Formulation, optimization, and characterization of whey protein isolate nanocrystals for celecoxib delivery.

AIM: Current study aimed to improve the solubility and release profile of the celecoxib for cancer application. However, the low water solubility of celecoxib limited its application for cancer chemotherapy. Hence, new drug delivery-based approaches are compulsory for the efficient delivery of hydrophobic celecoxib for chemotherapy. METHODS: The celecoxib-loaded nanocrystals were prepared by anti-solvent precipitation-ultrasonication technique, and the formulation was optimised through various process parameters. RESULTS: The optimised formulation had an average particle diameter of 171.09 ± 6.23 nm, with a PDI of 0.123 ± 0.009 and high ZP -27.3 ± 0.2 mV. The optimised formulation was stable, had higher entrapment efficiency 97.26 ± 1.12%. The conformational changes in the denatured protein solution were detected through fluorescence spectroscopy. The transmission electron microscopy investigation showed rod-shaped nanocrystals morphology, and no chemical interactions were observed in optimised formulation through FTIR. The DSC and PXRD analysis exhibited an amorphous state of the freeze-dried formulation drug. Also, optimised nanocrystals enhance drug solubility around 26.01-fold, 15.51-fold and 19.08-fold in purified water, pH 6.8 and pH 7.4, and accomplish sustained drug delivery, respectively. CONCLUSION: It can be concluded that biopolymer-coated celecoxib nanocrystals might be potential drug delivery of hydrophobic molecules for cancer therapy.

Enhanced cellular uptake and cytotoxicity of vorinostat through encapsulation in TPGS-modified liposomes.

Vorinostat (VOR) is known as one of the histone deacetylase inhibitors (HDACi) for cancer treatment, and the FDA approves it for cutaneous T cell lymphoma therapy. Poor solubility, permeability, and less anti-cancer activity are the main challenges for the effective delivery of VOR against various cancers. So, our team assumed that the surface-coated liposomes might improve the physicochemical properties of biopharmaceutics classification system class IV drugs such as VOR. The present study aimed to enhance the cytotoxicity and improve cellular uptake using TPGS-coated liposomes in breast cancer cells. Liposomes were fabricated by the film hydration following the probe ultra-sonication method. OR-LIPO and TPGS-VOR-LIPO showed an average particle size of 211.97 ± 3.42 nm with PDI 0.2168 ± 0.006 and 176.99 ± 2.06 nm with PDI 0.175 ± 0.018, respectively. TPGS-coated liposomes had better stability and revealed more than 80 % encapsulation efficiency than conventional liposomes. Transmission electron microscopy confirmed the TPGS coating around liposomes. Moreover, TPGS-coated liposomes enhanced the solubility and showed sustained release of VOR over 48 h. DSC and PXRD analysis also reveal an amorphous state of VOR within the liposomal formulation. MTT assay result indicates that the superior cytotoxic effect of surface-modified liposomes contrasts with the conventional and free VOR solution, respectively. Fluorescence microscopy and flow cytometry results also presented an enhanced cellular uptake of TPGS-coated liposomes against breast cancer cells, respectively. The current investigation's final results declared that TPGS-coated liposomes are promising drug carriers for the effective delivery of hydrophobic drugs for cancer therapy.