Conjugates of poly(DL‐lactide‐co‐glycolide) on amino cyclodextrins and their nanoparticles as protein delivery system

Abstract Poly(DL‐lactide‐co‐glycolide) (PLG) was chemically conjugated on two amino cyclodextrins, mono(6‐(2‐aminoethyl)amino‐6‐deoxy)‐β‐cyclodextrin and ethylenediamino bridged bis(β‐cyclodextrin), to afford novel amphiphilic conjugates. Those conjugates were then characterized with infrared spectrometry (IR), proton nuclear magnetic resonance (¹H NMR) and gel permeation chromatography (GPC). A repeat‐nanoprecipitation (RP‐NP) method was also developed to fabricate the nanoparticles of the conjugates with a water‐soluble model protein, bovine serum albumin (BSA). At the end of RP‐NP process, the availability of BSA was over 80% while the entrapment efficiency was 40–50% for each nanoprecipitation. The nanoparticles were rigid and spherical with diameters of 110–180 nm determined by transmission electron microscope (TEM), atomic force microscopy (AFM) and particle size analyzer. Nanoparticles possessed good steric stability during freeze‐drying and resuspensions due to the existence of cyclodextrins corona. Interactions between BSA and the conjugates in the nanoparticles were then elucidated with IR experiments. About 25% BSA adsorbed on the surface of nanoparticles due to the interaction and was easy to release in the first day. The release of BSA from the nanoparticles was in three phases: a burst effect in the first day, a followed plateau in about a week, and a sustained release of the protein over 14 days. By changing the lactide/glycolide ratio, the degradation time of the conjugates and the release rate of BSA could be controlled. The loss of CDs content was faster than that of overall Mw during degradation since CDs formed outer corona of the nanoparticles. Both the novel biomaterials and the nanosphere fabrication technique contributed to the maintenance of protein structure. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007