Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system.
The aim of this study was to generate a new type of nanoparticles made of chitosan (CS) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) and to evaluate their potential for the association and delivery of macromolecular drugs. CS and CM-beta-CD or mixtures of CM-beta-CD/tripolyphosphate (TPP) were processed to nanoparticles via the ionotropic gelation technique. The resulting nanoparticles were in the size range of 231-383 nm and showed a positive zeta potential ranging from +20.6 to +39.7 mV. These nanoparticles were stable in simulated intestinal fluid pH 6.8 at 37 degrees C for at least 4h. Elemental analysis studies revealed the actual integration of CM-beta-CD to CS nanoparticles. Insulin and heparin used as macromolecular model drugs, could be incorporated into the different nanocarriers with association efficiencies of 85.5-93.3 and 69.3-70.6%, respectively. The association of these compounds led to an increase of the size of the nanoparticles (366-613 nm), with no significant modification of their zeta potentials (+23.3 to +37.1 mV). The release profiles of the associated macromolecules were highly dependent on the type of molecule and its interaction with the nanomatrix: insulin was very fast released (84-97% insulin within 15 min) whereas heparin remained highly associated to the nanoparticles for several hours (8.3-9.1% heparin within 8h). In summary, CS-CD (cyclodextrin) nanoparticles may be considered as nanocarriers for the fast or slow delivery of macromolecules.
Krauland
Alexander H
AH
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Spain.
Alonso
María José
MJ
D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006493:Heparin / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry; D007419:Intestinal Secretions / Q000737:chemistry; D007700:Kinetics; D046911:Macromolecular Substances / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D053758:Nanoparticles; D010316:Particle Size; D011122:Polyphosphates / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004337:Drug Carriers; D007328:Insulin; D046911:Macromolecular Substances; C062590:O-carboxymethyl-O-ethyl-beta-cyclodextrin; D011122:Polyphosphates; D047392:beta-Cyclodextrins; D006493:Heparin; D048271:Chitosan; C005692:triphosphoric acid