Drug Delivery and Controlled Release

The great progress in drug delivery systems has recently been made in the treatment of a variety of diseases. Targeting delivery of drugs to the diseased lesions is one of the most important aspects of the drug delivery system. To convey a sufficient dose of drug to the lesion, suitable carriers of drugs are needed. Nano- and microparticle carriers have important potential applications for the administration of therapeutic molecules. Nanocapsules, which are ultrafine oily droplet-coated polymeric substances, are probably one of the most promising candidates for colloidal carriers. Surface engineering by the interfacial deposition method can provide a suitable size distribution and necessary surface characteristics to the nanocapsules. Microparticles and nanoparticles as colloidal drug carriers in the micrometer and submicrometer range have been developed to overcome solubility problems of poorly soluble drugs as well as for long acting injectable depot formulations and specific drug targeting options, and they have also been evaluated for ophthalmic drug delivery purposes. Figure 23 gives a diagrammatic representation of liposomes, nanospheres, and nanocapsules for drug targeting.

Drugs are loaded into the nanoparticles by several methods. One method is by producing the nanocapsules in the presence of the drug. Drugs may also be loaded into empty particles prepared ahead of time. The drug, the polymer, and the means of preparation all influence the type of interaction with the polymer, the attachment of the drug to the nanoparticles or nanocapsules, and the rate of their interaction. Encapsulating drug molecules inside host molecules has obvious benefits: (i) protection of the drug from degradation; (ii) control over the hydrophilic/lipophilic balance of the capsule by modification of the host molecule, and (iii) good potential for targeting of the drug by equipping the capsule with appropriate recognition groups.

Some important practices for which nanocapsules are used include the adsorbing and coating of organs and tissues, peroral administration of drugs, vaccinations, the delivery of anti-inflammatory drugs, and the delivery of drugs for diseases and tumors. Nanocapsules can be targeted to specific organs or tissues by coating their surface with different materials. Nanocapsules are useful in this application due to their stability. Liposomes, on the other hand, often disintegrate due to the surfactants that are present in this method. Nanocapsules are also often used for peroral administration. An example of this can be applied to the digestive system. In order to influence the mode of interaction of the intestinal fluids with the intestine, the properties of these fluids are monitored in different tissues in the gut. Liposomes are often depleted by the salts present in these intestinal fluids, whereas nanoparticles are stable in the presence of these substances. In vaccination methods, nanoparticles have an advantage due to their slow degradation. This slow process allows for a longer interaction of the antigen with the immunocompetent cells of the body. Nanocapsules, as well


Figure 23. Diagrammatic representation of liposomes, nanospheres and nanocapsules for drug targeting. From homepage of E. Fattal, http://efattal.free.fr/.

as many other colloidal carriers, are enabling new methods for therapy in drug delivery.

The research in this area is being carried out all over the world at a great pace. Research areas cover novel properties that have been developed increased efficiency of drug delivery, improved release profiles and drug targeting. Many kinds of nanocapsules have been synthesized by a combination of different polymers and medicines as the shell and the core of the nanocapsules. The polymers, such as polyalkylcyanoacrylate, polyisobutylcyanoacry-late, poly(N-a, N-e-L-lysinediylterephthaloyl), poly(D, L-lactide), poly(ethylcyanoacrylate), isohexylcyanoacrylate, poly-e-caprolactone, poly(ethylene imine), poly(ethylene oxide-b-sebacic acid), polymethylidene, etc., and natural materials, like gelatin, melamine resin, etc., have been used to encapsulate various medicines, like insulin, peptides, indomethacin, cisplatin, calcitonin, doxorubicine, ganglio-sides, dodecanoate, oligonucleotides, etc. In the Sections 6.3.1-6.3.5, we collect literature with the same or similar topics concerning the materials used for the shell and the core of the nanocapsules. Ocular delivery and in vitro/in vivo studies will be represented separately in Sections 6.3.6 and 6.3.7. In the last Section, we will collect the review articles on the topic of drug delivery and controlled release.

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