Polyethylene Glycol Polyester Block Copolymers: Biocompatible Carriers for Nanoparticulate Drug Delivery - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 44

and infectious diseases have very poor water solubility [1]. This
problem continues today in many pharmaceutical companies, as
high throughput combinatorial screening frequently identifies drug
targets with low water solubility [2-4]. Traditional techniques to
improve aqueous solubility, such as chemical modifications and pH
adjustments to form salts from ionizable groups often reduce or
destroy these drugs' therapeutic activity. Thus unmodified drugs
move on to become candidates and are so hydrophobic, they cannot
be delivered via intravenous infusion, or without cytotoxic delivery
vehicles such as Cremophor ® EL, Tween, or harsh organic solvents
such as ethanol and DMSO [5]. Therefore drug delivery vehicles that
can solubilize and encapsulate high concentrations of these drugs are
needed to formulate these prospective drug candidates. The polyester
core of these micelles can encapsulate these hydrophobic drugs
because alkane-rich (e.g., pentanes in poly-ε-caprolactones) segments
between these esters increase the thermodynamic affinity of the drugs
to the core. Polyester cores are biodegradable through esterases in
vivo . There are three main ester monomers commonly used as cores:
ε-caprolactone, D,L -Lactic acid, and D,L -Lactic acid-co glycolic acid.
Recently, there have been many excellent reviews on the drug delivery
from micelles of PEO-poly( D,L -Lactic acid) [6-10] and PEO-poly( D,L -
Lactic acid-co glycolic acid) [11-13]. Therefore this review will focus
on poly(ε-caprolactone) linear, star, and substituted cores in order to
highlight recent developments in this area. These include improving
stability, loading capacity, and tailoring release rates.
The poly(ethylene oxide) PEO portion of PEO-polyester micelles
resides at the periphery of the micelle and is often referred to as the
corona or shell. PEO has been deemed a “generally regarded as safe”
molecule by the FDA and has little or no immunogenicity. When the
micelles are less than approximately 200 nm in diameter, uptake by
the reticuloendothelial systems (RES) of the liver and the spleen is
limited. This lack of immune system recognition in conjunction with
reduced RES uptake dramatically increases the circulatory lifetime
of these micelles [14, 15]. In order for PEO- poly(ε-caprolactone)
(PCL) micelles to be clinically eff ective, they need to have structural
integrity in vivo , or low critical-micelle concentrations (CMC), and
control the release of the target drugs. The molecular weights of the
core and the shell can be designed to optimize micelle size, CMC,
encapsulation efficiency, and rate of drug release. Understanding
the thermodynamic affinity of a drug molecule for the micelle core
is paramount to the design of future drug delivery systems. This