Bone metastasis is a devastating complication of cancer that requires an immediate attention. Although our understanding of the metastatic process has improved over the years, yet a number of questions still remain unanswered, and more research is required for complete understanding of the skeletal consequences of metastasis. Furthermore, as no effective treatments are available for some of the most common skeleton disorders such as arthritis, osteoarthritis, osteosarcoma and metastatic bone cancer, there is an urgent need to develop new drugs and drug delivery systems for safe and efficient clinical treatments. Hence this article describes the potential of targeted delivery platforms aimed specifically at bone metastasized tumors. The review gives a brief understanding of the proposed mechanisms of metastasis and focuses primarily on the targeting moieties such as bisphosphonates, which represent the current gold standard in bone metastasis therapies. Special focus has been given to the targeted nanoparticulate systems for treating bone metastasis and its future. Also highlighted are some of the therapeutic targets that can be exploited for designing therapies for bone metastasis. Some of the patented molecules for bone metastasis prevention and treatment have also been discussed. Recently proposed HIFU-CHEM, which utilizes High Intensity Focused ultrasound (HIFU) guided by MRI in combination with temperature-sensitive nanomedicines has also been briefed. The study has been concluded with a focus on the innovations requiring an immediate attention that could improve the treatment modality of bone metastasis.

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.

In the present research, methotrexate (MTX) loaded ultra-small PLGA nanoparticles were formulated with an aim of passively targeting the bone for effective treatment of metastatic condition. Formulations were prepared by using 3 2 factorial designs to evaluate the impact of the formulation variables on the dependant variables. The prepared formulations were subjected for nano-characterization and in vitro haemolysis evaluation. Nanocharacterization with Malvern particle size analyser depicted a particle size below 10 nm, zeta potential ([30) indicating a very high stability with entrapment efficiency of formulation ([60 %) and drug release of [80 % sustaining for 7 days. Kinetic modelling showed that the formulations showed best fit for Korsmeyer Peppas model with r value of 0.9875. TEM and AFM studies showed ultra small nanoparticles with a spherical shape and smooth surface respectively. In-vitro bone affinity studies showed that the nanoformulation had higher affinity for Hydroxyapatite than the pure drug alone. In-vitro haemolytic assay showed a reduced haemotoxicity of the MTX when encapsulated in a nanosystem rather the pure drug.