Biodegradable dendrimers

Jianbin, T. Xingping, W. Xinping, W. Meihua, S. Weiwei, M. Youqing, S. p-Cyclodextrin-based biodegradable dendrimers for drug delivery. J. Control. Release 2011, 752 (Suppl. 1), el-el32. 

However, the progress of biodegradable dendritic compounds with suitable physicochemical and pharmacodynamic properties is challenging due to undesired and/or premature degradation during synthesis, purification, and subsequent functionalization and processing steps (van der Poll et al., 2010). In fact, these obstacles may explain the still reduced number of reports where biodegradable dendrimers are applied for a particular function in biomedicine (Leiro et al., 2015). 

Amir, R. J. Shabat, D. Self-immolative dendrimer biodegradability by multi-enzymatic triggering. Chem. Commun. 2004, 1614-1615. 

In our group, several dendrimers based on ( R)-3-hydroxybutanoic acid (HB) have been prepared [56-58]. The dendrimers were synthesized by the convergent strategy. Trimesic acid has been used as core unit and the benzyl esters of the dimer and the tetramer of HB as elongation units. In such a way dendrimers of 1st and 2nd generation (27-30) have been constructed (Fig. 13). Since poly(.R)-3-hydroxybutanoic acid (PHB) is known to be biodegradable [59, 60] the stability of the dendrimers 27-30 was tested in the presence of PHB-de-... 

Fig. 8 Nanosystems that may function as simultaneous drug delivery and imaging agents for targeting T cells (a) liposomal systems, (b) solid biodegradable nanoparticulates, and (c) macro-molecular dendrimer complexes. PEG polyethylene glycol, Gd-DTPA gadolininum-diethylene triamine penta acetic acid. (Adapted from [48])...

The chemical composition of particles can be just as varied as their shape. Commercial particles can consist of polymers or copolymers, inorganic constructs, metals and semiconductors, superparamagnetic composites, biodegradable constructs, and synthetic dendrimers and dendrons. Often, both the composition of a particle and its shape govern its suitability for a particular purpose. For instance, composite particles containing superparamagnetic iron oxide typically are used for small-scale affinity separations, especially for cell separations followed by flow cytometry analysis or fluorescence-activated cell sorting (FACS). Core-shell semiconductor particles, by... 

Particles from cationic lipids may also be useful for antisense therapy of skin disease — a nontoxic increase in the oligonucleotide uptake by cultivated keratinocytes and a sebocyte cell line has been reported [66]. Moreover, cationic dendri-mers also efficiently transfer reporter gene DNA to human keratinocytes cultivated in vitro. In the skin of hairless mice, in vivo transfection was possible with complexes, yet reporter gene expression was localized to perifollicular areas. Transfection, however, failed with the naked plasmid. For prolonged contact, biodegradable membranes coated with dendrimer/DNA complexes were used [67]. This hints at a follicular uptake of these complexes and indicates that gene transfection also may be possible with human skin, which has a thicker stratum comeum compared with mouse skin (eight to ten vs. two to three layers [58]). 

Dendrimers are three-dimensional hyperbranched, globular macromolecules that are capable of condensing DNA into small complexes, and thereby increase plasmid transfection efficiency (14). Dendrimers are typically stable in serum and not temperature sensitive, but are also non-biodegradable and cause significant cytotoxicity. 

Biodegradable Polymers as Drug Carriers, p. 176. Colloids and Colloid Drug Delivery System, p. 636. Dendrimers, p. 872. 

In industry, several dendrimers are already being synthesized on a hundred kilogram scale. The hopes for effective solubilizing systems suitable for medical applications may, however, not be justified. Phenolic ether or polyamine compounds are both normally not biodegradable so that major problems are foreseeable. An alternative is the employment of hydrolysable polyesters. One such compound already reported, is the imperfectly hyperbranched dendrimer which is easily accessible via thermal self-condensation of 3,5-bis(trimethyl-siloxyjbenzoyl chloride. This one-step procedure leads to a dendritic polyester... 

Keywords Active substances, additives, biodegradable systems, coated systems, dendrimers, environment sensitive systems, matrix diffusion systems, membrane controlled systems, micro, and nanoparticles, mucoadhesion... 

Biodegradable Polymers Used in Preparation of Dendrimers and Their Application... 

---