23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Ophthalmic drug-loaded N,O-carboxymethyl chitosan hydrogels: synthesis, in vitro and in vivo evaluation

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Aim:

          To investigate the ability of drug-loaded N, O-carboxymethyl chitosan (CMCS) hydrogels to modulate wound healing after glaucoma filtration surgery.

          Methods:

          The drug-loaded CMCS hydrogels were in situ synthesized using genipin as the crosslinker in the presence of 5-fluorouracil (5FU) or bevacizumab. Their structures were characterized by FTIR, ultraviolet-visible (UV-vis) spectroscopy and scanning electron microscopy (SEM). In-vitro drug release experiments and in vivo evaluation in rabbits were performed.

          Results:

          The results of FTIR, UV-vis spectroscopy and SEM analyses indicated that 5FU was encapsulated into the CMCS hydrogels that were crosslinked by genipin. The in vitro drug release experiments showed that nearly 100% of 5FU was released from the drug-loaded hydrogels within 8 h, but less than 20% bevacizumab was released after 53 h. The in vivo evaluation in rabbits indicated that the drug-loaded CMCS hydrogels were nontoxic to the cornea and were gradually biodegraded in the eyes. Furthermore, the drug-loaded CMCS hydrogels effectively inhibited conjunctival scarring after glaucoma filtration surgery and controlled postoperative intraocular pressure (IOP).

          Conclusion:

          The drug-loaded CMCS hydrogels provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.

          Related collections

          Most cited references17

          • Record: found
          • Abstract: found
          • Article: not found

          A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery.

          A novel pH-sensitive hydrogel system composed of a water-soluble chitosan derivative (N,O-carboxymethyl chitosan, NOCC) and alginate blended with genipin was developed for controlling protein drug delivery. Genipin, a naturally occurring cross-linking agent, is significantly less cytotoxic than glutaraldehyde and may provide a less extent of cross-linking to form a semiinterpenetrating polymeric network (semi-IPN) within the developed hydrogel system. The drug-loading process used in the study was simple and mild. All procedures used were performed in aqueous medium at neutral environment. In the study, preparation of the NOCC/alginate-based hydrogels was reported. Swelling characteristics of these hydrogels as a function of pH values were investigated. Additionally, release profiles of a model protein drug (bovine serum albumin, BSA) from test hydrogels were studied in simulated gastric and intestinal media. The semi-IPN formation of the genipin-cross-linked NOCC/alginate hydrogel was confirmed by means of the scanning electron microscopy-energy dispersive X-ray spectrometer (SEM-EDS) and the ninhydrin assays. The percentage of decrease of free amino groups and cross-linking density for the NOCC/alginate hydrogel cross-linked with 0.75 mM genipin were 18% and 26 mol/m(3), respectively. At pH 1.2, the swelling ratio of the genipin-cross-linked NOCC/alginate hydrogel was limited (2.5) due to formation of hydrogen bonds between NOCC and alginate. At pH 7.4, the carboxylic acid groups on the genipin-cross-linked NOCC/alginate hydrogel became progressively ionized. In this case, the hydrogel swelled more significantly (6.5) due to a large swelling force created by the electrostatic repulsion between the ionized acid groups. The amount of BSA released at pH 1.2 was relatively low (20%), while that released at pH 7.4 increased significantly (80%). The results clearly suggested that the genipin-cross-linked NOCC/alginate hydrogel could be a suitable polymeric carrier for site-specific protein drug delivery in the intestine.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Novel chitosan-based films cross-linked by genipin with improved physical properties.

            Novel cross-linked chitosan-based films were prepared using the solution casting technique. A naturally occurring and nontoxic cross-linking agent, genipin, was used to form the chitosan and chitosan/poly(ethylene oxide) (PEO) blend networks, where two types of PEO were used, one with a molecular weight of 20 000 g/mol (HPEO) and the other of 600 g/mol (LPEO). Genipin is used in traditional Chinese medicine and extracted from gardenia fruit. Importantly, it overcomes the problem of physiological toxicity inherent in the use of some common synthetic chemicals as cross-linking agents. The mechanical properties and the stability in water of cross-linked and un-crosslinked chitosan and chitosan/PEO blend films were investigated. It was shown that, compared to the transparent yellow, un-cross-linked chitosan/PEO blend films, the genipin-cross-linked chitosan-based film, blue in color, was more elastic, was more stable, and had better mechanical properties. Genipin-cross-linking produced chitosan networks that were insoluble in acidic and alkaline solutions but were able to swell in these aqueous media. The swelling characteristics of the films exhibit sensitivity to the environmental pH and temperature. The surface properties of the films were also examined by contact angle measurements using water and mixtures of water/ethanol. The results showed that, with the one exception of cross-linked pure chitosan in 100% water, the cross-linked chitosan and chitosan/PEO blends were more hydrophobic than un-crosslinked ones.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Antifibrotics and wound healing in glaucoma surgery.

              When medical and laser therapy fail to control intraocular pressure, glaucoma filtration surgery needs to be performed. Glaucoma surgery is unique in that its success is linked to interruption of the wound-healing response in order to maintain patency of the new filtration pathway. In this article we will review the wound-healing pathway and the pharmacologic interventions that have been employed clinically and experimentally to interrupt wound healing, particularly steroids and the antifibrotic agents 5-fluorouracil and mitomycin C. A review of the published literature looking at use of these agents to enhance success as well as the associated complications are presented, critiqued, and interpreted in order to put the studies in proper perspective. Future directions and recommendations regarding use of these agents are available and an introduction to newer wound modulating agents such as anti-transforming growth factor beta 2 is presented.
                Bookmark

                Author and article information

                Journal
                Acta Pharmacol Sin
                Acta Pharmacol. Sin
                Acta Pharmacologica Sinica
                Nature Publishing Group
                1671-4083
                1745-7254
                December 2010
                01 November 2010
                : 31
                : 12
                : 1625-1634
                Affiliations
                [1 ]Institute of Polymer Science, School of Chemistry and Chemical Engineering; BME Center, State Key Laboratory of Optoelectronic Materials and Technologies; DSAPM Lab and PCFM Lab, Sun Yat-sen University , Guangzhou 510275, China
                [2 ]Department of Ophthalmolgy, Sun Yat-sen Memorial Hospital of Sun Yat-sen University , Guangzhou 510120, China
                [3 ]Department of Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University , Guangzhou 510120, China
                Author notes
                [#]

                The first two authors contributed equally to this work.

                Article
                aps2010125
                10.1038/aps.2010.125
                4002939
                21042284
                9e4dec7c-50a6-4e6d-bf61-62280153ad9d
                Copyright © 2010 CPS and SIMM
                History
                : 22 February 2010
                : 27 May 2010
                Categories
                Original Article

                Pharmacology & Pharmaceutical medicine
                n,o-carboxymethyl chitosan,genipin,hydrogel,glaucoma,intraocular pressure,5-fluorouracil,bevacizumab

                Comments

                Comment on this article