دورية أكاديمية
In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis
| العنوان: | In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis |
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| المؤلفون: | Aristides D. Tagalakis, Shivam Madaan, Scott D. Larsen, Richard R. Neubig, Peng T. Khaw, Ian Rodrigues, Saurabh Goyal, Kin Sheng Lim, Cynthia Yu-Wai-Man |
| المصدر: | Journal of Nanobiotechnology, Vol 16, Iss 1, Pp 1-11 (2018) |
| بيانات النشر: | BMC, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Biotechnology LCC:Medical technology |
| مصطلحات موضوعية: | Nanocarrier, Sustained release, Inhibitor, Glaucoma, Fibrosis, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5 |
| الوصف: | Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1477-3155 |
| العلاقة: | http://link.springer.com/article/10.1186/s12951-018-0425-3Test; https://doaj.org/toc/1477-3155Test |
| DOI: | 10.1186/s12951-018-0425-3 |
| الوصول الحر: | https://doaj.org/article/01cbae81bc8b41f7bd5ccf2d64ab173fTest |
| رقم الانضمام: | edsdoj.01cbae81bc8b41f7bd5ccf2d64ab173f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14773155 |
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| DOI: | 10.1186/s12951-018-0425-3 |