Polyethylene Glycol Polyester Block Copolymers: Biocompatible Carriers for Nanoparticulate Drug Delivery - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 68

3.4 ConcludingRemarks
PEO-PCL micelles have many advantages many harsh traditional
pharmaceutical excipients (e.g., Cremophor ® EL or Tween 80) for
poorly water soluble drugs. They have been shown to be biocompatible
with multiple cell lines, can provide extended release, and can retain
a drugs biological activity in vitro and in vivo . One important factor in
the design of future PEO-PCL cores is the achievement of the lowest
possible CMC's (Table 3.1) to maximize micelle stability. In terms of
drug solubilization, increasing PCL block length with very poorly
water soluble or lipophilic drugs usually increases encapsulation
efficiency due to the lowered core polarity and increased viscosity. In
addition to optimizing core block length, it is possible to crosslink the
core and use very lipophilic additives such as α-tocopherol to improve
drug solubility. Increasing the number of core chains relative to the
corona through use of triblocks or star copolymers, though a viable
alternative to diblocks, does not significantly improve the stability
of these micelles nor increase the encapsulation efficiency. Micelles
stability does improve with increased PCL chain length or by adding
highly lipophilic substituent functional groups such as α-benzyl
carboxylate (Table 3.1). Conversely, the CMC will increase with the
addition of hydrophilic functional groups such as carboxylic acids.
Once the micelle structure has been optimized for in vitro solubility
and release, it is then relevant to evaluate the delivery vehicle in cell
culture and in vivo . A certain percentage of PEO-PCL micelles can
enter cells through a combination of clathrin-mediated endocytosis
and phagocytosis. Once the micelles have entered the cells they
tend to localize in cytoplasmic organelles, specifically the Golgi
apparatus and mitochondria. PEO-PCL micelles have been shown to
enhance the pharmacokinetics of drugs in vivo by increasing their
circulatory half-life and altering their tissue distribution. Micelles
can also protect red blood cell hemolysis upon injection. During
in vivo studies, optimization of the PEO block length can increase
the half-life of some drugs. With the development of new PCL core
chemistries, core stability may be increased with new substituents
or new exotic geometries.
References
1. Clardy, J., and Walsh, C. (2004). Lessons from natural molecules. Nature
432: 829-837.