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Positive effect of alendronate on bone turnover in ovariectomised rats’ osteoporosis: comparison of transdermal lipid-based delivery with conventional oral administration

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Abstract

Alendronate (ALD) is clinically indicated for the treatment of osteoporosis, but its therapeutic use has been marred by severe GIT adverse effects affecting quality of life in patients. In this study, we selected novel transdermal microemulsion (TDME) as a suitable carrier for ALD as the way of avoiding intestinal toxicity and highlighted its anti-osteoporotic efficacy with extensive pharmacokinetic and pharmacodynamic analysis. TDME achieved two fold increase in bioavailability as compared to oral administration in pharmacokinetic studies. To investigate the capability of TDME in alleviating symptoms of osteoporosis, it was administered to ovariectomised rats 2 months post-surgery. The results obtained after 2 months of treatment with ALD by trans-epidermal route exhibited improved bone density in DEXA scan of rats. These observations were further supported by biochemical investigations including analysis of bone formation and resorption markers. Moreover, TDME effectively suppressed the decline in bone mass of osteoporotic rats as determined through the biometric analysis and histopathological examination of bones. Additionally, skin histopath results showed no significant skin damage at the end of treatment. Overall, these findings demonstrate that the TDME system is a promising approach for the effective delivery of ALD, bypassing the adverse effects associated with oral administration.

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Funding

The authors sincerely acknowledge University Grants Commission-Basic Science Research (UGC-BSR) for the grant provided.

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  1. Poona College of Pharmacy, Department of Pharmaceutics, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra, 411038, India

    Mithila Boche & Varsha Pokharkar

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  1. Mithila Boche
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  2. Varsha Pokharkar
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Correspondence to Varsha Pokharkar.

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Boche, M., Pokharkar, V. Positive effect of alendronate on bone turnover in ovariectomised rats’ osteoporosis: comparison of transdermal lipid-based delivery with conventional oral administration. Drug Deliv. and Transl. Res. 8, 1078–1089 (2018). https://doi.org/10.1007/s13346-018-0558-9

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