PLGA based drug delivery systems (DDS) for the sustained release of insulin:insight into the protein/polyester interactionsand the insulin release behavior

VERONICA LASSALLE; MARÍA LUJÁN FERREIRA

JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY

JOHN WILEY & SONS LTD

Año: 2010 vol. 85 p. 1588 - 1596

0268-2575

AbstractBACKGROUND:Drug delivery systems (DDS)were designed using insulin as model drug and poly (lactic–co-glycolic) copolymers(PLGA) as polymeric matrix. The carriers were synthesized by direct self-assembly of the insulin and the polyester under mildconditions.RESULTS: The kind and level of association between the protein and the polymer were studied using computational methods(combined MM2/PM3) and spectroscopic tools (Fourier transform infrared (FTIR), energy dispersive X-ray (EDX) and X-rayfluorescence spectroscopy (XFS)). The effect of the number averagemolecular weight (Mn) of the copolymer on the associationefficiency (AE) drug–polymer aswell as on the release profile has been explored.Mathematical models were used to predict theinsulin release kinetic and mechanism.CONCLUSIONS: Satisfactory protein/PLGA association efficiencies (between 77 and 99%) were registered depending on theMn of the PLGA. Hydrophobic and hydrophilic interactions were detected between the protein and the polymeric network bycomputational analysis. In vitro release studies demonstrated that copolyesters of about 8600 and 1500 Da were suitable forthe gradual release of insulin while PLGA oligomers of average molecular weight between 700 and 800 Da were unsuitable asDDS. The insulin release kinetics fits well with the Korsmeyer model, following the anomalous transport mechanism.