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      A novel ocular delivery of brinzolamide based on gellan gum: in vitro and in vivo evaluation

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          Abstract

          Background

          The aim of the study was to develop a sustained ocular delivery of brinzolamide (BLZ) based on gellan gum.

          Methods

          The formulations were characterized for clarity, gelling capacity, rheological studies, pH, drug content, and in vitro drug-release behavior. In vivo rabbit eye irritation test was conducted to evaluate irritation of the BLZ gel drug-delivery system. The prepared BLZ formulations were then investigated in vivo and compared with commercially available BLZ eyedrops with regard to pharmacodynamics.

          Results

          The results showed that the optimum concentration of gellan gum was 0.25% w/v; the prepared liquid was converted into a flowing gel after the addition of simulated tear fluid. In vitro release profiles showed that the release of BLZ from the in situ gel exhibited sustained characteristics. Draize test results showed that BLZ in situ gels did not stimulate signs of eye tissue activity and were less irritating than BLZ solutions and commercial Azopt.

          Conclusion

          The results of pharmacodynamics implied that the novel preparation of BLZ in situ gel effectively prolonged the intraocular pressure-lowering effect after administration.

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          Most cited references 26

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          Application of gellan gum in pharmacy and medicine.

          Over the past few decades, microbial polysaccharides have been under intense investigation due to their advantageous physicochemical properties. A great structural diversity of these biomolecules has led to multiple applications in food industry, personal care products, pharmacy and medicine. Currently, one of the most widely studied and fully described member of this group is gellan. It is a linear polymer produced by Sphingomonas elodea. A polymer chain of gellan consists of a tetrasaccharide repeating unit of l-rhamnose, d-glucose and d-glucuronate. So far most of the studies have been focused on the application of gellan as a food ingredient. However, due to the unique structure and beneficial properties, gellan is currently described as a potent multifunctional additive for various pharmaceutical products. Specific gelling properties in different media led to the development of controlled release forms based on gellan. Various formulations have been studied including oral, ophthalmic, nasal and other. Recent reports suggest that gellan-based materials can also be used in regenerative medicine, stomatology or gene transfer technology. Copyright © 2014 Elsevier B.V. All rights reserved.
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            Gellan gum-based hydrogels for intervertebral disc tissue-engineering applications.

            Intervertebral disc (IVD) degeneration is a challenging clinical problem that urgently demands viable nucleus pulposus (NP) implant materials. The best suited biomaterial for NP regeneration has yet to be identified, but it is believed that biodegradable hydrogel-based materials are promising candidates. In this work, we have developed ionic- and photo-crosslinked methacrylated gellan gum (GG-MA) hydrogels to be used in acellular and cellular tissue-engineering strategies for the regeneration of IVDs. The physicochemical properties of the developed hydrogels were investigated by Fourier-transform infrared spectroscopy, (1) H nuclear magnetic resonance and differential scanning calorimetry. The swelling ability and degradation rate of hydrogels were also analysed in phosphate-buffered saline solution at physiological pH for a period of 30 days. Additionally, the morphology and mechanical properties of the hydrogels were assessed under a scanning electron microscope and dynamic compression, respectively. An in vitro study was carried out to screen possible cytotoxicity of the gellan gum-based hydrogels by culturing rat lung fibroblasts (L929 cells) with hydrogel leachables up to 7 days. The results demonstrated that gellan gum was successfully methacrylated. We observed that the produced GG-MA hydrogels possess improved mechanical properties and lower water uptake ability and degradation rate as compared to gellan gum. This work also revealed that GG-MA hydrogels are non-cytotoxic in vitro, thus being promising biomaterials to be used in IVD tissue-engineering strategies. Copyright © 2010 John Wiley & Sons, Ltd.
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              In situ gel systems as 'smart' carriers for sustained ocular drug delivery.

              In situ gel systems refer to a class of novel delivery vehicles, composed of natural, semisynthetic or synthetic polymers, which present the unique property of sol-gel conversion on receipt of biological stimulus. The present review summarizes the latest developments in in situ gel technology, with regard to ophthalmic drug delivery. Starting with the mechanism of ocular absorption, the review expands on the fabrication of various polymeric in situ gel systems, made up of two or more polymers presenting multi-stimuli sensitivity, coupled with other interesting features, such as bio-adhesion, enhanced penetration or sustained release. Various key issues and challenges in this area have been addressed and critically analyzed. The advent of in situ gel systems has inaugurated a new transom for 'smart' ocular delivery. By virtue of possessing stimuli-responsive phase transition properties, these systems can easily be administered into the eye, similar to normal eye drops. Their unique gelling properties endow them with special features, such as prolonged retention at the site of administration, followed by sustained drug release. Despite the superiority of these systems as compared with conventional ophthalmic formulations, further investigations are necessary to address the toxicity issues, so as to minimize regulatory hurdles during commercialization.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2018
                23 February 2018
                : 12
                : 383-389
                Affiliations
                Department of Ophthalmology, Ruijin Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Zhengshen Zhou, Department of Ophthalmology, Ruijin Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Ruijin Er Road, Shanghai 200025, People’s Republic of China, Tel +86 21 6437 0045, Email zzs10595@ 123456rjh.com.cn
                Article
                dddt-12-383
                10.2147/DDDT.S153405
                5825998
                © 2018 Sun and Zhou. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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