4 years ago

Enzyme-catalyzed functionalization of poly(L-lactic acid) for drug delivery applications

Enzyme-catalyzed functionalization of poly(L-lactic acid) for drug delivery applications
Polymer-based drug delivery systems are attracting interest for biomedical and, in particular, oncology-related applications due to interesting characteristics in terms of prolonged drug release. In this study, we investigated a new poly(lactic acid) (PLA)-based drug delivery system in which the cationic chemotherapeutic drug doxorubicin was adsorbed via ionic interactions. PLA, a polyester already widely used for biomedical applications due to its biocompatibility and quick assimilation, was initially activated by mild enzymatic surface hydrolysis with cutinase, generating new carboxylic and hydroxyl groups without affecting the bulk properties of the PLA. After the enzyme activation of PLA, the Mn remained almost unchanged, 182kDa versus 188kDa for untreated PLA measured by gel permeation chromatography. In contrast, chemical hydrolysis substantially degraded the PLA films as indicated by a decrease of Mn from 188kDa to 18kDa. Surface imaging using Scanning Electron Microscopy revealed an increase of granular porosity on the surface upon enzymatic activations while Atomic Force Microscopy showed an increase of the surface roughness from 50 to 170nm. The hydrophilicity of the enzymatically activated films dramatically increased, as demonstrated by the decrease of the Water Contact Angle from 50° to less than 20°. The negative charges generated on the PLA films was exploited for loading with positively charged doxorubicin; with increasing extent of enzymatic hydrolysis a higher amount of surface functional groups were generated. Desorption studies indicated that the release of doxorubicin from the PLA surface depended on the ionic strength of the medium, thus confirming the ionic nature of the interactions.

Publisher URL: www.sciencedirect.com/science

DOI: S1359511316306456

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