Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Analysis of Microvascular Permeability in Peritumor Brain Edema of Fibrous Meningiomas.

INTRODUCTION: This study aims to analyze the permeability of intra- and peri-meningiomas regions and compare the microvascular permeability between peritumoral brain edema (PTBE) and non-PTBE using DCE-MRI. METHODS: This was a retrospective of patients with meningioma who underwent surgery. The patients were grouped as PTBE and non-PTBE. The DCE-MRI quantitative parameters, including volume transfer constant (Ktrans), rate constant (Kep), extracellular volume (Ve), and mean plasma volume (Vp), obtained using the extended Tofts-Kety 2-compartment model. Logistic regression analysis was conducted to explore the risk factor of PTBE. RESULTS: Sixty-three patients, diagnosed as fibrous meningioma, were included in this study. They were 17 males and 46 females, aged from 32 to 88 years old. Kep and Vp were significantly lower in patients with PTBE compared with those without (Kep: 0.1852 ± 0.0369 vs. 0.5087 ± 0.1590, p = 0.010; Vp: 0.0090 ± 0.0020 vs. 0.0521 ± 0.0262, p = 0.007), while there were no differences regarding Ktrans and Ve (both p > 0.05). The multivariable analysis showed that tumor size ≥10 cm3 (OR = 4.457, 95% CI: 1.322-15.031, p = 0.016) and Vp (OR = 0.572, 95%CI: 0.333-0.981, p = 0.044) were independently associated with PTBE in patients with meningiomas. CONCLUSION: DCE-magnetic resonance imaging·Meningioma·Blood vessel MRI can be used to quantify the microvascular permeability of PTBE in patients with meningioma.

Novel Bradykinin Receptor Inhibitors Inhibit Proliferation and Promote the Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the ERK Pathway.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Studies have shown that bradykinin (BK) is highly expressed in liver cancer. We designed the novel BK receptor inhibitors J051-71 and J051-105, which reduced the viability of liver cancer cells and inhibited the formation of cancer cell colonies. J051-71 and J051-105 reduced cell proliferation and induced apoptosis in HepG2 and BEL-7402 cells, which may be due to the inhibition of the extracellular regulated protein kinase (ERK) signaling pathway. In addition, these BK receptor inhibitors reversed the cell proliferation induced by BK in HepG2 and BEL-7402 cells by downregulating B1 receptor expression. Inhibiting B1 receptor expression decreased the protein levels of p-ERK and reduced the malignant progression of HCC, providing a potential target for HCC therapy.

Light and Ethylene Coordinately Regulate the Phosphate Starvation Response through Transcriptional Regulation of PHOSPHATE STARVATION RESPONSE1.

Plants have evolved an array of adaptive responses to low Pi availability, a process modulated by various external stimuli and endogenous growth regulatory signals. Little is known about how these signaling processes interact to produce an integrated response. Arabidopsis thaliana PHOSPHATE STARVATION RESPONSE1 (PHR1) encodes a conserved MYB-type transcription factor that is essential for programming Pi starvation-induced gene expression and downstream Pi starvation responses (PSRs). Here, we show that loss-of-function mutations in FHY3 and FAR1, encoding two positive regulators of phytochrome signaling, and in EIN3, encoding a master regulator of ethylene responses, cause attenuated PHR1 expression, whereas mutation in HY5, encoding another positive regulator of light signaling, causes increased PHR1 expression. FHY3, FAR1, HY5, and EIN3 directly bind to the PHR1 promoter through distinct cis-elements. FHY3, FAR1, and EIN3 activate, while HY5 represses, PHR1 expression. FHY3 directly interacts with EIN3, and HY5 suppresses the transcriptional activation activity of FHY3 and EIN3 on PHR1 Finally, both light and ethylene promote FHY3 protein accumulation, and ethylene blocks the light-promoted stabilization of HY5. Our results suggest that light and ethylene coordinately regulate PHR1 expression and PSRs through signaling convergence at the PHR1 promoter.

Microbial HSP70 peptide epitope 407-426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer.

