Tapan K Dash1, V Badireenath Konkimalla2. 1. School of Biological Sciences, National Institute of Science Education and Research (NISER), Homi Bhabha National Institute (HBNI), PO- Bhimpur-Padanpur, Via- Jatni, Khurda, 752050, India. 2. School of Biological Sciences, National Institute of Science Education and Research (NISER), Homi Bhabha National Institute (HBNI), PO- Bhimpur-Padanpur, Via- Jatni, Khurda, 752050, India. badireenath@niser.ac.in.
Abstract
PURPOSE: To select P-glycoprotein (P-gp) inhibitor from natural source for reversal of DOX resistance in K562 cells and to develop selected one in to nanoformulation in combination with DOX. METHODS: DOX resistant K562 (K562R) cells were developed and reversal of resistance by P-gp inhibitor was validated by co-treatment with verapamil. The p-gp inhibitors were evaluated for their potential to inhibit P-gp (calcein assay) and to reverse drug resistance (XTT cell viability assay). The selected agent, curcumin was formulated in to liposome along with DOX and characterized for size, zeta potential, encapsulation efficiency and release rate. Uptake, P-gp inhibition and reversal of acquired drug resistance in K562R cells were performed. RESULTS: P-gp inhibitors such as biochanin-A and curcumin were marked suitable for combination with DOX. However, only curcumin could increase the sensitivity of DOX at all dosing levels, therefore used for further studies. Liposomes loaded with curcumin were formulated and characterized where a prolonged release was observed. The uptake of liposomal curcumin was comparable to nanodispersed curcumin but had lower cytotoxicity. DOX and curcumin coloaded liposomes successfully reversed DOX resistance in K562 cells. CONCLUSION: The coloaded liposomes increased the safety of curcumin with improved efficacy thus can be employed for reversal of acquired DOX resistance.
PURPOSE: To select P-glycoprotein (P-gp) inhibitor from natural source for reversal of DOX resistance in K562 cells and to develop selected one in to nanoformulation in combination with DOX. METHODS:DOX resistant K562 (K562R) cells were developed and reversal of resistance by P-gp inhibitor was validated by co-treatment with verapamil. The p-gp inhibitors were evaluated for their potential to inhibit P-gp (calcein assay) and to reverse drug resistance (XTT cell viability assay). The selected agent, curcumin was formulated in to liposome along with DOX and characterized for size, zeta potential, encapsulation efficiency and release rate. Uptake, P-gp inhibition and reversal of acquired drug resistance in K562R cells were performed. RESULTS:P-gp inhibitors such as biochanin-A and curcumin were marked suitable for combination with DOX. However, only curcumin could increase the sensitivity of DOX at all dosing levels, therefore used for further studies. Liposomes loaded with curcumin were formulated and characterized where a prolonged release was observed. The uptake of liposomal curcumin was comparable to nanodispersed curcumin but had lower cytotoxicity. DOX and curcumin coloaded liposomes successfully reversed DOX resistance in K562 cells. CONCLUSION: The coloaded liposomes increased the safety of curcumin with improved efficacy thus can be employed for reversal of acquired DOX resistance.
Authors: Kathleen M Giacomini; Shiew-Mei Huang; Donald J Tweedie; Leslie Z Benet; Kim L R Brouwer; Xiaoyan Chu; Amber Dahlin; Raymond Evers; Volker Fischer; Kathleen M Hillgren; Keith A Hoffmaster; Toshihisa Ishikawa; Dietrich Keppler; Richard B Kim; Caroline A Lee; Mikko Niemi; Joseph W Polli; Yuichi Sugiyama; Peter W Swaan; Joseph A Ware; Stephen H Wright; Sook Wah Yee; Maciej J Zamek-Gliszczynski; Lei Zhang Journal: Nat Rev Drug Discov Date: 2010-03 Impact factor: 84.694
Authors: Dhruba J Bharali; Imtiaz A Siddiqui; Vaqar M Adhami; Jean Christopher Chamcheu; Abdullah M Aldahmash; Hasan Mukhtar; Shaker A Mousa Journal: Cancers (Basel) Date: 2011-10-26 Impact factor: 6.639