Browsing by Author "Loca, Dagnija"

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    Development of local strontium ranelate delivery systems and long term in vitro drug release studies in osteogenic medium
    (2018-12-01) Loca, Dagnija; Smirnova, Anastasija; Locs, Janis; Dubnika, Arita; Vecstaudza, Jana; Stipniece, Liga; Makarova, Elina; Dambrova, Maija; Faculty of Pharmacy
    It has been recognized that the operative stabilization of osteoporotic fractures should be followed up with an appropriate osteoporosis treatment in order to decrease the risk of repeated fractures. Despite the good clinical results of strontium ranelate (SrRan) towards the osteoporosis treatment, high drug doses and long treatment period cause an increased risk of serious side effects. Novel local SrRan/poly(lactic acid) (SrRan/PLA) delivery systems containing from 3.57 ± 0.28 wt% to 24.39 ± 0.91 wt% of active substance were developed. In order to resemble the naturally occurring processes, osteogenic media (OM) was used as a release medium for long term (121 days) in vitro drug release studies and UV/VIS method for the determination of SrRan content in OM was developed and validated. Biomimetic calcium phosphate precipitates were found on the surface and in the pores of prepared delivery system after microcapsule exposure to OM for 121 days as well as SrRan particles, indicating that the release of the drug have not been completed within 121 days. In vitro cell viability evaluation approved no cytotoxic effects of microcapsule suspensions and extracts.
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    Development of local strontium ranelate delivery systems and long term in vitro drug release studies in osteogenic medium
    (2018-12-01) Loca, Dagnija; Smirnova, Anastasija; Locs, Janis; Dubnika, Arita; Vecstaudza, Jana; Stipniece, Liga; Makarova, Elina; Dambrova, Maija; Faculty of Pharmacy
    It has been recognized that the operative stabilization of osteoporotic fractures should be followed up with an appropriate osteoporosis treatment in order to decrease the risk of repeated fractures. Despite the good clinical results of strontium ranelate (SrRan) towards the osteoporosis treatment, high drug doses and long treatment period cause an increased risk of serious side effects. Novel local SrRan/poly(lactic acid) (SrRan/PLA) delivery systems containing from 3.57 ± 0.28 wt% to 24.39 ± 0.91 wt% of active substance were developed. In order to resemble the naturally occurring processes, osteogenic media (OM) was used as a release medium for long term (121 days) in vitro drug release studies and UV/VIS method for the determination of SrRan content in OM was developed and validated. Biomimetic calcium phosphate precipitates were found on the surface and in the pores of prepared delivery system after microcapsule exposure to OM for 121 days as well as SrRan particles, indicating that the release of the drug have not been completed within 121 days. In vitro cell viability evaluation approved no cytotoxic effects of microcapsule suspensions and extracts.
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    Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction
    (2006-12) Liepinsh, Edgars; Vilskersts, Reinis; Loca, Dagnija; Kirjanova, Olga; Pugovichs, Osvalds; Kalvinsh, Ivars; Dambrova, Maija
    The inhibition of gamma-butyrobetaine (GBB) hydroxylase, a key enzyme in the biosynthesis of carnitine, contributes to lay ground for the cardioprotective mechanism of action of mildronate. By inhibiting the biosynthesis of carnitine, mildronate is supposed to induce the accumulation of GBB, a substrate of GBB hydroxylase. This study describes the changes in content of carnitine and GBB in rat plasma and heart tissues during long-term (28 days) treatment of mildronate [i.p. (intraperitoneal) 100 mg/kg/daily]. Obtained data show that in concert with a decrease in carnitine concentration, the administration of mildronate caused a significant increase in GBB concentration. We detected about a 5-fold increase in GBB contents in the plasma and brain and a 7-fold increase in the heart. In addition, we tested the cardioprotective effect of mildronate in isolated rat heart infarction model after 3, 7, and 14 days of administration. We found a statistically significant decrease in necrotic area of infarcted rat hearts after 14 days of treatment with mildronate. The cardioprotective effect of mildronate correlated with an increase in GBB contents. In conclusion, our study, for the first time, provides experimental evidence that the long-term administration of mildronate not only decreases free carnitine concentration, but also causes a significant increase in GBB concentration, which correlates with the cardioprotection of mildronate.