Comparison of two polymeric carrier formulations for controlled release of hydrophilic and hydrophobic drugs

Abstract

Two temperature sensitive drug carriers, poly (N-isopropylacrylamide-co-acrylic acid) (PNIPA-co-AA) and poly (N-isopropylacrylamide-vinyl pyrrolidone-acrylic acid) (PNIPA-VP-AA), were successfully synthesized through free radical mechanism. The diameters of PNIPA-co-AA and PNIPA-VP-AA particles can be regulated to be less than 100 nm, which were related to surfactant sodiumdodecyl sulfate and initiator ferrous ammonium sulfate, respectively. The lower critical solution temperature (LCST) of them can be manipulated to be higher than 40 °C, which was correlated to amount of acrylic acid (AA) that was copolymerized with NIPA. Hydrophilic anti-tumor drugs, 5-fluorouracil (5-Fu) and hydrophobic drug thalidomide were entrapped into PNIPA-co-AA and PNIPA-VP-AA, respectively. For different interaction mechanism between drug and carrier, 5-Fu was prone to be entrapped in PNIPA-co-AA with loading efficiency larger than 10% (w/w), while thalidomide was entrapped in PNIPA-VP-AA up to 80% (w/w). Fluorescein, an angiography agent, was used to evaluate the drug loading mechanism between PNIPA-VP-AA and poor water-soluble drug. In vitro drug release behavior from these two drug carriers were significantly different and showed temperature dependent, which demonstrated that PNIPA-co-AA and PNIPA-VP-AA are promising candidates for different controlled drug delivery system.