA-loaded fiber implant formulation resulted in faster recovery based on their staining scores.

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Preparation and In Vitro/In Vivo Evaluation of Cyclosporin A-Loaded Nanodecorated Ocular Implants for Subconjunctival Application

Cited by 42 publications

References 27 publications

Gold nano‐decorated aligned polyurethane nanofibers for enhancement of neurite outgrowth and elongation

Gold nano‐decorated aligned polyurethane nanofibers for enhancement of neurite outgrowth and elongation

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano-decorated subconjunctival implants

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