Enteric Polymer Based on pH-Responsive Aliphatic PolycarbonateFunctionalized with Vitamin E To Facilitate Oral Delivery of Tacrolimus.

To improve the bioavailability oforally administered drugs, we synthesized a pH-sensitive polymer (poly(ethyleneglycol)–poly(2-methyl-2-carboxyl-propylene carbonate)–vitaminE, mPEG–PCC–VE) attempting to integrate the advantages of enteric coating and P-glycoprotein(P-gp) inhibition. The aliphatic polycarbonate chain was functionalizedwith carboxyl groups and vitamin E via postpolymerization modification.Optimized by comparison and central composite design, mPEG113–PCC32–VE4exhibited low criticalmicelle concentration of 1.7 × 10–6mg/mL andhigh drug loading ability for tacrolimus (21.2% ± 2.7%, w/w).The pH-responsive profile was demonstrated by pH-dependent swellingand in vitrodrug release. Less than 4.0% tacrolimuswas released under simulated gastric fluid after 2.5 h, whereas animmediate release was observed under simulated intestinal fluid. ThemPEG113–PCC32–VE4micellessignificantly increased the absorption of P-gp substrate tacrolimusin the whole intestine. The oral bioavailability of tacrolimus micelleswas 6-fold higher than that of tacrolimus solution in rats. This entericpolymer therefore has the potential to become a useful nanoscale carrierfor oral delivery of drugs. [ABSTRACT FROM AUTHOR]