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

1. General IntroductionA significant disadvantage of many existing inhaled drugs is the relatively short duration ofresultant clinical effects and most medications in aerosol form require inhalation at least 3-4times daily (167). This often leads to poor patient compliance with the therapeutic regime andincreases the possibility of associated side effects due to the risk of self-administration of thedrug by the patients. A reduction in the frequency of dosing would be convenient, particularlyfor chronic treatments such as those for asthma. Sustained release of such drugs in the lungwould be particularly beneficial since they could be delivered to and retained at the targetedreceptors for a prolonged period of time and thus minimise the biodistribution throughout thesystemic circulation.The potential advantages of achieving sustained release to the lung has been shown by theimproved therapeutic effects obtained with a corticosteroid inhaled four times a day comparedto two times a day (168). Controlled release of drugs within the pulmonary tree also offersmany distinct advantages for agents which are administered for systemic actions. Many ofthese, in the future, are likely to be potent proteins and peptides designed to regulateimportant biological responses (169) and the pulmonary route provides many potentialadvantages compared to other portals of delivery. Currently, a number of methods have beeninvestigated as potential pulmonary sustained-release systems for short-acting drugs. Theseinclude the incorporation of drugs in liposomes and in particular in biodegradablemicrospheres.The use of controlled release polymeric systems is an approach that holds promise forimproving the duration and effectiveness of inhaled drugs, for both local and systemic action(170).Initial studies with polymeric aerosol systems showed that properly engineered, large porousparticles (LPP) were also capable of delivering bioactive insulin to the blood of rats andcontrol glucose levels for 96 h. The previous longest sustained delivery of insulin to the bloodvia the lungs was only 6 h, using liposomes that were intratracheally instilled into rat lungs.Since then, only limited examples of polymeric aerosol systems have been reported. Forexample, cationic polymers, such as polyethyleneimine (PEI) and poly-l-lysine (PLL),complexed with DNA have also been tested in the airways as a method to achieve transientgene expression.For example albumin microspheres can be prepared by either physical denaturation orchemical cross-linking of albumin droplets. The role of albumin microspheres as drugdelivery systems for targeted and sustained release after intravenous administration has been31