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Precision engineering designed phospholipid-tagged pamidronate complex functionalized SNEDDS for the treatment of postmenopausal osteoporosis

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Abstract

Disodium pamidronate, a second-generation bisphosphonate is a potent drug for the treatment of osteoporosis, which has been very well established by previous literature. It has very low oral permeability, leading to its low oral bioavailability, which restrict this drug to being administered orally. Therefore, the present research work includes the development of an orally effective nanoformulation of pamidronate. In this work, disodium pamidronate was complexed with phospholipon 90G for the enhancement of permeability and to investigate the phospholipon 90G–tagged pamidronate complex–loaded SNEDDS for oral delivery with promises of enhanced bioavailability and anti-osteoporotic activity. The rational design and optimization was employed using Central Composite Design (Design Expert® 12, software) to optimize nanoformulation parameters. In this work, a commercially potential self nano-emulsifying drug delivery system (SNEDDS) has been developed and evaluated for improved oral bioavailability and better clinical acceptance. The hot micro-emulsification and ultracentrifugation method with vortex mixing was utilized for effective tagging of phospholipon 90G with pamidronate and then loading into the SNEDDS nanocarrier. The optimized Pam-PLc SNEDDS formulation was characterized for particle size, PDI, and zeta potential and found to be 56.38 ± 1.37 nm, 0.218 ± 0.113, and 22.41 ± 1.14 respectively. Also, a 37.9% improved bioavailability of pamidronate compared to marketed tablet was observed. Similarly, in vivo pharmacokinetic studies suggest a 31.77% increased bone density and significant enhanced bone biomarkers compared to marketed tablets. The developed formulation is safe and effectively overcomes anti-osteoporosis promises with improved therapeutic potential. This work provides very significant achievements in postmenopausal osteoporosis treatment and may lead to possible use of nanotherapeutic-driven emerging biodegradable carriers-based drug delivery.

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Acknowledgements

Author highly acknowledges the financial support of Nano Mission, Department of Science and Technology, Govt. of India, bearing the file no. SR/NM/NS-1162/2015.

Funding

Author received complete financial assistance from Dept. of Science and Technology, New Delhi, file so. SR/NM/NS-1162/2015.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India

    Pavitra Solanki, Mohd. Danish Ansari, Mohd. Aqil, Farhan J. Ahmad & Yasmin Sultana

  2. Department of Physiology, Hamdard Institute of Medical Sciences & Research, Jamia Hamdard, New Delhi-110062, India

    Mohd. Iqbal Alam

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Contributions

Pavitra Solanki: writing, concept, methodology and final draft; Mohd. Danish Ansari: methodology, review; Mohd. Aqil: reviewing, concept; Farhan J. Ahmad: evaluation, methodology; Yasmin Sultana: supervision, evaluation and final draft.

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Correspondence to Yasmin Sultana.

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I conducted animal studies myself with integrity, fidelity, and honesty. I openly take responsibility for my actions, and only make agreements, which I intend to keep. I did not intentionally engage in or participate in any form of malicious harm to another person or animal. Prior approval was taken from the institutional animal ethical committee for use of female wistar rats.

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This research work was approved by Institutional Animal Ethics Committee, Jamia Hamdard, New Delhi wide animal protocol no. 1726.

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Solanki, P., Ansari, M.D., Alam, M.I. et al. Precision engineering designed phospholipid-tagged pamidronate complex functionalized SNEDDS for the treatment of postmenopausal osteoporosis. Drug Deliv. and Transl. Res. 13, 883–913 (2023). https://doi.org/10.1007/s13346-022-01259-7

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