Biodegradable PLA-g-PEG Bioconjugates for Targeted Drug Delivery
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesisAlternative title
Bionedbrytbar PLA-g-PEG som konjugerats med aktiv substans för målsökande läkemedelsfrisättning (Swedish)
Polymer therapeutics as drug delivery systems have gained significant interest during the last years. The reason being their possibility to circumvent many of the drawbacks connected to drugs used today. Conventional polyesters have several favorable properties necessary for the mentioned purpose but their lack of functional groups often limits their use.
In this study we will try to overcome this limitation by presenting the first steps of a new synthesis pathway to achieve a telechelic-functionalized polymer scaffold. By providing the polymer with functional handles further post-polymerization steps are made possible. Polylactide (PLA) chains featuring azide functionality were successfully grafted from an initiating species on a peptide with the amino acid sequence Gly-Arg-Gly-Asp-Ser (GRGDS) via ring-opening polymerization. Incorporation of oligo(ethylene glycol) chains featuring azide moieties into the PLA backbone will allow for active drug delivery. In future studies, a cell-penetrating peptide for improved cellular uptake and a third functionality enabling attachment of homing devices to promote targeted delivery will be installed.
Ring-opening polymerization of lactide showed to initiate successfully from the peptide as was confirmed by proton nuclear magnetic resonance spectroscopy (1H NMR). Liquid chromatography mass spectrometry (LCMS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) also confirmed the formation of a polymer-peptide conjugate and PLA chains with a degree of polymerization (DP) between 1 and 4 were detected. 1H NMR and Correlation spectroscopy (COSY) showed a downfield shift of the peak originating by the protons next to the terminal hydroxyl group. This indicates that initiation solely occurs from the hydroxyl group and not from other nucleophilic groups also present on the peptide. This was further confirmed by Nuclear Overhauser Effect spectroscopy (NOESY) and Heteronuclear single quantum coherence spectroscopy (HSQC) where a correlation between the PLA chain and the peptide strand was detected.
Place, publisher, year, edition, pages
2015. , 60 p.
Polylactide, peptide-polymer conjugate, targeted drug delivery, polymer therapeutics, Ringsdorf’s notion
IdentifiersURN: urn:nbn:se:kth:diva-174289OAI: oai:DiVA.org:kth-174289DiVA: diva2:858564