Reversal of multidrug resistance in vitro by co-delivery of MDR1 targeting siRNA and doxorubicin using a novel cationic poly(lactide-co-glycolide) nanoformulation

• Published in: International journal of pharmaceutics Vol. 475; no. 1-2; pp. 372 - 384
• Main Authors: Misra, Ranjita, Das, Manasi, Sahoo, Bhabani Sankar, Sahoo, Sanjeeb K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.11.2014
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; ATP Binding Cassette Transporter, Sub-Family B - metabolism; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cationic nanoparticles; Cations - administration & dosage; Cations - chemistry; Cell Line, Tumor; Chemistry, Pharmaceutical - methods; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Drug Delivery Systems - methods; Drug Resistance, Multiple - drug effects; Drug Resistance, Multiple - genetics; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Humans; MCF-7 Cells; MCF-7/ADR cells; Multidrug resistance; Nanoparticles - administration & dosage; Nanoparticles - chemistry; P-gp; Polyglactin 910 - administration & dosage; Polyglactin 910 - chemistry; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - chemistry; siRNA; MCF-7/ADR cells; Cationic nanoparticles; siRNA; P-gp; Doxorubicin; Multidrug resistance
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.08.056

[Display omitted] Over expression of drug efflux transporters such as P-glycoprotein (P-gp) cumulatively leading to multidrug resistance (MDR) embodies a major hindrance for successful cancer therapy. A paradigm nanomedicinal approach involving an anticancer drug and modulators of drug resistance within one multifunctional nanocarrier-based delivery system represent an ideal modality for the treatment of MDR. In this regards, we have developed a cationic polymeric nanoparticulate system loaded with MDR1-siRNA and doxorubicin. Results indicated augmented synergistic effect of combinational nanoformulation in overcoming MDR in MCF-7/ADR cells. Therefore, the above regime could be a promising co-delivery system for effective therapy of drug resistant breast cancer.