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      Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

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          Abstract

          Ocular drug delivery is challenging due to the presence of anatomical and physiological barriers. These barriers can affect drug entry into the eye following multiple routes of administration (e.g., topical, systemic, and injectable). Topical administration in the form of eye drops is preferred for treating anterior segment diseases, as it is convenient and provides local delivery of drugs. Major concerns with topical delivery include poor drug absorption and low bioavailability. To improve the bioavailability of topically administered drugs, novel drug delivery systems are being investigated. Nanocarrier delivery systems demonstrate enhanced drug permeation and prolonged drug release. This review provides an overview of ocular barriers to anterior segment delivery, along with ways to overcome these barriers using nanocarrier systems. The disposition of nanocarriers following topical administration, their safety, toxicity and clinical trials involving nanocarrier systems are also discussed.

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          Ocular drug delivery.

          Ripal Gaudana, Hari Krishna Ananthula, Ashwin Parenky … (2010)
          Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.
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            Microemulsion-based media as novel drug delivery systems.

            M.Jayne Lawrence, Gareth Rees (2000)
            Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. In order to appreciate the potential of microemulsions as delivery vehicles, this review gives an overview of the formation and phase behaviour and characterization of microemulsions. The use of microemulsions and closely related microemulsion-based systems as drug delivery vehicles is reviewed, with particular emphasis being placed on recent developments and future directions.
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              Structure and design of polymeric surfactant-based drug delivery systems.

              Vladimir P. Torchilin (2001)
              The review concentrates on the use of polymeric micelles as pharmaceutical carriers. Micellization of biologically active substances is a general phenomenon that increases the bioavailability of lipophilic drugs and nutrients. Currently used low-molecular-weight pharmaceutical surfactants have low toxicity and high solubilization power towards poorly soluble pharmaceuticals. However, micelles made of such surfactants usually have relatively high critical micelle concentration (CMC) and are unstable upon strong dilution (for example, with the blood volume upon intravenous administration). On the other hand, amphiphilic block co-polymers are also known to form spherical micelles in solution. These micelles have very high solubilization capacity and rather low CMC value that makes them very stable in vivo. Amphiphilic block co-polymers suitable for micelle preparation are described and various types of polymeric micelles are considered as well as mechanisms of their formation, factors influencing their stability and disintegration, their loading capacity towards various poorly soluble pharmaceuticals, and their therapeutic potential. The basic mechanisms underlying micelle longevity and steric protection in vivo are considered with a special emphasis on long circulating drug delivery systems. Advantages and disadvantages of micelles when compared with other drug delivery systems are considered. New polymer-lipid amphiphilic compounds such as diacyillipid-polyethylene glycol, are described and discussed. These compounds are very attractive from a practical point of view, since they easily micellize yielding extremely stable micelles with very high loading capacity. Micelle passive accumulation in the areas with leaky vasculature (tumors, infarct zones) is discussed as an important physiology-based mechanism of drug delivery into certain target zones. Targeted polymeric micelles prepared by using thermo- or pH-sensitive components or by attaching specific targeted moieties (such as antibodies) to their outer surface are described as well as their preparation and some in vivo properties. The fast growing field of diagnostic micelles is analyzed. Polymeric micelles are considered loaded with various agents for gamma, magnetic resonance, and computed tomography imaging. Their in vitro and in vivo properties are discussed and the results of the initial animal experiments are presented.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceutics
                Journal ID (iso-abbrev): Pharmaceutics
                Journal ID (publisher-id): pharmaceutics
                Title: Pharmaceutics
                Publisher: MDPI
                ISSN (Electronic): 1999-4923
                Publication date (Electronic): 27 February 2018
                Publication date Collection: March 2018
                Volume: 10
                Issue: 1
                Electronic Location Identifier: 28
                Affiliations
                [1 ]College of Pharmacy and Pharmaceutical Sciences, The University of Toledo Health Science Campus, Toledo, OH 43614, USA; RindaDevi.Bachu@ 123456rockets.utoledo.edu (R.D.B.); Pallabita.Chowdhury@ 123456rockets.utoledo.edu (P.C.); Zahraa.AlSaedi@ 123456rockets.utoledo.edu (Z.H.F.A.-S.)
                [2 ]Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, 2300 4th St. NW, Washington, DC 20059, USA
                Author notes
                [* ]Correspondence: pkarla@ 123456howard.edu (P.K.K.); sboddu@ 123456utnet.utoledo.edu (S.H.S.B.); Tel.: +202-806-6543 (P.K.K.); +419-383-1959 (S.H.S.B.)
                Article
                Publisher ID: pharmaceutics-10-00028
                DOI: 10.3390/pharmaceutics10010028
                PMC ID: 5874841
                PubMed ID: 29495528
                SO-VID: c0cde774-7831-4be4-be62-e4584bee1172
                Copyright © © 2018 by the authors.
                License:

                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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 22 December 2017
                Date accepted : 23 February 2018
                Categories
                Subject: Review

                Keywords: anterior segment,novel drug delivery systems,polymeric nanocarriers,disposition,toxicity
                Data availability:
                Keywords: anterior segment, novel drug delivery systems, polymeric nanocarriers, disposition, toxicity

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