Optimization of the Formulation Design of Chitosan Microspheres Containing Cisplatin

Abstract

This study describes an orthogonal experimental design to optimize the formulation of cisplatin (CDDP)-loaded chitosan microspheres (namely, CDDP-DAC-MS) which were produced by an emulsion-chemical cross-linking technique. Seven factors and three levels for each factor that might affect the formulation of microspheres were selected and arranged in an L27(3(13)) orthogonal experimental table. A desirability function (df) calculated according to the trapping efficiency of CDDP, the drug content (%, w/w), and the size distribution of each batch of microspheres was introduced as an index of the microsphere formulation. The overall desirability functions (DF) were produced and treated by a statistic analytical system to optimize the formulation. Moreover, the contour maps were produced to analyze the influence of the seven factors on the size distribution, the drug content, and the drug trapping efficiency. The established optimum procedure was reproducible. Scanning electron micrographs showed that CDDP-DAC-MS were spherical with a coarse surface. The average diameter, drug content, and drug trapping efficiency of CDDP-DAC-MS were 74.8 microns, 20.8% (w/w), and 77.5%, respectively. The in vitro release of cisplatin from chitosan microspheres in saline was retarded compared with that from saline solution; the release of CDDP from chitosan microspheres was suggested to be controlled by the dissolution and diffusion of the drug from the chitosan matrix.

Triamcinolone-loaded glutaraldehyde cross-linked chitosan microspheres: Prolonged release approach for the treatment of rheumatoid arthritis

“…A similar extended release was reported by Jameela et al (1994) about mitoxantrone, an anti-neoplastic agent for over 4 weeks at 27°C. A similar biphasic release was observed by Wang et al (1996), where the release of CDDP from the chitosan microspheres in saline was sustained for more than 6 h with an initial rapid release phase (Bodmeier & Chen, 1998).…”

“…An initial burst effect was observed in all the batches of microsphere formulations, which may be due to the drug being adsorbed (or) located near the surface of the microspheres (Ravi et al, 2008). This might probably be due to the existence of drug crystals in the droplets, owing to its slight water solubility during the formation of (w/o) emulsion (Wang et al, 1996). When a watersoluble (or even slightly water-soluble) drug is encapsulated into microspheres, the release rate is often rapid and accompanied by a burst effect (Ravi et al, 2008).…”

Chitosan-Coated Fe₃O₄ Magnetic Nanoparticles as Carrier of Cisplatin for Drug Delivery

“…9 indicates that cisplatin accumulation within HeLa cells was more accelerated. The drug-release rate from the glutaraldehyde crosslinked chitosan microsphere was controlled by the dissolution and diffusion of the drug from the chitosan matrix (Wang et al, 1996).…”

“…Unfortunately, in many cases, these methods are often limited by a lack of potential drugs to reach the site of therapeutic action (Reedijk, 1999;Gonzalez et al, 2001). Considering that the cytotoxic effect of cisplatin can be harmful for healthy cells, one solution to using MNPs as drug carriers is using a polymer that can minimize drug degradation, prevent undesirable side effects, and provide controlled release of the drug (Wang et al, 1996;Ishihara et al, 2006;Kohli et al, Step 1: Oleic acid ligands were exchanged with APTS, particles became water dispersible.…”

Chitosan and sodium alginate—Based bioadhesive vaginal tablets

“…Under the conditions of the time of cross-linking and the amount of glutaraldehyde used, a loose cross-linking is achieved. 13 Tablets containing 20% metronidazole and weighing 200 or 500 mg were prepared by direct compression of drug powder mixture using flat face, 9-or 12-mm punch ( Table 1). A particle size of less than 160 μm for all components was selected to avoid any fraction segregation.…”