title: Sterically stabilized polymeric nanoparticles with a combinatorial approach for multi drug resistant cancer: in vitro and in vivo investigations.
abstract: 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.affiliation: Nano Research Lab Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Sobiya
authors.initials: S
authors.lastname: Zafar
authors.affiliation: Nano Research Lab Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Lalit Mohan
authors.initials: LM
authors.lastname: Negi
authors.affiliation: Nanobiotech Lab Department of Zoology, Kirori Mal College, University of Delhi, New Delhi 110007, India.
authors.forename: Anita Kamra
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Nanobiotech Lab Department of Zoology, Kirori Mal College, University of Delhi, New Delhi 110007, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Nanobiotech Lab Department of Zoology, Kirori Mal College, University of Delhi, New Delhi 110007, India.
authors.forename: Aakriti
authors.initials: A
authors.lastname: Tyagi
authors.affiliation: Dabur Research Foundation, Sahibabad, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Singh
authors.affiliation: Nano Research Lab Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: Nano Research Lab Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India. Electronic address: stalegaonkar@gmail.com.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003840:Deoxycholic Acid / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D065546:Drug Liberation; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004355:Drug Stability; D005260:Female; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology; D006569:Hesperidin; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D010316:Particle Size; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D017208:Rats, Wistar; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D004337:Drug Carriers; D044950:Flavanones; D009363:Neoplasm Proteins; D003840:Deoxycholic Acid; D006820:Hyaluronic Acid; D011794:Quercetin; D008942:Mitoxantrone; D006569:Hesperidin; C013015:hesperetin
keywords: CD44; Hyaluronic acid; Long circulating; Multidrug resistance; Nanoparticles