Biomedical Engineering Reference
In-Depth Information
10.4.3.5
Poly(Alkylcyanoacrylate) Loaded with Tegafur or 5-Fluorouracil
Other members of the poly(alkylcyanoacrylate) family besides PECA have
also been investigated for forming nanospheres containing magnetite and
anticancer drugs [104]. In this investigation, the drug encapsulation and
release characteristics of four types of poly(alkylcyanoacrylate) nanosphere with
a magnetite core and loaded with tegafur (a broad-spectrum anticancer drug)
were compared. The four polymers used were poly(ethyl - 2 - cyanoacrylate)
( PE - 2 - CA ), poly(butylcyanoacrylate) ( PBCA ), poly(hexylcyanoacrylate) ( PHCA )
and poly(octylcyanoacrylate) ( POCA ). Two drug - loading methods were tested:
(i) absorption or entrapment of the drug in the polymer matrix by addition
of the drug during preparation of the magnetite/poly(alkylcyanoacrylate)
core-shell nanospheres (
130 - 150 nm) via emulsion polymerization of the respec-
tive alkylcyanoacrylate monomer; or (ii) surface adsorption onto the preformed
magnetite/poly(alkylcyanoacrylate) nanospheres after incubation in the drug
solution.
For the fi rst method, the effects of pH of the polymerization medium and drug
concentration on the tegafur absorption density (
∼
m) and encapsulation effi cacy
(%) for the four types of composite nanosphere tested are listed in Table 10.1. The
drug loading was maximum at pH 4 (10
− 4
M
HCl), since polymerization rate
becomes slower and the absorption falls with increasing H
+
. The amount of drug
loaded was higher with a polymer matrix of shorter alkyl chain length, and this
can be explained by the faster polymerization kinetics of shorter- chain monomers.
The presence of the magnetite core was found not to affect the amount of drug
encapsulated. The release of the encapsulated tegafur from nanospheres followed
a biphasic process: fi rst, an early rapid release of approximately 60% within 60 min,
while the remaining 40% was released slowly during the next 120 min. The initial
rapid release was attributed to the loss of surface-associated and poorly entrapped
tegafur, while the slower drug release may have been due to a disintegration of
the poly(alkylcyanoacrylate) matrix, to drug diffusion through this polymeric
matrix, or both.
For the second method, the drug loading was increased with alkyl chain length
and, in each case, the release was almost complete after 60 min. A comparison
between all of the polymeric matrices showed drug release to be slightly slower
when the alkyl chain was longer, this being due to the slightly stronger interaction
of the lipophilic drug with the more hydrophobic poly(alkylcyanoacrylate)
surfaces.
The same group also prepared similar types of magnetite core/
poly(alkylcyanoacrylate) shell colloidal nanospheres loaded with 5-fl uorouracil (a
hydrophilic, broad-spectrum anticancer drug) [105]. When the same two drug-
loading methods as described above were tested, the overall effects of pH and alkyl
chain length of the polymeric matrix on 5-fl uorouracil loading were similar to
those with tegafur. However, the drug release was slightly slower from polymeric
matrices of shorter alkyl chain length; this was most likely due to the slightly
stronger interaction of hydrophilic 5-fl uorouracil with the less-hydrophobic
poly(alkylcyanoacrylate) surfaces.
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