Correlation Between N-Demethyl Imatinib Trough Concentration and Serious Adverse Reactions in Patients with Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

BACKGROUND: Imatinib is the first-line treatment for gastrointestinal stromal tumors; however, the clinical prognosis and adverse reactions of patients vary owing to individualized discrepancies in plasma exposure. METHODS: To determine the safe interval for steady-state plasma trough concentrations (C min ) of imatinib and its active metabolite, N-demethyl imatinib (NDI), 328 plasma samples from 273 patients treated with imatinib were retrospectively analyzed. Imatinib C min and NDI C min were tested, and adverse reactions were recorded. The association between imatinib C min , NDI C min , and serious adverse reactions was evaluated. RESULTS: The C min range of imatinib was 209.5-4950.0 ng/mL, with the mean value and SD of 1491.8 ± 731.4 ng/mL. The C min range of NDI was 80.0-2390.0 ng/mL with the mean value and SD of 610.8 ± 281.5 ng/mL. NDI C min was positively correlated with imatinib C min , whereas the ratio of NDI C min to imatinib C min (NDI C min /imatinib C min ) was negatively correlated with imatinib C min . Univariate logistic regression analysis demonstrated that the treatment objective, daily dose, imatinib C min , NDI C min , and imatinib C min + NDI C min were significantly associated with serious adverse reactions. Multivariate logistic regression analysis showed that NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. CONCLUSIONS: NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. Monitoring NDI C min was beneficial for the rational application of imatinib and individualized treatment of patients with gastrointestinal stromal tumors.

Global Trends and Frontier in Research on Pancreatic Alpha Cells: A Bibliometric Analysis from 2013 to 2023.

PURPOSE: Over the past 20 years, much of the research on diabetes has focused on pancreatic beta cells. In the last 10 years, interest in the important role of pancreatic alpha cells in the pathogenesis of diabetes, which had previously received little attention, has grown. We aimed to summarize and visualize the hotspot and development trends of pancreatic alpha cells through bibliometric analysis and to provide research direction and future ideas for the treatment of diabetes and other islet-related diseases. METHODS: We used two scientometric software packages (CiteSpace 6.1.R6 and VOSviewer1.6.18) to visualize the information and connection of countries, institutions, authors, and keywords in this field. RESULTS: A total of 532 publications, published in 752 institutions in 46 countries and regions, were included in this analysis. The United States showed the highest output, accounting for 39.3% of the total number of published papers. The most active institution was Vanderbilt University, and the authors with highest productivity came from Ulster University. In recent years, research hotspots have concentrated on transdifferentiation, gene expression, and GLP-1 regulatory function. Visualization analysis shows that research hotspots mainly focus on clinical diseases as well as physiological and pathological mechanisms and related biochemical indicators. CONCLUSIONS: This study provides a review and summary of the literature on pancreatic alpha cells through bibliometric and visual methods and shows research hotspot and development trends, which can guide future directions for research.

Norvancomycin plasma concentration monitoring in hemodialysis patients with end stage kidney disease: A retrospective cohort study.

Blood concentration monitoring plays an important role in the rational use of norvancomycin. However, the reference interval for the norvancomycin plasma concentration in the treatment of infections in hemodialysis patients with end stage kidney disease is undefined. To determine the safe and effective interval for the norvancomycin plasma trough concentration, 39 patients treated with hemodialysis and norvancomycin were analyzed retrospectively. The norvancomycin plasma concentration before hemodialysis was tested as the trough concentration. The associations of the norvancomycin trough concentration with efficacy and adverse reactions were evaluated. No norvancomycin concentration above 20 µg/mL was detected. The trough concentration, but not the dose, had a significant effect on the anti-infectious efficacy. Compared with the low norvancomycin trough concentration group (<9.30 µg/mL), the high concentration group (9.30-20.0 µg/mL) had improved efficacy (OR = 15.45, p < 0.01) with similar side effects (OR = 0.5417, p = 0.4069). It is beneficial to maintain the norvancomycin trough concentration at 9.30-20.0 µg/mL to achieve a good anti-infectious effect in hemodialysis patients with end stage kidney disease. Plasma concentration monitoring provides a data basis for the individual treatment of infections with norvancomycin in hemodialysis patients.

