Polymeric drugs have been investigated in experimental as well as clinical settings such as SMANCS and L-asparaaginase since 1970 s. Accumulated data show that there are common characteristics among wide range of polymer therapeutics : i. e. prolonged plasma half-life, highly efficient tumor targeting capability and EPR (enhanced permeability and retention) effect. The factors involved in EPR effect are common denominators in both cancer and inflammation, indicating that EPR effect of polymer drugs can be applicable to infectious and inflammatory diseases in addition to cancer. Remarkable clinical effects of PEG-interferon α conjugates and related issues are also described as promising future prospects of polymeric drugs.

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In 1975 Prof. Ringsdorf already proposed the systematic model for polymeric drugs (polymer-drug conjugates or macromolecular prodrugs), so-called “Ringsdorf's model”, aiming at enhancement and prolongation of activity of drugs, and reduced side-effects of drugs. In this review, the authors introduce the recent advances in macromolecular prodrug researches, from the stand-points of the structures(shapes) of polymeric carriers, the controlled release by polymer-drug linkages and the drug-targeting by homing devices, with discussing about what kind of concepts proposed in the “Ringsdorf's model” have been achieved or progressed.

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This review presents the outstanding contributions and preparative techniques in mainly polymeric nanoparticles used as drug delivery systems. Nanoparticles discussed here vary in the diameter from 10 to 1000 nm. The formation of nanoparticles composed of one polymer chain and many polymer chains is reviewed in terms of the intrapolymer and interpolymer self-association and methods of preparation and drug loading are briefly described. Several methods to prepare nanoparticles by dispersing the preformed polymers are also demonstrated, e. g., solvent evaporation method and solvent diffusion method. Particles can be produced via a polymerization process from monomers. The preparative techniques for nanoparticles include emulsion polymerization, miniemulsion polymerization, and microemulsion polymerization. For drug incorporation, preparation of core-shell nanoparticles is also described. As a novel approach to fabricate nanopartides, supra-molecular structured materials such as dendrimers are introduced. Finally, our attempts to utilize nanoparticles for cell-death induction are stated and the concept of ‘cell-death programmed cell’ is proposed in this literature.

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Recent progress and further application of polyethylene glycol (PEG)-graftedliposomes were reviewed. PEG coating on the liposomal surface reduces the uptake by reticuloendothelial system to prolong the circulation in blood. In addition to the conventional preparation procedure, such as hydration or reversed phase evaporation method, PEG liposomes were also prepared by incubation of PEG-lipid derivatives with pre-formed liposomes. In the latter case, PEG molecules were coated on only outer surface of the liposomal membranes. Encapsulation efficiency, permeability and stability of PEG-grafted liposomes depend on the kind of PEG-lipid derivatives used. Especially, conformational change of grafted PEG from mushroom to brush structure influences on the encapsulation efficiency, permeability and finally the long-circulation properties. Passive targeting with PEG liposomal carrier system has been investigated in the field of cancer chemotherapy. Doxorubicin-encapsulated PEG liposomes(Doxil) in AIDS-related Kaposi's sarcoma is the only PEG liposomal product commercially available. As for active targeting following passive targeting to the target site, two types of PEG-immunoliposomes and ligand-attached liposomes were studied in terms of the targeting and receptor-mediated endocytosis into the target cells. There are many advantages on the use of PEG liposomal formulation for drug delivery, however, questions on the benefit of PEG-coating have been raised from the resent study. In addition to the long-circulation property of PEG liposomes, further functional properties such as degradation or fusogenicity should be required for the PEG liposomal drug delivery in the future.

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The two major somatic gene transfer approaches employ viral or nonviral vectors. Viral vectors have been shown to be efficient in delivering DNA to cells in vitro and in vivo. However, they are deficient in several areas, For example, adenoviral vectors induce a host immune response, rendering these vectors ineffective in repeated applications. Alternatively, poor transfection efficiency is the major drawback of non-viral vector. If the transgfection efficiency can be improved, the non-viral vectors would have potential of becoming the vectors for choice for gene therapy. We revealed that addition of ligand or lectin to liposome yields large enhancement of transfection efficiency in human lung cancer cells. These results indicated ligand or lectin-facilitated transfection is an efficient gene delivery strategy. Employment of cell type-specific ligands or lectins may allow for efficient cell type-specific gene targeting.

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Recently, an organotypic culture technique has been applied to develop three-dimentional skin tissues. This skin model can be used to predict the percutaneous absorption as well as the treatment of wounds and the safty and efficacy assesrnent of various skin care products. This paper has investigated the penetration and metabolism through a human skin model, Living Skin Equivalent (LSE), and discussed usefulness of this skin model for percutaneous absorption. The steady-state penetration rate of prednisolone (PN) through the LSE was 13.3 times higher than that through hairless mouse skin. On the other hand, a prednisolone prodrug, prednisolone 21-acetate(PNA), was metabolized to PN in the LSE in a similar manner in the human skin. Therefore, the culture-skin model may be used for the prediction of metabolic profiles in human skin.

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