Polymer-based targeting

Polymeric microparticles have been studied and developed for several years. Their contribution in the pharmacy field is of utmost importance in order to improve the efficiency of oral delivery of drugs. As drug carriers, polymer-based microparticles may avoid the early degradation of active molecules in undesirable sites of the gastrointestinal tract, mask unpleasant taste of drugs, reduce doses and side effects and improve bioavailability. Also, they allow the production of site-specific drug targeting, which consists of a suitable approach for the delivery of active molecules into desired tissues or cells in order to increase their efficiency. 

Bayer MaterialScience (Germany) in the Project "Dream Production" combines part of waste streams of coal-fired power plants, CO2, with the production of polymers. The target is the design and development of a technical process able to produce C02-based polyether polycarbonate polyols on a large scale. The first step was to convert the C02 in new polyols, and these polyols showed similar properties such as products already on the market and can be processed in conventional plans as well (Figure 22). 

Bellocq NC, Pun SH, Jensen GS, Davis ME (2003) Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery. Bioconjug Chem 14 1122-1132... 

Davis ME (2009) The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle from concept to clinic. Mol Pharmaceutics 6 659-668... 

Of the non-antibody, non-liposome based drug targeting strategies, most of the (limited) clinical experience has been obtained with polymer-based conjugates of anticancer drugs. The most widely employed drugs for this application are cytotoxic agents such as doxorubicin and... 

Attempts to optimize polymer-based electrodes for trace analysis have started very recently. Ceresa et al. have reported an ion-selective electrode optimized for the determination of Pb2+ in drinking water. The detection limit was 0.7 ppb (3 x 10 9M) which is somewhat poorer than the best LOD reported so far for Pb2+-selective electrodes [10] but the former was optimized for ruggedness and response time rather than LOD. Nevertheless, the obtained LOD was still adequate for the targeted application since it was about 20-fold lower than the 15 ppb action limit for Pb2+ in drinking water imposed by the USA EPA [79]. The authors used ICPMS as a reference method and obtained excellent correlation for samples of concentration 3nM. It was shown that the calibration procedure required ca. 10 min for stable readings in micromolar to nanomolar concentration levels. Moreover, the authors... 

Polymer-based colloidal drug delivery carriers include polymeric micelles, nano- and micro- particles, or coated particles, and hydrogels [886,890,891]. These are being developed for vaccines and anti-cancer drugs, for targeting of specific treatment sites within the body, and as vehicles for ophthalmic and oral delivery. Methods for the creation of multi-layer coatings are reviewed by Sukhorukov [892] (see also Figure 14.4). Numerous examples are cited by Ravi Kumar [893]. 

Overall, key takeaways from the nonpoly meric paclitaxel delivery studies were that despite their improvement of angiographic parameters, paclitaxel-eluting stents without a polymer carrier did not demonstrate a positive effect on clinical outcomes, as seen with polymer-based paclitaxel elution (65), discussed in the next section. Potential reasons for the failure of such an approach could be loss of drug to the systemic circulation prior to reaching the target site during the stent deployment procedure, variability associated with the dose delivered to the lesion, and lack of control over drug-release kinetics due to the absence of a polymer carrier. 

The alternative approach is to use non-viral vectors, such lipid-based, peptide-based and polymer-based delivery systems, as described in detail in Chapter 14. Liposomes are relatively easy to manufacture, are generally non-toxic and are devoid of the capability to cause an infection (see Section 5.3.1). However, a number of limitations are associated with their use. For example, it is difficult to direct liposomes to a particular type of cell. Liposome/DNA complexes which may be internalized by the target cells are... 

It is important to maintain low cytotoxicity, since transfection reagent-mediated toxicity could potentially mask the true phenotype of a target gene being studied. This chapter will attempt to describe the use of several cationic lipid/polymer-based transfection reagents for the in vitro delivery of siRNA and DNA. Emphasis will be laid on the key parameters that affect transfection efficacy. 

Transferrin-containing CD polymer-based nanoparticles were studied as nucleic acid delivery system that can be modified for targeted delivery of small interfering ribonucleic acid (siRNA) to cancer cells. Molecular studies showed that the siRNA CD nanoparticles reduced levels of Ewing s transcript by 80% and inhibited growth of cultured Ewing s tumor cell line. It was also reported that this delivery system indicated a lack of toxicity [39],... 

A self-assembly DNA-conjugated polymer-based DNA detection method was previously mentioned. This study showed specific immobilization to a gold substrate with the self-assembly technique, not physical adsorption and great selectivity to fully matched DNA instead of nonspecific adsorption due to self-assembly DNA-conjugated polyallylamine and PAA coating [67,68]. However, a major problem was that we needed to prepare many kinds of DNA-conjugated polymer to analyze many kinds of target DNA due to direct modification of probe DNA to the polymer side chain. 

Thus, the selective enrichment of the target analyte was successfully demonstrated using the imprinted polymer. Conventional SPE sometimes needs to be combined with a different type of SPE or other separation steps to complete pre-purification, because compounds with similar chemical properties may accompany the analyte as impurities. On the other hand, imprinted polymer is an affinity-type SPE sorbent that exhibits specificity for an analyte therefore, the imprinted polymer-based SPE is able to streamline the whole procedure of analysis. Although aqueous conditions were employed here, it is also notable that the utility in organic solvents is one of the useful characteristics of imprinted polymers as SPE sorbents [18,19]. 

Numerous polymer-based therapeutics are on the market or undergoing clinical evaluation to treat cancer and other diseases. Many of them are low molecular weight drug molecules or therapeutic proteins that are chemically linked to water-soluble polymers to increase drug solubility, drug stability, or enable site-specific transport of drugs to target tissues affected by the disease. 

The energy conversion from light to mechanical response is one of the most fascinating targets in or nic photochromic systems. Section 15.2 already indicated the light-driven droplet displacement. This section introduces the motion of Az polymers themselves. Rapid motions observed here mi t allow for applications of actuators of polymer-based micromachine systems. The photoinduced surface-relief generation described in the latter part of this section (Section 15.4.2) deals with much thicker films than monolayers. Howevei the mass miration in thicker films is closely related to the structure and properties of the monolayer systems. 

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