Tumor-derived autophagome (DRibble) is an effective therapeutic cancer vaccine inducing T cell recognition and death of tumor cells in mice. However, the potential for improved anti-tumor response still remains. Our previous study demonstrated that two repeats of a mycobacterial HSP70407-426 (M2) peptide acted as adjuvant in improving anti-tumor efficacy of human umbilical vein endothelial cell (HUVEC) vaccine. Here, a DRibble vaccine conjugated with M2 (DRibble-M2) was designed as a novel vaccine to enhance anti-tumor activity. Compared with DRibble alone, DRibble-M2 vaccination more significantly inhibited the growth of mouse Lewis lung cancer both in a subcutaneous tumor model and in a lung metastasis model. Higher expression of antigen-specific CTL was induced by DRibble-M2. DRibble-M2 induced higher CD83 and CD86 expression in DC2.4 and also improved the internalization of DRibble antigen into DC2.4. Our data indicated that DRibble-M2 is a potential vaccine for clinical cancer therapy.

Occurrence and bioaccumulation of polybrominated diphenyl ethers in sediments and paddy ecosystems of Liaohe River Basin, northeast China.

Concentrations of 16 polybrominated diphenyl ether (PBDE) congeners were measured in river sediments, paddy soils and three species of paddy-field organisms (crab, loach and carp) collected from the Liaohe River Basin, northeastern China. The total contents of PBDEs (∑16PBDEs) in sediments and paddy soils were in the ranges of 273.4-3246.3pg/g dry weight (dw), and 192.1-1783.8pg/gdw, respectively. BDE 209 was the dominant congener both in sediments and paddy soils. The concentrations of ∑16PBDEs in sediments were significantly higher than those in the adjacent paddy soils, indicating a potential transport of PBDEs from river to paddy ecosystems via river water irrigation. The biota-soil accumulation factor (BSAF) was calculated as the ratio between the lipid-normalized concentration in paddy-field organisms and the total organic carbon-normalized concentration in paddy soil. The average BSAF values of ∑15PBDEs followed the sequence of crab (3.6)>loach (3.3)>carp (2.1). BDE 154 had the highest BSAF value, and a parabolic trend between BSAF values of individual PBDE congeners and their logKOW values was observed. In view of the fact that crab had the larger BSAF value and higher lipid content, the ecological risk and health risk for crab cultivation in paddy fields should be of particular concern.

Mannosylated Chitosan Nanoparticles Based Macrophage-Targeting Gene Delivery System Enhanced Cellular Uptake and Improved Transfection Efficiency.

Gene transfer mediated by mannosylated chitosan (MCS) is a safe and promising approach for gene and vaccine delivery. MCS nanoparticles based gene delivery system showed high in vivo delivery efficiency and elicited strong immune responses in mice. However, little knowledge about the cell binding, transfection efficiency and intracellular trafficking of MCS nanoparticles had been acquired. In this study, using gastrin-releasing peptide as a model plasmid (pGRP), the binding of MCS/pGRP nanoparticles to macrophages and the intracellular trafficking of MCS/pGRP nanoparticles in macrophages were investigated. MCS-mediated transfection efficiency in macrophages was also evaluated using pGL-3 as a reporter gene. The results showed that the binding and transfection efficiency of MCS nanoparticles in macrophages was higher than that of CS, which was attributed to the interaction between mannose ligands in MCS and mannose receptors on the surface of macrophages. Observation with a confocal laser scanning microscope indicated the cellular uptake of MCS/pGRP nanoparticles were more than that of CS/pGRP nanoparticles in macrophages. MCS/pGRP nanoparticles were taken up by macrophages and most of them were entrapped in endosomal/lysosomal compartments. After the nanoparticles escaping from endosomal/lysosomal compartments, naked pGRP entered the nucleus, and a few MCS might enter the nucleus in terms of nanoparticles. Overall, MCS has the potential to be an excellent macrophage-targeting gene delivery carrier.

Prevalence of small vessel disease and incidental DWI-positive lesions in patients with aneurysmal subarachnoid hemorrhage versus intracerebral hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. PATIENTS AND METHODS: We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. RESULTS: We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. DISCUSSION AND CONCLUSION: Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.

Enhanced antitumor efficacy by combination treatment with a human umbilical vein endothelial cell vaccine and a tumor cell lysate-based vaccine.

