Osteoporosis, due to its prevalence worldwide, is a serious health problem. Topical administration of quercetin, a phytoestrogen, in the form of deformable transfersomes, could be used to treat osteoporosis to overcome its low oral solubility and bioavailability. Formulation process of transfersomes was screened by fractional factorial design and further optimized using full factorial design. Transfersomes showed good characteristics such as entrapment efficiency, particle size, zeta potential, and polydispersity index (83.0 ± 2.2%, 75.95 ± 2 nm, − 13.6 ± 6 mv and 0.333, respectively). Transfersomes were further loaded into chitosan film and showed good permeation through rat skin. Further, glucocorticoid-induced osteoporosis rat model showed induction of osteoporosis after day 30. On day 45, treatment with chitosan film containing quercetin-loaded transfersomes showed remarkable rise in femur thickness, length, density as well as in serum biochemical parameters such as calcium, phosphorous, alkaline phosphatase, and tartrate-resistant alkaline phosphatase compared to positive control group. Tensile strength of osteoporotic femur bone was also found to be increased and was comparable with normal group. Histomicrographic analysis of femur bone exhibited less disruptive and lytic changes. Thus, all the above findings indicated the beneficial effects of quercetin-loaded transfersome chitosan film, due to decline in osteoclastogenesis and osteoblast apoptosis, which further favored increase in osteoblast numbers and mineralization of bones. Thus, chitosan film containing quercetin-loaded transfersomes was found to be good alternative to oral administration of quercetin to treat osteoporosis, while easy applicability of film in the form of wrist band anytime, anywhere, and even at work achieve patient compliance.
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Authors thanked Mohini Organics Pvt. Ltd., India, for providing gift sample of Tween 80 as well as Vav Lipids Pvt. Ltd., India, for generously providing phosphatidylcholine. Authors also thanked Preclinical Research And Development Organization (PRADO) for performing and guiding us on histomorphometric analysis.
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