Chitosans microspheres

A review of chitosan microspheres as carrier for drugs pubUshed recently by Sinha et al. provides insight into the exploitation of the various properties of chitosan to microencapsulate drugs. Various techniques used for preparing chitosan microspheres and evaluation protocols have also been reviewed, together with the factors that affect the entrapment efficiency and release ki-nefics of drugs [194]. 

Spray-drying of chitosan salt solutions provides chitosan microspheres having diameters close to 2-5 p.m and improved binding fimctionaUty. The chitosan microsphere free-flowing powder is compressible and hence most suitable as a drug carrier [ 195-204]. The following are some examples. 

Chitosan has been recently found to be soluble in alkaline media, viz. NH4HCO3 solutions, where it assumes the ammonium carbamate form Chit-NHC02 NH4, i.e., a transient anionic form that keeps it soluble at pH 9.6, while reversibly masking the polycationic nature of chitosan. Because ammonium carbamates and NH4HCO3 decompose thermally and liberate CO2, NH3 and water, this alkaline system is suitable for producing chitosan microspheres by spray-drying (Table 1) [206]. 

The ability of chitosan hydrochloride to enhance the transcorneal permeability of the drug has been demonstrated [289]. Polyethylene oxide (PEO) was used as a base material to which ofloxacin-containing chitosan microspheres prepared by spray-drying were added and powder compressed resulting in circular inserts (6 mm). 

Chitosan microsphere-encapsulated human growth hormone seems to be quite effective in early bone consolidation in distraction osteogenesis [342]. 

E. Gavini, A. B. Heqqe, G. Rassu, V. Sanna, C. Testa, G. Pirisino, J. Karlsen, and P. Giunchedi. Nasal administration of carbamazepine using chitosan microspheres in vitro/in vivo studies. Int J Pharm 307 9-15 (2006). 

FIG. 6. Scheme of possible drug release from Eudragit microencapsulated chitosan microspheres (adapted from Ref. 78). 

Wakerly, Z., Fell, J.T., Attwood, D., and Parkins, D., Peetin/ethyl eellulose film-eoating formulations for colonic drug delivery, Pharm. Res., 13 1210-1212 (1996). Lorenzo-Lamosa, M.L., Remunan-Lopez, C., Vila-Jato, J.L., and Alonso, M.J., Design of microencapsulated chitosan microspheres for colonic drug delivery, J. Contr. Rel, 52 109-118 (1998). 

Ramdas, M., Dileep, K.J., Anitha, Y., Paul, W., and Sharma, C.P., Alginate encapsulated bioadhesion chitosan microspheres for intestinal drug delivery, J. Biomater. Appl, 13 290-296 (1999). 

Other teehniques used for studying molecular interactions between polymers and mueus inelude ultracentrifugation, surface plasmon resonance, and electromagnetic transduction [4,34]. Ilium and co-workers [35] investigated the interaction of chitosan microspheres using turbidimetric measurements and adsorption studies of mucin to the mierospheres. 

Aral, C., Akbuga, J. (2003). Preparation and in vitro transfection efficiency of chitosan microspheres, containing plasmid DNA poly (L-lysine) complexes. J. Pharm. Phantn. Sci., 6(3), 321-326. 

Desai, K.G., Park, H.J. (2005). Encapsulation of vitamin C in tripolyphosphate cross-linked chitosan microspheres by spray drying. Journal of Microencapsulation, 2, 179-192. 

Alginate-chitosan microspheres of PHEAfopa adductlnt. J. Pharm.116 39-44. 

Carreno-Gomez, B., and R. Duncan. 1997. Evaluation of the biological properties of soluble chitosan and chitosan microspheres. Int J Pharm 148 231. 

El-Gibaly, I. 2002. Development and in vitro evaluation of novel floating chitosan microcapsules for oral use comparison with non-floating chitosan microspheres, Int J Pharm 249 7. 

Varshosaz, J., H. Sasrai, and R. Alinagari. 2004. Nasal delivery of insulin using chitosan microspheres. J Microencapsul 21 761. 

Hejazi, R., and Amiji, M. Stomach-specific anti-H. pylori therapy II. Gastric residence studies of tetracycline-loaded chitosan microspheres in gerbils. Pharm. Dev. Technol. 8 252-262, 2003. 

Bogataj, M., and Mrhar, A. Mucoadhesion of polycarbophil and chitosan microspheres on isolated guinea pig vesical and intestinal mucosa. J. Contr. Rel. 48 340-341, 1997. 

In an interesting illustration of the first strategy, Sakaguchi and coworkers covalently attached hemoglobin to an aminopropyl silica particle and then polymerized organoalkoxysilanes on the surface of the hemoglobin-modified silica particle.85 The template was removed via treatment with oxalic acid.85 In more recent work, Zhang and coworkers utilized a similar approach. In their case, the sphere was made from the functionalized biopolymer, chitosan.86 The model template protein, bovine serum albumin, was covalently attached to the chitosan microsphere and then coated with a composite sol prepared from TEOS and an aminosilane.86... 

Cross-linked Chitosan Microspheres Coated with Polysaccharides or Lipid... 

The procedure for the preparation of cross-linked chitosan microspheres coated with polysaccharide or lipid for intelligent drug delivery systems is illustrated in Fig. 11 [230]. 

Chitosan molecular weight has also been reported to influence drug release. Jiang et al. [94] studied Bordetella bronchiseptica dermonecrotoxin (BBD) release from chitosan microspheres prepared by tripolyphosphate ionic gelation. It has been shown that the BBD release rate increased with chitosan molecular weight decrease. It has been explained by the weaker BBD interaction with chitosan of lower molecular weight and lower content of free amine groups, responsible for their interaction. 

Chitosan microspheres were shown to enhance nasal bioavailability of several peptide drugs such as insulin and goserelin. A simple chitosan-insulin powder formulation provided about 20% of absolute insulin bioavailability in sheep [96], Improved bioavailability (of 44%, in rats) was obtained when insulin was loaded into chitosan microspheres prepared with ascorbyl palmitate as cross-linking agent [91]. Chitosan microspheres have also been shown to improve nasal goserelin absorption providing about 40% bioavailability relative to goserelin intravenous application [9],... 

Besides the polymer derivatization, combining the polymers in microsphere preparations can result in improved drug delivery and absorption characteristics. Hyaluronic acid-chitosan microspheres appeared to improve the absorption of incorporated gentamicin compared to the individual polymers, assembling the mucoadhesive potential of both polymers and the penetration-enhancing effect of chitosan [51,52],... 

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