Fabrication, characterization and optimization of berberine-loaded PLA nanoparticles using coaxial electrospray for sustained drug release.

BACKGROUND: Berberine (BBR) broadly found in medicinal plants has a major application in pharmacological therapy as an anticancer drug. Clinical applications of this promising natural drug are limited due to its poor water solubility and low bioavailability. OBJECTIVE: In this study, for the first time, we synthesized core-shell BBR-loaded PLA nanoparticles (NPBs) by using coaxial electrospray (CES) to solve the poor bioavailability of BBR. METHODS: Three-factor (feeding rate, polymeric solution concentration and applied voltage), three-level, Box-Behnken design was used for optimization of the size and particle size distribution of the prepared NPBs. RESULTS: Based on the results of response surface methodology, the NPBs with the mean size of 265 nm and particle size distribution of 43 nm were synthesized. A TEM image was used to well illustrate the core-shell structure of the NPBs. Encapsulation efficiency and BBR loading capacity for the optimized NPBs were determined at about 81% and 7.5%, respectively. Release of NPBs was examined at pH 7.4 and 5.8. NPBs had a slower release profile than free BBR in both pH values, and the rate of BBR release was more and faster in acidic pH than in physiological one. Effects of the NPBs on the drug release were confirmed by data fitting with six kinetic models. NPBs showed an increased cytotoxic efficacy against HCT116 cells (IC50 = 56 µM), while NIH3T3 cells, non-neoplastic fibroblast cells, (IC50 > 150 µM) were less affected by NPBs. Flow cytometry demonstrated that the cellular uptake of NPBs were higher than BBR at different concentrations. CONCLUSIONS: A new approach was developed in this study to prepare NPBs using the CES process for improving the efficiency and controlled BBR release. It is concluded that nano-scaled NPBs prepared by CES can improve toxicity and chemotherapeutic properties of BBR against cancerous cells. We believe that these NPBs can exhibit further potential in cancer drug delivery systems. Graphical abstract.

Polyphenols targeting diabetes via the AMP-activated protein kinase pathway; future approach to drug discovery.

Regarding the widespread progression of diabetes, its related complications and detrimental effects on human health, investigations on this subject seems compulsory. AMP-activated protein kinase (AMPK) is a serine/threonine kinase and a key player in energy metabolism regulation. AMPK is also considered as a prime target for pharmaceutical and therapeutic studies on disorders such as diabetes, metabolic syndrome and obesity, where the body energy homeostasis is imbalanced. Following the activation of AMPK (physiological or pharmacological), a cascade of metabolic events that improve metabolic health is triggered. While there are several publications on this subject, this is the first report that has focused solely on polyphenols targeting diabetes via AMPK pathway. The multiple characteristics of polyphenolic compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the AMPK signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. PPs could potentially occupy a significant position in the future anti-diabetic drug market.

Antinociceptive and anti-inflammatory effects of olive oil (Olea europeae L.) in mice.

CONTEXT: Olive [Olea europaea L. (Oleaceae)] is a long-lived evergreen tree that is widespread in different parts of the world. OBJECTIVE: Olive oil has been reported to relieve pain; however, there is still insufficient data in the literature on the subject. Thus, it is considered worthwhile investigating the antinociceptive and anti-inflammatory effects of olive oil in adult male Balb/C mice. MATERIALS AND METHODS: The antinociceptive effects were studied using formalin, hot plate and writhing tests. The acute anti-inflammatory effects of olive oil in mice were studied using xylene ear edema test. Olive oil (1, 5 and 10 ml/kg body wt.) was injected intraperitoneally. Intact animals served as controls. RESULTS: Our results showed that the olive oil only decreased the second phase of formalin-induced pain. In the hot plate test, olive oil did not raise the pain threshold over the 60 min duration of the test. Olive oil exhibited antinociceptive activity against writhing-induced pain by acetic acid. In the xylene ear edema test, olive oil showed significant anti-inflammatory activity in the mice. DISCUSSION AND CONCLUSION: The present data indicated that olive oil has antinociceptive and anti-inflammatory effects in mice but further investigation of these effects is required to elucidate the mechanism(s) involved in analgesic and anti-inflammatory effects of Olea europaea oil.

Achillea santolina reduces serum interleukin-6 level and hyperalgesia during complete Freund's adjuvant-induced inflammation in male Wistar rats.

OBJECTIVE: Immune system is involved in the etiology and pathophysiologic mechanisms of inflammation. Medicinal plants are an important source of substances which are claimed to induce non-specific immunomodulatory effects. In view of this and on account of the interleukin (IL)-6's role in inflammation and pain induction, this study investigated the effects of Achillea santolina extracts on inflammation which was induced by complete Freund's adjuvant (CFA) in male Wistar rats. METHODS: Both methanolic and defatted extracts prepared from aerial parts of the plant were examined. Inflammatory symptoms such as hyperalgesia and paw edema in CFA-injected rats' paw were measured by radiant heat and plethysmometer during different stages of study respectively. Serum IL-6 level was checked by rat standard enzyme-linked immunosorbent assay specific kit. RESULTS: The results indicated dose-related effects of methanolic extract on paw edema, hyperalgesia and serum IL-6 level reduction in rats. Methanolic extract of A. santolina exhibited significant antihyperalgesic and anti-inflammatory effects during pretreatment and short-term treatment at dose of 200 mg/kg and there was no significant difference between 200 and 400 mg/kg doses of this extract. Defatted extract did not show significant effect on CFA-induced inflammation during different stages of treatment (P>0.05). Short-term treatment with methanolic extract at dose of 200 mg/kg was more effective than indomethacin in edema, hyperalgesia and serum IL-6 level reduction (P<0.01, P<0.01 and P<0.05 respectively). CONCLUSION: These results suggest that methanolic extract of A. santolina possesses potent anti-inflammatory and immunomodulatory activities during pretreatment and short-term administration.