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Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation

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Yadav, Monika and Guzmán Aránguez, Ana Isabel and Pérez de Lara, María Jesús and Singh, Mandeep and Singh, Joga and Kaur, Indu Pal (2019) Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation. Materials Science and Engineering C (103). ISSN 0928-4931

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Official URL: https://doi.org/10.1016/j.msec.2019.05.015




Abstract

Primary treatment for glaucoma relies on chronic instillation (daily) of intraocular pressure (IOP) lowering eye drops. Present study tends to develop and assess a novel sustained release bimatoprost loaded nanovesicular (BMT-NV) - thermosensitive in-situ gelling implant (BMT-NV- GEL-IM), for subconjunctival delivery. BMT-NVs developed using novel composition and method of preparation, (IPA/700/DEL/2014) and industrially viable methodology were characterized and evaluated comprehensively for ocular suitability. Their incorporation into an in-situ gelling formula was safe (in vitro and in vivo) and stable upon sterilization. Autoclavability was an important consideration, as a preservative-free, single-use BMT-NV- GEL-IM will avoid side- effects associated with repetitive application of drops containing preservatives like benzalkonium chloride (BAK). An extended in vitro release of BMT (80.23%) was observed for 10 days while the IOP lowering effect extended over 2 months with single subconjunctival injection of BMT-NV-GEL-IM in rats. No clinical signs of irritation, inflammation, or infection were observed in any injected eye, throughout the study, as also confirmed by histology. Furthermore, single administration of BMT-NV-GEL as topical drop lowered the IOP over 5 days. Presence of significant diffuse fluorescence in confocal microscopy of internal eye tissues post-in vivo application, as subconjunctival implant, even after 2 month and eye drops upto1 week provide direct evidence of successful sustained delivery. We thus provide an improved modality for antiglaucoma medication in patients who are challenged to adhere to a regimen of daily eye drops.


Item Type:Article
Additional Information:

Received 24 October 2018; Received in revised form 7 May 2019; Accepted 7 May 2019; Available online 10 May 2019

Uncontrolled Keywords:Glaucoma; Nanomedicine; Sustained delivery; Fluorescence; Cytotoxicity; Ocular
Subjects:Medical sciences > Medicine > Ophtalmology
Medical sciences > Optics > Eyes anatomy
Medical sciences > Pharmacy > Biochemistry
ID Code:55831
Deposited On:24 Jun 2019 07:41
Last Modified:24 Jun 2019 07:41

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