Outcomes of intravitreal melphalan for vitreous seedings in retinoblastoma resistant to systemic chemotherapy

Khaqan, Hussain Ahmad; Imtiaz, Usman; Buksh, Hasnain Muhammad; Rehman, Hafiz Ateeq Ur; Naz, Raheela

doi:10.1016/j.phoj.2020.10.002

Cited by 2 publications

(2 citation statements)

References 22 publications

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“…Cryotherapy results in a formation of a chorioretinal scar [ 35 ]. Additionally, cryoprobes are commonly used in the safety-enhanced technique of intravitreal injection [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Cryotherapy in Vitreous Concentrations of Topotecan Delivered by Episcleral Hydrogel Implant

et al. 2022

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Transscleral diffusion delivery of chemotherapy is a promising way to reach the vitreal seeds of retinoblastoma, the most common intraocular malignancy in childhood. In this in vivo study, the delivery of topotecan via lens-shaped, bi-layered hydrogel implants was combined with transconjunctival cryotherapy to assess whether cryotherapy leads to higher concentrations of topotecan in the vitreous. The study included 18 New Zealand albino rabbits; nine rabbits received a topotecan-loaded implant episclerally and another nine rabbits received transconjunctival cryotherapy superotemporally 2 weeks before implant administration. Median vitreous total topotecan exposures (area under the curve, AUC) were 455 ng·h/mL for the cryotherapy group and 281 ng·h/mL for the non-cryotherapy group, and were significantly higher in the cryotherapy group, similar to maximum levels. Median plasma AUC were 50 ng·h/mL and 34 ng·h/mL for the cryotherapy and non-cryotherapy groups, respectively, with no statistically significant differences between them. In both groups, AUC values in the vitreous were significantly higher than in plasma, with plasma exposure at only approximately 11–12% of the level of vitreous exposure. The results confirmed the important role of the choroidal vessels in the pharmacokinetics of topotecan during transscleral administration and showed a positive effect of cryotherapy on intravitreal penetration, resulting in a significantly higher total exposure in the vitreous.

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“…Cryotherapy results in a formation of a chorioretinal scar [ 35 ]. Additionally, cryoprobes are commonly used in the safety-enhanced technique of intravitreal injection [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Cryotherapy in Vitreous Concentrations of Topotecan Delivered by Episcleral Hydrogel Implant

et al. 2022

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“…Intravitreal injection of Melphalan, L-Phenylalanine mustard (4-di-(2-chloroethyl) amino phenylalanine, with the high potential of anticancer activity, is preferred for retinoblastoma treatment [8][9][10]. Because some local and systemic side effects of Melphalan have been noted, secondary toxicity concerns and rapid elimination, low bioavailability, and accumulation of chemotherapeutic drugs in the site of tumors are the most prevalent limitations of this anticancer drug [11,12].…”

Section: Introductionmentioning

confidence: 99%

Lauric acid-grafted biopolymeric nanoparticles for efficient Melphalan delivery across the corneal layers for retinoblastoma: ex vivo and in vivo permeation study

Mohseni¹,

Shojaei²,

Naseripour³

et al. 2022

Adv. Nat. Sci: Nanosci. Nanotechnol.

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Intravitreal injection of chemotherapy drugs for intraocular retinoblastoma, for the prevalent pediatric malignancy treatment with the side effects of severe infection. This study tried to synthesize the novel approach to deliver Melphalan to the vitreous cavity through the cornea to increase drug efficacy with non-invasive effects. For this purpose, lauric acid-grafted chitosan-alginate and chitosan-alginate loaded by Melphalan nanoparticles were fabricated. Fourier-transform infrared spectroscopy (FTIR) and x-ray diffraction (XRD) were the basic characterizations of chitosan modification. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) are the other assessments of synthesized nanoparticles. Drug encapsulation and in vitro release were studied using UV-spectroscopy, also ex vivo and in vivo corneal permeation was studied using Franz diffusion cell, fluorescence microscopy, and in vivo animal imaging. FTIR and XRD confirm the successful grafting of lauric acid and spherical shape with the average size of 50 nm and 80 nm observed for modified and chitosan-alginate nanoparticles respectively. In the release study, encapsulation efficiency of 98% with sustained drug release of 80% for 100 h with the Fickian drug diffusion mechanism was reported. Ex vivo corneal permeation exhibited an improved drug penetration rate in the sample of lauric acid-grafted-chitosan-alginate nanoparticles with the results of 5.8 times higher than chitosan-alginate nano-carriers and 15.5-fold compared to drug solution. Also, in vivo study shows that the designed nanoparticles containing Melphalan reached the vitreous cavity with high efficacy. Current investigations illustrate the novel Melphalan delivery with sustained behavior through the cornea with the high potential of corneal layer penetration for retinoblastoma management.

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Outcomes of intravitreal melphalan for vitreous seedings in retinoblastoma resistant to systemic chemotherapy

Cited by 2 publications

References 22 publications

The Role of Cryotherapy in Vitreous Concentrations of Topotecan Delivered by Episcleral Hydrogel Implant

The Role of Cryotherapy in Vitreous Concentrations of Topotecan Delivered by Episcleral Hydrogel Implant

Lauric acid-grafted biopolymeric nanoparticles for efficient Melphalan delivery across the corneal layers for retinoblastoma: ex vivo and in vivo permeation study

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