Remediation of preservative ethylparaben in water using natural sphalerite: Kinetics and mechanisms.

As a typical class of emerging organic contaminants (EOCs), the environmental transformation and abatement of preservative parabens have raised certain environmental concerns. However, the remediation of parabens-contaminated water using natural matrixes (such as, naturally abundant minerals) is not reported extensively in literature. In this study, the transformation kinetics and the mechanism of ethylparaben using natural sphalerite (NS) were investigated. The results show that around 63% of ethylparaben could be absorbed onto NS within 38 hr, whereas the maximum adsorption capacity was 0.45 mg/g under room temperature. High temperature could improve the adsorption performance of ethylparaben using NS. In particular, for the temperature of 313 K, the adsorption turned spontaneous. The well-fitted adsorption kinetics indicated that both the surface adsorption and intra-particle diffusion contribute to the overall adsorption process. The monolayer adsorption on the surface of NS was primarily responsible for the elimination of ethylparaben. The adsorption mechanism showed that hydrophobic partitioning into organic matter could largely govern the adsorption process, rather than the ZnS that was the main component of NS. Furthermore, the ethylparaben adsorbed on the surface of NS was stable, as only less than 2% was desorbed and photochemically degraded under irradiation of simulated sunlight for 5 days. This study revealed that NS might serve as a potential natural remediation agent for some hydrophobic EOCs including parabens, and emphasized the significant role of naturally abundant minerals on the remediation of EOCs-contaminated water bodies.

SP8 and SP9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression.

Dopamine receptor DRD1-expressing medium spiny neurons (D1 MSNs) and dopamine receptor DRD2-expressing medium spiny neurons (D2 MSNs) are the principal projection neurons in the striatum, which is divided into dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). Progenitors of these neurons arise in the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the transcription factor genes Sp8 and Sp9 lose virtually all D2 MSNs as a result of reduced neurogenesis in the LGE, whereas D1 MSNs are largely unaffected. SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3 Thus, this study defines components of a transcription pathway in a regionally restricted LGE progenitor domain that selectively drives the generation of D2 MSNs.

A Blockchain-Based Trusted Edge Platform in Edge Computing Environment.

Edge computing is a product of the evolution of IoT and the development of cloud computing technology, providing computing, storage, network, and other infrastructure close to users. Compared with the centralized deployment model of traditional cloud computing, edge computing solves the problems of extended communication time and high convergence traffic, providing better support for low latency and high bandwidth services. With the increasing amount of data generated by users and devices in IoT, security and privacy issues in the edge computing environment have become concerns. Blockchain, a security technology developed rapidly in recent years, has been adopted by many industries, such as finance and insurance. With the edge computing capability, deploying blockchain platforms/applications on edge computing platforms can provide security services for network edge environments. Although there are already solutions for integrating edge computing with blockchain in many IoT application scenarios, they slightly lack scalability, portability, and heterogeneous data processing. In this paper, we propose a trusted edge platform to integrate the edge computing framework and blockchain network for building an edge security environment. The proposed platform aims to preserve the data privacy of the edge computing client. The design based on the microservice architecture makes the platform lighter. To improve the portability of the platform, we introduce the Edgex Foundry framework and design an edge application module on the platform to improve the business capability of Edgex. Simultaneously, we designed a series of well-defined security authentication microservices. These microservices use the Hyperledger Fabric blockchain network to build a reliable security mechanism in the edge environment. Finally, we build an edge computing network using different hardware devices and deploy the trusted edge platform on multiple network nodes. The usability of the proposed platform is demonstrated by testing the round-trip time (RTT) of several important workflows. The experimental results demonstrate that the platform can meet the availability requirements in real-world usage scenarios.

[Improvement in compatibility of hot melt pressure-sensitive adhesive with cinnamon volatile oil and in vitro transdermal property by physical blending].

