動注化学療法における pharmacokinetics と臨床

Xanthan gum is an extracellular polymer produced mainly by the bacterium Xanthomonas campestris. Traditionally it plays an important role in industrial applications as thickener, emulsion stabilizer and it has been added to water-based drilling fluids due to its pseudoplastic behavior and thermal stability. The structural properties of xanthan in solution can be tuned by the temperature and ionic strength; under high ionic strength or low temperature, xanthan chains are arranged in helical conformation, whereas under low ionic strength or high temperature, xanthan chains are coiled. Xanthan high molecular weight favors the building up of physical and chemical networks, which have been used as carriers for drugs and proteins and as scaffolds for cells. In combination with other polymers xanthan has been applied as excipient in tablets or as supporting hydrogels for drug release applications, particularly due to its acid resistance. The large versatility of xanthan gum opens the possibility for the creation of new architectures and additional applications involving this fascinating polymer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42035.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/app.42035

Xanthan gum: a versatile biopolymer for biomedical and technological applications

Designing hydrogel particles for controlled or targeted release of lipophilic bioactive agents in the gastrointestinal tract

Aceclofenac-loaded chitosan-tamarind seed polysaccharide interpenetrating polymeric network microparticles.

In this paper, methoxypoly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelle formulations as promising nano-carriers for poorly water soluble drugs were investigated for the delivery of diclofenac to the eye. Diclofenac loaded MPEG-PCL micelles were prepared by a simple solvent-diffusion method and characterized by dynamic light scattering (DLS), atomic force microscopy (AFM), Fourier transform infra-red (FTIR), X-ray diffraction (XRD), differential scanning calorimetery (DSC), etc. With the analysis of XRD and DSC, the diclofenac was present as an amorphous state in the formulation. The in vitro release profile indicated a sustained release manner of diclofenac from the micelles. Meanwhile, in vivo studies on eye irritation were performed with blank MPEG-PCL micelles (200 mg ml(-1)). The results showed that the developed MPEG-PCL micelles were non-irritants to the eyes of rabbits. In vitro penetration studies across the rabbit cornea demonstrated that the micelle formulations exhibited a 17-fold increase in penetration compared with that of diclofenac phosphate buffered saline (PBS) solution. The in vivo pharmacokinetics profile of the micelle parent drug in the aqueous humor of the rabbit was evaluated and the data showed that the diclofenac loaded MPEG-PCL micelles exhibited a 2-fold increase in AUC(0-24 h) than that of the diclofenac PBS solution eye drops. These results suggest a great potential of our micelle formulations as a novel ocular drug delivery system to improve the bioavailability of the drugs.

Diclofenac/biodegradable polymer micelles for ocular applications.

Xanthan gum (XG), a trisaccharide branched polymer and poly vinyl alcohol (PVA), was used to develop pH-sensitive interpenetrating network (IPN) microspheres by emulsion cross-linking method in the presence of glutaraldehyde as a cross-linker to deliver model anti-inflammatory drug, diclofenac sodium (DS) to the intestine. Various formulations were prepared by changing the ratio of XG:PVA, extent of cross-linking in order to optimize the formulation variables on drug encapsulation efficiency, and release rate. Formation of interpenetrating network and the chemical stability of DS after penetration of microspheres was confirmed by Fourier Transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were done on the drug loaded microspheres which confirmed molecular dispersion of DS in the IPN. Microspheres formed were spherical with smooth surfaces, as evidenced by scanning electron microscopy (SEM), and mean particle size, as measured by laser light scattering technique ranged between 310.25-477.10 microm. Drug encapsulation of up to 82.94% was achieved as measured by UV method. Both equilibrium and dynamic swelling studies and in vitro release studies were performed in pH 1.2 and 6.8. Release data indicated a Fickian trend of drug release which depends on the extent of cross-linking and the ratio of XG:PVA present in the microsphere. When subjected to in vivo pharmacokinetic evaluation in rabbits, microparticles show slow and prolonged drug release when compared with DS solution. Based on the results of in vitro and in vivo studies it was concluded that these IPN microspheres provided oral controlled release of water-soluble DS.

Novel interpenetrating network microspheres of xanthan gum–poly(vinyl alcohol) for the delivery of diclofenac sodium to the intestine—in vitro and in vivo evaluation

Saikat Barik

Papers

Novel interpenetrating network microspheres of xanthan gum–poly(vinyl alcohol) for the delivery of diclofenac sodium to the intestine—in vitro and in vivo evaluation