Abstract
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 32 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. Nano-characterization 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.
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Acknowledgments
The authors gratefully acknowledge financial support and granting research fellowship (45/16/2014-Nan/BMS) from ICMR (Indian Council of Medical Research, Govt of India, New Delhi). Authors are thankful to Dr. Shobha Rani R. H., Principal, Al-Ameen College of Pharmacy, Bangalore, for providing the necessary facilities to carry out the research work. Authors are also grateful to Machen Product India Pvt. Ltd. (Mumbai), India for providing the gift sample of MTX. Special thanks to Mount Carmel Institue, Bangalore for carrying out AFM analysis.
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Raichur, V., Devi, V.K. Formulation and evaluation of osteotropic drug delivery system of methotrexate with a potential for passive bone targeting. Journal of Pharmaceutical Investigation 47, 335–347 (2017). https://doi.org/10.1007/s40005-016-0265-9
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DOI: https://doi.org/10.1007/s40005-016-0265-9