149
In cultures where polymers loaded with Dox were added,
slight sediments were observed 24 h upon their addition at the
highest concentration tested. However, cultures with lower concentrations of the Dox-loaded polymers as well as those where
Pacl-loaded polymers were added were clear of sediments. Paclloaded polymers (i.e., PEOPacl) were found to be the most active
among the three loaded polymers tested. From the two Doxloaded polymers, PEODox-loaded polymer (PEODox) was found
to be the less active as it showed only marginal antiproliferative
activity against BxPC-3 cells. The PLL polymer (i.e., PLLDox)
exhibited higher activity, which in fact was very close to that of
Myocet in regard to its antiproliferative and cytostatic activity. The
significantly lower activity of the PEODox might be due to the
lower stability that these nanoparticles showed.
Empty PEO and PLL polymers were also tested for acute toxicity
in immunocompromised (SCID) mice. Both polymersomes were
administered intraperitoneally in a single injection to the animals at
the following doses: 200, 133, 100, and 67 mg
.
kg
−1
. Animals were
subsequently weighted and observed for a period of 7 days for
signs of toxicity or changes in their routine. The only side effect
observed during this period was a light sedation starting 5 min and
progressing until 15 min after the administration of the 200 mg
.
kg
−1
dose for both PEO-b-PBLG-b-PLL and PLL-b-PBLG-d7-b-PLL
polymers. All animals recovered 24 h later and no further sign of
toxicity was recorded until the end of the observation period.
6 Conclusions
Comparing the ABA triblock copolypeptide and ABC terpolymer,
both formed polymersomes in water, due to the macromolecular
architecture of the polymers along with the use of a rod middle
block.
It was found that the hydrophilic block with the higher volume
fraction in the ABC architecture remains in the outer periphery of
the formed vesicle. Therefore, it is possible to select between two
different hydrophilic blocks to be at the outer periphery just by
choosing their molecular characteristics. In case one of these is
PEO, it is preferred to be in the shell due to its properties.
Positively charged nanoparticles are incorporated faster into
the cell due to the presence of negatively charged species on the
cell membranes. This would result in higher accumulation of drug
within the cells for the ABA copolypeptide rather than the ABC,
and consequently higher activity. It is expected to further elucidate
the structure-delivery relationship in order to achieve more efficient complex structures in terms of activity and selective delivery
of multiple anticancer drugs and genes.
5.5 In Vivo
Toxicity Study
Nanostructured Polymersomes for Controlled Drug Delivery
In cultures where polymers loaded with Dox were added,
slight sediments were observed 24 h upon their addition at the
highest concentration tested. However, cultures with lower concentrations of the Dox-loaded polymers as well as those where
Pacl-loaded polymers were added were clear of sediments. Paclloaded polymers (i.e., PEOPacl) were found to be the most active
among the three loaded polymers tested. From the two Doxloaded polymers, PEODox-loaded polymer (PEODox) was found
to be the less active as it showed only marginal antiproliferative
activity against BxPC-3 cells. The PLL polymer (i.e., PLLDox)
exhibited higher activity, which in fact was very close to that of
Myocet in regard to its antiproliferative and cytostatic activity. The
significantly lower activity of the PEODox might be due to the
lower stability that these nanoparticles showed.
Empty PEO and PLL polymers were also tested for acute toxicity
in immunocompromised (SCID) mice. Both polymersomes were
administered intraperitoneally in a single injection to the animals at
the following doses: 200, 133, 100, and 67 mg
.
kg
−1
. Animals were
subsequently weighted and observed for a period of 7 days for
signs of toxicity or changes in their routine. The only side effect
observed during this period was a light sedation starting 5 min and
progressing until 15 min after the administration of the 200 mg
.
kg
−1
dose for both PEO-b-PBLG-b-PLL and PLL-b-PBLG-d7-b-PLL
polymers. All animals recovered 24 h later and no further sign of
toxicity was recorded until the end of the observation period.
6 Conclusions
Comparing the ABA triblock copolypeptide and ABC terpolymer,
both formed polymersomes in water, due to the macromolecular
architecture of the polymers along with the use of a rod middle
block.
It was found that the hydrophilic block with the higher volume
fraction in the ABC architecture remains in the outer periphery of
the formed vesicle. Therefore, it is possible to select between two
different hydrophilic blocks to be at the outer periphery just by
choosing their molecular characteristics. In case one of these is
PEO, it is preferred to be in the shell due to its properties.
Positively charged nanoparticles are incorporated faster into
the cell due to the presence of negatively charged species on the
cell membranes. This would result in higher accumulation of drug
within the cells for the ABA copolypeptide rather than the ABC,
and consequently higher activity. It is expected to further elucidate
the structure-delivery relationship in order to achieve more efficient complex structures in terms of activity and selective delivery
of multiple anticancer drugs and genes.
5.5 In Vivo
Toxicity Study
Nanostructured Polymersomes for Controlled Drug Delivery