Alginate Based Microparticle Drug Delivery Systems for the Treatment of Eye Cancer
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Alginate based Microparticle Drug Delivery System for the Treatment of Eye Cancer Yerkesh O.Batyrbekov1, Dinara Rakhimbaeva2, Kuanyshbek Musabekov2 and Bulat Zhubanov1 1 Institute of Chemical Sciences, 106 Valikhanov Street, Almaty, 050010, Kazakhstan 2 Kazakh State University, 95 Karasai batyr str., 050012 Almaty, Kazakhstan ABSTRACT Alginate based microparticle drug delivery systems were prepared for the sustained release of antitumor drugs. Two drugs, cyclophosphane and 5-fluorouracil, were encapsulated into the microparticles. The drug loaded microparticles were fabricated using a very convenient method under very mild conditions by the gelation of alginate with calcium cation. Modified microparticles were obtained by syringed dropwise a solution of drugs in sodium alginate into chitosan solution in calcium chloride. The effect of polymers concentration and the drug loading (1.0, 5.0 and 10%) on the release profile of drugs were investigated. The amount of drug release was much higher initially (approximately 25%), followed by a constant slow release profile. All the release data show the typical pattern for a matrix controlled mechanism. The cumulative amount of drug released from alginate gels was linearly related to the square root of the time and the release rate decreased this time. The process is controlled by the diffusion of antitumor drugs through the chitosan coating. Scanning electron microscopy (SEM) and particle size analysis revealed differences between the formulations as to their appearance and size distribution. The experiments for anticancer action of alginate microparticles were determined at 120 inbreeded white rats (females, weight 120-125 g, age 2-3 month) infected by malignant Rhabdomyoma strain at the dose of 10 000 cells. Medical-biological tests show that the duration of anticancer activity for the drug-containing alginate microparticles increases at 5-8 times in comparison of free drugs. Such systems may have potential for controlled delivery of antitumor drugs for the treatment of eye cancer. INTRODUCTION Calcium alginate has been one of the most extensively investigated polymers forming microparticles in the presence of divalent cations. The alginates is a natural copolymer composed of D-mannuronic acid (M) and L-guluronic acid (G) arranged in MM and GG blocks interrupted by regions of more random distribution of M and G units [1]. Specific intermolecular cooperative interactions occur between calcium and G blocks owing to the buckled ribbon structure of the polyguluronic acid, which is so-called “egg-box” junction zones. The rigid structure and large pore size of the microparticles are useful for the encapsulation of different drugs, enzymes and proteins [2-4]. The perspective field of alginate microparticles application is the development of Drug Delivery systems for the treatment of eye cancer such as retinoblastoma. One of the basic difficulties of anticancer chemotherapy is absence of the directed and controlled transport of drug in tumor cells. An ideal cancer che
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