Angiogenesis inhibitors combined with other anticancer drugs have been shown to inhibit tumor growth in animal models and some of them were recently used in clinical trials. In the present study, a whole hepatocellular carcinoma cell lysate based vaccine with diphtheria toxin (DT) and two tandem repeats of microbial HSP70 peptide epitope 407-426 (2 mHSP70407-426, M2) as adjuvant, which was called HDM, was combined with a whole human umbilical vein endothelial cell (HUVEC) vaccine to develop a combination treatment regimen. This combination treatment regimen was named HUVEC-HDM, which was supposed to enhance its antitumor efficiency. HUVEC-HDM was administrated subcutaneously in both prophylactic and therapeutic procedures. Compared to either single vaccine, HUVEC-HDM induced a more significant inhibition on the growth and metastasis of H22 hepatocellular carcinoma in mice and prolonged the survival of tumor-bearing mice. Besides, HUVEC-HDM immunization elicited strong humoral and cellular immune responses targeting tumor cell as well as tumor angiogenesis, which could be responsible for the enhanced antitumor effect. Moreover, histochemistry analysis showed that HUVEC-HDM induced large areas of continuous necrosis within tumors, correlating well with the extent of tumor inhibition. These results not only highlight the superiority of the combined HUVEC-HDM treatment regimen, but also support the translation of such approaches into the clinic for the treatment of patients with hepatocellular carcinoma.

Improved efficacy of therapeutic vaccination with viable human umbilical vein endothelial cells against murine melanoma by introduction of OK432 as adjuvant.

Vaccination with xenogeneic or syngeneic endothelial cells targeting tumor angiogenesis is effective for inhibiting tumor growth. OK432, an effective adjuvant, was mixed with viable human umbilical vein endothelial cells (HUVECs) to prepare a novel HUVECs-OK432 vaccine, which could have an improved therapeutic efficacy. In this study, HUVECs-OK432 was administrated in mice by subcutaneous injection in a therapeutic procedure. The results showed that a stronger HUVEC-specific Abs and cytotoxic T lymphocyte immune response were elicited, which resulted in significant inhibition on the growth of B16F10 melanoma and remarkably prolonged survival of B16F10 melanoma-bearing mice compared with HUVECs. Besides, parallel results were obtained in vitro showing a stronger inhibition of HUVEC proliferation by immune sera of HUVECs-OK432 than that of HUVECs. Moreover, histochemistry and immunohistochemistry analysis showed that HUVECs-OK432 induced large areas of continuous necrosis within tumors and significantly reduced the vessel density, correlating well with the extent of tumor inhibition. Our present results suggest that OK432 could be employed as an effective adjuvant for HUVEC vaccines and therefore should be useful for adjuvant immunotherapy of cancer.

Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.

Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p < 0.01) and intramuscular administration of a pGRP solution (p < 0.05) to mice. In addition, immunization with MCS/pGRP nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p < 0.01) or that in the pGRP group (1.12 ± 0.37 g) (p < 0.05). Cell binding and cellular uptake results indicated that MCS/pGRP nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.

School climate and academic burnout in medical students: a moderated mediation model of collective self-esteem and psychological capital.

BACKGROUND: The study burnout of medical students is more and more serious, which directly affects the study style of university and the learning quality of students. This has aroused the high attention of researchers and universities. This study aimed to explore the mechanism of the influence of school climate on academic burnout among medical students in Chinese cultural context. METHODS: 2411 medical students (50.52% female; mean age = 19.55, SD = 1.41, rang = 17-24 years) were investigated with psychological environment questionnaire, collective self-esteem scale, psychological capital scale and academic burnout scale. The data were analyzed by using a moderated mediation model with SPSS and the Process 4.0 macro. RESULTS: The results revealed that: (1) school climate had a significant negative predictive effect on academic burnout among medical students controlling for gender, grade and age (B = -0.40, p < 0.001). (2) Collective self-esteem played a partial mediating role in school climate and academic burnout (indirect effect = -0.28, 95% CI = [-0.32,-0.25], accounting for 52.83%). (3) The first and second half of the indirect effect of school climate on medical students' academic burnout were moderated by psychological capital (B = 0.03, p < 0.01; B = -0.09, p < 0.001).High level of psychological capital can enhance the link between school climate and collective self-esteem as well as the link between self-esteem and academic burnout. CONCLUSION: Creating a good school atmosphere and improving the level of collective self-esteem and psychological capital are beneficial to improve the academic burnout of medical students.

Advancements of molecular imaging and radiomics in pancreatic carcinoma.

Despite the recent progress of medical technology in the diagnosis and treatment of tumors, pancreatic carcinoma remains one of the most malignant tumors, with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation. This paper focuses on the research progress of magnetic resonance imaging, nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma. We also briefly described the achievements of our team in this field, to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

Gold-catalyzed efficient synthesis of 2,4-disubstituted furans from aryloxy-enynes.

