title: Surface engineered nanostructured lipid carriers for targeting MDR tumor: Part II. In vivo biodistribution, pharmacodynamic and hematological toxicity studies.
abstract: Irinotecan loaded nanostructured lipid carrier (NLC-Ir) was surface decorated with hyaluronic acid graft polymer. Hyaluronic acid is a biocompatible, non-antigenic and hydrophilic, CD-44 ligand that can impart many useful features to the nanocarrier for anticancer drug delivery. The present investigation demonstrated that hyaluronic acid coated HA-NLC had significantly lower haemolytic potential as compared to uncoated NLC. Further, HA-NLC had a reduced plasma protein interaction and low macrophage uptake. The in vivo tumor targeting and pharmacodynamics efficacy of HA-NLC was studied in Ehrlich's Ascites Tumor (EAT) allograft model. Radio scintigraphic biodistribution studies revealed that HA-NLC carrier got accumulated in the tumor tissues in good proportion. Additionally, the content of radioactivity associated with tumor tissues remained constant at 2, 4 and 24 h (2.41, 2.48 and 2.47%, respectively), while it got reduced in other organs. Furthermore, tumor to muscle ratio of radioactivity suggested a better accumulation of HA-NLC in tumor tissues that was significantly enhanced (P<0.05) with time. In vivo antitumor activity of hyaluronan coated HA-NLC-Ir was 5.8 and 2.6 times higher as compared to control and free drug solution respectively. Furthermore, encapsulation of irinotecan in HA-NLC-Ir nanocarrier was found to have reduced the thrombocytopenia and neutropenia associated with free irinotecan. Thus, it can be inferred that the hyaluronic acid decorated nanocarrier can provide a haemo-compatible, non-toxic and target based delivery system for the effective management of cancer.
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: 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
authors.affiliation: Preclinical Department, Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Jaggi
authors.affiliation: Nano Biotechnology Lab, Department of Zoology, K.M. College, Delhi University, Delhi 110007, India.
authors.forename: Anita Kamra
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Department of Cell Biology, Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Verma
authors.affiliation: Department of Cell Biology, Dabur Research Foundation, Ghaziabad 201010, Uttar Pradesh, India.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Dobhal
authors.affiliation: Nano Biotechnology Lab, Department of Zoology, K.M. College, Delhi University, Delhi 110007, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D000077146:Irinotecan; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D000077146:Irinotecan; D006820:Hyaluronic Acid; D002166:Camptothecin
keywords: Ehrlich's ascites tumor; Hyaluronic acid; Irinotecan; NLC; Tumor targeting