Radiolabelled polymers

PIBCA nanospheres were injected subcutaneously to rats. Autoradiographic pictures obtained after using radiolabelled polymer have shown a progressive staining reduction in the muscular tissue suggesting that nanospheres were slowly biodegraded. In the same study, nanospheres were found to release a peptide (GRF) in a sustained manner. Comparison of the AUC of free GRF and GRF-loaded nanospheres showed that in addition to the slow release process nanospheres were able to improve the bioavailability of the peptide. This improvement could be attributed to the fact that free administered GRF is very quickly metabolized at the injection site, whereas it is partly protected from massive enzymatic degradation when it is administered associated with nanospheres. ... 

Autoradiography can directly identify and localize radiolabelled polymers in tissues Autoradiograms have very impressively shown the overall topography of polymer distribution in whole-body or organ sections . Similar techniques have been adopted for fluorescence-labelled polymers. ... 

One of the simplest methods to study adsorption at the oil water interface is to measure the variation of interfacial tension as a function of concentration. If the polymer used for adsorption is monodisperse, then the Gibbs equation (51) may be used to estimate the surface excess. However, if the polymer is polydis-perse, this method will give erroneous values of the surface excess because the larger molecules will tend to adsorb preferentially, and the equation is imable to account for this adsorption behavior. As a result, most of the data available in the literature report the change in the interfacial tension as a function of concentration without attempting to convert it into an adsorbed amoimt. Apart from interfacial tension measurements, other techniques such as total internal reflection fluorescence microscopy (52) and scintillation measurements from radiolabeled polymers (53) have also been used to measure the adsorption at the liquid-liquid interface. 

The adsorption of HEC and JR polymers on hair was studied by Goddard et al. [42] using radiolabelled polymers. In all experiments, the concentration of polymer was kept constant at 0.1 % and the amount sorbed (mg/g) was measured as a function of time for several days. The sorption of HEC reached equilibrium in 5 minutes, whereas with the charged JR polymers it did not reach its equilibrium value even after 2 days. The results are shown in Eig. 1.48, which shows the variation of the amount sorbed (mg/g) with time. 

Time -- 180 days or less if radiolabeled polymer is used 365 days or less. 

The potential role of enzymes in the degradation of polymers which are more stable than the aliphatic polyesters has also been studied by Williams "" and others." It has been shown that poly(ethylene terephthalate), an aromatic polyester, is degraded by enzymes with esterase activity and that nylon 6,6 and certain poly(ether urethane)s are degraded by a variety of enzymes under in vitro conditions. These studies were carried out using specially synthesized radiolabelled polymers. The only type of polymer not to suffer any degradation at all in the experiments of Williams was poly(methyl methacrylate). 

Whilst this prediction of in vivo stability is largely borne out in practice, there is some evidence that other factors are involved and that unexpected degradation mechanisms operate within the body. One of the first observations of degradation of these polymers was made by Oppenheimer" who was working on the carcinogenic properties of plastics. In attempting to elucidate the mechanisms by which plastic films induced tumours after subcutaneous implantation in rodents, certain radiolabelled polymers were employed. " C-labelled polystyrene, polyethylene and poly(methyl methacrylate) were implanted and urine, faeces and respiratory CO2 were monitored for periods over a year. With the polystyrene, nothing radioactive was excreted in the urine until 21 weeks, but some radioactivity was detected after this time. With polyethylene, radioactive species were excreted after 26 weeks and with poly(methyl methacrylate), this occurred after 54 weeks. 

The actual time required for poly-L-lactide implants to be completely absorbed is relatively long, and depends on polymer purity, processing conditions, implant site, and physical dimensions of the implant. For instance, 50—90 mg samples of radiolabeled poly-DL-lactide implanted in the abdominal walls of rats had an absorption time of 1.5 years with metaboHsm resulting primarily from respiratory excretion (24). In contrast, pure poly-L-lactide bone plates attached to sheep femora showed mechanical deterioration, but Httie evidence of significant mass loss even after four years (25). 

Aromatic fluorodenitration was first discovered in the reaction of polychloro-nitrobenzenes with potassium fluoride, when 2,3,5,6-tetrachlorofluorobenzene was prepared in 37% yield from 2,3,5,6-tetrachloronitrobenzene 105] The technique has been adapted to prepare aryl fluorides from other activated nitro aromatics for applications in pharmaceutical and polymer chemistry (equation 31) Fluorodenitration also has been applied to prepare radiolabeled ( F) fluo-roaromatics [74, 106]... 

Polymer formed using radiolabeled initiators may be isolated and analyzed to determine the concentration of initiator-derived residues and calculate the initiator efficiency. Radiolabeled initiators have also been used extensively to establish the relati ve reactivity of monomers towards radicals. 107,5 -5 2... 

Komarek, R.J., Gardner, R.M., Buchanan, C.M. and Gedon, S. (1993). Biodegradation of radiolabelled cellulose acetate and cellulose propionate. Journal of Applied Polymer Science, 50(10), 1739-1746. 

In vivo methods, which are few, measure the residence time of bioadhesives at the application site [47]. Techniques like y-scintigraphy, the perfused intestinal loop and radiolabeled transit studies using Cr-labeled bioadhesive polymer [48] and Tc-labeled polycarbophil [49] have been employed for this purpose. 

The first attempt to radiolabel drug particles (instead of polymers like polystyrene or Teflon particles) for pharmaceutical aerosols was carried out on fenoterol and salbutamol by Kohler et al. [12] Scheme 3). However, it was later found that their method would change the particle size distribution of the labelled aerosol, resulting in a coarser aerosol than the imlabelled product. After subsequent improvement by Summers et al. [18] Scheme 4), this method has become widely used for radiolabelling MDIs. It is preferred over other methods as it does not involve extraction with tetraphenylarsonium chloride and chloroform. 

Title Preparation of Radiolabeled Haloaromatics via Polymer-Bound Intermediates... 

Polymer precursors of radiolabeled 4-13 iodine benzoic, (I), and amide derivatives were previously prepared by the authors (4) as illustrated in Eq. (3). 

Surugiu et al. [67] have introduced an Enzyme Immuno-Like Assays (EzILA) for the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The label was a 2,4-D conjugate with the tobacco peroxidase (TOP) enzyme, which allows for both colorimetric and chemiluminescent detection. In this case, the polymer imprinted with 2,4-D was synthesized in the form of microspheres. In contrast, despite its higher binding capacity for radiolabeled 2,4-D, a conventional MIP prepared by bulk polymerization showed only weak binding of the 2,4-D-TOP tracer. 

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