Effects of timolol-related ophthalmic solutions on cultured human conjunctival cells

Kawase, Kazuhide; Lin, Wenzhong; Aoyama, Yumiko; Yamamoto, Tetsuya; Shimazawa, Masamitsu; Hara, Hideaki

doi:10.1007/s10384-010-0881-2

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…In addition, it was reported that gelling temperature was affected not only by the pluronic F127 concentration but also by the proportions of combined pluronic F127 and pluronic F68 [ 49 ]. Moreover, temperature-sensitive MC and pH-sensitive Carbopol are also frequently used as agents when combining two ISGs [ 50 , 51 ]. We prepared the Tra-NP-incorporated ISNGs with the combination of pluronic F127 and MC, pluronic 68, Carbopol, and determined the concentration of the ISG base following previous reports for ISG systems [ 32 , 47 , 48 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

“…Corneal damage was observed after the treatment with nTRA-Car/F127-L ( Figure 4 ). It has been reported that pH-sensitive gels are more toxic in comparison to temperature-sensitive gels, and pH-sensitive gels easily damage conjunctival cells [ 51 ]. Therefore, this result suggested that the corneal toxicity of nTRA-Car/F127 was caused by Carbopol and pH-sensitive gels, and caution is necessary with long-term use of nTRA-Car/F127-H.…”

Section: Discussionmentioning

confidence: 99%

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Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles

et al. 2021

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We previously designed ophthalmic formulations (nTRA) containing tranilast nanoparticles (Tra-NPs) with high uptake into ocular tissues. In this study, we used in situ gel (ISG) bases comprising combinations of pluronic F127 (F127) and methylcellulose (MC/F127), pluronic F68 (F68/F127), and Carbopol (Car/F127), and we developed in situ gels incorporating Tra-NPs (Tra-NP-incorporated ISNGs) such as nTRA-F127, nTRA-MC/F127, nTRA-F68/F127, and nTRA-Car/F127. Moreover, we demonstrated the therapeutic effect on conjunctival inflammation using lipopolysaccharide-induced rats. Each Tra-NP-incorporated ISNG was prepared by the bead mill method, the particle size was 40–190 nm, and the tranilast release and diffusion from formulation were nTRA > nTRA-F127 > nTRA-F68/F127 > nTRA-Car/F127 > nTRA-MC/F127. In the Tra-NP-incorporated ISNGs, the tranilast residence time in the lacrimal fluid, cornea, and conjunctiva was prolonged, although the Cmax was attenuated in comparison with nTRA. On the other hand, no significant difference in conjunctival inflammation between non- and nTRA-F127-instilled rats was found; however, the nTRA-F68/F127, nTRA-Car/F127, and nTRA-MC/F127 (combination-ISG) attenuated the vessel leakage, nitric oxide, and tumor necrosis factor-α expression. In particular, nTRA-F68/F127 was significant in preventing the conjunctival inflammation. In conclusion, we found that the combination-ISG base prolonged the residence time of Tra-NPs; however, Tra-NP release from the formulation was attenuated, and the Tmax was delayed longer than that in nTRA. The balance of drug residence and diffusion in lacrimal fluid may be important in providing high ocular bioavailability in formulations containing solid nanoparticles.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles

et al. 2021

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“…An in situ gelling system seems to be a good candidate for prolonging the drug residence time and enhancing absorption into the ocular surface (Wu et al, 2019;Yadav et al, 2019). Three systems, thermosensitive, ion-activated (Rupenthal et al, 2011) and pH-sensitive (Bawa et al, 2009), have been introduced, and the thermosensitive type systems widely used in comparison with other two types, since they involve less ocular stimulation (Kawase et al, 2010). Various polymers, such as methylcellulose (MC), alginic acid, gellan gum, chitosan, xyloglucan and pectin, can potentially be used for in situ gelling systems (Madan et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva

Nagai

Minami

Deguchi

et al. 2020

Front. Bioeng. Biotechnol.

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We previously developed ophthalmic formulations containing tranilast nanopartaicles (ophthalmic TL-NPs formulations), and found them to show high uptake into ocular tissues. In this study, we aimed to design an in situ gel incorporating TL-NPs with 0.5-3% methylcellulose (MC, type SM-4) to ensure long residence time of the drug at the ocular surface. The ophthalmic TL-NPs formulations were prepared by the bead mill method, which yielded a mean particle size of˜93 nm with or without MC (0.5-3%). Although the dispersibility of TL particles in ophthalmic formulations increased with the MC content, the diffusion behavior of TL particles in the dispersion medium decreased with MC content. In an in vivo study using rats, the TL content in the lacrimal fluid was enhanced with MC content in the ophthalmic TL-NPs formulations, and the optimum amount of MC (0.5-1.5%) enhanced the TL content in the cornea and conjunctiva, and an anti-inflammatory effect of TL in rats instilled with ophthalmic TL-NPs formulations was observed. On the other hand, excessive MC (3%) prevented the corneal uptake of TL-NPs after instillation, and the anti-inflammation effect of TL was lower than that of ophthalmic TL-NPs formulations with optimum MC (0.5-1.5%). In conclusion, we found that gel formulations of TL-NPs with 0.5 and 1.5% MC provided a prolonged pre-corneal and pre-conjunctival contact time of TL, and resulted in higher TL contents in the cornea and conjunctiva following instillation in comparison with TL-NPs with or without 3% MC. This is probably due to the balance between the higher residence time and faster diffusion of TL-NPs on the ocular surface. These findings provide significant information that can be used to design further studies aimed at developing ophthalmic nanomedicines.

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“…In-situ forming gels show sol-to-gel transitions in response to one or two or even more combinations of stimuli, including UV irradiation, temperature, and pH changes, solvent exchange (Al-Tahami and Singh, 2007). Based on stimuli, in situ gel can be divided into in situ gel activated ions (Rupenthal et al, 2011), thermosensitive and sensitive to pH from all three in situ the gel in situ thermosensitive gel has a higher safety (Kawase et al, 2010). In situ, this thermosensitive gel will undergo the process of transitioning from sole to gel during heating or cooling; it can occur due to changes in intermolecular (Ruel-Gariépy and Leroux, 2004).…”

Section: Introductionmentioning

confidence: 99%

The Advantages of In situ Gel from Every Different Formulation

Sopyan¹,

Intani²,

S³

et al. 2020

ijrps

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The in situ gel system is one of the polymer-based solutions that show the sol phase transition to gel. In addition to being used to improve bioavailability, this gel is also used to make the drug increase the residence time in the area of use, so that it can provide maximum effectiveness via enhancing of per cent permeation, The use of in situ gel, usually used in ocular administration of drugs, for the treatment of cancer, administration of drugs in the vaginal, rectal, topical, oral, and any route administration. There are many formulations of in situ gel formation that are used for medicinal preparations for many purposes, with different lengths of stay. Searching for articles is done online, browsing the PubMed and Google scholar site with the keyword "Formulation In situ Gel". The fourty articles used, there were 40 in situ gel formulations with gelling agents and also different uses. The purpose of this article review is to look at the superiority of in situ gel formulations and to compare various in situ gel formulations studied from 40 articles used, so that it can be seen which formulation is most often used and has a good effect on drugs preparations.

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Effects of timolol-related ophthalmic solutions on cultured human conjunctival cells

Abstract: Compared with Timoptol and Timoptol XE, Rysmon TG and Timabak showed milder toxicity on human conjunctival cells in vitro.

Cited by 8 publications

References 23 publications

Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles

Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles

An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva

The Advantages of In situ Gel from Every Different Formulation

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