Dendritic drug delivery systems

Dendrimers have been targeted in medical applications such as drug delivery as a consequence of their advantageous solubility characteristics, coupled to their multifunctional architecture, which enables drugs to be bound on or within the dendrimer, either via covalent or non-covalent means. 

The solubility characteristics of poly(ethylene glycol) systems in water has led to the employment of this polymer in alternative drug delivery systems. For example, Schluter 

Poly(amidoaniine) dendrimers have also been used to derivatise fullerenes with similar applications in mind [34]. 

---

Dendritic drug-delivery systems are acquiring increasing significance in the development of new cancer drugs having fewer side effects [60 b]. Thanks to a... 

Figure 8.4 The PEG terminated poly(aryl ether) dendritic drug delivery system reported by Frechet and co-workers [23].

Y. Zhao, X. Fan, D. Liu, and Z. Wang, PEGylated thermo-sensitive poly(amidoamine) dendritic drug delivery systems, Itit J Phartn, 409 (1-2), 229-36,2011. 

The application of dendritic polymers as drug delivery systems has gained interest mainly due to their inertness relative to temperature, solvent, and pH extremes [38]. However, dendritic polymers require further improvements in biocompability and biodistribution profiles. The cytotoxicity of dendrimers currently has been primarily studied in vitro. 

At the most fundamental level, monolayers of surfactants at an air-liquid interface serve as model systems to examine condensed matter phenomena. As we see briefly in Section 7.4, a rich variety of phases and structures occurs in such films, and phenomena such as nucleation, dendritic growth, and crystallization can be studied by a number of methods. Moreover, monolayers and bilayers of lipids can be used to model biological membranes and to produce vesicles and liposomes for potential applications in artificial blood substitutes and drug delivery systems (see, for example, Vignette 1.3 on liposomes in Chapter 1). 

An important application of dendritic polymers being explored in medicine is in advanced drug delivery systems. However, most applications within this field, described in the literature, deal with dendrimers and not with hyperbranched polymers. In a study on the effect of dendrimer size when used inside the human body, it was found [61] that large dendrimers Mw ca. 87,000) were excreted into the urine within two days, whereas smaller dendrimers (Myj ca. 5,000) accumulated mostly in the liver, kidney and spleen with no urine excretion. Hyperbranched polymers, being mostly polydisperse, are thus unsuitable in vivo applications. 

An important apphcation of dendritic polymers being explored in medicine is in advanced drug delivery systems. However, most appfications within this field, described in the literature, deal with dendrimers and not with hyperbranched polymers. Hyperbranched polymers, being mostly polydisperse, are unsuitable in vivo applications (Roberts et al., 1996). 

Targeted drug delivery systems for the anticancer drug Taxotere were built from jS-CyD by monoconjugation with mannosyldendritic branches. Binding inhibition of horseradish peroxidase-labeled Concanavalin A to yeast mannan by mannosylated yS-CyDs was examined. The IC50 values of 95, 96, 97, 98, and 99 were 800, 780, 91, 110, and 8 pM, respectively. 97 solubilized Taxotere similarly to monobranched CyDs [34]. The solubility of Taxotere in water can by increased 1000-fold by 97. 

PV. Kumar, H. Agashe, T. Dutta, N.K. Jain, PEGylated dendritic architecture for development of a prolonged drug delivery system for an antitubercular drug, Curr. Drug Deliv. 4 (2007) 11-19. 

Besides the examples given, a variety of other dendritic structures have been used to prepare carrier and drug delivery systems. For example, a... 

Fig. 4 Novel drug delivery systems using stimuli-responsive polymers, (a) Morphology changes of poly(2-isopropyl- 2-oxazoline) (PiPrOx) and poly(benzyl ether)dendrons dendritic-linear block copolymers conjugates are Temperature- and pH-dependent.[105] (Copyright 2012, Royal Society of Chemistry) (b) Protein-binding-induced disassembly of dendron-based micelles. This inducible micelle disassembly is selective to the targeted protein and the disassembly can mediate release of the encapsulated therapeutic drugs.[106] (Copyright 2010, American Chemical Society)...

Dendritic architectures (Rg. 3.8a) show very benefidal properties for the development of drug delivery systems and thus many different systems based on dendrimers,dendroms or hyperbranched polymers have been developed (Oliveira et al., 2010). In general, one can distinguish between two different release mechanisms from dendritic molecules depending on the way the... 

The problems of bio-functional polymers were diseussed on the 4 session. This session included 6 lectures. The speakers gave information about biofunctional dendritic architectures, biocompatible and bioactive polymers containing saccharide fimctionality, design and mechanisms of antimicrobial polymers, control of protein adsorption on functionalized electrospun fibers, microcapsules and nanoparticles for controlled delivery and repair, smart nanocarriers for bioseparation and responsive drug delivery systems. 

---