Drug delivery system of curcumin to the lungs based on poly(3-alloxyloxy-1,2-propylene succinate)-sebacic acid copolymers.

Abstract

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 (M_n = 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.