Abstract
Hydrophobically modified polyelectrolytes (HMP) are polymers with a high content of ionizable groups bonded to hydrophobic groups. Copolymers of poly(acrylic acid) and Pluronic surfactants constitute a special class of HMP whereby poly(propylene oxide) segments act as hydrophobes. The poly(propylene oxide) segments possess temperature-dependent aqueous solubility and the solutions of the Pluronic-poly(acrylic acid) copolymers (MW > 3,000,000) undergo a sol-gel transition when kept at body temperature. Due to the presence of the poly(acrylic acid) segments, the Pluronic-poly(acrylic acid) copolymers are bioadhesive. We have examined the hypothesis that the in-situ gelling polymer formulations of Pluronic-poly(acrylic acid) copolymers may have an enhanced retention in the nasal cavity. The effects of putative bioadhesive (Carbomer 934P) and thermogelling (Pluronic F127) polymers on nasal clearance were compared with Pluronic-poly(acrylic acid) copolymers using a rat model. The enhancement of the residence time of fluorescent labels by the Pluronic-poly(acrylic acid) copolymers was shown to be 5-8-fold that of Carbomer, and 3-6-fold that of Pluronic F127. The results unequivocally demonstrate the superior retention of the HMP that combines bioadhesive and thermogelling capabilities over either a bioadhesive polyelectrolyte or a polymer of a low molecular weight that undergoes a sol-gel transition.
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