title: In vivo efficacy studies of layer-by-layer nano-matrix bearing kaempferol for the conditions of osteoporosis: a study in ovariectomized rat model.
abstract: A prototype formulation based on layer-by-layer (LbL) nano-matrix was developed to increase bioavailability of kaempferol with improved retention in bone marrow to achieve enhanced bone formation. The layer-by-layer nano-matrix was prepared by sequential adsorption of biocompatible polyelectrolytes over the preformed kaempferol-loaded CaCO(3) template. The system was pharmaceutically characterized and evaluated for osteogenic activity in ovariectomized (OVx) rats. Data have been compared to the standard osteogenic agent parathyroid hormone (PTH). Single oral dose of kaempferol loaded LbL nano-matrix formulation increased bioavailability significantly compared to unformulated kaempferol. Three months of Formulated kaempferol administration to osteopenic rats increased plasma and bone marrow Kaempferol levels by 2.8- and 1.75-fold, respectively, compared to free Kaempferol. Formulated Kaempferol increased bone marrow osteoprogenitor cells, osteogenic genes in femur, bone formation rate, and improved trabecular micro-architecture. Withdrawal of Formulated kaempferol-in OVx rats resulted in the maintenance of bone micro-architecture up to 30days, whereas micro-architectural deterioration was readily observed in OVx rats treated with unformulated kaempferol-within 15days of withdrawal. The developed novel formulation has enhanced anabolic effect in osteopenic rats through increased stimulatory effect in osteoblasts. Treatment post-withdrawal sustenance of formulated kaempferol could become a strategy to enhance bioavailability of flavanoids.
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Kumar
authors.forename: Girish K
authors.initials: GK
authors.lastname: Gupta
authors.forename: Vikram
authors.initials: V
authors.lastname: Khedgikar
authors.forename: Jyoti
authors.initials: J
authors.lastname: Gautam
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kushwaha
authors.forename: Bendangla
authors.initials: B
authors.lastname: Changkija
authors.forename: Geet K
authors.initials: GK
authors.lastname: Nagar
authors.forename: Varsha
authors.initials: V
authors.lastname: Gupta
authors.forename: Ashwni
authors.initials: A
authors.lastname: Verma
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
authors.forename: Naibedya
authors.initials: N
authors.lastname: Chattopadhyay
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
authors.forename: Ritu
authors.initials: R
authors.lastname: Trivedi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002119:Calcium Carbonate / Q000737:chemistry; D004195:Disease Models, Animal; D004573:Electrolytes / Q000737:chemistry; D005260:Female; D044949:Kaempferols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D053758:Nanoparticles; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000188:drug therapy / Q000473:pathology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004573:Electrolytes; D044949:Kaempferols; D010281:Parathyroid Hormone; C006552:kaempferol; D002119:Calcium Carbonate