Tuning nanoparticle size and drug encapsulation through chemistry and formulation strategies of A-B amphiphilic block copolymers
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Phan Thi Dieu, Hien
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Abstract
Amphiphilic block copolymers have been widely adopted in various biomedical applications as a potential drug delivery system, allowing for the production of polymeric micelles or nanoparticles (NPs) with small size, enhanced drug encapsulation as well as superior colloidal stability. Herein, a series of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) block copolymers having variable PLA lengths (15, 25 and 50 units) were synthesized using a facile and metal-free ring opening polymerisation (ROP) in order to alter the amphiphilic balance of the different macromolecules. The structures and compositions of polymers were investigated using nuclear magnetic resonance (NMR), fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). NPs were formulated from the resulting polymers via nanoprecipitation, and a wide range of processing parameters were accessed to study their effects on final particle size, including polymer chemistry, nature of solvents, presence of salt and ratio of solvent to non-solvent. Additionally, their stability in a typical cell culture media and protein binding assay were studied, highlighting the different NP properties according to the nature of amphiphilic balance and intra-intermolecular interactions available. Polymers were coupled with Cy5 for evaluating their cellular uptake against MDA-MB-231 human breast cancer cells using flow cytometry. Finally, NPs with the smallest mean diameters and highest stability were further employed to encapsulate a hydrophobic dye (Sudan IV) as a drug model via nanoprecipitation. In addition, an innovative nanocoating method was also applied for the encapsulation studies of the same dye. The novel nanocoating exhibited an improved drug loading (20%) compared to the solvent displacement method (only 3%). These preliminary results suggested that nanocoating shows promises for the encapsulation of hydrophobic drugs and could be further exploited as a potential formulation strategy in a variety of drug delivery systems.
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Amphiphilic block copolymers, Drug delivery system, Nanoparticles, Polymeric micelles