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Poly(2-oxazoline)- and poly(2-oxazine)- based hydrogels and nanoformulations for drug delivery applications

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Title: Poly(2-oxazoline)- and poly(2-oxazine)- based hydrogels and nanoformulations for drug delivery applications
Author(s): Kinnunen, Moonika
Contributor: University of Helsinki, Faculty of Science
Degree program: Master 's Programme in Materials Research
Specialisation: Polymer Materials Chemistry
Language: English
Acceptance year: 2022
In this project, poly(2-methyl-2-oxazoline)-block-poly(2-n-butyl-2-oxazine)-block-poly(2-methyl-2- oxazoline) (PMeOx-b-PnBuOzi-b-PMeOx) and poly(2-methyl-2-oxazoline)-block-poly(2-n-propyl-2- oxazine) (PMeOx-b-PnPrOzi) with block lengths of 35-20-35 and 100-100, respectively, were synthesized. When dispersed in water these thermoresponsive polymers aggregate into micellar aggregates or form hydrogels. Polymers were characterized with 1H-NMR, GPC, and DLS. Age-related macular edema and diabetic macular edema are the most common reasons for blindness in industrialized countries. The triamcinolone acetonide, a corticosteroid used to treat both of these macular edemas, was loaded into the polymeric micelles or hydrogel of synthesized polymers using the thin film method. The loading efficiency for a triblock copolymer ((PMeOx35-b-PnBuOzi20- b-PMeOx35) polymeric micelles was 4 % at the polymer/drug ratio of 10/4 and for a hydrogel (PMeOx100-b-PnPrOzi100) it was 48 % with the same polymer/drug ratio. The properties of the PMeOx100-b-PnPrOzi100 hydrogel formulations with the drug were studied with rheological measurements, DSC, DLS, and GPC of formulations. The formulation showed storage modulus of 3 kPa and the gelation temperature at 16 °C. From the DSC two glass transition temperatures were obtained, Tg1 at around 12 °C and Tg2 at around 74 °C. The particle size distribution of the formulation obtained with DLS showed that there were assumingly micelles or vesicles with a hydrodynamic radius between 20 and 80 nm. The drug release from the hydrogel formulation was studied with the dialysis membrane method and all the drug was released within 24 hours. Both copolymers formed quite unstable formulations with the drug. The results from this study gives information how polyoxazoline- and polyoxazine-based materials can be used to encapsulate and release corticosteroids, such as triamcinolone acetonide. To increase the drug loading capacity and to stabilize formulations, some surfactants for the drug could be tested in the future.
Keyword(s): drug delivery triamcinolone acetonide nanoformulations poly(2-oxazoline) poly(2-oxazine) hydrogel

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