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Sterically stabilized polymeric nanoparticles with a combinatorial approach for multi drug resistant cancer: In vitro and in vivo investigations.
MedLine Citation:
PMID:  25445525     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The present work describes the preparation of sterically stabilize polymeric nanoparticles of mitoxantrone dihydrochloride (MTO) along with an efflux transporter (Pgp/BCRP) inhibitor that enhance the circulation time of nanoparticles and simultaneously surmount the problem of multidrug resistance (MDR). Mitoxantrone dihydrochloride being hydrophilic in nature had very low entrapment efficiency (%E.E.), thus in order to further enhance the lipophilicity and the %E.E., it was complexed with sodium deoxycholate (SDC) and this MTO-SDC-complex was used to formulate nanoparticles with/without Pgp/BCRP inhibitor by nanoprecipitation technique and was characterized for various in vitro and in vivo attributes. In vitro cell line studies were conducted on MCF7, A2780(p) and A2780(adr) cells. Furthermore, the targeting potential of hyaluronic acid (HA) coated nanoparticles for CD44 receptors was investigated using the MCF7 cell line. A reduction in the IC50 value observed with the inhibitor loaded nanoparticles in different cell lines indicated the BCRP/Pgp inhibiting ability of the formulated nanoparticles. The reduced macrophage uptake and the increased residence time in blood demonstrated the long circulating behaviour of the nanoparticles. The enhanced cellular uptake of HA coated nanoparticles in MCF7 cells revealed their targeting potential. The HA coated nanoparticles along with efflux transporter inhibitor exhibits a great potential for targeted chemotherapy in CD44 overexpressing MDR breast cancer.
Authors:
Sobiya Zafar; Lalit Mohan Negi; Anita Kamra Verma; Vijay Kumar; Aakriti Tyagi; Pratibha Singh; Zeenat Iqbal; Sushama Talegaonkar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-1
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  477     ISSN:  1873-3476     ISO Abbreviation:  Int J Pharm     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  454-468     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier B.V.
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