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Chemiczne aspekty celowanej terapii przeciwnowotworowej II. Połączenia nośnik -lek

Werengowska K. M., Wiśniewski M., Terzyk A.P., Gurtowska N., Drewa T. A., Olkowska J.

Wiadomości Chemiczne

2012

[Z] 66, 7-8

637-670

Traditional anticancer therapy is usually low effective. Popular and common drugs applied in anticancer therapy are characterized by low solubility and nonspecific biodistribution in an organism. The chemotherapy kills not only cancer but also healthy cells [4]. Building of modern drug delivery systems based on nanocarriers is a new method of anticancer treatment. The present study is directed towards nanomaterials (as carbon nanotubes, liposomes, polymeric micelles) as modern drug carriers. Thus, we characterized mechanisms of actions of traditional chemotherapeutics: paclitaxel, cisplatin and doxorubicin (Figs. 3–5) [1, 15, 21]. The purpose of this study is a description of the bioconjugation of drug-nanocarrier. Chemotherapeutics can be connected to external or internal surfaces of nanocarriers (Fig. 6) [6]. We described two main methods of drug delivery from internal space of nanocarriers: nanoextraction and nanocondensation (Fig. 7) [32]. The type of drug-carrier bonding can be covalent or noncovalent. We report recent advances in the field showing the formation of esters (Figs. 10–11) [28, 29, 53, 54], acethylhydrazone (Fig. 12) [55–61], amides [62–64], and disulfides groups [12, 65]. These reactions depend on functional groups in structures of drugs and require suitable modification of nanocarrier surfaces. In practice, the functionalization of nanocarrier surface is associated with the covering with polymers including PE G, HPMA, PG and PL GA [3]. Adsorption is the most popular process of bonding chemotherapeutic and nanomaterials (Fig. 13) [66]. Special attention is paid to electrostatic interaction between drugs: paclitaxel [74], cisplatin [59, 76, 77], doxorubicin [67–73] and nanocarriers: carbon nanotubes and/or polymeric micells. By application of modern anticancer therapy, drugs are preserved from lysosomal degradation and to fast reaction in biological environment. Finally, nanocarriers improve adsorption of drug and increase concentration of drug only in cancer tissues [6, 7].

Chemiczne aspekty celowanej terapii przeciwnowotworowej I. Kowalencyjne połączenia ligand-nośnik

Werengowska K. M., Wiśniewski M., Terzyk A.P., Gurtowska N., Drewa T. A.

Wiadomości Chemiczne

2011

[Z] 65, 9-10

887-915

In this study we describe the most popular biomedical engineering nanoparticles including carbon nanotubes [17-20], liposomes [4-7], polymeric micells [11-13], quantum dots [3, 21-23], hydrogels [24-27], dendrimers [14-16] which are recently considered as modern drug carriers. These nanomaterials are applied for cancer diagnostic and targeted delivery of active compounds as chemotherapeutics in so called targeted therapy. Thus, we characterized the ideas of targeted therapy for which compositions of carriers with antibody are constructed (Figs. 3, 4). We also compared the traditional and targeted mechanisms [1, 3, 28-29] of drug delivery (Fig. 2). During targeted therapy only the essential dose of drug (less than during conventional chemotherapy) is delivering to the cancer cell. In additional, the application of targeted therapy reduces side effects, being very characteristic for the traditional treatment. The anticancer compound can selectively hits the target only, due to the presence of the ligands attached to the surface of nanocarirer. We characterized ligands which are often use in nanomedicine: antibodies [33-37], folic acid [30-33], peptides [33, 38, 39], aptamers [33, 40, 41] and transferrin [33, 42-44]. The purpose of this study is description of the bioconjugation of ligand-nanocarrier. This step is necessary and very important in synthesis of the novel drug delivery systems in targeted anticancer therapy. We report recent advances in the field showing the formation of amides (Figs. 6-8) [51-57], thioethers (Figs. 9-11) [52, 60-66], disulfides (Fig. 12) [69], and acethyl-hydrazone groups (Fig. 13) [73]. Special attention is paid to the process such as Diels-Alder (Figs. 14, 15) [74, 75] and "click chemistry" through the cycloaddition of Huisgen (Figs. 16, 17) [79-82]. We describe also the reaction of Staudinger [83] and the process of formation Schiff 's base [84]. The processes enable very mild and selective modification of the carriers through formation of amide bound. These methods ware less popular but allow the fictionalization of nanocarriers in biomedical application. Each reaction or process needs special and individual environment and conditions, which are summarized in Table 1.