Toxicity and Clearance of a Combination of Liposome-Encapsulated Ganciclovir and Trifluridine

Peyman, Gholam A.; Schulman, Joel A.; Khoobehi, Bahram; Alkan, H.; Tawakol, Magdy E.; Mani, Hamid

doi:10.1097/00006982-198909030-00012

Cited by 24 publications

(4 citation statements)

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“…Synthesis steps of CAB and ACB. Reagents and conditions: (i) HCl, NaNO 2 , 0 °C, 1.0 h then NaOH, phenol, 0 °C, 4.0 h; (ii) 1,4dibromobutane, K 2 CO 3 , KI, reflux, 48 h; (iii) DCC, DMAP, 25 °C, 24 h. delivery since they can decrease rapid clearance from vitreous cavity to enhance the intravitreal half-life of drugs, and reduce toxicity associated with higher dosage [17,18]. In our previous work, the positively charged cholesterol derivative combined liposome showed higher drug delivery efficiency and longer drug retention time in the rat retina than the neutral ones [19].…”

Section: Introductionmentioning

confidence: 99%

Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

et al. 2014

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In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4'-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4'-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes' stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats' retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.

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Section: Introductionmentioning

confidence: 99%

Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

et al. 2014

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“…Intravitreal doses of 400 μ g produced no discernible ophthalmoscopic or histologic changes and no changes in electroretinography B-waves [24]. Peyman also demonstrated no evidence of retinal toxicity by clinical or light microscopic examination at different time intervals up to 14 days after intravitreal injections of liposome-encapsulated GCV (94 µ g/0.1 mL) and trifluridine (102 µ g/0.1 mL) [25]. As their dosage was much lower than ours, no abnormal changes after intravitreal injection were reasonable.…”

Section: Discussionmentioning

confidence: 99%

Retinal and Corneal Toxicity and Pharmacokinetic Analysis of Intraocular Injection of Ganciclovir in Rabbit Eyes

Sun

Peng

Lü

et al. 2019

Journal of Ophthalmology

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Purpose. To evaluate the safety and pharmacokinetic changes of ganciclovir (GCV) intraocular injection. Methods. GCV (2 mg/0.1 mL) was injected into rabbit eyes. Aqueous GCV concentration was detected by high-performance liquid chromatography. Potential toxicity was assessed by slit-lamp examination, optical coherence tomography, fundus examination, confocal microscopy, and histology. Results. Aqueous GCV concentrations were 24.83 ± 6.41 μg/mL, 0.65 ± 0.52 μg/mL, and undetected on the 1st, 3rd, and 7th day after intravitreal injection. GCV could not be detected on the first day after intracameral injection. No corneal abnormality was found after intravitreal injection, but retinal edema was observed on the first day which receded later. Corneal edema was obvious with endothelial cytoarchitecture damaged after intracameral injection; fluid retention also existed in retina. Conclusions. GCV intravitreal injection offers effective, sustained drug concentration in the anterior chamber, and its damage to retina receded over time. Intracameral injection results in rapid drug elimination and severe damage to endothelium and thus is not recommended.

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“…In order to develop new drug delivery systems to increase drug vitreous half-life, different formulations and approaches have been tried [2][3][4][5][6][7]. Liposomes have been used to extend the drug half-life of some intravitreally delivered compounds [2,[4][5][6]8].…”

Section: Introductionmentioning

confidence: 99%

“…Liposomes have been used to extend the drug half-life of some intravitreally delivered compounds [2,[4][5][6]8]. First generation liposomal drug delivery systems trap the drug in the aqueous center of liposomes to establish a slow drug release mechanism.…”

Section: Introductionmentioning

confidence: 99%

Ganciclovir Release Rates in Vitreous from Different Formulations of 1-O-Hexadecylpropanediol-3-Phospho-Ganciclovir

Cheng

Hostetler²,

Toyoguchi³

et al. 2003

Journal of Ocular Pharmacology and Therapeutics

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Toxicity and Clearance of a Combination of Liposome-Encapsulated Ganciclovir and Trifluridine

Cited by 24 publications

References 0 publications

Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina

Retinal and Corneal Toxicity and Pharmacokinetic Analysis of Intraocular Injection of Ganciclovir in Rabbit Eyes

Ganciclovir Release Rates in Vitreous from Different Formulations of 1-O-Hexadecylpropanediol-3-Phospho-Ganciclovir

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