Chemical immobilization of retinoic acid within poly(epsilon-caprolactone) nanoparticles based on drug-polymer bioconjugates

Abstract

All-trans-retinoic acid (RA) was chemically conjugated to biodegradable poly(epsilon-caprolactone) (PCL10; number-average M-w approximate to 1250) via an ester linkage. The conjugation was carried out using N,N-dicyclohexylcarbodiimide and 4-dimethyl aminopyridine as a coupling agent. The molar ratio of the drug to the polymer was 1.11 as determined by H-1-NMR analysis. DSC and WAXD results showed that the formation of crystalline structures of RA was effectively suppressed by conjugation with PCL. The RA-PCL conjugates were formulated into nanoparticles by a spontaneous phase-inversion technique. Morphological characteristics of the resultant nanoparticles and drug-loading efficiencies were compared with those of free RA-loaded nanoparticles. The drug-loading efficiency of RA-PCL conjugates was almost 100%, while that of free RA was only similar to12%. The majority of unconjugated RA was found to form undesirable free-drug crystals out of nanoparticles, as observed by TEM analysis. This study demonstrates that the conjugation approach of RA to PCL can be an effective means to immobilize and encapsulate RA within nanoparticles for pharmaceutical applications. (C) 2003 Wiley Periodicals, Inc.