Kuplennik, N.; Sosnik, A. Enhanced Nanoencapsulation of Sepiapterin within PEG-PCL Nanoparticles by Complexation with Triacetyl-Beta Cyclodextrin. Molecules2019, 24, 2715.
Kuplennik, N.; Sosnik, A. Enhanced Nanoencapsulation of Sepiapterin within PEG-PCL Nanoparticles by Complexation with Triacetyl-Beta Cyclodextrin. Molecules 2019, 24, 2715.
Kuplennik, N.; Sosnik, A. Enhanced Nanoencapsulation of Sepiapterin within PEG-PCL Nanoparticles by Complexation with Triacetyl-Beta Cyclodextrin. Molecules2019, 24, 2715.
Kuplennik, N.; Sosnik, A. Enhanced Nanoencapsulation of Sepiapterin within PEG-PCL Nanoparticles by Complexation with Triacetyl-Beta Cyclodextrin. Molecules 2019, 24, 2715.
Abstract
In this work, we investigated for the first time the complexation of sepiapterin (SP), the natural precursor of the natural essential cofactor tetrahydrobiopterin, that displays mild water-solubility and short biological half-life, with the hydrophobic triacetyl-β-cyclodextrin (TAβCD) to improve its encapsulation within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone) (mPEG-PCL) nanoparticles. First, TAβCD-SP complexes were produced by spray-drying of TAβCD/SP binary solutions by utilizing the Nano Spray Dryer B-90 HP. Then, dry powders were characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and transmission and scanning electron microscopy (SEM and TEM, respectively) and compared to the complex components and physical mixtures (PMs). Next, SP was encapsulated within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone) (mPEG-PCL) nanoparticles by nanoprecipitation of a SP/TAβCD complex/mPEG-PCL solution. In addition to complex nanoencapsulation, we assessed encapsulation of pure SP by nanoprecipitation with an intermediate step, which comprised the co-drying of SP, TAβCD and mPEG-PCL copolymer solution in organic solvent; this step aimed to promote the formation of molecular interactions between SP, TAβCD and the PCL blocks in the copolymer. SP-loaded mPEG-PCL nanoparticles were characterized by dynamic light scattering (DLS) and SEM. Nanoparticles with size of 74-75 nm and small polydispersity index (PDI <0.1) were obtained when SP-TAβCD equimolar spray-dried complex was used for nanoencapsulation, and SEM analysis indicated the absence of free SP crystals. Moreover, the encapsulation efficiency (%EE) and drug loading (DL) were 85% and 2.6%, respectively, as opposed to those achieved with pure SP encapsulation (14% and 0.6%, respectively). Overall, our results confirm that spray-drying of SP/TAβCD solutions at the appropriate molar ratio leads to the hydrophobization of the relatively hydrophilic SP molecule, enabling its encapsulation within mPEG-PCL nanoparticles.
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