Hot melt pressure-sensitive adhesive(HMPSA) has broad application potential in the field of traditional Chinese medicine(TCM) plasters due to its high drug loading, weak skin irritation, satisfactory adhesion, etc. compared with rubber plasters.However, the structure of HMPSA is prone to suffer from the damage caused by volatile oils in TCM plasters. In view of this, a kind of HMPSA with a stable structure was prepared by physical blending of DINCH, polypropylene wax and liquid rubber(LIR) in the present study, which is denoted as DPL. The dosage of cinnamon volatile oil(CVO), the model drug, was selected with viscosity, softening point and cohesion as evaluation indexes. The interaction between DPL and HMPSA was investigated by Fourier transform infrared spectroscopy(FT-IR) and differential scanning calorimetry(DSC). The compatibility of HMPSA with CVO and its transdermal ability were studied by in vitro transdermal test, adhesion, scanning electron microscopy( SEM) and rheological evaluation. The results showed that 5% CVO began to damage the structure of HMPSA. The initial adhesion and holding adhesion of DPL-modified HMPSA(DPL-HMPSA) were not significantly changed compared with those of HMPSA, whereas the 180° peel strength was decreased. FI-IR unraveled that DPL formed the n-π conjugated system with styrene-isoprene-styrene block copolymer(SIS), and there was no significant difference in the glass transition temperature according to DSC results, which indicated the good compatibility of DPL with HMPSA. With 5% CVO loaded, the drug content of DPL-HMPSA was 1. 14 times higher than that of HMPSA, and the decrease rate of drug content in DPL-HMPSA was 16% lower than that in HMPSA after 3 months. SEM demonstrated that CVO did not cause obvious structural damage to DPL-HMPSA. Rheological evaluation revealed that the storage modulus and loss factor of DPL-HMPSA were higher than those of HMPSA, and the cohesion was also stronger. The percutaneous penetration rate of cinnamaldehyde in DPL-HMPSA was 2. 25 times that of HMPSA. In conclusion, DPL-HMPSA had more stable structure, better compatibility with CVO, and higher in vitro transdermal efficiency of cinnamaldehyde than before the modification. This study can provide reference for the mitigation of the matrix structure damage caused by volatile oil components in TCM plasters and the enhancement of the content and in vitro transdermal rate of drug.

Repression of Death Receptor-Mediated Apoptosis of Hepatocytes by Hepatitis B Virus e Antigen.

Hepatitis B virus (HBV) e antigen (HBeAg) is associated with viral persistence and pathogenesis. Resistance of HBV-infected hepatocytes to apoptosis is seen as one of the primary promotors for HBV chronicity and malignancy. Fas receptor/ligand (Fas/FasL) and the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) system plays a key role in hepatic death during HBV infection. We found that HBeAg mediates resistance of hepatocytes to FasL or TRAIL-induced apoptosis. Introduction of HBeAg into human hepatocytes rendered resistance to FasL or TRAIL cytotoxicity in a p53-dependent manner. HBeAg further inhibited the expression of p53, total Fas, membrane-bound Fas, TNF receptor superfamily member 10a, and TNF receptor superfamily member 10b at both mRNA and protein levels. In contrast, HBeAg enhanced the expression of soluble forms of Fas through facilitation of Fas alternative mRNA splicing. In a mouse model, expression of HBeAg in mice injected with recombinant adenovirus-associated virus 8 inhibited agonistic anti-Fas antibody-induced hepatic apoptosis. Xenograft tumorigenicity assay also found that HBeAg-induced carcinogenesis was resistant to the proapoptotic effect of TRAIL and chemotherapeutic drugs. These results indicate that HBeAg may prevent hepatocytes from FasL and TRAIL-induced apoptosis by regulating the expression of the proapoptotic and antiapoptotic forms of death receptors, which may contribute to the survival and persistence of infected hepatocytes during HBV infection.

Microporous Carbon Nanofibers Derived from Poly(acrylonitrile-co-acrylic acid) for High-Performance Supercapacitors.

