Polyanhydrides - Biodegradable Polymers - page 50

which cannot be metabolized by the body and the dimer may remain in the body
for 6 months [34]. RA ( cis - 12 - hydroxyoctadeca - 9 - eonoic acid) was found to be the
most appropriate alternative for the synthesis of the fatty acid-based polyanhy-
drides. It is one of the few commercially available fatty acids which have the
additional 12-hydroxy group. The advantage of RA is that it is a bifunctional fatty
acid containing a hydroxyl group along the acid group and, therefore, can be
incorporated into the polyanhydride backbone by the formation of an ester bond.
RA - based polymers are the newest addition to the polyanhydride series which
were fi rst investigated in the late 1990s [16]. However, polymers produced were
for solid implant that need surgical intervention for application to the body system.
Recent work is more focused on converting this solid form to liquid injectable
form which can form solid or semisolid implants after administration by injection
[16] . For this, the fi rst series of efforts were made with SA as the other monomer
and this also included two subtypes; one is insertion of RA in preformed SA chains
[35] and second is usual melt condensation carried out at lower temperature in
one-pot synthesis, where dicarboxylic acid derivative of RA and SA are condensed
together to from random copolymer rather than block copolymer [36]. Both of
these efforts lead to the formation of polymers in the liquid injectable state.
Although the common physicochemical properties such as low melting point,
hydrophobicity, fl exibility, biocompatibility, and biodegradability desired for a
drug carrier possessed by all RA-based polyanhydrides, the liquid state was
achieved only with the polymer having more than 70% of RA content.
Low molecular weight polymers synthesized by one pot-low temperature con-
densation method afforded the release of anticancer drug, methotrexate for around
10 days [36]. Although a change in the ratio of RA maleate (RAM) to SA was having
a role, the faster release from the higher RAM containing polymer was elucidated
on the basis of polymer crystallinity, which hinders the release by inhibiting water
penetration in the device which decreases with increase in RAM content [16].
Similar kinds of results were found in polymers obtained by insertion of RA in
SA chains [35, 37], where these polymers were loaded with cisplatin (5% w/w) and
paclitaxel (5-20% w/w) and drug release was faster with the pasty polymers.
In vivo evaluation of bupivacaine-loaded P(SA:RA)(2:8) injectable polymer was
made in terms of effi cacy and toxicity for producing motor and sensory block when
injected near the sciatic nerve [38]. Single injection of 10% bupivacaine in the
polymer caused motor and sensory block that lasted 30 h without causing any
adverse effects.
Ricinoleic lactones were utilized for the synthesis of copolyester by ring-opening
polymerization (ROP) [20]. RA lactones were synthesized by using dicyclohexyl-
carbodimide and (dimethylamino)pyridine as catalysts. Various macrolactones
were obtained, mono- to haxalactone depending on the number of RA moieties
which participate in the lactone ring formation. Polymerization of the RA lactones
with catalysts commonly used for ring-opening polymerization of lactones, under
specifi c reaction conditions, resulted in oligomers. Polymerization of
chromatography- purifi ed dilactone with Sn(Oct) 2 resulted in the formation of
longer oligomers (weight average M w

= 5700). However, copolymerization with