title: Bone metastasis targeting: a novel approach to reach bone using Zoledronate anchored PLGA nanoparticle as carrier system loaded with Docetaxel.
abstract: In spite of good research in drug delivery, bone targeting remains largely unexplored. Even some of the bone diseases are seldom cured just because of poor distribution of drug at the bone site. Zoledronate (ZOL) having strong affinity towards bone and its utility in bone metastasis management makes it perfect ligand for bone targeting. Recent studies revealed that ZOL in combination with docetaxel showed significant synergism in the management of bone metastasis. From the results, it is clear that ZOL-conjugated PLGA nanoparticles (NPs) showed more cellular uptake than pegylated PLGA NPs with change in cellular uptake route. In vitro studies on MCF-7 and BO2 cell line revealed that ZOL anchored PLGA-PEG NPs showed enhanced cell cytotoxicity, increase in cell cycle arrest and more apoptotic activity. PLGA-PEG-ZOL NPs found to block mevalonate pathway and increase accumulation of apoptotic metabolites such as ApppI. In vivo animal studies using technetium-99m radiolabeling showed prolong blood circulation half-life, reduced liver uptake and significantly higher retention of ZOL tagged NPs at the bone site with enhanced tumor retention. Here, we can conclude that the targeting ability of ZOL enhanced by strong affinity to bone, enhanced endocytosis of ZOL anchored PLGA-PEG NPs.
authors.affiliation: TIFAC Centre of Relevance and Excellence in New Drug Delivery Systems, GH Patel Pharmacy Building, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Ramanlal Chaudhari
authors.forename: Abhinesh
authors.initials: A
authors.lastname: Kumar
authors.forename: Vinoth Kumar
authors.initials: VK
authors.lastname: Megraj Khandelwal
authors.forename: Mukesh
authors.initials: M
authors.lastname: Ukawala
authors.forename: Arehalli S
authors.initials: AS
authors.lastname: Manjappa
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Mishra
authors.forename: Jukka
authors.initials: J
authors.lastname: Monkkonen
authors.forename: Rayasa S
authors.initials: RS
authors.lastname: Ramachandra Murthy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001859:Bone Neoplasms / Q000188:drug therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000077211:Zoledronic Acid