Chemistry Reference
In-Depth Information
(organosiloxane) polymer in 1995 [56], a degradable polysiloxane dendrimer was
embedded into a methacrylate resin and an acidic hydrolysis allowed the degradation
of the dendrimer for making some nanocavities, in an analogy to molecular imprint-
ing [57]. Those four events made the early experimental history of a real intention to
use the degradable properties of a dendrimer or a hyperbranched polymer.
Early in the 1920s, only a few reports existed on degradable dendrimers. Some new
interests slowly grew up in 2000 from the first photorelease of some molecular species
by a photo-induced covalent fragmentation where dendrimers could be seen as a
“covalent reservoir” of those species [58]. McGrath reinforced the concept of
“cleavable dendrimers” [59].
However, several circumstantial events almost happened in the same period, and
really propulsed the field of cleavable dendrimers toward an exponential production
of publications and patents, after breaking the news in many journals in 2003. Three
independent research groups lead by de Groot, Shabat, and McGrath investigated
some controlled chemical and biochemical means to cleave dendrimers by some
well-thought strategies involving cascade reactions and some initiators or triggers
(see below). A few expressions were put forward in many headlines of journals:
exploding dendrimers [60], self-immolative dendrimers [61], and self-destructive
dendrimers [62].
In 2007, the first compilation of literature data dedicated to degradable or cleavable
dendrimers was published by us [1]. Nowadays, a literature search (ISI Web of
Knowledge
, all databases) estimated to bemore than 135 publications the results of a
search with the terms “degradable or biodegradable dendrimers,” where degradation
and covalent cleavage of chemical bonds were declared as important factors. We can
roughly estimate to more than 1070 manuscripts (excluding patents) using the search
terms “dendrimers and drug delivery,” including 210 reviews with 25% (52) of the
production in 2008 and only a few ones published before 1999 (4). The number of
manuscripts exponentially increased from 1993, when a transfection of DNA with
PAMAM dendrimers was demonstrated [26]. Solely in 2008, 208 publications (20%)
were produced, compared to 25 in the year 2000 (2.3%). The vast majority of the
studies concerned the following domains: pharmacy, biochemistry, chemistry,
materials science, and oncology. However, the number of publications describing
the release of drugs by covalent bonds dissociation via a dendrimer-drug conjugate
is much less important, compared to a noncovalent drug delivery via an encap-
sulation (or an inclusion complex). As a comparative study [48], even if dendrimers
are excellent vectors and vehicles for drug transportation, the field of polymer
therapeutics [10,63-67] largely bypassed the number of publications in dendri-
mer-based delivery (roughly 7000 versus 1070). Relative to dendrimers, the field
of degradable polymers already acquired a certain scientific maturity many years
ago [68].
The development of degradable dendrimers could only progress after mastering
the synthetic strategies and the methodologies for making them, where many
chemical reactions for assembling dendrimers were specifically chosen for their
simplicity, for a neglected amount of by-products, for an easy purification and for
some high-yielding processes over multiple bonds formation, without too much
