Journal of pharmaceutical analysis · 2025
Drug delivery system of curcumin to the lungs based on poly(3-alloxyloxy-1,2-propylene succinate)-sebacic acid copolymers.
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Knap Karolina, Kwiecień Konrad, Czajkowski Jonasz, Szostecki Rafał, Niewolik Daria, Jaszcz Katarzyna, Olinga Peter, Reczyńska-Kolman Katarzyna, Pamuła Elżbieta
Аннотация
Polyanhydrides are attractive materials for drug delivery matrices as a result of their cytocompatibility and fast degradation rate. Here, we synthesized and characterized copolymers of poly(3-allyloxy-1,2-propylene succinate) (PSAGE) and sebacic acid (SBA). The successful polymerization was confirmed by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FTIR) spectroscopy analyses. The material with PSAGE and 60% of SBA copolymer (PSAGE-SBA60) was more hydrophilic than the PSAGE and 80% of SBA copolymer (PSAGE-SBA80) (water contact angle 82.2° ± 11.6° vs. 98.6° ± 8.9°, respectively). PSAGE-SBA60 also had a lower molecular weight than PSAGE-SBA80 (Mn = 6400 Da vs. 9800 Da). Both polyanhydrides were used to encapsulate curcumin (CUR) as a potential anti-inflammatory, antimicrobial and anticancer agent. The unloaded microparticles (MPs) and CUR-loaded MPs were produced using the emulsification/solvent evaporation method. The CUR was uniformly distributed within the MPs, as confirmed by fluorescence microscopy. All MPs had a geometric diameter < 5 μm and their surface charge was negative. MPs_PSAGE-SBA80 + CUR had the best aerodynamic properties, as shown by laser diffraction measurements and flowability parameters, i.e., Carr index and Hausner ratio. The MPs obtained from PSAGE-SBA60 degraded faster than those of PSAGE-SBA80. All MPs were noncytotoxic at a concentration of up to 100 μg/mL in the in vitro model (BEAS-2B lung epithelial cells) and ex vivo precision-cut tissue slices (PCTSs) rat model. The developed MPs are promising CUR carriers for pulmonary delivery in a dry powder formulation.