title: The development, characterization and in vivo anti-ovarian cancer activity of poly(propylene imine) (PPI)-antibody conjugates containing encapsulated paclitaxel.
abstract: Mesothelin, protein is frequently expressed in ovarian cancers. However, a full understanding of the biological functions of mesothelin is lacking. Here, we investigate the drug targeting potential of antibody conjugated modified half-generation poly (propylene imine) dendrimers i.e. immunodendrimers toward ovarian cancer with a model anti-cancer agent, paclitaxel (PTX). The synthesized plain 4.5G dendrimers as well as immunodendrimers were characterized by FT-IR, (1)H-NMR, TEM, and flow cytometry. Immunodendrimers exhibited considerably reduced hemolytic-, hepato- and nephrotoxicity. MTT cytotoxicity, flow cytometry and cell morphology studies were conducted in OVACAR-3 and A-431 cell. We demonstrate that PTX loaded immunodendrimers reduced the tumor volume significantly. The biodistribution studies further confirmed the targeting efficiency and higher biodistribution of immunodendrimers into the mesothelin protein expressing ovarian cancer cells. The results concluded that the developed immunodendrimers have potential to deliver significantly higher amount of the bioactive and have improved therapeutic outcome.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, India. Electronic address: jnarendr@yahoo.co.in.
authors.forename: Narendra K
authors.initials: NK
authors.lastname: Jain
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, India.
authors.forename: Manoj S
authors.initials: MS
authors.lastname: Tare
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University, Sagar, India. Electronic address: vijaymishra2@gmail.com.
authors.forename: Vijay
authors.initials: V
authors.lastname: Mishra
authors.affiliation: Department of Pharmacy, RITM, Lucknow, India.
authors.forename: Pushpendra K
authors.initials: PK
authors.lastname: Tripathi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D050091:Dendrimers; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D000090204:Mesothelin; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine / Q000379:methods; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011126:Polypropylenes / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; C000715528:Msln protein, mouse; D011126:Polypropylenes; C443641:poly(propyleneimine); D007770:L-Lactate Dehydrogenase; D000090204:Mesothelin; D017239:Paclitaxel
keywords: Cytotoxicity; Immunodendrimers; Ovarian cancer; Poly(propylene imine) dendrimer; Tumor growth inhibition