Pó inalável microparticulado com nanopartículas poliméricas contendo Curcumina e Piperina: desenvolvimento, caracterização físico-química e citotoxicidade em linhagens tumorais de pulmão.

Abstract

Curcumin (CUR) is a polyphenol from the plant Curcuma longa L. and among the various biological effects, there is antitumor action. Piperine (PIP) is an alkaloid present in the plant Piper nigrum L. also having antitumor activity. Its coadministration with CUR is interesting because it has the ability to reduce the clearance of this active substance. In the microparticulate system loaded with nanoparticles, the microparticles function as an intermediate carrier for the efficient deposition of nanoparticles with drugs in the lungs. The objective of this work was to develop and characterize a microparticle powder containing polymeric nanoparticles of CUR and PIP and to evaluate the nanoparticles against 3 cell lines (tumor: A549, NCI-H292 and control: MRC-5). Two nanoparticle formulations containing CUR and PIP and PCL and PEG polymers were developed from the nanoemulsion method using sonication. Subsequently, these nanoparticles were transformed into a dry powder using spray drying and mannitol as an excipient. Nanoparticles with sizes (244.50±23.00 and 223.70±21.00 nm), zeta potentials (-11.30±1.6 to -14.60±2.2 mV) and polydispersion indices were obtained. (0.135±0.18 and 0.117±0.15) are suitable. The microparticles showed adequate aerodynamic diameter values (3.63±0.90 and 2.56±0.63 µm). An analytical method by high performance liquid chromatography (HPLC) was developed and validated for quantification of drugs in nanocarriers. The method proved to be specific, linear, precise, accurate and robust, in the range of 25 to 45 µg.mL-1 for CUR and PIP, being able to quantify these two substances simultaneously. The incorporation efficiency for both drugs was greater than 90%. NCP-0 and NCP-1 presented spherical shape and nanometric scale. MNCP-0 and MNCP-1 showed a spherical shape, micrometric dimensions with little roughness and the presence of nanometric structures on the surface in addition to agglomerates of mannitol crystals. No changes were observed in the functional groups of the drugs in the infrared spectra (FTIR). X-ray diffraction (XRD) analyzes indicated that the incorporation of polymeric nanoparticles of CUR and PIP to microparticles with mannitol led to amorphization of the drugs. In vitro studies showed that the NCP-1 formulation significantly reduced the cell viability of the A549 and NCI-H292 strains, being selective for these cells (IS>2), when compared to MRC-5 cells. The morphological analyzes showed the presence of the process of death by apoptosis for A549 and NCI-H292 cells. The NCP-1 formulation showed a selective cytotoxic effect by the association of CUR and PIP for the tumor cells under study.