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

Ranjita Misra; Manasi Das; Bhabani Sankar Sahoo; Sanjeeb K Sahoo

doi:10.1016/j.ijpharm.2014.08.056

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

Int J Pharm. 2014 Nov 20;475(1-2):372-84. doi: 10.1016/j.ijpharm.2014.08.056. Epub 2014 Aug 29.

Authors

Ranjita Misra¹, Manasi Das¹, Bhabani Sankar Sahoo¹, Sanjeeb K Sahoo²

Affiliations

¹ Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar, Orissa, India.
² Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar, Orissa, India. Electronic address: sanjeebsahoo2005@gmail.com.

PMID: 25178825
DOI: 10.1016/j.ijpharm.2014.08.056

Abstract

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.

Keywords: Cationic nanoparticles; Doxorubicin; MCF-7/ADR cells; Multidrug resistance; P-gp; siRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / metabolism
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / chemistry
Cations / administration & dosage
Cations / chemistry*
Cell Line, Tumor
Chemistry, Pharmaceutical / methods
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
Nanoparticles / administration & dosage
Nanoparticles / chemistry*
Polyglactin 910 / administration & dosage
Polyglactin 910 / chemistry*
RNA, Small Interfering / administration & dosage*
RNA, Small Interfering / chemistry

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents
Cations
RNA, Small Interfering
Polyglactin 910
Doxorubicin