Biodegradable linkers

Modification of the drug structure by the covalent attachment of a water-solubilizing group through a biodegradable linker (e.g. poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), a water-soluble polymethacrylate derivative, a poly(amino acid) such as poly... 

Synthetic products have acquired a negative association due to synthetic food additives, but they show many valuable properties, especially in medical applications. Synthetic polymers are valuable for therapeutic use since they can be produced in a well-defined and controlled fashion, overcoming the greatest setback of natural polymers the batch-to-batch variation. Synthetic polymers often exhibit increased cytotoxicity due to the strong positive charge, but since they can be freely modified in order to introduce desired properties, their biocompatibility can be improved, for example by incorporation of biodegradable linkers and bioactive functionalities. ... 

FIGURE 2.3.1 An example of polymerization systems dextran carrying polymerizable methacrylate groups via biodegradable linkers can be polymerized to form biodegradable hydrogels. Reprinted with permission from Ref. [17]. 

The linker group that bridges the cationic lipid headgroup with the hydrocarbon moiety controls the biodegradability of a cationic amphiphile. Most of the linker bonds are ether, ester, or amide bonds (Fig. 1). Compounds with ether links generally render better transfection efficiency. However, they are more stable and may cause higher toxicity, while cationic lipids with ester links such as DOTAP are more biodegradable and less cytotoxic in cultured cells [28, 39]. Noteworthy,... 

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. 

Fig. 3 A tumor-targeted polymer-drug conjugate. The major elements include (i) a polymeric drug-carrier that is water-soluble, bicompatible or biodegradable, non-immunogenic (ii) targeting moieties (iii) a linker between a drug and the carrier. The linker can be a) a chemical bond such as ester or amide. An ester bond is more stable at lysosomal pH than at plasma pH (7.4) while an amide bond is stable at both lysosomal and plasma pH b) an oligopeptide linker that is degradable by specific enzymatic hydrolysis and c) an acid labile linker that is degradable at lysosomal pH but stable at plasma pH.

The linker determines the chemical stability and biodegradability of the cationic lipids. The most common link is the alkyl ether. 

Various researches have concentrated on biodegradable polymers, many of natural origin. - Work on biodegradable aoss-linkers that are commonly used for the construction of three-dimensional hydrogel networks has been reviewed. ... 

The group of Nagata incorporated UV-curable moieties directly into the main chain of the related polymers [41-43]. Thus, photocurable, biodegradable multiblock SMPs were prepared by polycondensation from PCL diol, PEG, and 5-cinnamoyloxyisophthalic acid [41]. The latter compounds acted as UV cross-linker without any photoinitiator. The semicrystalline photosets exhibited Tg----60 C, and in the range 35-47°C. Both and R values were... 

The feasibihty of the Diels-Alder coupling was shown on the example of biodegradable polyester by Ninh and Bettinger [47]. In this case, hyperbranched poly(glycerol-co-sebacate) with pendant furan groups was coupled with a bifunctional maleimide cross-linker to produce an elastomeric material. POSS moieties may serve as cross-linking sites, as well. Ishida et al. [48] have shown how a... 

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