A validated RP-HPLC method for the determination of piperidone analogue of curcumin.

Curcumin (Diferuloylmethane) is a natural product extracted from the root of Curcuma longa. 5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone, the piperidone analogue of curcumin (PAC), was one of the analogues that, demonstrated potential anticancer effects against breast and colon cancers compared with native curcumin. A simple, accurate, and rapid isocratic reverse phase high performance liquid chromatography (HPLC) analytical method utilizing UV detection was developed and validated for the determination of PAC utilizing C18 column with run time was 7 min. Chromatogram showed a peak of PAC at retention time of 5.8±0.92 min. The method was validated for linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. Linear relationship (r > 0.99) was observed between AUP of PAC and the corresponding concentrations over 100-10000µg/mL. The LOQ of this assay was 3.9ng/mL with a corresponding relative standard deviation of 4.8 and 4.0%. The LOD was 13.1ng/mL at a signal-to-noise ratio of >3.

A Novel Inhalable Dry Powder to Trigger Delivery of Voriconazole for Effective Management of Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) is a fatal fungal infection with a high mortality rate. Voriconazole (VCZ) is considered a first-line therapy for IPA and shows efficacy in patients for whom other antifungal treatments have been unsuccessful. The objective of this study was to develop a high-potency VCZ-loaded liposomal system in the form of a dry-powder inhaler (DPI) using the spray-drying technique to convert liposomes into a nanocomposite microparticle (NCMP) DPI, formulated using a thin-film hydration technique. The physicochemical properties, including size, morphology, entrapment efficiency, and loading efficiency, of the formulated liposomes were evaluated. The NCMPs were then examined to determine their drug content, production yield, and aerodynamic size. The L3NCMP was formulated using a 1:1 lipid/L-leucine ratio and was selected for in vitro studies of cell viability, antifungal activity, and stability. These formulated inhalable particles offer a promising approach to the effective management of IPA.

The curcumin analogue PAC has potent anti-anaplastic thyroid cancer effects.

Anaplastic thyroid carcinoma (ATC) is the rarest type of thyroid cancer, but is the common cause of death from these tumors. The aggressive behavior of ATC makes it resistant to the conventional therapeutic approaches. Thus, the present study was designed to evaluate the anti-ATC efficacy of the piperidone analogue of curcumin (PAC). We have shown that PAC induces apoptosis in thyroid cancer cells in a time-dependent fashion through the mitochondrial pathway. Immunoblotting analysis revealed that PAC suppressed the epithelial-to-mesenchymal transition (EMT) process in ATC cells by upregulating the epithelial marker E-cadherin and reducing the level of the mesenchymal markers N-cadherin, Snail, and Twist1. This anti-EMT effect was confirmed by showing PAC-dependent inhibition of the proliferation and migration abilities of ATC cells. Furthermore, PAC inhibited the AKT/mTOR pathway in ATC cells. Indeed, PAC downregulated mTOR and its downstream effectors p70S6K and 4E-BP1 more efficiently than the well-known mTOR inhibitor rapamycin. In addition to the promising in vitro anticancer efficacy, PAC significantly suppressed the growth of humanized thyroid tumor xenografts in mice. Together, these findings indicate that PAC could be considered as promising therapeutic agent for anaplastic thyroid carcinomas.