The influence of additives in modulating drug delivery and degradation of PLGA thin films

Poly(_D,L-lactic-co-glycolic acid) (PLGA) is the most frequently used bioresorbable polymer for the controlled release of drugs. Hydrophilic additives such as poly(ethylene glycol) (PEG) are commonly incorporated into PLGA to enhance the release of hydrophobic drugs such as paclitaxel (PCTX). Understanding the factors and mechanisms that govern drug release in a blended system is important to be able to modify the delivery properties of the drugs. This study evaluated the mechanical properties of PCTX-eluting PLGA thin films that incorporate PEG additives under constant hydration, which mimics physiological conditions. The presence of additives resulted in varying extents of phase separation, which changed the degradation and release profiles of the PLGA films. The incorporation of long-chain additives resulted in large phase-separated additive-rich domains that gave rise to large pores, high mass loss, and a high burst release of PCTX from the extensive dissolution and leaching of additives upon hydration. Subsequently, the degradation rate of PLGA films was reduced by the out-diffusion of acidic byproducts through these water-filled pores and channels; these byproducts would otherwise accumulate and contribute to higher degradation rates due to the autocatalysis of PLGA. The preferential association between PCTX and PEG additives in the phase-separated PLGA films was exploited to enhance the release of hydrophobic PCTX, and statistical correlations were established between the simultaneous release of PCTX and additives. This significant correlation could provide useful information for the prediction of hydrophobic drug release profiles and the selection or preparation of localized drug delivery systems with the use of PEG additives. © 2013 Nature Publishing Group All rights reserved.