A series of (E)-1-aryloxy-1-en-3-ynes has been prepared by Sonogashira coupling of 2-bromo-3-aryloxypropenoates with terminal alkynes using Pd(PPh(3))(4) and CuI as the catalysts in Et(3)N. The resulting enynyl-aryl ethers are found to be highly applicable to the synthesis of 2,4-disubstituted furans with an ester group at C-4 position through an Au/Ag-catalyzed annulation reaction under extremely mild reaction conditions.

Protective antitumor immunity induced by tumor cell lysates conjugated with diphtheria toxin and adjuvant epitope in mouse breast tumor models.

Cancer cell vaccine-based immunotherapy has received increasing interest in many clinical trials involving patients with breast cancer. Combining with appropriate adjuvants can enhance the weak immunogenic properties of tumor cell lysates (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively elicited tumor-specific polyclonal immune responses, including humoral and cellular immune responses. High levels of antibodies against TCL were detected in the serum of immunized mice with ELISA and verified with Western blot analyses. The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2 inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor model. These findings demonstrate that TCL conjugated with appropriate adjuvants induced effective antitumor immunity in vivo. Improvements in potency could further make cancer cell vaccines a useful and safe method for preventing cancer recurrence after resection.

School Psychological Environment and Learning Burnout in Medical Students: Mediating Roles of School Identity and Collective Self-Esteem.

Learning burnout is an important indicator that reflects an individual's learning state. Understanding the influencing factors and mechanism of learning burnout of medical students has practical significance for improving their mental health. This study aimed to explore the mediating roles of school identity and collective self-esteem between school psychological environment and learning burnout in medical students. A total of 2,031 medical students (942 men and 1,089 women, age range: 17-23 years) were surveyed using the School Psychological Environment Questionnaire (SPEQ), School Identity Questionnaire (SIQ), Collective Self-esteem Scale (CSES), and Learning Burnout Scale (LBS). The results showed the following: (1) school psychological environment had a negative effect on learning burnout among medical students (ß = -0.19, p < 0.001), and (2) school identity and collective self-esteem played significant mediating roles between school psychological environment and learning burnout [95% CI = (-0.43, -0.31)]. Specifically, there were three paths that school psychological environment and learning burnout: first, through the independent mediating role of school identity; second, through the independent mediating role of collective self-esteem; and third, through the chain mediating roles of school identity and collective self-esteem. The findings reveal that school psychological environment not only directly influences the learning burnout of medical students but also indirectly influences it through school identity and collective self-esteem. Thus, this study has some important implications for prevention and intervention of learning burnout among medical students.

Computed Tomography Radiomics-Based Prediction of Microvascular Invasion in Hepatocellular Carcinoma.

Background: Due to the high recurrence rate in hepatocellular carcinoma (HCC) after resection, preoperative prognostic prediction of HCC is important for appropriate patient management. Exploring and developing preoperative diagnostic methods has great clinical value in treating patients with HCC. This study sought to develop and evaluate a novel combined clinical predictive model based on standard triphasic computed tomography (CT) to discriminate microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: The preoperative findings of 82 patients with HCC, including conventional clinical factors, CT imaging findings, and CT texture analysis (TA), were analyzed retrospectively. All included cases were divided into MVI-negative (n = 33; no MVI) and MVI-positive (n = 49; low or high risk of MVI) groups. TA parameters were extracted from non-enhanced, arterial, portal venous, and equilibrium phase images and subsequently calculated using the Artificial Intelligence Kit. After statistical analyses, a clinical model comprising conventional clinical and CT image risk factors, radiomics signature models, and a novel combined model (fused radiomic signature) was constructed. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was used to assess the performance of the various models in discriminating MVI. Results: We found that tumor diameter and pathological grade were effective clinical predictors in clinical model and 12 radiomics features were effective for MVI prediction of each CT phase. The AUCs of the clinical, plain, artery, venous, and delay models were 0.77 (95% CI: 0.67-0.88), 0.75 (95% CI: 0.64-0.87), 0.79 (95% CI: 0.69-0.89), 0.73 (95% CI: 0.61-0.85), and 0.80 (95% CI: 0.70-0.91), respectively. The novel combined model exhibited the best performance, with an AUC of 0.83 (95% CI: 0.74-0.93). Conclusions: Models derived from triphasic CT can preoperatively predict MVI in patients with HCC. Of the models tested here, the novel combined model was most predictive and could become a useful tool to guide subsequent personalized treatment of HCC.

