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

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3. Aim of the WorkDuring the last three decades, therapeutic systems based on polymers, both natural andsynthetic, have shown to be effective in controlling rate or time of drug release, in enhancingdrug targeting specificity while lowering systemic drug toxicity, and providing protection forpharmaceuticals against degradation.An important consideration in the treatment of pulmonary infections is the fact that the MTBand MAC have the capability of surviving intra-cellulary in the host macrophages for longperiods of time (246). Therefore, the ability of the antibacterial agent to eradicate themicrorganisms within the macrophage is of key importance.However, most of the anti-mycobacteria drugs presently in use fail to penetrate macrophages.For this reason, many researchers are considering the use of appropriately engineered deliverysystems for these drugs, in order to make them therapeutically effective. It is well known thatmicro-encapsulation technology can be used to accomplish sustained release of antibiotics,when they are formulated in larger sizes than 50 µm, or to target drug delivery systems tospecific cells (i.e., macrophages), when antibiotics are formulated in smaller sizes
3. Aim of the WorkBiodegradable microparticles composed of poly(lactide-co-glycolide) (PLGA) can beconsidered as a well established drug delivery system, having high potential to serve ascarriers for drugs as well as vaccines (252, 253). One such application is the alveolar deliveryof RFP. PLGA has been used before for the preparation of RFP loaded microspheres, andseveral studies have been carried out mainly for evaluation of the formulation parameters thatinfluence the release kinetics of RFP from particles. Furthermore, it has been established thatthese particles can reach alveolar macrophages after aerosol delivery and enhance thetherapeutic effect of RFP in vivo (254). In addition, while RFP-loaded PLGA microsphereshave been prepared and evaluated in vivo previously, no relevant pre-formulation studiesinvolving their behaviour during nebulization, have been carried out.In the present study we compared chitosan, PLGA or mixtures of the two polymers (Chitosamcoated PLGA particles) for the preparation of particulate RFP delivery systems that may beadministered to the lungs by nebulization. For this, the three types of particles were preparedand their ability to encapsulate RFP was evaluated. After this, using the same nebulizationdevice we evaluated the nebulization ability of the different types of microparticles prepared.During this study we also compared properties of freshly prepared and freeze-driedmicrospheres in order to evaluate freeze-dried formulations for rapid re-hydration just beforenebulization.During this work we studied the influence of several formulation parameters on microparticlesize distribution, encapsulation efficiency (E%) and nebulization efficiency (NE%).Since association of RFP with particles is a prerequisite for achieving high RFPconcentrations in alveolar macrophages, the most important characteristic for these particles istheir ability to retain the drug during the nebulization process, which was also evaluated.Furthermore, a morphological assessment of the particles by Scanning Electron Microscopywas carried out. Toxicity of the prepared microspheres was also evaluated by using A549alveolar epithelial cells51
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Page 5 and 6: Table Of Contents1. GENERAL INTRODU
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Page 10 and 11: 1. General Introduction1.1. Pulmona
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Page 14 and 15: 1. General Introductionis the fact
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Page 20 and 21: 201. General Introductionliquid (84
Page 22 and 23: 1. General IntroductionAerosol size
Page 24 and 25: 1. General Introductionof numerous
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Page 46 and 47: 2. Chitosan And PLGAdichloromethane
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7. RFP Loaded PLGA Coated Chitosan
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8. Final Discussion and Conclusions
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9. References9. References1. Fred S
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9. References40. Wayne L.G., Good R
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1269. References88. Carpenter R.L.
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1289. References135. Fukushima S.;
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9. References173. Zeng X.M., Martin
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9. References219. Berthold A., Crem
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9. Referencesmediates target gene e
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