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

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1. General Introductionintermittent administration. Exfoliative dermatitis is more frequent in HIV-positive TBpatients. Temporary oliguria, dyspnoea and haemolytic anaemia have also been reported inpatients taking the drug three times weekly. These reactions usually subside if the regimen ischanged to one with daily dosage. However, dose-related hepatitis can occur which ispotentially fatal.RFP induces hepatic enzymes, and may increase the dosage requirements of drugsmetabolized in the liver. These include corticosteroids, steroid contraceptives, oralhypoglycaemic agents, oral anticoagulants, phenytoin, cimetidine, cyclosporin and digitalisglycosides.1.6. Microspheres as Controlled Delivery SystemsDrug delivery systems (DDS) that can precisely control the release rates or target drugs to aspecificbody site have had an enormous impact on the healthcare system. The last two decades in thepharmaceutical industry have witnessed an avant-garde interaction among the fields ofpolymer and material science, resulting in the development of novel drug delivery systems(128). Carrier technology offers an intelligent approach for drug delivery by coupling the drugto a carrier particle such as microspheres, nanoparticles, liposomes, etc. which modulates therelease and absorption characteristics of the drug.Conventional drug administration does not usually provide rate-controlled release or targetspecificity. In many cases, conventional drug delivery provides sharp increases of drugconcentration at potentially toxic levels. Following a relatively short period at the therapeuticlevel, drug concentration eventually drops off until re-administration.Today new methods of drug delivery are possible: desired drug release can be provided byrate-controlling membranes or by implanted biodegradable polymers containing dispersedmedication. Over the past 25 years much research has also been focused on degradablepolymer microspheres for drug delivery. Microspheres constitute an important part of theseparticulate DDS by virtue of their small size and efficient carrier characteristics.Administration of medication via such systems is advantageous because microspheres can beingested, injected or inhaled; they can be tailored for desired release profiles and in somecases can even provide organ-targeted release. The idea of controlled release from polymersdates back to the 1960s through the employment of silicone rubber (129) and polyethylene(130). The lack of degradability in these systems implies the requirement of eventual surgical26
1. General Introductionremoval and limits their applicability. In the 1970s biodegradable polymers were suggested asappropriate drug delivery materials circumventing the requirement of removal (131). The ideaof polymer microspheres as delivery systems was reported as early as the 1960s (132) anddegradation was incorporated by Mason et al. (133) through the employment of a degradablepolymer.Recent literature shows that suspensions of degradable microspheres can be employed forsustained drug release at desirable doses. Biocompatibility can be achieved by the use ofnatural polymers such as cellulose, chitin, and chitosan or by the employment of semisynteticpolymers made from naturally occurring monomers such as lactic and glycolic acids.Polymers derived from synthetic monomers also show excellent delivery properties.However, their toxicity effects may require evaluation. The factors affecting drug release arecontrollable; they are attributed to properties such as polymer molecular weight, as well asmicrosphere size, distribution, morphology and make-up.For preparation of microspheres using biodegradable polymers, it is important to choose anappropriate encapsulation process which meets the following requirements. First, thechemical stability and biological activity of the incorporated drugs should be maintainedduring the encapsulation process. For example, since most proteins are readily denatured uponcontact with hydrophobic organic solvents or acidic/basic aqueous solutions, the processshould avoid such harshenvironments. Second, the encapsulation efficiency and the yield of the microparticles shouldbe high enough for mass production. Third, the microparticles produced should have thereasonable size range. Fourth, the release profile of the drug should be reproducible withoutthe significant initial burst. Fifth, the process employed should produce free-flowingmicroparticles, thus making it easy to prepare uniform suspension of the microparticles. Thereare a number of techniques available for microencapsulation of drugs such as the emulsionsolventevaporation/extraction method, spray drying, phase separation-coacervation,interfacial deposition, precipitation method, in situ polymerization, etc. Each method has itsown advantages and disadvantages. The choice of a particular technique depends on theattributes of the polymer and the drug, the site of the drug action, and the duration of thetherapy (134, 135, 136).Increasing or controlling the encapsulation efficiency (E%) is desirable, it can prevent the lossof precious medication and it can help to extend the duration and dosage of treatment. Yang etal. (137) have provided a revealing study which correlated the encapsulation efficiency to27
Page 1: European Union Ministero dell’Uni
Page 5 and 6: Table Of Contents1. GENERAL INTRODU
Page 7: 7.1.4. Release Studies/Stability St
Page 10 and 11: 1. General Introduction1.1. Pulmona
Page 12 and 13: 1. General Introductionmucosa, and
Page 14 and 15: 1. General Introductionis the fact
Page 16 and 17: 1.3. Lung Anatomy1. General Introdu
Page 18 and 19: 1. General Introductionhighly vascu
Page 20 and 21: 201. General Introductionliquid (84
Page 22 and 23: 1. General IntroductionAerosol size
Page 24 and 25: 1. General Introductionof numerous
Page 28 and 29: 1. General Introductionsphere prepa
Page 30 and 31: 1. General Introductionit, respecti
Page 32 and 33: 1. General Introductionthe subject
Page 34 and 35: 1. General IntroductionA. zahoor et
Page 36 and 37: 2. Chitosan And PLGA2.1. Chitosan a
Page 38 and 39: 2. Chitosan And PLGAfor the prepara
Page 40 and 41: 2. Chitosan And PLGAmainly controll
Page 42 and 43: 2. Chitosan And PLGAAt present, a n
Page 44 and 45: 2. Chitosan And PLGAneed to be a go
Page 46 and 47: 2. Chitosan And PLGAdichloromethane
Page 49 and 50: 3. Aim of the Work49
Page 51: 3. Aim of the WorkBiodegradable mic
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5. RFP Loaded Chitosan Microspheres
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6. RFP Loaded PLGA Microspheres Pre
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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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