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.

Radiolabeled methotrexate as a diagnostic agent of inflammatory target sites: A proof-of-concept study

“…To the best of our knowledge, this study is the first to report direct evidence of hydroxyapatite binding of 99m Tc-MTX. This information might prove useful in the current research for bone-targeted drug delivery ( 18 , 19 ). The results are promising and set the stage for further study on the development and application of 99m Tc-MTX as a tool for early detection and imaging of inflammation in RA.…”

New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors

“…Similarly, Raichur et al 34 prepared anchored bone nanoparticles with selective bone affinity and methotrexate release nanoparticles by coupling ZOL with PLGA nanoparticles. Comprehensive evaluation methods, including infrared spectroscopy and nuclear magnetic resonance studies, in vitro dissolution studies, bone localization studies, in vivo biodistribution of experimental animal model studies and a series of studies, show that ZOL is an effective bone-targeted drug delivery carrier.…”

Polyaniline as a Sacrificing Template for the Synthesis of Ultra-small Co3O4 Nanoparticles for the Sensitive and Selective Detection of Methotrexate (MTX)

“…In the recent past, the designing a facile, fast, and very sensitive analytical method for the determination of MTX has received considerable attention. Currently, the analytical techniques such as capillary electrophoresis [9,0], high performance liquid chromatography [10] and uorescence spectroscopy [11][12][13] have been found highly accurate for the determination of MTX from biological samples. These standard analytical methods are costly and require multistep for the sample preparation which restricted their clinical applicability.…”