Administration of raloxifene hydrochloride nanosuspensions partially attenuates | Forum

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freemexy Aug 12 '19

Postmenopausal osteoporosis is a systemic skeletal disease of fragility fractures due to the loss of the mass and the deterioration of the microarchitecture of bone. This study aimed to assess the effects of raloxifene hydrochloride nanosuspensions (RLX-NSps) on ovariectomized (OVX)-induced osteoporotic rats, and the underlying mechanisms were also investigated in vivo and ex vivo. RLX-NSps were successfully prepared, and the obtained RLX-NSps had a mean particle size of (91.17 ± 0.73) nm, PDI value of 0.201 ± 0.03 and zeta potential of (36.3 ± 1.8) mV. RLX-NSps showed a clear colloidal solution with light yellow opalescence. RLX-NSps were stable in artificial intestinal fluid, artificial gastric fluid, PBS, isotonic glucose and physiological saline.Raloxifene powder
The OVX mice were administered an RLX-NSps or RLX solution for 3 weeks. The bone micro-tomographic histomorphometry and bone mineral density (BMD) were assessed by micro-CT, and the biochemical markers procollagen type I N-terminal propeptide (P1NP) and beta-isomerized C-telopeptide (β-CTX) were determined from serum. Finally, primary bone marrow stromal cells (BMSCs) were isolated from the tibia and cultured to evaluate cell proliferation and osteogenic differentiation. The results demonstrated that the RLX-NSp group had a better effect on the bone microarchitecture than the RLX solution group. Therefore, RLX-NSps could partially attenuate bone loss more effectively than RLX solution in OVX mice by inhibiting bone resorption and improving the ability of BMSCs to proliferate and their osteogenic differentiation to some extent. Based on these results, nanosuspensions (NSps) may be a promising delivery system for postmenopausal osteoporosis therapy.

Postmenopausal osteoporosis is a relatively common metabolic bone disease that leads to increasing skeletal fragility and the risk of fractures due to rapid bone loss.1–3 Over half of adults over the age of 50 are diagnosed with osteoporosis, and among them, most women have postmenopausal osteoporosis.4,5 They can be affected with osteoporotic fractures throughout their remaining lifetime.6
There are two major therapeutic approaches for osteoporosis. One is anabolic agents that function by means of improving bone formation, such as parathyroid hormone,7 and the other is antiresorptive agents, which function by means of inhibiting osteoclast-mediated bone resorption, such as bisphosphonates.8 Estrogen deficiency, which is related to the loss of ovarian function, leads to bone loss and is a marker of osteoporosis as a result of excessive bone resorption.9–11 To prevent postmenopausal bone loss, estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) have been applied.12 It was reported that it can increase the risk of endometrial cancer and is slightly related to an increased risk of breast cancer after using estrogen for a long time.13,14 In contrast with estrogen, many studies have demonstrated that RLX has no side effects in terms of the stimulatory effect on the endometrium and the breast.15–17