Enzyme-catalyzed functionalization of poly(L-lactic acid) for drug delivery applications
| Autor: | Enrique Herrero Acero, David L. Kaplan, Alessandro Pellis, Jeannine M. Coburn, Georg M. Guebitz, Lucia Silvestrini, Lucia Gardossi, Denis Scaini |
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| Přispěvatelé: | Pellis, Alessandro, Silvestrini, Lucia, Scaini, Deni, Coburn, Jeannine M., Gardossi, Lucia, Kaplan, David L., Herrero Acero, Enrique, Guebitz, Georg M. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Biocompatibility
Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Applied Microbiology and Biotechnology Biochemistry doxorubicin Gel permeation chromatography Hydrolysis poly(lactic acid) (PLA) Enzymatic hydrolysis Organic chemistry enzymatic hydrolysi Chemistry enzymatic hydrolysis 021001 nanoscience & nanotechnology Controlled release 0104 chemical sciences Chemical engineering Ionic strength Drug delivery Humicola insolens cutinase (HiC) drug delivery controlled release Surface modification 0210 nano-technology |
| Popis: | 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 M n 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 M n 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. |
| Databáze: | OpenAIRE |
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