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

4. RFP Loaded Chitosan Microspheres Prepared by Precipitation MethodStability of chitosan microspheres at pH 1.2 was also evaluated by studying the drug release.As can be seen in figure 4.9, the release in this acidic medium is even faster than that obtainedat pH 4.4. Obviously, this is related to the highly acidic release medium that caused the higherionization of the D-glucosamine residues with a resulting faster and higher swelling degree,and a very fast release of the drug. As it is evident from the graph, a strong burst effect wasfound with from 22.3 to 41.5% of RFP released in the first 2 hrs of the experiments. However,also in this case the crosslinking with GA led a decrease of the drug release rate.4.2.7. Mucoadhesive StudiesAdvantages of mucoadhesive properties of particles for inhalation therapy are a cause ofargue among scientists. In fact, considering the meaning of mucoadhesion and taking intoaccount the lung mucociliary clearance it could seems a disadvantage. However, it is wellknown that the mucociliary clearance is more important in the upper airways while particulateadhesion to the mucus layer of the lungs can activate macrophage activity. Finally, it is alsoimportant to underline that chitosan exerts a transient inhibitory effect on mucociliaryclearance of the bioadhesive formulations due to its surface charge, molecular contact andflexibility, and this is a further advantage for the delivery of RFP to the lungs and in particularto macrophages where the MTB and MAC are able to replicate.Since a strong interaction exists between mucin and chitosan, mucin should be spontaneouslyadsorbed to the surface of the chitosan microspheres. For this reason, the mucoadhesivebehaviour of chitosan microspheres was assessed by suspending chitosan microspheres indifferent amounts of mucin aqueous solutions at room temperature. As can be seen in figure4.10 the amount of mucin adsorbed increased by increasing mucin concentration. Theseresults confirmed that chitosan microspheres have the ability to adsorb mucin. No statisticallydifference could be observed in the capability to adsorb mucin between uncross- and crosslinkedmicrospheres (Figure 4.10) although a higher mean value of adsorbed mucin wasalways obtained from the uncross-linked microspheres. The adsorption of mucin to chitosan isexpected to be dominated by the electrostatic attraction between positively charged chitosanand negatively charged mucin (the negative charge of mucin is due to the ionization of sialicacid). Therefore, surface charge of chitosan microspheres represented by zeta potential wouldinfluenced the amount absorbed. For all the batches the amount of adsorbed mucin decreasedwith decreasing in zeta potential.67