Polymers clinical applications

Since the pioneer work by Merigan in 1967 [1], many kinds of synthetic or natural polyanionic polymers have been examined for their biological activities [2-8], such as cytotoxicity, antiviral activity, antitumor activity, and immunomodulating activity. Although the biological results were interesting, the extent of activity for clinical application was still low. 

The technique is currently not used as widely as UV, visible and infrared spectrometry partly due to the high cost of instrumentation. However, it is a powerful technique for the characterization of a wide range of natural products, raw materials, intermediates and manufactured items especially if used in conjunction with other spectrometric methods. Its ability to identify major molecular structural features is useful in following synthetic routes and to help establish the nature of competitive products, especially for manufacturers of polymers, paints, organic chemicals and pharmaceuticals. An important clinical application is NMR imaging where a three-dimensional picture of the whole or parts of a patient s body can be built up through the accumulation of proton spectra recorded over many different angles. The technique involves costly instrumentation but is preferable to... 

Of these the last one has been most widely used, since heparin-modified polymeric materials exhibit the highest and by today unsurpassed effects of thromboresistance enhancement. Many of these materials have not only proved to be potent in trials on animals, but have already found clinical application. These achievements have stimulated continuous interest in heparin-containing polymers (HCP) which is best manifested by listing the investigations performed in the field in recent years and still under way. They involve the new procedures for the synthesis of HCP providing minimal loss of activity of bound heparin, the studies of interactions of HCP with blood and its individual components, as well as on the mechanism of enhanced thromboresistance of HCP, and the search for new tasks for HCP. 

It is anticipated that in the coming years, a number of HA-derivatives will appear for clinical application in Dermatology that contain cross-linked HA polymers as well as HA-ester derivatives obtained by the conjugation of the carboxylic acid of HA with various drugs in their alcohol forms. The HA polymer, because of its intrinsic biocompatibility, reactivity, and degradability, will have many uses in the rapidly expanding field of tissue engineering and in the tissue substitutes of the future. 

A review article on synthetic polymers with antiviral activity and their clinical application has been published by Tarasov et al. (51). 

Vast pharmacological investigations have so far been carried out only with the preparations PVP and PVNO, which had already found clinical applications. For other polymers there are only scattered data which, however, do not show any particularities in comparison with PVP and PVNO. 

Clinical applications of thermosensitive hydrogels based on NIPAAm and its derivatives have limitations [121], The monomers and cross-linkers used in the synthesis of the hydrogels are still not known to be biocompatible and biodegradable. The observation that acrylamide-based polymers activate platelets upon contact with blood, together with the unclear metabolism of poly(NIPAAm), requires extensive toxicity studies before clinical applications can merge. 

Okano and coworkers have patterned poly(N-isopropylacryl-amide) (PNIPAAm), a material similar to BSA and PEG in that it does not adhere to cells at room temperature. In this experiment, a composite solution of PNIPAAm dissolved in propanol (55 wt%) was uniformly coated inside a commercial cell culture dish. The polymer was then patterned, using standard e-beam lithography, onto the surface of a cell culture dish to test the dynamic behavior of cells for potential clinical applications. A metal mask (60 mm o.d. 

Polymer libraries are covered according to their numerous applications, each described through a specific example. The reported examples include libraries of copolymers as liquid/solid supports with different compositions, libraries of biodegradable materials for clinical applications, libraries of stationary phases for GC/LC separations, libraries of polymeric reagents or catalysts, libraries of artificial polymeric receptors or molecularly imprinted polymers, and libraries of polymeric biosensors. The opportunities that could arise in the near future from novel applications of polymer libraries are also briefly discussed. 

Adsorbents are used in medicine mainly for the treatment of acute poisoning, whereas other extracorporeal techniques based on physico-chemical principles, such as dialysis and ultrafiltration, currently have much wider clinical applications [1]. Nevertheless, there are medical conditions, such as acute inflammation, hepatic and multi-organ failure and sepsis, for which mortality rates have not improved in the last forty years. These conditions are usually associated with the presence of endotoxin - lipopolysaccharide (LPS) or inflammatory cytokines - molecules of peptide/protein nature [2]. Advantages of adsorption over other extracorporeal techniques include ability to adsorb high molecular mass (HMM) metabolites and toxins. Conventional adsorbents, however, have poor biocompatibility. They are used coated with a semipermeable membrane of a more biocompatible material to allow for a direct contact with blood. Respectively, ability of coated adsorbents to remove HMM solutes is dramatically reduced. In this paper, preliminary results on adsorption of LPS and one of the most common inflammatory cytokines, TNF-a, on uncoated porous polymers and activated carbons, are presented. The aim of this work is to estimate the potential of extracorporeal adsorption technique to remove these substances and to relate it to the porous structure of adsorbents. 

Although the interesting results obtained in many smdies, the lack of cUnical-grade polymers and the difficulties in the production of uniform capsules with excellent repeatability and reproducibUity, stiU hmits the clinical applications of this technology [26]. 

Nanoparticles were first developed in the mid-seventies by Birrenbach and Speiser. Later on, their application for the design of drug delivery systems was made available by the use of biodegradable polymers that were considered to be highly suitable for human applications. At that time, the research on colloidal carriers was mainly focusing on liposomes, but no one was able to produce stable lipid vesicles suitable for clinical applications. In some cases, nanoparticles have been shown to be more active than liposomes due to their better stability.This is the reason why in the last decades many drugs (e.g., antibiotics, antiviral and antiparasitic drugs, cytostatics, protein and peptides) were associated to nanoparticles. 

Drug Stability Principles and Practices, Jens T. Carstensen Pharmaceutical Statistics Practical and Clinical Applications, Second Edition, Revised and Expanded, Sanford Bolton Biodegradable Polymers as Drug Delivery Systems, edited by Mark Chasin and Robert Langer... 

Among the many classes of polymeric materials now available for use as biomaterials, non-degradable, hydrophobic polymers are the most widely used. Silicone, polyethylene, polyurethanes, PMMA, and EVAc account for the majority of polymeric materials currently used in clinical applications. Consider, for example, the medical applications listed in Table A.l most of these applications require a polymer that does not change substantially during the period of use. This chapter describes some of the most commonly used non-degradable polymers that are used as biomaterials, with an emphasis on their use in drug delivery systems. 

R.L. Dunn, Clinical Applications and Update on the Poly(a-hydroxy acids). Biomedical Applications of Synthetic Biodegradable Polymers (Ed. J.O. Hollinger), CRC Press, New York, p. 17-31,1995. 

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