chitosan and plga microspheres as drug delivery ... - UniCA Eprints

2. Chitosan And PLGAdichloromethane and methanol) where the second component is used to increase theconcentration of drug in the dispersed phase. Hydrophobic drugs often present less of achallenge to formulate in slowly degradable microparticle systems, relative to hydrophilicdrugs, as they are often soluble in the organic solvents used, but are insoluble in water. Manyhydrophobicdrugs that have been encapsulated in biodegradable microparticles include (242).For example taxol has been successively encapsulated in PLGA microparticles with highefficiency (> 90%) (242, 243, 244). The maximum amount of drug encapsulated in themicroparticles typically depends on its solubility in the organic solvent used in theformulation. Taxol is now a common anticancer agent used against a wide variety of solidtumors including breast and ovarian cancers. It is insoluble in water and has a limitedsolubility in ethanol. Taxol has been encapsulated in PLGA microparticles of varying LA/GAratios using very simple O/W emulsions (244). The authors used dichloromethane as thesolvent for both PLGA (mol wt: 10,000) and taxol. A 4% gelatin solution was used as thecontinuous phase with simple mechanical mixing. An encapsulation efficiency of 98% frommicroparticles with an average diameter of 30 µm was achieved using 75:25 PLGA with noadditional additives. The in vitro release displayed a slow-sustained release of taxol with noinitial burst. In fact, the release was so slow that isopropyl myristate was added to change themicroparticle matrix to allow the formation of channels that would allow for faster diffusionof taxol from the microparticle. These results are not unexpected considering the hydrophobicnature of the drug and the immiscible nature of the solvents used for both phases of theemulsion. Thermodynamically, taxol must remain solvated in the dichloromethane untilwhich time the solvent is completely removed and, thus, the drug is homogeneouslyencapsulated in the newly formed microparticle. Because the release of taxol from PLGAmicroparticles is typically quite slow, the most significant obstacle in formulating thesemicroparticles is obtaining a sustained release of therapeutic levels of drug. Thus, additivessuch as isopropyl myristate, sucrose, and the use of PLGAs of varying molecular weight andhydrolytic degradation rates have been investigated as a means of accelerating the release oftaxol (244, 245).This biodegradable polymer can be successfully used as controlled delivery systems for manytype of drugs and for different route of administration. These systems could provide sustainedrelease of macromolecules ranging from a few days to several months, which avoid the dailymultiple administration. Furthermore, encapsulation in polymer matrix also protects labilemolecules from the degradation by enzymes. The application of these controlled delivery46