The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol

Gladys Rosario Ramos Yacasi, María Luisa García López, Marta Espina García, Alexander Parra Coca, Ana Cristina Calpena Campmany Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, University of Barcelona, Barcelona, Spain Abstrac...

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Autores principales: Ramos Yacasi GR, García López ML, Espina García M, Parra Coca A, Calpena Campmany AC
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Publicado: Dove Medical Press 2016
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spelling oai:doaj.org-article:5395200fd217440c80ba2f212747127d2021-12-02T06:26:52ZThe influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol1178-2013https://doaj.org/article/5395200fd217440c80ba2f212747127d2016-08-01T00:00:00Zhttps://www.dovepress.com/the-influence-of-freeze-drying-and-upsih-irradiation-in-pre-clinical-s-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Gladys Rosario Ramos Yacasi, María Luisa García López, Marta Espina García, Alexander Parra Coca, Ana Cristina Calpena Campmany Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, University of Barcelona, Barcelona, Spain Abstract: This study investigated the suspension of poly(ε-caprolactone) nanoparticles as an ocular delivery system for flurbiprofen (FB-PεCL-NPs) in order to overcome the associated problems, such as stability, sterility, tolerance, and efficacy, with two different FB-PεCL-NP formulations. The formulations were stabilized with poloxamer 188 (1.66% and 3.5%) and submitted individually for freeze-drying and γ-irradiation with polyethylene glycol 3350 (PEG3350) and d-(+)-trehalose (TRE). Both formulations satisfied criteria according to all physicochemical parameters required for ocular pharmaceuticals. The FB-PεCL-NP formulations showed non-Newtonian behavior and sustained drug release. Ex vivo permeation analysis using isolated ocular pig tissues suggested that the presence of PEG3350 results in a reduction of FB transcorneal permeation. Moreover, TRE improved the penetration of FB across the cornea, especially after γ-irradiation. In addition, both formulations did not show a significant affinity in increasing FB transscleral permeation. Both formulations were classified as nonirritating, safe products for ophthalmic administration according to hen’s egg test-chorioallantoic membrane and Draize eye test. Furthermore, an in vivo anti-inflammatory efficacy test showed that irradiated FB-PεCL-NPs prepared with PEG3350 (IR-NPsPEG) have longer anti-inflammatory effects than those presented with irradiated FB-PεCL-NPs prepared with TRE (IR-NPsTRE). IR-NPsPEG showed a suitable physical stability after an aqueous reconstitution over .30 days. This study concludes that both formulations meet the Goldman’s criteria and demonstrate how irradiated nanoparticles, with innovative permeation characteristics, could be used as a feasible alternative to a flurbiprofen solution for ocular application in clinical trials. Keywords: nanoparticles, flurbiprofen, polyethylene glycol 3350, d-(+)-trehalose, freeze-drying, γ-irradiationRamos Yacasi GRGarcía López MLEspina García MParra Coca ACalpena Campmany ACDove Medical PressarticleNanoparticlesFlurbiprofenPoly(ethylene glycol) 3350D-(+)-trehaloseFreeze-dryingϒ -irradiationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4093-4106 (2016)
institution DOAJ
collection DOAJ
language EN
topic Nanoparticles
Flurbiprofen
Poly(ethylene glycol) 3350
D-(+)-trehalose
Freeze-drying
ϒ -irradiation
Medicine (General)
R5-920
spellingShingle Nanoparticles
Flurbiprofen
Poly(ethylene glycol) 3350
D-(+)-trehalose
Freeze-drying
ϒ -irradiation
Medicine (General)
R5-920
Ramos Yacasi GR
García López ML
Espina García M
Parra Coca A
Calpena Campmany AC
The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol
description Gladys Rosario Ramos Yacasi, María Luisa García López, Marta Espina García, Alexander Parra Coca, Ana Cristina Calpena Campmany Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, University of Barcelona, Barcelona, Spain Abstract: This study investigated the suspension of poly(ε-caprolactone) nanoparticles as an ocular delivery system for flurbiprofen (FB-PεCL-NPs) in order to overcome the associated problems, such as stability, sterility, tolerance, and efficacy, with two different FB-PεCL-NP formulations. The formulations were stabilized with poloxamer 188 (1.66% and 3.5%) and submitted individually for freeze-drying and γ-irradiation with polyethylene glycol 3350 (PEG3350) and d-(+)-trehalose (TRE). Both formulations satisfied criteria according to all physicochemical parameters required for ocular pharmaceuticals. The FB-PεCL-NP formulations showed non-Newtonian behavior and sustained drug release. Ex vivo permeation analysis using isolated ocular pig tissues suggested that the presence of PEG3350 results in a reduction of FB transcorneal permeation. Moreover, TRE improved the penetration of FB across the cornea, especially after γ-irradiation. In addition, both formulations did not show a significant affinity in increasing FB transscleral permeation. Both formulations were classified as nonirritating, safe products for ophthalmic administration according to hen’s egg test-chorioallantoic membrane and Draize eye test. Furthermore, an in vivo anti-inflammatory efficacy test showed that irradiated FB-PεCL-NPs prepared with PEG3350 (IR-NPsPEG) have longer anti-inflammatory effects than those presented with irradiated FB-PεCL-NPs prepared with TRE (IR-NPsTRE). IR-NPsPEG showed a suitable physical stability after an aqueous reconstitution over .30 days. This study concludes that both formulations meet the Goldman’s criteria and demonstrate how irradiated nanoparticles, with innovative permeation characteristics, could be used as a feasible alternative to a flurbiprofen solution for ocular application in clinical trials. Keywords: nanoparticles, flurbiprofen, polyethylene glycol 3350, d-(+)-trehalose, freeze-drying, γ-irradiation
format article
author Ramos Yacasi GR
García López ML
Espina García M
Parra Coca A
Calpena Campmany AC
author_facet Ramos Yacasi GR
García López ML
Espina García M
Parra Coca A
Calpena Campmany AC
author_sort Ramos Yacasi GR
title The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol
title_short The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol
title_full The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol
title_fullStr The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol
title_full_unstemmed The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol
title_sort influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using d-(+)-trehalose and polyethylene glycol
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/5395200fd217440c80ba2f212747127d
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