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Discovery of nano-piperolactam A: A nonsteroidal contraceptive lead acting through down-regulation of interleukins.
Nanomedicine : Nanotechnology, Biology, and Medicine 2018 November 7
Elevated serum interleukins (IL-6, IL-1β) over baseline concentration help in blastocyst adhesion to the uterine endometrium in the early phase of pregnancy. A nano PLA (Piperolactam A)-HPBCD (2-hydroxy-propyl-β-cyclodextrin) inclusion complex was developed as an interleukin down-regulator that exhibited 100% anti-implantation activity in rodents at a dose as low as 2.5-5.0 mg/kg. On metabolomics study, among major glyco-lipo-protein metabolites, only serum low-density lipoprotein (LDL) or very low-density lipoprotein (VLDL) levels revealed alteration by the formulation. Administration of PLA-HPBCD did not cause changes in serum estrogen and progesterone levels. However, IL-6 and IL-1β failed to increase post PLA-HPBCD administration; hence, it is assumed to be the mode of the drug's abortifacient action. In addition, absence of signs of either acute or chronic toxicity suggests the formulation was considerably non-toxic. Therefore, the nano-PLA conjugate promises as a non-steroidal contraceptive lead apart from ormeloxifene, the only non-steroidal anti-fertility agent currently available globally.
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