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Amphiphilic Poly(2-isopropyl-2-oxazoline)-block-poly(lactide) Nanoparticles as Drug Delivery Vehicles

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Title: Amphiphilic Poly(2-isopropyl-2-oxazoline)-block-poly(lactide) Nanoparticles as Drug Delivery Vehicles
Author(s): Tavaststjerna, Miisa
Contributor: University of Helsinki, Faculty of Science, none
Discipline: none
Degree program: Master's Programme in Materials Research
Specialisation: Polymer Materials Chemistry
Language: English
Acceptance year: 2020
Further proof of the unique morphologies of water-soluble poly(2-isopropyl-2-oxazoline)-block-poly(DL-lactide) and poly(2-isopropyl-2-oxazoline)-block-poly(L-lactide) (PiPOx-b-PDLLA and PiPOx-b-PLLA) nanoparticles was obtained via Fluorescence Spectroscopy. Additionally, loading and release studies were carried out with hydrophobic curcumin molecules to outline the potential of the amphiphilic block copolymers in drug delivery applications. To study the morphology of the nanoparticles, absorption and emission spectra of pyrene were measured in water dispersions of the nanoparticles at several concentrations. The obtained I1/I3, I337/I333.5 and partitioning constant (Kv) values were compared to corresponding data from a control core/shell nanoparticle poly(ethylene glycol)-block-poly(DL-lactide) (PEG-b-PDLLA). Of the three different amphiphilic polymers, PEG-b-PDLLA showed the smallest and PiPOx-b-PDLLA the highest Kv value. This indicates, that PiPOx-b-PDLLA core is less hydrophobic and looser compared to the dense cores of PEG-b-PDLLA and PiPOx-b-PLLA, making it capable of encapsulating the greatest amount of pyrene. In the loading and release studies, the nanoparticles were loaded with curcumin and placed in dialysis against PBS Tween® 80 solution. Curcumin content of the samples was monitored over a week by measuring the emission spectra of curcumin. PiPOx-b-PDLLA showed greater potential as a drug delivery agent: It formed more stable nanoparticles, showed higher loading capacities, higher encapsulation efficiencies and slower release rates. Flash nanoprecipitation method (FNP) was also used to prepare the same nanoparticles with and without encapsulated curcumin. In addition to the encapsulation efficiencies, sizes of the nanoparticles were determined via dynamic light scattering (DLS). PiPOx-b-PLLA forms the smallest nanoparticles with lowest encapsulation efficiencies, thus agreeing well with the higher density of PLLA core. All three investigated amphiphilic copolymers formed stable nanoparticles in water at room temperature. On the contrary, stability of the nanoparticles was found to be poor in saline solutions at body temperature. Mixing PEG-b-PDLLA with PiPOx-b-PLA in a ratio of 20:80 w-% increased the stability of the nanoparticles in physiological conditions simultaneously uncovering the thermoresponsive character of the PiPOx-blocks. Turbidity measurements of PEG-b-PDLLA mixed with PiPOx-b-PDLLA in ratio of 20:80 w-% showed slight decrease in transmittance at the 30 °C, which corresponds to the cloud point of PiPOx-b-PDLLA in PBS solution. However, it remains unclear, whether the increased stability is due to the PEG-b-PDLLA mixing in the same micelles with PiPOx-b-PDLLA, thus hindering the aggregation of the nanoparticles upon the cloud point of the PiPOx-blocks.
Keyword(s): polymer chemistry amphiphilic polymers drug delivery curcumin flash nanoprecipitation

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