Carbon nanofiber (CNF)-based supercapacitors have promising applications in the field of energy storage. It is desirable, but remains challenging, to develop CNF electrode materials with large specific surface area (SSA), high specific capacitance (SC), and high power density, as well as excellent cycling stability and high reliability. Herein, acrylonitrile-acrylic acid copolymer P(AN-co-AA) was synthesized for the preparation of nitrogen-doped microporous CNFs. Thermal degradation of the AA segment leads to the formation of micropores that are distributed not only on the CNF surface, but also inside the material. The microporous structure and nitrogen content can be manipulated at the molecular level by adjusting the weight ratio between AN and AA, and the SSA and SC could reach as high as 1099 m2 g-1 and 156 F g-1 , respectively. After KOH activation, the activated CNFs have an extremely high SSA of 2117 m2 g-1 and SC of 320 F g-1 , which are among the highest values ever reported for electric double-layer supercapacitors with an alkaline electrolyte. Furthermore, the capacitance retention, which can be maintained at 99 % even after 16 000 cyclic tests, reveals outstanding durability and repeatability.

Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons.

Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2F/- mice), GSX2+ and ASCL1+ neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1, and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development.

Co-hybridized composite nanovesicles for enhanced transdermal eugenol and cinnamaldehyde delivery and their potential efficacy in ulcerative colitis.

Percutaneous absorption of drugs can be enhanced by ethosomes, which are nanocarriers with excellent deformability and drug-loading properties. However, the ethanol within ethosomes increases phospholipid membrane fluidity and permeability, leading to drug leakage during storage. Here, we developed and characterized a new phospholipid nanovesicles that is co-hybridized with hyaluronic acid (HA), ethanol and the encapsulated volatile oil medicines (eugenol and cinnamaldehyde [EUG/CAH]) for transdermal administration. In comparison with EUG/CAH-loaded ethosomes (ES), the formulation stability and percutaneous drug absorption of EUG/CAH-loaded HA-immobilized ethosomes (HA-ES) were significantly improved. After transdermal administration of HA-ES, the interstitial cells of Cajal in the colon of rats with trinitrobenzene sulfonate-induced ulcerative colitis (UC) were significantly increased, and the stem cell factor/c-kit signaling pathway was partly repaired. Overall, HA-ES possesses excellent deformability and showed improved efficacy against UC compared with ES, which is demonstrated as a promising transdermal delivery vehicle for volatile oil medicines.

Hepatitis B virus core protein promotes hepatocarcinogenesis by enhancing Src expression and activating the Src/PI3K/Akt pathway.

Hepatitis B virus core protein (HBc) is expressed preferentially in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). HBc can function as an oncogene arising from its gene regulatory properties, but how it contributes functionally to hepatocarcinogenesis remains unclear. In this study, we determined the molecular and functional roles of HBc during HBV-associated hepatocellular tumorigenesis. HBc increased tumor formation of hepatoma cells. Moreover, expression of HBc specifically promoted proliferation of hepatoma cells in vitro. Mechanistic investigations revealed that these effects were caused by activation of the Src/PI3K/Akt pathway through proximal switch from inactive Src to the active form of the kinase by HBc. HBc-mediated sarcoma (Src) kinase activation was associated with down-regulation of C-terminal Src kinase (Csk). In addition, HBc enhances Src expression by activation of alternative Src 1A promoter in an Sp1 transcription factor-dependent manner. Proliferation induced by stable HBc expression was associated with increased G1-S cell cycle progression mediated by Src kinase activation. HBc-induced cellular proliferation and tumor formation were reversed by administration of the Src inhibitor saracatinib. Together, our findings suggest that HBc promotes tumorigenesis of hepatoma cells by enhancing the expression of total Src and the active form of the kinase and subsequently activates Src/PI3K/Akt signaling pathway, revealing novel insights into the underlying mechanisms of HBV-associated hepatocarcinogenesis.-Liu, W., Guo, T.-F., Jing, Z.-T., Yang, Z., Liu, L., Yang, Y.-P., Lin, X., Tong, Q.-Y. Hepatitis B virus core protein promotes hepatocarcinogenesis by enhancing Src expression and activating the Src/PI3K/Akt pathway.

Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development.

