Enzyme-catalyzed functionalization of poly(L-lactic acid) for drug delivery applications. (August 2017)

• Record Type: Journal Article
• Authors: Pellis, Alessandro; Silvestrini, Lucia; Scaini, Denis; Coburn, Jeannine M.; Gardossi, Lucia; Kaplan, David L.; Herrero Acero, Enrique; Guebitz, Georg M.
• Is Part Of: Process biochemistry. Volume 59:Part A(2017)
• Page Start: 77
• Page End: 83
• Publication Date: 2017-08
• Subjects: Poly(lactic acid) (PLA) -- Doxorubicin -- Enzymatic hydrolysis -- Humicola insolens cutinase (HiC) -- Drug delivery -- Controlled release; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2016.10.014
• Languages: English
• ISSNs: 1359-5113

Abstract

Graphical abstract: Enzymatic, environmentally-friendly method for the surface functionalization of PLA films without affecting bulk properties. Onto the enzymatically activated surface doxorubicin, a chemotherapeutic drug, was coupled and adsorption and release kinetics investigated. Highlights: Surface enzymatic functionalization of PLA films was successfully achieved. Doxorubicin loading and release studies were performed and optimized. An electrostatic interaction-dependent release of the drug was observed. Abstract: 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, 182 kDa versus 188 kDa 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 188 kDa to 18 kDa. 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 170 nm. 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.