C. Ramkissoon-ganorkar et al., Effect of molecular weight and polydispersity on kinetics of dissolution and release from pH/temperature-sensitive polymers, J BIOM SC P, 10(10), 1999, pp. 1149-1161
N-isopropylacrylamide (NIPAAm) polymers exhibit a lower critical solution t
emperature (LCST). Aqueous solutions of these polymers are soluble below th
eir LCST and precipitate above their LCST. The LCST is dependent on pH for
polymers with ionizable groups because of a change in hydrophilicity with i
onization and electrostatic repulsion that cause a shift in the LCST.
We have designed a novel polymeric delivery system that utilizes linear, pH
/temperature-sensitive terpolymers of NIPAAm, butyl methacrylate (BMA) and
acrylic acid (AA). This system allows the aqueous loading of drugs in polym
eric beads with high loading efficiency while preserving the bioactivity of
the protein drug. Furthermore, the unique properties of the pH/temperature
-sensitive polymeric bead make it a potential system for oral drug delivery
of peptide and protein drugs to different regions of the intestinal tract.
This study aims at investigating the effect of polydispersity and molecular
weight (MW) of terpolymers of poly(NIPAAm-co-BMA-co-AA) with feed mol rati
o of NIPAAm/BMA/AA 85/5/10 on the polymer dissolution rate and on the relea
se kinetics of a model protein, namely insulin. Varying the weight average
MW (M-W) and polydispersity of the polymer modulated the polymer dissolutio
n rate and the release rate of insulin from pH/temperature-sensitive polyme
ric beads. An increase in the polydispersity of the polymer through the add
ition of high MW polymer chains caused a decrease in the release rate of in
sulin and in the polymer dissolution rate. High MW polymer chains impose a
certain degree of interaction between polymer chains due to chain entanglem
ent. There is a limiting value of MW above which chain entanglement has no
effect on drug release rate.