Neural stem cells in the postnatal telencephalic ventricular-subventricular zone (V-SVZ) generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) into the olfactory bulb (OB). The Sp8 and Sp9 transcription factors are expressed in neuroblasts, as well as in the immature and mature interneurons in the V-SVZ-RMS-OB system. Here we show that Sp8 and Sp9 coordinately regulate OB interneuron development: although Sp9 null mutants show no major OB interneuron defect, conditional deletion of both Sp8 and Sp9 resulted in a much more severe reduction of OB interneuron number than that observed in the Sp8 conditional mutant mice, due to defects in neuronal differentiation, tangential and radial migration, and increased cell death in the V-SVZ-RMS-OB system. RNA-Seq and RNA in situ hybridization reveal that, in Sp8/Sp9 double mutant mice, but not in Sp8 or Sp9 single mutant mice, newly born neuroblasts in the V-SVZ-RMS-OB system fail to express Prokr2 and Tshz1 expression, genes with known roles in promoting OB interneuron differentiation and migration, and that are involved in human Kallmann syndrome.

Highly sensitive fiber-optic accelerometer using a micro suspended-core fiber.

A compact fiber-optic accelerometer was proposed and demonstrated experimentally based on Fabry-Perot interference (FPI). The device consists of a suspended-core fiber embedded in a hollow-core fiber, forming an enclosed cavity structure. A short section of multi-mode fiber (MMF) was spliced on the leading-in single-mode fiber (SMF), which worked as a micro lens to focus the light to decrease the transmission loss. A well-defined interference spectrum was achieved by a low-fitness FP interferometer formed by both the end-face of lead-in fiber and the end-face of suspended-core fiber. Thanks to the outstretched FP cavity by suspended-core fiber, the sensor is highly sensitive to vibration along the fiber axis. Moreover, a one-dimensional mechanical transducer was used to improve the frequency band of the sensor. By the side-band filtering technology, the vibration was detected and analyzed by a simple intensity interrogation technology.

Compact fiber-optic ultrasonic sensor using an encapsulated micro-cantilever interferometer.

A compact optical fiber Fabry-Perot interferometer is proposed and demonstrated for ultrasound wave (UW) measurement. The sensor consists of a suspended cantilever in a sealed hollow-core fiber, while the end-face of the leading-in fiber together with the end-face of the suspended fiber act as two reflection mirrors and form an air cavity. A short section of graded index fiber is also employed as a micro-lens to improve the fringe contrast of the interference spectral pattern. Due to the suspended fiber structure, the sensor presents high sensitivity to UW loading, which allows the freely suspended fiber to be stretched and compressed easily. By spectral side-band filtering technology, a simple intensity interrogation technology is used for UW demonstration. Moreover, the sealed sensor structure avoids disturbance from other environment parameters, thus presenting good stability for UW detection.

Transcutol® P/Cremophor® EL/Ethyl Oleate-Formulated Microemulsion Loaded into Hyaluronic Acid-Based Hydrogel for Improved Transdermal Delivery and Biosafety of Ibuprofen.

In the present study, a novel transdermal delivery system was developed and its advantages were demonstrated. Ibuprofen is a commonly used anti-inflammatory, antipyretic, and analgesic drug; however, because of its short biological half-life, it must be frequently administered orally and is highly irritating to the digestive tract. To prepare a novel transdermal delivery system for ibuprofen, a microemulsion was used as a drug carrier and dispersed in a hyaluronic acid-based hydrogel (ME/Gel) to increase percutaneous drug absorption while avoiding gastrointestinal tract irritation. The prepared microemulsion had a droplet size of ~ 90 nm, and the microemulsion had good stability in the hydrogel. Rheological tests revealed that the ME/Gel is a pseudoplastic fluid with decreased viscosity and increased shear rate. It displayed a certain viscoelasticity, and the microemulsion distribution displayed minor effects on the rheological characteristics of the hydrogel system. There was no significant difference in the rheology of the ME/Gel at 25°C and 32°C (normal skin surface temperature), which is beneficial for clinical application. Drug transdermal flux was significantly higher than that of the hydrogel and commercial cream groups (p < 0.01). The 24-h cumulative drug permeation amount was 1.42-fold and 2.52-fold higher than that of the hydrogel and cream groups, respectively. By loading into the ME/Gel, the cytotoxicity of the drug to HaCaT cells was reduced. These results indicate that the prepared ME/Gel can effectively improve transdermal ibuprofen delivery and the biosafety of the drug and could therefore have applicability as a drug delivery system.

