For the treatment of metastatic bone cancer, local delivery of therapeutic agents is preferred compared to systemic administration. Delivery of an anti-cancer drug and a protein that helps in bone regeneration simultaneously is a challenging approach. In this study, a nanoparticulate carrier which delivers a protein and an anti-cancer drug is reported. Bovine serum albumin (BSA) as a model protein was loaded into hydroxyapatite (HA) nanoparticles (NPs) and methotrexate (MTX) conjugated to poly(vinyl alcohol) was coated onto BSA-loaded HA NPs. Coating efficiency was in the range of 10-17 wt%. In vitro drug release showed that there was a steady increase in the release of both BSA and MTX with 76% of BSA and 88% of MTX being released in 13 days. Cytotoxicity studies of the NPs performed using human osteosarcoma (OMG-63) cell line showed the NPs were highly biocompatible and exhibited anti-proliferative activity in a concentration-dependent manner. © 2017 IOP Publishing Ltd.

Sampath Kumar T S

Department of Metallurgical and Materials Engineering

S Ram Prasad

Athipettah Jayakrishnan

biocompatibility

Body fluids

Bone

Cell culture

Diseases

Enzyme inhibition

Hydroxyapatite

Mammals

Nanoparticles

Polyvinyl alcohols

Surface plasmon resonance

Bovine serum albumins

Core-shell nanoparticles

HYBRID NANOPARTICLE

methotrexate

osteosarcoma

Proteins

antineoplastic agent

Bovine serum albumin

drug carrier

nanoparticle

polyvinyl alcohol

Animal

Bone tumor

bovine

chemistry

drug delivery system

drug release

tumor cell line

Animals

Antineoplastic Agents

Bone Neoplasms

Cattle

Cell Line, Tumor

Drug Carriers

Drug Delivery Systems

Drug Liberation

Durapatite

Serum Albumin, Bovine

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Nanotechnology

The delivery of multiple drugs with bone substitutes is the current strategy for the treatment of bone diseases. In this study, hydroxyapatite nanoparticles (HA NPs) as a core and poly(vinyl alcohol) (PVA) as the corona were developed for the dual delivery of anti-cancer drugs methotrexate (MTX) and gemcitabine (GEM). MTX was conjugated to PVA through ester linkages with a high payload of around 20%. GEM was then physically loaded onto the MTX conjugated-PVA-HA NPs with a loading efficiency of 83%. In vitro drug release studies of GEM-loaded-MTX conjugated-PVA-HA NPs in phosphate buffered saline (pH 7.4) showed a combined release of both MTX (25%) and GEM (60%) at the end of 10 days. Physically loaded MTX showed a burst release of around 50% compared to 16% by conjugated MTX within 24 h which supports the significance of conjugating drug molecules. Cell viability studies using osteosarcoma MG-63 cells confirmed that polymer grafted NPs were non-cytotoxic, while the drug-loaded NPs showed dose-dependent cytotoxicity. The synthesized NPs will be a promising bone-substitute material for the co-delivery of many therapeutic molecules for the treatment of bone diseases. © 2019 Elsevier B.V.

Journal of Drug Delivery Science and Technology

Hydroxyapatite-poly(vinyl alcohol) core-shell nanoparticles for dual delivery of methotrexate and gemcitabine for bone cancer treatment

As mannose receptors are known to be over-expressed in cancer cells, we synthesized polymannose-doxorubicin (PM-DOX) conjugates with the objective of targeting the drug to cancer cells. DOX was conjugated to oxidized PM through Schiff’s linkages to obtain PM-DOX conjugates. In order to examine the superior targeting efficacy of PM-DOX conjugate, sodium alginate (SA) was conjugated to DOX by similar chemistry and compared with PM-DOX conjugate. The cytotoxicity of the conjugates was investigated in A549 cell lines using MTT Assay and the cell uptake and retention studies, were performed using flow cytometry and cell imaging. In vitro drug release studies with both PM-DOX and SA-DOX conjugates showed an initial burst release of DOX up to 37–39% at 1 h, followed by a steady release up to 58–62% at 24 h in human plasma while negligible release was observed in phosphate buffered saline. The conjugates exhibited negligible hemolytic potential to human erythrocytes compared to free DOX. The PM-DOX conjugate showed better cytotoxic potential against A549 cells at lower concentration (equivalent to 0.27 μg/mL of DOX) at 72 h compared to free DOX and SA-DOX conjugate. Further, PM-DOX conjugate showed enhanced uptake by the cells in comparison with SA-DOX conjugate thereby confirming the target specificity of PM to the cancer cells. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Journal of Biomaterials Science, Polymer Edition

Conjugating doxorubicin to polymannose: a new strategy for target specific delivery to lung cancer cells

Resorbable ceramics such as biphasic calcium phosphates (BCP) are ideal candidates as drug delivery systems. The BCP ceramic is based on the optimum balance of the most stable hydroxyapatite (HA) phase and more soluble tricalcium phosphate phase (TCP). Doxycycline is a broad-spectrum antibiotic used for the local treatment of periodontitis. The development of BCP microspheres and its release kinetics with doxycycline have been studied. The BCP ceramic powder were prepared by microwave processing and characterised by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) methods. The BCP microspheres were formed by liquid immiscibility effect using gelatin and paraffin oil. Difference in the morphology of the microspheres as a function of gelatin content has been observed. Scanning electron microscope indicated spherical and porous morphology of the microspheres. Drug incorporation was studied at varying pH and the pH 7 was found to be optimal for drug loading. Release pattern tend to depend on the morphology of BCP microspheres. An optimum release of 80% drug has been observed for BCP microsphere with HA:TCP = 65:35 ratio. The surface area measurement results also correlate with drug release obtained. © 2007 Springer Science+Business Media, LLC.

Journal of Materials Science: Materials in Medicine

BCP ceramic microspheres as drug delivery carriers: Synthesis, characterisation and doxycycline release

Advanced Drug Delivery Reviews

Dual-controlled release system of drugs for bone regeneration

Scientific Reports

Different Inhibitory Effect and Mechanism of Hydroxyapatite Nanoparticles on Normal Cells and Cancer Cells In Vitro and In Vivo

RSC Advances

pH dependent chemical stability and release of methotrexate from a novel nanoceramic carrier

Biomaterials

Controlled dual delivery of BMP-2 and dexamethasone by nanoparticle-embedded electrospun nanofibers for the efficient repair of critical-sized rat calvarial defect

Ceramic core with polymer corona hybrid nanocarrier for the treatment of osteosarcoma with co-delivery of protein and anti-cancer drug

Journal	Nanotechnology
Publisher	Institute of Physics Publishing
ISSN	09574484
Open Access	No