title: Zolendronic Acid-Conjugated PLGA Ultrasmall Nanoparticle Loaded with Methotrexate as a Supercarrier for Bone-Targeted Drug Delivery.
abstract: Drug delivery to deep-seated tissues such as bone has been a major complication till date. This preferential drug delivery is further important in targeting anti-tumour agents to bone metastasis owing to its complexity. The present study involves the formulation of PLGA nanoparticles and conjugation with zolendronic acid-a bisphosphonate which will anchor the nanosystem to bone due to its selective bone affinity. The conjugated nanosystem was characterized for particle size by TEM (average 36 nm) and morphology by AFM depicting surface irregularities due to ZOL conjugation on the surface of nanoparticles. NMR spectral data also showed the involvement of terminal -OH group of PLGA in bond formation with ZOL. Bone localization studies showed higher accumulation of the ZOL-conjugated nanosystem in bone than non-conjugated nanoparticles. This was confirmed with bone mineral affinity and specificity assay wherein the conjugated nanosystem was found to selectively bind to hydroxyapatite in comparison to other bone minerals. The biodistribution studies depicted that the conjugated nanosystem was selectively targeted to the bone area with concentrations of methotrexate reaching up to 127.4 ± 1.41 μg in 1 h. Hence, this multipronged approach using (1) ultrasmall size of nanoparticles, (2) bone selective polymer and (3) suitable bone-targeting agent resulted in mutual synergism for the specific delivery of the anti-tumour agent to the bone.
authors.affiliation: Department of Pharmaceutics, Al-Ameen College of Pharmacy, Near Lalbagh Main Gate, Hosur Road, Bangalore, 560027, Karnataka, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Raichur
authors.affiliation: Department of Pharmaceutics, Al-Ameen College of Pharmacy, Near Lalbagh Main Gate, Hosur Road, Bangalore, 560027, Karnataka, India. drvkusumdevi@gmail.com.
authors.forename: Kusum Devi
authors.initials: KD
authors.lastname: Vemula
authors.affiliation: Department of Pharmacology, Al-Ameen College of Pharmacy, Near Lalbagh Main Gate, Hosur Road, Bangalore, 27, Karnataka, India.
authors.forename: Naini
authors.initials: N
authors.lastname: Bhadri
authors.affiliation: Department of Pharmacology, Al-Ameen College of Pharmacy, Near Lalbagh Main Gate, Hosur Road, Bangalore, 27, Karnataka, India.
authors.forename: Rema
authors.initials: R
authors.lastname: Razdan
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D004164:Diphosphonates / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D007093:Imidazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D008727:Methotrexate / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D011100:Polyglycolic Acid; D000077211:Zoledronic Acid; D008727:Methotrexate
keywords: AFM; TEM; bone localization; bone mineral affinity; hydroxyapatite; targeted drug delivery