Polyanhydrides - Biodegradable Polymers - page 51

lactide resulted in copolymers of low molecular weight. Polymers with molecular
weights in the range 5000-16,000 were obtained with melting temperatures of
100-130 °C for copolymers containing 10-50% (w/w) RA residues. The polymers
were off-white in color that became yellow with an increase of the RA content. The
molecular weights of the polymers decreased with an increase in the content of
the RA lactone. It was hypothesized that more reactive lactide activated fi rst by
catalyst polymerizes and only in the end some RA lactones react. The reaction was
terminated because of the RA lactones' low reactivity. This low reactivity can be
attributed to the low ring strain and to the steric hindrance of the ester bond by
the fatty acid side chain. In vitro degradation of RA-LA copolymers showed
that copolymerization with RA had some effect on the degradation rate and the
polymer physical properties, which is related to the low incorporation of RA in
the polymer. Addition of RA to PLA is expected to improve the hydrophobicity
of the polymer and thus drug release profi le.
In continuation of the above study, synthesis methods other than ROP like
transesterifi cation and melt condensation were also utilized [21]. The liquid state
of the polymer, which makes it a potential candidate for directly injectable drug
delivery carrier, was achieved when RA content increased more than 15% and 50%
in case of melt condensation and transesterfi cation, respectively.
Polymers synthesized by all three methods were compared for the release of
hydrophilic and hydrophobic drugs viz. 5-FU and triamcinolone, respectively.
5-FU release was faster in all cases with the total release lasting for 17 days from
polymers prepared by transesterifi cation and melt condensation. Slower 5-FU
release was obtained from polymer prepared by ROP (40% in 17 days). The same
pattern was observed for triamcinolone, where release was obtained only 5% in
17 days from ROP polymer in contrast to the 30% from polymer synthesized by
transesterifi cation. The difference was attributed to the diblock nature of ROP
polymer, its high crystallinity, and melting point, all of which inhibit water pen-
etration and thus degradation, which fi nally shows up in release profi les [21] .

3.2.6
Amino Acid - Based Polyanhydrides

Amino acid -based PAs were fi rst reported in 1990s by Domb [39]. However, recent
progress in this class has been made in terms of producing crosslinked PAs which
are suitable for in vivo use [24, 40]. Earlier, alanine-containing crosslinked PAs in
which linkages were produced by irradiation of methacrylated end groups which
when hydrolyzed gave rise to nonbiodegradable products having limited biocom-
patibility. To overcome these limitations, crosslinked amino acid PAs were pro-
duced having exclusively anhydride bonds which are hydrolabile in nature.
Crosslinked amino acid-containing polyanhydrides based on N - trimellitylimido -

β - alanine ( TMA - ala ) or N - trimellitylimido - glycine ( TMA - gly ) and SA were synthe-

sized by copolycondensation using 1,3,5-benzenetricarboxylic acid prepolymer as
a crosslinking agent. Crosslinking was confi rmed by single melting peak of the
polymer in differential scanning calorimeter (DSC) studies [40]. Monomeric SA