Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (−33 to −41 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer.

Freeze- and spray-dried inclusion complexes (ICs) of chlorhexidine (CHX) in β-cyclodextrin were characterized by Fourier transform (FT)-Raman, 1H nuclear magnetic resonance (NMR), and photoacoustic spectroscopy. The active Raman modes of CHX were simulated using the density functional theory. By considering semiempirical calculations, it was observed that the guest penetrates on the wider rim of the host in a proportion of 1:2. We observe from the FT-Raman analysis that the drying method influences the CHX:β-cyclodextrin conformational adjustment by the rearrangement of hydrophilic biguanides of the guest. The photoacoustic spectroscopy results inferred that the freeze-drying method provided a better inclusion due to a lower interaction between phenyl groups and hexamethylene of CHX. The freeze-dried IC achieved a faster dissolution pattern. These ICs provided immediate drug dissolution profiles in an aqueous medium better than a pure drug. The release profiles of freeze- and spray-dried ICs were explained by Fickian diffusion. These data support further planning and development projects of novel immediate release systems based on CHX.

Curcumin (CUR) shows potential use for treating cancer. However, CUR has low solubility and reduced bioavailability, which limit its clinical effect. Therefore, the development of nanocarriers can overcome these problems and can ensure the desired pharmacological effect. In addition, it is mandatory to prove the quality, the efficacy, and the safety for a novel nanomedicine to be approved. In that sense, this paper aimed (a) to prepare CUR-loaded polyethylene glycol-poly(ε-caprolactone) nanocapsules; (b) to validate an analytical method by high performance liquid chromatography (HPLC) for quantifying CUR in these nanoformulations; (c) to evaluate the physicochemical stability of these formulations; and to investigate their cytotoxicity on NIH-3T3 mouse fibroblast cells. The HPLC method was specific to CUR in the loaded nanocapsules, linear (r = 0.9994) in a range of 10.0 to 90.0 µg.mL-1 with limits of detection and quantification of 0.160 and 0.480 µg.mL-1 , respectively. Precision was demonstrated by a relative standard deviation lower than 5%. Suitable accuracy (102.37 ± 0.92%) was obtained. Values of pH, particle size, polydispersity index, and zeta potential presented no statistical difference (p > 0.05) for CUR-loaded nanoparticles. No cytotoxicity HIGHLIGHTS  A simple and low-cost HPLC method for determining curcumin in nanocapsules was validated.  PEG-PCL nanocapsules containing curcumin showed suitable stability over 60 days.  No cytotoxicity was observed against NIH-3T3 mouse embryo fibroblast cell line.  PEG-PCL nanocapsules containing curcumin can be further investigated for cancer treatment. 2 Rudnik, L.A.C.; et al.