Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells

Background: Psoralen (PSO), a major active component of Psoralea corylifolia, has been shown to overcome multidrug resistance in cancer. A drug carrier comprising a lipid-monolayer shell and a biodegradable polymer core for sustained delivery and improved efficacy of drug have exhibited great potential in efficient treatment of cancers. Methods: The PSO-loaded lipid polymer hybrid nanoparticles were prepared and characterized. In vitro cytotoxicity assay, cellular uptake, cell cycle analysis, detection of ROS level and mitochondrial membrane potential (ΔΨm) and western blot were performed. Results: The P-LPNs enhanced the cytotoxicity of doxorubicin (DOX) 17-fold compared to free DOX in multidrug resistant HepG2/ADR cells. Moreover, P-LPNs displayed pro-apoptotic activity, increased levels of ROS and depolarization of ΔΨm. In addition, there were no significant effects on cellular uptake of DOX, cell cycle arrest, or the expression of P-glycoprotein. Mechanistic studies suggested that P-LPNs enhanced DOX cytotoxicity by increased release of cytochrome c and enhanced caspase3 cleavage, causing apoptosis in HepG2/ADR cells. Conclusion: The lipid-polymer hybrid nanoparticles can be considered a powerful and promising drug delivery system for effective cancer chemotherapy. Keywords: lipid-polymer hybrid nanoparticles, psoralen, drug delivery, HepG2, ADR cells, apoptosis.This work was supported by the National Natural Science Foundation of China (81273707), the Ministry of Education in the New Century Excellent Talents (NECT-12-0677), the Natural Science Foundation of Guangdong (S2013010012880, 2016A030311037), the Science and Technology Program of Guangzhou (2014J4500005, 201704030141), the Science Program of the Department of Education of Guangdong (2013KJCX0021, 2015KGJHZ012), the Science and Technology Program of Guangdong (2015A050502027), and the Special Project of International Scientific and Technological Cooperation in Guangzhou Development District (2017GH16)

Extraction of Polysaccharide from Spirulina and Evaluation of Its Activities

Background. Polysaccharide of Spirulina platensis (PSP) is a kind of water-soluble polysaccharide extracted from Spirulina platensis. It has been proved to have antitumor, antioxidation, antiaging, and antivirus properties. And it has a promising prospect for wide application. Objective. This study aims to identify an extraction process for high-purity polysaccharide in Spirulina (PSP) through a series of optimization methods and then evaluates its initial antiaging activities. Methods. Four kinds of extraction methods—hot-water extraction, alkali extraction, ultrasonic-assisted extraction, and freeze-thaw extraction—were compared to find the optimal one, which was further optimized by response surface methodology. PSP was obtained after the crude PSP was deproteinized and depigmented. The antiaging effects of PSP were preliminarily evaluated through in vitro cell experiments. Results. The alkali extraction method was determined as the optimal method, with the optimized extraction process consisting of a solid-liquid ratio of 1 : 50, a pH value of 10.25, a temperature of 89.24°C, and a time of 9.99 h. The final PSP contained 71.65% of polysaccharide and 8.54% of protein. At a concentration of 50 μg/mL, PSP exerted a significant promoting effect on the proliferation and traumatic fusion of human immortalized epidermal cells HaCaT. Conclusion. An extraction method for high-purity PSP with a high extraction rate was established, and in vitro results suggest antioxidation and antiaging activities

Protective effects of psoralen polymer lipid nanoparticles on doxorubicin - induced myocardial toxicity

Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity