Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro and In Vivo Studies.

Nanostructured lipid carriers (NLC) exhibit high skin targeting efficiency and good safety. They are promising vehicles for topical drug delivery. This study aims to increase the skin distribution of podophyllotoxin (POD) by incorporating it into NLCs. Two kinds of POD-loaded NLCs (POD-NLCs)-POD-NLCformulation 1 and POD-NLCformulation 2-were prepared and characterized. Their skin targeting efficiencies were compared by conducting in vitro and in vivo experiments. Obviously smaller mean particle size was observed for POD-NLCformulation 1 (106 nm) than POD-NLCformulation 2 (219 nm), whereas relatively low POD loadings (less than 0.5%) were observed for both POD-NLCformulation 1 (0.33%) and POD-NLCformulation 2 (0.49%). Significantly higher in vitro and in vivo rat skin deposit amounts of POD (p ˂ 0.01) were detected after the topical application of POD-NLCformulation 1 compared to POD-NLCformulation 2. To visualize the skin distribution behavior of hydrophobic active pharmaceutical ingredients (APIs) when NLCs were used as carriers, POD was replaced with Nile red (NR-a hydrophobic fluorescent probe), and the distribution behavior of NR-NLCformulation 1 and NR-NLCformulation 2 in rat skin in vivo was observed using confocal laser scanning microscopy (CLSM). Higher fluorescent intensity was observed in rat skin after the topical application of NR-NLCformulation 1 than NR-NLCformulation 2, suggesting that higher skin targeting efficiency might be obtained when NLCs with smaller mean particle size were used as carriers for hydrophobic APIs. This result was in accordance with those of skin distribution evaluation experiments of POD-NLCs. Skin irritation property of POD-NLCformulation 1 was investigated and no irritation was observed in intact or damaged rabbit skin, suggesting it is safe for topical use. Our results validated the safety of NLCs when applied topically. More importantly, mean particle size might be an important parameter for formulation optimization when NLCs are used as carriers for hydrophobic APIs for topical application, considering that their loading is relatively low.

The metabolomic study on atherosclerosis mice and its application in a traditional Chinese medicine Sishen granule.

Although an atherosclerosis (AS) model using low-density lipoprotein receptor deletion mice has been widely applied, its pathological pathway in metabolite level is still not clear. To further reveal the metabolite profile and identify the potential biomarkers in AS development, a serum metabolomic approach was developed based on reversed-phase liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). The established metabolomic platform was also used for elucidating the therapeutic mechanism of a traditional Chinese medicine named Sishen granule (SSKL). Twenty-one potential biomarkers in AS mouse serum were identified. Through functional analysis of these biomarkers, inflammation, proliferation, dysfunction of energy metabolism and amino acid metabolism were considered the most relevant pathological changes in AS. DNA damage products were found for the first time in the metabolomic study of AS. The network established by 20 biomarkers revealed that pyruvate metabolism, citrate cycle, fatty acid metabolism and urea metabolism were seriously disturbed. This metabolomic study not only supplied a systematic view of the progression of AS but also provided a theoretical basis for the treatment of AS. This metabolomic study also demonstrated that SSKL had therapeutic effectiveness for AS through partly reversing the inflammation reaction and amino acid metabolism dysfunction. Copyright © 2015 John Wiley & Sons, Ltd.

Metabolomic study on the faecal extracts of atherosclerosis mice and its application in a Traditional Chinese Medicine.

The intestinal microbiota and their metabolites are closely related to the formation of atherosclerosis (AS). In this study, a metabolomic approach based on the reversed-phase liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) platform was established to analyze the metabolic profiling of fecal extracts from AS mice model. The established metabolomic platform was also used for clearing the effective mechanism of a Traditional Chinese Medicine (TCM) named Sishen granule (SSKL). Totally, sixteen potential biomarkers in faeces of AS mice were identified and 5 of them could be reversed by SSKL. Through functional analysis of these biomarkers and the established network, lipid metabolism, cholesterol metabolism, energy cycle, and inflammation reaction were considered as the most relevant pathological changes in gastrointestinal tract of AS mice. The metabolomic study not only revealed the potential biomarkers in AS mice' faeces but also supplied a systematic view of the pathological changes in gastrointestinal metabolite in AS mice. This metabolomic study also demonstrated that SSKL had the therapeutic effectiveness on AS through partly reversing the lipid metabolism, inflammation and energy metabolism.