Optical fiber humidity sensor based on the direct response of the polyimide film.

An optical fiber humidity sensor based on an optical Fabry-Perot interferometer is proposed and experimentally demonstrated. The sensor is constructed by a short section of hollow-core fiber coated with a polyimide (PI) film. Taking advantage of the direct response of the PI film, a sensitivity of up to 1.309 nm/%RH can be achieved in the humidity change range from 40% RH to 80% RH. The temperature sensitivity is measured to be 43.57 pm/°C when the temperature changes from 25°C to 55°C. Because of its simple structure, fast response time, convenient production, and good reproducibility, the proposed sensor will be competitive in the field of cultural relic humidity monitoring and pharmaceutical storage.

Quantification and risk assessment of organic products resulting from non-thermal plasma removal of toluene in nitrogen.

RATIONALE: Non-thermal plasma (NTP) has proven to be an effective approach for the removal of volatile organic compounds (VOCs). However, harmful organic by-products, produced during NTP-mediated removal of VOCs, hinder practical applications of this technology. It is necessary to characterize the organic by-products to assess their health risks. METHODS: A method is proposed for analyzing and evaluating organic by-products for NTP-mediated removal of VOCs in this work. NTP generated by a coaxial dielectric barrier discharge (DBD) reactor was used for the removal of a model VOC, toluene, in nitrogen. Organic products were characterized using a real-time proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS) apparatus. RESULTS: The PTR-TOF-MS apparatus has been shown to be effective for real-time high-sensitivity detection of trace VOCs. The main observed organic compounds, with concentrations on the order of ppb/ppm, were hydrogen cyanide, acetonitrile, propanenitrile, benzene, benzonitrile, and benzyl nitrile, etc. CONCLUSIONS: A health-related index (HRI) was introduced to assess the health risks associated with these organic products. The HRI was not correlated with the removal efficiency (η), with higher η possibly yielding higher HRI, associated with higher health risks. Specific input energy (SIE) was a key factor affecting the formation of the observed organic products and their HRI values. We conclude that in practical applications, SIE, HRI, and η must be balanced.

Nanostructured lipid carriers for percutaneous administration of alkaloids isolated from Aconitum sinomontanum.

BACKGROUND: Lipid-based nanosystems have great potential for transdermal drug delivery. In this study, nanostructured lipid carriers (NLCs) for short-acting alkaloids lappacontine (LA) and ranaconitine (RAN) isolated from Aconitum sinomontanum (AAS) at 69.47 and 9.16% (w/w) yields, respectively, were prepared to enhance percutaneous permeation. Optimized NLC formulations were evaluated using uniform design experiments. Microstructure and in vitro/in vivo transdermal delivery characteristics of AAS-loaded NLCs and solid lipid nanoparticles (SLNs) were compared. Cellular uptake of fluorescence-labeled nanoparticles was probed using laser scanning confocal microscopy and fluorescence-activated cell sorting. Nanoparticle integrity during transdermal delivery and effects on the skin surface were also investigated. RESULTS: NLC formulations were less cytotoxic than the AAS solution in HaCaT and CCC-ESF cells. Moreover, coumarin-6-labeled NLCs showed biocompatibility with HaCaT and CCC-ESF cells, and their cellular uptake was strongly affected by cholesterol and lipid rafts. Significantly greater cumulative amounts of NLC-associated LA and RAN than SLN-associated alkaloids penetrated the rat skin in vitro. In vivo microdialysis showed higher area under the concentration-time curve (AUC)0-t for AAS-NLC-associated LA and RAN than for AAS-SLN-associated alkaloids. CONCLUSIONS: NLC formulations could be good transdermal systems for increasing biocompatibility and decreasing cytotoxicity of AAS. AAS-NLCs showed higher percutaneous permeation than the other preparations. These findings suggest that NLCs could be promising transdermal delivery vehicles for AAS.