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      Ophthalmic In Situ Gels with Balsam Poplar Buds Extract: Formulation, Rheological Characterization, and Quality Evaluation

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          Abstract

          Balsam poplar buds are a raw material with a high content of polyphenols. Various polyphenols are known for their anti-inflammatory and antioxidant properties. In this study, an aqueous extract of balsam poplar buds was prepared in order to use environmentally friendly and non-aggressive solvents. The aqueous extract was lyophilized, and a 1% aqueous solution of lyophilized balsam poplar buds extract (L1) was prepared. L1 solution was used as a source of polyphenols for the production of ophthalmic in situ gels, so as to develop a product featuring antioxidant properties. Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) were selected as gelling agents for the in situ gels. In order to select the formulations with the best conditions of use, formulations of different polymer concentrations (P407—10%, 12%, 15%; HPMC—0.5%, 0.75%) were prepared, choosing the same amount of the active polyphenol source L1. The physicochemical properties, rheological parameters, stability, and irritant effect on the rabbit corneal cell line (SIRC) were evaluated. Formulations in which P407 and HMPC concentrations were 10/0.75% and 12%/0.75% reached a gelation point close to the ocular surface temperature; the gels remained stable for 30 days and did not cause an irritant effect on the SIRC cell line.

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          Plant polyphenols as dietary antioxidants in human health and disease

          Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.
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            The use of mucoadhesive polymers in ocular drug delivery.

            In the present update on mucoadhesive ocular dosage forms, the tremendous advances in the biochemistry of mucins, the development of new polymers, the use of drug complexes and other technological advances are discussed. This review focusses on recent literature regarding mucoadhesive liquid (viscous solutions, particulate systems), semi-solid (hydrogel, in situ gelling system) and solid dosage forms, with special attention to in vivo studies. Gel-forming minitablets and inserts made of thiomers show an interesting potential for future applications in the treatment of ocular diseases.
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              Ocular drug delivery systems: An overview.

              The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                24 June 2021
                July 2021
                : 13
                : 7
                : 953
                Affiliations
                [1 ]Department of Clinical Pharmacy, Faculty of Pharmacy, Lithuanian University of Health Sciences, Sukileliai Avenue 13, LT-50161 Kaunas, Lithuania; Kristina.perminaite@ 123456lsmu.lt (K.P.); Kristina.ramanauskiene@ 123456lsmuni.lt (K.R.)
                [2 ]Department of Analytical & Toxicological Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, Sukileliai Avenue 13, LT-50161 Kaunas, Lithuania; mindaugas.marksa@ 123456lsmu.lt (M.M.); liudas.ivanauskas@ 123456lsmuni.lt (L.I.)
                Author notes
                [* ]Correspondence: Monika.stanciauskaite@ 123456lsmu.lt ; Tel.: +370-679-670-17
                Article
                pharmaceutics-13-00953
                10.3390/pharmaceutics13070953
                8308992
                34202901
                51ca0796-ef68-4cc1-8184-7a05360b420a
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 17 May 2021
                : 13 June 2021
                Categories
                Article

                balsam poplar buds,polyphenols,ocular delivery,in situ gel,cell viability

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