Biomedical Engineering Reference
In-Depth Information
water. The ACN can then be removed through solvent evaporation
under vacuum. High loading efficiencies as great as 95% were
achieved, and this efficiency was shown to have an optimal PCL block
length. With constant PEO block length (5 kDa), the PCL block at 2.5
kDa loaded 95% fenofibrate, 4 kDa 90%, and 1 kDa only 30%. It
would have been expected that the loading capacity would increase
as the PCL block length increases. Thus the PCL block length should
be optimized to obtain the highest encapsulation efficiency for each
prospective drug.
Another instance of solvent evaporation in drug loading of PEO-
PCL is cyclosporine A (CsA), an immunosuppressive agent with
low water solubility [45]. Three diff erent polymers were compared
among loading capacity, release, and size, each with a constant
PEO block molecular weight of 5 kDa, and PCL block molecular
weights of 5, 13, and 24 kDa. Utilizing diff erent solvents during
solvent extraction, Aliabadi et al. were able to show that THF gave
smaller micelles (40-86 nm in diameter) compared with acetone,
which gave 80-100 nm-diameter micelles among the same series of
PEO-PCL polymers. The release profile of CsA in PEO-PCL (13 kDa)
was evaluated in comparison with the current formulation of CsA
in Cremophor ® EL (Sandimmune ® ) in phosphate-buff ered saline
(PBS) with 4% bovine serum albumin (BSA). The Cremophor ®
EL formulation depicted a burst-type release with approximately
80% of the drug cumulatively released at 12 h, while the PEO-PCL
formulation showed a more sustained release: releasing only 10%
over the same time frame. The PEO-PCL block copolymer had a
lower CMC of 6 × 10 -7 M compared with Cremophor ® EL (4 × 10 -5
M), and a lower relative micelle core viscosity, and thus diff usion
of CsA was limited and the release was sustained. The same series
of PEO-PCL polymers were investigated with respect to their
ability to encapsulate and release the amphiphilic anti-anginal and
anti-arrhythmic drug amiodarone (AMI). [41] Both a commercial
formulation in the surfactant polysorbate 80 with benzyl alcohol and
free AMI precipitate immediately upon dilution in aqueous milieu
and induce red blood cell hemolysis. Increasing the length of the PCL
block increased the loading amount of the amphiphilic drug AMI and
reduced hemolysis in Sprague-Dawley rats. Only 20-40% of AMI in
PEO-PCL (13 kDa) micelles precipitated after a 2× dilution into PBS
at 37°C compared with 100% precipitation for free AMI. However,
it should be noted that when 5 mg of AMI was loaded in PEO-PCL
 
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