Category: Formulation and Quality
Purpose: Colorectal cancer (CRC) is highly prevalent worldwide and considered as the most occurring cancer in Saudi Arabia, and despite the progress in therapeutic approaches still leads to significant mortality. Emergence of failure of most CRC therapy contributes to failure of drugs delivery and poor prognosis, and thus warrants development of new strategies for managing the disease. Many efforts have been made in the last decade to treat CRC as also nanoparticulate drug delivery systems are making a significant contribution in the improvement of drug delivery to colon cancer cells. The utilization of nanoparticles as a drug delivery system considered as one of the promising strategies for CRC therapy. One of main polymer utilized for preparing nanoparticles is Poly(lactic-co-glycolic acid) (PLGA) which is a biocompatible member of the aliphatic polyester family of biodegradable polymers. Also, Quercetin (QT) which is natural products and a model drug with low bioavailability that restricted its use, has been used here as anticancer drug.>
Methods: The main aim of present study was to prepare the Quercetin (QT) loaded PLGA and the emulsifying agent vitamin-TPGS-based nanoparticles to enhance the anticancer effect in colon cancer cells. QT is encapsulated in PLGA particles via single- or double-emulsion. PLGA degrades slowly via hydrolysis in aqueous environments, and encapsulated agents are released over time. Nanoparticles morphology and particle size are determined with scanning electron microscopy and Dynamic Light Scattering. Cell viability, colony formation, oxidative stress, and apoptosis were also evaluated to determine the toxic effects of the QT-NPs. This study also aimed to assess the therapeutic effect of QT-NPs on the growth of HT-29 human colon cancer cells.
Results: The QT-NPs were Nano sized and has a spherical shape and has exhibited controlled release kinetics. The QT-NPs showed sustained QT release over 72 h. Flow cytometer and fluorescence microscopy showed a remarkable uptake of nanoparticles in colon cancer cells in a time-dependent manner. Also, anticancer drugs inhibited CRC cell viability in a dose-dependent manner albeit QT-NPs alone or when combined with oxaliplatin therapy was more effective than any drug alone. The use of TPGS remarkably enhance the anticancer effect of NPs in HT-29 colon cancer cells. The 2-fold lower IC50 value of QT-NPs indicates the superior anticancer effect of nanoparticle-based formulations. Moreover, it induced a remarkable apoptosis of colon cancer cells. We also found that the NPs significantly improved the cellular uptake efficiency in HT-29 cancer cell lines, resulting in the efficient cell killing compared with free agents and plain NPs. The findings from this study provide important insights into the use of TPGS and PLGA nanoparticle together for the better antitumor effect in colon cancers.
Conclusion: These findings might be a promising therapeutic approach of QT-PLGA NPs in combination with other anticancer drugs in treatment of CRCs. Also, this drug delivery system has been noticed to be more efficacious in terms of stability, sustained drug release, improved bioavailability, and enhanced anticancer activity.