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Prevention of ovariectomy osteopenia in rats after vaginal administration of Hyaff 11 microspheres containing salmon calcitonin

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Abstract

The benzyl ester of hyaluronic acid (Hyaff 11) is a highly mucoadhesive polymer and can be processed into microspheres that can effectively deliver incorporated drugs by closely adhering to the mucosal surface and by protecting the drug from enzymatic inactivation. In this study, Hyaff 11 microspheres have been investigated as novel delivery system for the vaginal administration of salmon calcitonin (sCT) to ovariectomized rats. Moreover, this particular animal model has been used to evaluate the biological activity of the polypeptide after vaginal and I.M. administration by measuring the skeletal effect of sCT. A total of 66 female rats were used: 6 rats served as the basal group; 12 were subjected to sham operation and left without pharmacological treatment; 48 underwent bilateral ovariectomy and these were divided at random into four groups of 12 animals. One group was not submitted to pharmacological treatment; another was treated daily with sCT I.M.; in the other two groups, the hormone was incorporated into Hyaff 11 microspheres and was daily administered by vaginal route as dry powder or dispersed in pessaries. Sixty days after surgery, rats were sacrificed and the proximal third of the right tibia was removed and prepared for histomorphometry. Treatment with sCT, independent of the administration route, largely prevented the bone volume loss of the nontreated ovariectomized group. Prevention mainly depended on the maintenance of the trabecular number and on the increase of the trabecular thickness. Independent of the administration procedure, sCT greatly reduced the increase of tartrateresistant acid phosphatase-positive poly- and, particularly, mononucleated osteoclasts found in the nontreated ovariectomized group. The increase of mineral appositon rate of the nontreated ovariectomized group was significantly prevented in the sCT treated groups. The results demonstrate that vaginal administration of sCT, as well as I.M. administration, prevent bone loss due to ovariectomy mainly by inhibiting osteoclastic resorption.

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Authors and Affiliations

  1. Department of Experimental Medicine and Pathology, Section of Pathological Anatomy, “La Sapienza” University of Rome, Viale Regina Elena 324, I-00161, Rome, Italy

    E. Bonucci & P. Ballanti

  2. C.N.R.S.M., Brindisi, Italy

    P. A. Ramires

  3. Fidia Advanced Biopolymers, Abano Terme, Padova, Italy

    J. L. Richardson & L. M. Benedetti

Authors
  1. E. Bonucci
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  2. P. Ballanti
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  3. P. A. Ramires
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  4. J. L. Richardson
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  5. L. M. Benedetti
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Bonucci, E., Ballanti, P., Ramires, P.A. et al. Prevention of ovariectomy osteopenia in rats after vaginal administration of Hyaff 11 microspheres containing salmon calcitonin. Calcif Tissue Int 56, 274–279 (1995). https://doi.org/10.1007/BF00318046

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  • DOI: https://doi.org/10.1007/BF00318046

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