Liposomes are spherical vesicles composed of single or multiple lipid bilayers commonly synthesized for the creation of drug-delivery vehicles. Poly(ethylene glycol) (PEG) and cholesterol are two established moieties implemented in liposomal drug-delivery systems to aid in stealth, permeability, and fluidity. Despite their numerous advantages, PEG and cholesterol exhibit various drawbacks. In human patients, PEG may accumulate in the liver, causing anaphylaxis in certain cases. Furthermore, cholesterol is not covalently bound to the liposome, and can subsequently move freely into other cellular membranes, resulting in the disassembly of the liposome. To address these challenges, we investigated the utility of dextran, a biodegradable glucose polysaccharide, as a potential replacement for both PEG and cholesterol in liposomes. Specifically, we synthesized a series of amphiphilic dextran-based block copolymers to compare their liposomal packing ability relative to PEGylated cholesterol: AcDex-b-PEG, AcDex-b-PEG-b-AcDex, and Dex-b-polystyrene (PS). For each block copolymer, 10k-dextran was brominated at the C-6 position, which was subsequently displaced with 5k-PEG-NH₂ or 5k-PS-NH₂ via S_N2 reaction. After synthesizing the diblock and triblock, the C2-4 hydroxyl groups on dextran were acetylated to evaluate dextran as a potential hydrophobic component of a liposome. Block formation was supported by ¹H nuclear magnetic resonance spectroscopy, which showed signals corresponding to the dextran backbone between 3-4 ppm, signals from PEG around 3.3 ppm, and signals from the acetyl groups between 1.5-2.5 ppm. Fourier transform-infrared spectroscopy validated the successful acetylation of dextran through the disappearance of the hydroxyl absorbance band (3,000-3,600 cm^-1) and the appearance of a carbonyl absorbance band (1,700 cm^-1). The block copolymers displayed increased thermal stability relative to their respective starting materials, as they all had higher onset of degradation temperatures according to thermal gravimetric analysis. The future goals of this project are to confirm block copolymer formation using size exclusion chromatography and to measure liposomal stability relative to PEGylated cholesterol using Langmuir pressure-area isotherms.

Jeffrey Thompson

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