pH-sensitive behavior of two-component hydrogels composed of N,O-carboxymethyl chitosan and alginate.
ABSTRACT A two-component pH-sensitive hydrogel system composed of a water-soluble chitosan derivative (N,O-carboxymethyl chitosan, NOCC) and alginate cross-linked by genipin, glutaraldehyde or Ca2+ was investigated. Preparation and structures of these hydrogels and their swelling characteristics and release profiles of a model protein drug (bovine serum albumin, BSA) in simulated gastrointestinal media are reported. At pH 1.2, the swelling ratios of the hydrogels cross-linked by distinct methods were limited. Of note is that the lowest swelling ratios of test hydrogels were found at pH 4.0. At pH 7.4, the carboxylic acid groups on test hydrogels became progressively ionized and led to a significant swelling. There was barely any BSA released from the glutaraldehyde-cross-linked hydrogel throughout the entire course of the study. The amounts of BSA released at pH 1.2 from the genipin- and Ca(2+)-cross-linked hydrogels were relatively low (approx. 20%). At pH 4.0, there was still significant BSA release from the Ca(2+)-cross-linked hydrogel, while the cumulative BSA released from the genipin-cross-linked hydrogel was limited due to its shrinking behavior. At pH 7.4, the amount of BSA released from the genipin- and Ca(2+)-cross-linked hydrogels increased significantly (approx. 80%) because the swelling of both test hydrogels increased considerably. The aforementioned results indicated that the swelling behaviors and drug-release profiles of these test hydrogels are significantly different due to their distinct cross-linking structures.
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ABSTRACT: The oral delivery of proteins and peptide drugs is considered a major challenge. These types of therapeutics are readily degraded, if taken orally, due to the harsh high acidity of stomach and enzymatic attack in the upper small intestinal tract. Water-soluble copolymers of sodium acrylate (AAs) grafted onto carboxymethyl cellulose (CMC) were prepared and characterized using Fourier transform spectroscopy, differential scanning calorimetry, and X-ray diffraction. The obtained graft copolymers were then used in a combination with sodium alginate to develop a new series of pH-sensitive interpenetrating polymeric network (IPN) hydrogels through ionotropic gelation with divalent ions (Ca(2+)). Morphology of the developed hydrogels was investigated using SEM. Swelling characteristics, at distinct compositions, were also studied at 37°C in two consecutive buffer solutions of pH 2.1 and 7.4 (similar to that of gastric and intestinal fluids, respectively). The release profiles of bovine serum albumin, as a model protein, from test IPN hydrogel films were studied in simulated gastric and intestinal fluids. In addition, the drug release process was confirmed by means of SEM. Swelling studies of the developed IPN hydrogels at different pH values confirmed their pH-sensitive nature. The equilibrium swelling extents of the hydrogels were found to be dependent on the grafting yield of CMC/AAs graft copolymer. The IPN hydrogels attained equilibrium swelling percentages in the range 445-740%. In addition, the amount of bovine serum albumin released within 2 hours in pH 2.1 was relatively low (less than 18.1%). This amount increased up to 68% after 8 hours in pH 7.4. From the obtained preliminary data, it seems that the IPN hydrogels developed in this contribution can be tailored to act as good potential carriers for oral delivery of protein drugs. These hydrogels showed a promising protection of protein drugs from the harsh acidity of stomach and, at the same time, they conferred sustained drug release in the intestinal fluid.Drug Development and Industrial Pharmacy 02/2011; 37(2):121-30. · 1.54 Impact Factor
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ABSTRACT: Carboxymethylchitosan (CMCS) microspheres were prepared by the carboxymethylation of chitosan (CS) beads using monochloroacetic acid. The CMCS microspheres were crosslinked using two different methods: the amine-amine crosslinker genipin and carbodiimide chemistry, yielding Gen-X CMCS and X-CMCS beads, respectively. The Gen-X CMCS beads were found to have poor degradation and drug release profiles. The X-CMCS microspheres displayed good potential for use in tissue engineering applications in which degradation and local drug delivery are desired. The X-CMCS beads displayed enzymatic degradation of 82.7 ± 1.2% in 100 μg/mL lysozyme after 1 month. An extended release of rhBMP-2 for at least 45 days was also observed with the X-CMCS microspheres. Scaffolds were formed by fusing beads together, and the X-CMCS beads were successfully incorporated into composite X-CMCS/CS scaffolds. The composite scaffolds had increased degradation of 14.5 ± 6.6% compared to 0.5 ± 0.4% for CS-only scaffolds, and the X-CMCS/CS scaffolds released more rhBMP-2 at all timepoints. The composite scaffolds also supported the attachment and proliferation of SAOS-2 cells. The addition of X-CMCS beads resulted in fabrication of scaffolds with improved properties for use in bone tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.Journal of Biomedical Materials Research Part B Applied Biomaterials 01/2013; · 2.31 Impact Factor
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ABSTRACT: The chitosan-based biomaterials are an emerging class of materials with great application in pharmaceutical and biomedical fields, particularly in systems for controlled drug delivery and tissue engineering. The abundance of chitosan, a natural resource economically attractive, and the presence of an unusual set of chemical and biological properties of high utility for specific areas are among the reasons why chitosan constitutes an excellent material for drug delivery. The growing interest in this biopolymer in pharmaceutical and biomedical areas has created opportunities for development of specialized materials mainly through chemical and physical modifications of its molecule, which promote new biological activities in the polymer. These strategies include the combination of chitosan with other polymers (both natural and synthetic) and inorganic materials for producing composite materials. As is not possible to mention all the applications of chitosan and its derivatives due to their high number and variety, this review will be mainly concerned the most innovative aspects of controlled drug delivery systems, namely those consisting of nanoparticles and in situ formed injectable matrices.01/2012: pages 1489-1509;