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)-b-cyclodextrin and ethylenediamino bridged bis(b-cyclodextrin), to afford novel amphiphilic conjugates. Those conjugates were then characterized with infrared spectrometry (IR), proton nuclear magnetic resonance ( 1 H 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.

Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect

“…The burst effect -considered a drawback for any sustained releaseis a parameter that generally increases when increasing the drug/PLGA ratio. A rather high ratio (1:1) was used in our work, but the burst effect was similar or lower than those reported by other authors using the same encapsulation technique [51][52][53]. Zero order, first order, Higuchi and Korsmeyer-Peppas models were fitted to the release data, but the latter showed the more accurate fitting, according to AIC values ( Table 3).…”

Targeted Delivery with Peptidomimetic Conjugated Self-Assembled Nanoparticles

“…PVA-graft-PLGA NPs have been used for local delivery of Paclitaxel in restenosis treatment but an initial burst release dominates the early release profile followed by a slow continuous release of a small fraction of the drug (56). Amino cyclodextrin conjugated PLGA polymers have been used to produce biodegradable NPs as a carrier for delivery of proteins (57).…”

Cyclodextrins and Polymer Nanoparticles

“…Considering the advantage of working with poly(lactideco-glycolide) (PLGA) copolymers, because it is possible to control their degradation rate by the molar ratio of the lactic and glycolic acid in the polymer, Gao et al [49] prepared two types of nanoparticles: b-CDen-PLGA [with the mono(6-(2aminoethyl)amino-6-deoxy)-b-CD] and B-b-CDen-PLGA (with the ethylenediamino-bridged bis-b-CD). They used the repeated nanoprecipitation method and freeze-dried the nanoparticles obtained.…”