Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis.

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.

Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting.

As a new strategy for treatment of ductal carcinoma in situ, biocompatible and bioadhesive nanoemulsions for intraductal administration of the cytotoxic agent piplartine (piperlongumine) were optimized in this study. To confer bioadhesive properties, the nanoemulsion was modified with chitosan or hyaluronic acid. Tricaprylin was selected as the nanoemulsion non-polar phase due to its ability to dissolve larger drug amounts compared to isopropyl myristate and monocaprylin. Use of phosphatidylcholine as sole surfactant did not result in a homogeneous nanoemulsion, while its association with polysorbate 80 and glycerol (in a surfactant blend) led to the formation of nanoemulsions with droplet size of 76.5 ±â€¯1.2 nm. Heating the aqueous phase to 50 °C enabled sonication time reduction from 20 to 10 min. Inclusion of either chitosan or hyaluronic acid resulted in nanoemulsions with similar in vitro bioadhesive potential, and comparable ability to prolong mammary tissue retention (to 120 h) in vivo without causing undesirable histological alterations. Piplartine was stable in both nanoemulsions for 60 days; however, the size of loaded NE-HA was maintained at a similar range for longer periods of time, suggesting that this nanoemulsion may be a stronger candidate for intraductal delivery.

Enkephalinase inhibition facilitates sexual behavior in the male rat but does not produce conditioned place preference.

The effects of two enkephalinase inhibitors, SCH 34826 and phospho-leu-phe, on male rat sexual behavior and conditioned place preference were evaluated. SCH 34826, administered intraperitoneally, reduced the ejaculation latency to both the first and second ejaculation at a dose of 30 mg/kg. This dose also reduced the first postejaculatory interval. No other effect was obtained with this drug. Phospho-leu-phe, administered intracerebroventricularly, increased mount and intromission latency at doses of 50 and 100 micrograms. A dose of 25 micrograms reduced the latency to the first ejaculation as well as the number of preejaculatory intromissions. The postejaculatory interval was also reduced at this dose. SCH 34826, 100 and 30 mg/kg, and phospho-leu-phe, 25 micrograms, had no effect in the conditioned place preference procedure. These observations seem to suggest that there is no functionally relevant tonic release of enkephalins. Therefore, the effects obtained on sexual behavior may indicate that enkephalins are released before and during the course of sexual activity. The function of such a release could be to facilitate ejaculatory mechanisms in the way found in the present studies. Previous work has shown that ejaculation-induced reward is opioid dependent, further supporting the hypothesis of opioid release during sexual activity. Taken together, these data suggest an important role for opioids, probably enkephalins, in the physiological control of sexual behavior.