Polyethylene Glycol Polyester Block Copolymers: Biocompatible Carriers for Nanoparticulate Drug Delivery - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 60

compared with diblock PEO-PCL micelles. Therefore micelles with
more dense lipophilic cores have been developed, such as substituted
PCL blocks and star copolymers.

3.2.4 Drug Delivery from Star Copolymer Micelles of

PEO and PCL

Three and Four arm star copolymers with PCL as the center of the
star and PEO conjugated to the ends have were characterized in
terms of their size distribution and CMC [66]. Polymerization for
the PCL block was initiated off of pentaerythritol terminating with
a hydroxyl, for the four-star copolymers (Figure 3.4). A carboxylic
acid was then added to one end of the PEO chain through reacting
succinic anhydride with a terminal hydroxyl. The PEO's carboxylic
acid was then attacked by the hydroxyl of the four-star PCL block.
For three-star armed copolymers, diblock PEO-PCL copolymers were
conjugated to the 1,3,5-Benzenetricarboxylic acid (initiator) through
PCL, after activating the initiator with thionyl chloride. The diblock
PEO-PCL copolymers used for the three-star-armed copolymers had
CMCs on the order of 10 -7 M, and the CMC of the three- and four-star
copolymers was sequentially lowered from 5 × 10 -8 M to 2 × 10 -8 M,
respectively. This study demonstrated that eff ectively increasing the
number of arms branched off of the core did increase the stability
of the micelles through lower CMCs. It should be noted that when
the ends of the star copolymers have PCL blocks with large enough
molecular weights and the center is PEO; these polymers can gel and
even phase separate in aqueous solution [67].
Another study evaluated the drug delivery potential of four-
arm PCL-PEO star copolymers with all-trans-retinoic acid ( at RA)
[34]. This work characterized a four-arm center block of PCL (19.6
kDa) with 2 kDa PEO conjugated to each end. Micelles were formed
by drop-wise precipitation from organic solvent into water, or by
sonicating a polymer and drug suspension in water. Sonication
produced larger micelles (144 nm in diameter compared with
77 nm) and had higher loading efficiencies (10% compared with
6%). Additionally, micelles produced by sonication extended the
cumulative release of at RA to 40% at 170 h, compared with the
complete release of at RA in drop wise prepared micelles over the
same time frame. To further increase the stability of these micelles,
Allen and colleagues developed six-arm-star copolymers, using