Rutin nanosuspension for potential management of osteoporosis: effect of particle size reduction on oral bioavailability, in vitro and in vivo activity

Abstract

Clinical significance of Rutin (RUT) is limited by poor dissolution rate and low oral bioavailability. The study was designed to improve the physicochemical and therapeutic potential of the drug by formulating nanosuspension (NS) for osteoporosis. Rutin nanosuspension (RUT-NS) was prepared after screening a range of stabilizers and their combinations at a different concentration by antisolvent precipitation technique. Effect of precipitation on crystallinity (differential scanning calorimetry DSC, X-ray diffraction studies XRD), morphology (scanning electron microscopy, SEM) and chemical interaction (attenuated total reflectance fourier-transform infrared spectroscopy ATR-FTIR) were studied through biophysical techniques. An optimized nanosuspension exhibited a minimum particle size of 122.85 ± 5.02 nm with higher dissolution of RUT-NS (87. 63 ± 2.29%) as compared to pure drug (39.77 ± 2.8 6%). The enhanced intestine absorption and apparent permeability were achieved due to the improved particle size, surface area and dissolution. RUT-NS displayed greater (3 folds) AUC_0–24 h than pure drug. In vitro assays with RUT-NS depicted an increased cell proliferation, antioxidant (ROS) activity and osteocalcin production in MG-63 osteoblast cells. The augmented biochemical in vivo biomarkers and bone quality proved the protective effect of RUT-NS. The results supported RUT-NS as a potential therapy for maintaining bone health.

Graphical Abstract

Keywords:

• Antisolvent precipitation
• antioxidant
• MG-63 cell lines
• nanosuspension osteoporosis
• rutin

Acknowledgments

The authors are thankful to Director NIPER, Hyderabad, for the support. The work is funded by the Ministry of Chemicals and Fertilisers, Government of India. Jitendra Wankar would like to thank European Commission, Science Foundation Ireland for Marie Curie Cofund Fellowship and NUI Galway Ireland for support.

Disclosure statement

No potential conflict of interest was reported by the author(s).