TY - JOUR
T1 - Quercetin-loaded solid lipid nanoparticles improve osteoprotective activity in an ovariectomized rat model
T2 - A preventive strategy for post-menopausal osteoporosis
AU - Ahmad, Naseer
AU - Banala, Venkatesh Teja
AU - Kushwaha, Priyanka
AU - Karvande, Anirudha
AU - Sharma, Shweta
AU - Tripathi, Ashish Kumar
AU - Verma, Ashwni
AU - Trivedi, Ritu
AU - Mishra, Prabhat Ranjan
N1 - Publisher Copyright:
© 2016 Royal Society of Chemistry.
PY - 2016
Y1 - 2016
N2 - A formulation of quercetin-based solid lipid nanoparticles (QSLNs) was developed to increase the bioavailability of quercetin, with an aim to evaluate its effects on bone health in comparison to free quercetin (Q). The QSLNs were prepared by emulsification solvent evaporation followed by a cold homogenization method. The QSLNs were spherical when observed under atomic force microscopy, with an average diameter of 172.9 ± 12.65 nm. This formulation was pharmaceutically characterized and then evaluated for osteoprotective activity in ovariectomized (OVx) rats. A single oral dose of QSLNs (5 mg kg-1 d-1) significantly increased the bioavailability compared to free quercetin. The oral administration of QSLNs to ovariectomized rats increased serum quercetin levels by 3.5-fold compared to free quercetin. After 12 weeks of treatment, the bone mineral density of the femur, tibia and lumbar spine L-5 measured by micro-computed tomography (μCT) was restored in the QSLNs group, and was equivalent to the sham control group compared to in the OVx group, but the QSLNs had no effect on adipogenesis and uterine weight in OVx rats. μCT analysis showed that the QSLNs group had an improved trabecular microarchitecture in the distal femoral, proximal tibial and lumbar spine cancellous bones. The developed quercetin formulation based on solid lipid nanoparticles inhibited bone loss in osteopenic rats. Q and QSLNs inhibited the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast cells differentiation and the expression of osteoclast-specific genes in in vitro experiments using bone marrow cells treated with RANKL and M-CSF. The data from this study suggest that, overall, QSLNs treatment recovers bone loss (femur, BV/TV; ∼21%, p < 0.01) more so than in the Q treatment group, while both inhibit bone loss without showing any hyperplasic effect on the uteri in OVx rats.
AB - A formulation of quercetin-based solid lipid nanoparticles (QSLNs) was developed to increase the bioavailability of quercetin, with an aim to evaluate its effects on bone health in comparison to free quercetin (Q). The QSLNs were prepared by emulsification solvent evaporation followed by a cold homogenization method. The QSLNs were spherical when observed under atomic force microscopy, with an average diameter of 172.9 ± 12.65 nm. This formulation was pharmaceutically characterized and then evaluated for osteoprotective activity in ovariectomized (OVx) rats. A single oral dose of QSLNs (5 mg kg-1 d-1) significantly increased the bioavailability compared to free quercetin. The oral administration of QSLNs to ovariectomized rats increased serum quercetin levels by 3.5-fold compared to free quercetin. After 12 weeks of treatment, the bone mineral density of the femur, tibia and lumbar spine L-5 measured by micro-computed tomography (μCT) was restored in the QSLNs group, and was equivalent to the sham control group compared to in the OVx group, but the QSLNs had no effect on adipogenesis and uterine weight in OVx rats. μCT analysis showed that the QSLNs group had an improved trabecular microarchitecture in the distal femoral, proximal tibial and lumbar spine cancellous bones. The developed quercetin formulation based on solid lipid nanoparticles inhibited bone loss in osteopenic rats. Q and QSLNs inhibited the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast cells differentiation and the expression of osteoclast-specific genes in in vitro experiments using bone marrow cells treated with RANKL and M-CSF. The data from this study suggest that, overall, QSLNs treatment recovers bone loss (femur, BV/TV; ∼21%, p < 0.01) more so than in the Q treatment group, while both inhibit bone loss without showing any hyperplasic effect on the uteri in OVx rats.
UR - http://www.scopus.com/inward/record.url?scp=84992220390&partnerID=8YFLogxK
U2 - 10.1039/c6ra17141a
DO - 10.1039/c6ra17141a
M3 - Article
AN - SCOPUS:84992220390
SN - 2046-2069
VL - 6
SP - 97613
EP - 97628
JO - RSC Advances
JF - RSC Advances
IS - 100
ER -