Surprising Performance of Alginate Beads for the Release of Low-Molecular-Weight Drugs Magdy M. Elnashar, 1 Mohamed A. Yassin, 2 Abou El-Fetouh Abdel Moneim, 2 Elsayed M. Abdel Bary 3 1 Laboratory of Advanced Materials and Nanotechnology, Department of Polymers, Center of Excellence, National Research Centre, Cairo, Egypt 2 Department of Packing and Packaging Materials, National Research Centre, Cairo, Egypt 3 Polymer Laboratory, Chemistry Department, Faculty of Science, Mansoura University, ET-35516 Mansoura, Egypt Received 17 July 2009; accepted 23 November 2009 DOI 10.1002/app.31836 Published online 4 February 2010 in Wiley InterScience (www.interscience.wiley.com). ABSTRACT: The model of low-molecular-weight drugs has been encapsulated within alginate beads hardened with calcium chloride. The drug’s release kinetic using 3% (w/v) alginate has shown a surprising behavior after 2 h, where the release kinetic was shifted from Fickian to case II transport mechanism contradicting other authors like Akihiko et al. (J Control Release 1999, 58, 21). To support this finding, we studied the swelling of dried gel beads of 2 and 3% (w/v) alginate, which showed a sudden decrease in the swelling of 3% (w/v) alginate after 2 h due to a partial bursting of the beads. This sudden bursting was clearly observed using the optical microscope to emphasize the new findings. Calcium alginate beads revealed pH sensitivity, where 2% (w/v) alginate beads showed a maximum swelling of 5000% in alkaline medium at pH 7.4, compared with a negligible swelling percent of 60% in acidic medium (pH 1.2). Accordingly, it could be a good candidate for targeting smart and low-molecular-weight drugs to the intestine. V C 2010 Wiley Periodicals, Inc. J Appl Polym Sci 116: 3021–3026, 2010 Key words: biopolymer; controlled intestinal drug release; hydrogel, release kinetics; low-molecular-weight drugs INTRODUCTION Drug delivery systems have been extensively stud- ied over the last years, and polymers are now being studied as a method of controlling the release of drugs. 1 Biodegradable polymers are one of the key materials for these devices and have advantages over nondegradable implants. The main advantage is that biodegradable devices degrade and are absorbed by the body during and/or after drug release; this allows us to bypass the need for surgical removal of the device. 2 It is naturally an advantage if substances that are already permitted for use in the pharmaceutical or food industries can be uti- lized. Hydrogels, such as alginates, carrageenans, and chitosans, are polysaccharide families belonging to this category that are commercially available, have diverse applications, 3–5 and are available at a reasonable cost. Another advantage is to use drug carriers, which are easily prepared using a simple method such as alginate. Alginate is a water-soluble linear polysaccharide extracted from brown seaweed and is composed of alternating blocks of 1–4 linked a-L-guluronic and b-D-mannuronic acid residues. Alginate has the ability to form hydrogel in the pres- ence of multivalent cations like Ca 2þ in aqueous medium, and it shows excellent features such as immunogenecity, biocompatibility, bioadhesion, and nontoxicity. These features make it a very attractive biomaterial for use in many types of applications such as wound dressing, scaffold for tissue engineer- ing, and pharmaceutical industries. 6 Although many authors 7,8 have studied Ca–Alg beads as a matrix for drug delivery system, optimi- zation of the preparation parameters was not clear; there are many conflicts between authors, and this was the main reason for doing this work. For exam- ple, Bajpai and Rasika 9 reported that using high algi- nate concentration 4% (w/v) gave stable beads for drug delivery system, whereas Arica et al. 10 reported that beads prepared with 1% (w/v) alginate sus- tained the release of 5-fluorouracil. Also, the concen- tration of CaCl 2 as a crosslinking agent showed vari- ous results. Ga ˚serød et al. 11 reported that by increasing the concentration of CaCl 2 to 3% (w/v) should increase the porosity of beads, leading to higher diffusion of entrapped drug. While Mayur et al. 12 found that using 0.5% (w/v) of CaCl 2 gives weak gel because of insufficient crosslinking of Correspondence to: M. M. Elnashar (magmel@gmail.com). Journal of Applied Polymer Science, Vol. 116, 3021–3026 (2010) V C 2010 Wiley Periodicals, Inc.