Curcumin-loaded PLGA Nanoparticles Conjugated with Anti-P-glycoprotein Antibody to Overcome Multidrug Resistance

Abstract

<b>Background:</b> The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein(P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrugresistance(MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a humancervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and <br/><b>Methods</b>: First, we determined the MDRreversingproperty of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp,in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared withCur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated.Moreover, the stability of the NPs was determined in various solutions. <br/><b>Results</b>: The combined treatment ofpaclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatmentalone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but notwith NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remaineda consistent size, proving their stability in various solutions. <br/><b>Conclusions</b>: Our functional Cur-NPs-APgp maybe a suitable candidate for application in a drug delivery system for overcoming drug resistance. The furtherdevelopment of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDRmodulator or as an anticancer drug.