Recent Progress in Polymer Therapeutics as Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 109

proliferative, anti-angiogenic properties [41]. The anti-angiogenic
agents TNP-470 and alendronate were also conjugated with HPMA
copolymer using the RAFT technique [32]. The combination of these
two agents showed to have a synergistic anti-angiogenic eff ect.
Therefore, the conjugation of both TNP-470 and alendronate with
HPMA copolymer could serve both as an efficient bone drug delivery
system and as a potent anti-cancer combination therapy.
Another fascinating direction is the combined delivery of a
drug with DNA or RNA. For example, Wang et al. [164] designed a
biodegradable cationic amphiphilic copolymer, composed of poly( N -
methyldietheneamine sebacate) (PMDS) cationic main chain and
cholesterol side chains. This copolymer self-assembles in aqueous
solution forming a hydrophobic cholesterol core and a cationic shell.
Paclitaxel was encapsulated in the hydrophobic core, while IL-12-
encoded plasmid was used as therapeutic gene electrostatically
attached to the cationic shell. These polymeric micelles were
delivered into 4T1 mouse breast tumors, showing a significantly
reduced growth rate of the tumors. In vitro examination of paclitaxel
and Bcl-2-targeted siRNA combination using these polymeric
micelles showed synergistic eff ect as well [164].
As demonstrated in the examples above, polymeric systems
are the ideal platform for true combination therapy, where the
therapeutics are given simultaneously in one injection and share
the same pharmacokinetic profile. This exciting field holds great
promise and is rapidly evolving.

4.8 Summary and a Look into the Future

There is a growing number of polymer therapeutics entering clinical
trials. As we can see in this chapter, the literature is full of studies
on polymer-drug conjugates, polymer-protein conjugates, defined-
shape polymer architectures, and polyplexes. However, only few
polymeric nano-carriers have reached the market. One obstacle is
the regulatory issue. All polymer therapeutics are considered new
chemical entities (NCEs) [165], since the drug is covalently bound
to the polymeric carriers, as opposed to the conventional drug
delivery systems, in which the drug is entrapped. The heterogeneity
of the polymer product, molecular weight, and biodegradability of
the polymer backbone are important parameters that influence the