Matrix metalloproteinase-sensitive thermogelling polymer for bioresponsive local drug delivery

• Published in: Acta biomaterialia 2011-05, Vol.7 (5), p.1984-1992
• Main Authors: Garripelli, Vivek Kumar, Kim, Jin-Ki, Son, Sejin, Kim, Won Jong, Repka, Michael A., Jo, Seongbong
• Format: Article
• Language: English
• Subjects: antineoplastic agents; Biocompatible Materials - chemistry; Biodegradable; body temperature; Calorimetry, Differential Scanning; Cell Line, Tumor; Cell Survival - drug effects; Chromatography, Gel; Circular Dichroism; composite polymers; cytotoxicity; Drug Delivery Systems; engineering; gelatinase A; gelatinization temperature; gelation; Gels - chemistry; Humans; Hydrogel; hydrophobicity; Magnetic Resonance Spectroscopy; Matrix metalloproteinase-2; Matrix Metalloproteinases - pharmacology; Micelles; Molecular Weight; paclitaxel; Paclitaxel - pharmacology; Phase Transition - drug effects; Pluronic; Poloxamer - pharmacology; Polymers - chemistry; solubility; Solubility - drug effects; Temperature; Thermosensitive; Viscosity - drug effects
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2011.02.005

Development of a successful bioresponsive drug delivery system requires exquisite engineering of the materials so that they are able to respond to signals stemming from the physiological environment. In this study we propose a new Pluronic® based thermogelling system containing matrix metalloproteinase-2 (MMP2) responsive peptide sequences. A novel thermosensitive multiblock co-polymer comprising an MMP2-labile octapeptide (Gly–Pro–Val–Gly–Leu–Ile–Gly–Lys) was synthesized from a Pluronic® triblock co-polymer. The polymer was designed to form a thermogel at body temperature and degrade in the presence of MMP overexpressed in a tumor. The synthesized polymer was a multiblock co-polymer with ∼2.5 U of Pluronic®. The multiblock co-polymer solutions exhibited reverse thermal gelation around body temperature. The gelation temperatures of the multiblock co-polymer solutions were lower than those of the corresponding Pluronic® monomer at a particular concentration. The cytotoxicity of the synthesized polymer was lower compared with the monomer. The solubility of the hydrophobic anticancer drug paclitaxel was enhanced in the polymer solutions by micelle formation. The synthesized polymer was preferentially degraded in the presence of MMP. Paclitaxel release was dependent on the enzyme concentration. These findings suggest that the synthesized polymer has potential as a controlled drug delivery system due to its unique phase transition and bioresponsive behavior.