Novel Non-invasive Transcranial Electrical Stimulation for Parkinson's Disease.

Conventional transcranial electrical stimulation (tES) is a non-invasive method to modulate brain activity and has been extensively used in the treatment of Parkinson's disease (PD). Despite promising prospects, the efficacy of conventional tES in PD treatment is highly variable across different studies. Therefore, many have tried to optimize tES for an improved therapeutic efficacy by developing novel tES intervention strategies. Until now, these novel clinical interventions have not been discussed or reviewed in the context of PD therapy. In this review, we focused on the efficacy of these novel strategies in PD mitigation, classified them into three categories based on their distinct technical approach to circumvent conventional tES problems. The first category has novel stimulation modes to target different modulating mechanisms, expanding the rang of stimulation choices hence enabling the ability to modulate complex brain circuit or functional networks. The second category applies tES as a supplementary intervention for PD hence amplifies neurological or behavioral improvements. Lastly, the closed loop tES stimulation can provide self-adaptive individualized stimulation, which enables a more specialized intervention. In summary, these novel tES have validated potential in both alleviating PD symptoms and improving understanding of the pathophysiological mechanisms of PD. However, to assure wide clinical used of tES therapy for PD patients, further large-scale trials are required.

Increased detection of circulating tumor DNA by short fragment enrichment.

BACKGROUND: Circulating cell-free DNA (cfDNA) detection for non-invasive diagnosis requires higher sensitivity and accuracy due to the low circulating tumor DNA (ctDNA) content. Many methods have been developed to improve detection of ctDNA, including ultra-deep sequencing or enrichment of shorter cfDNA fragments, such as those in the range of 90-150 bp. METHODS: Here, we developed a method for single-stranded DNA (ssDNA) library preparation with a large proportion of magnetic beads to enrich the shorter cfDNA fragments. We aimed to determine if this could increase the ctDNA content and thus improve the sensitivity of ctDNA detection by testing the method in blood samples from patients with advanced cancers (non-small cell lung cancers, esophageal squamous cell carcinoma, cholangiocarcinoma, colorectal cancer and liver cancer). RESULTS: This method was able to obtain shorter cfDNA both in commercial cfDNA references and real world clinical cfDNA samples. Plasmid simulation experiments showed that using a large proportion of magnetic beads to construct the library could obtain more ctDNA derived from shorter-fragment plasmids, which could significantly improve the detection of ctDNA especially in the low-variant allele frequency sample. In real-world clinical samples, this method may be able to increase the opportunity to obtain alteration reads from short fragments, which was important to low frequency detection. CONCLUSIONS: The ssDNA library preparation with large proportion of magnetic beads could increase the opportunity to obtain alteration reads from short fragments, which is crucial for low variant allele frequency detection.

Effect of poly(amidoamine) dendrimers on corneal penetration of puerarin.

The aim of this study was to investigate the effect of Poly(amidoamine) (PAMAM) dendrimers on corneal permeation of puerarin (PUE). Permeation studies were performed using excised cornea of rabbits by a Valia-Chien diffusion apparatus. Drug-treatment studies were carried out by measuring the penetration of puerarin on cornea in PAMAM-PUE physical mixture or PAMAM-PUE complex, and cornea-treatment studies were carried out by measuring the penetration of puerarin on PAMAM dendrimer pretreated cornea in puerarin solution. The results showed that the permeability coefficient of puerarin in PAMAM-PUE physical mixture was enhanced by 2.48 (G3), 1.99 (G4) and 1.36 (G5) times on average, respectively compared to control. However, no significant permeability enhancement of puerarin in PAMAM-PUE complex was found compared to control. This may attribute to free drug concentration was lower in PAMAM-PUE complex which served as a depot and exhibited slow-released behavior of drug. Cornea-treatment studies showed that the lag time of puerarin was decreased, while the cumulative amount within 2.5 h (Q(2.5)) and the permeability coefficient of puerarin increased compared to control. The permeability coefficient of puerarin was linear correlated to the molecular weight of PAMAM dendrimer (r(2)=0.99). This indicates that higher generation of PAMAM dendrimer more easily interact with cornea or loosen the epithelium cell junctions than lower generation to increase the flux of puerarin. Overall, the study showed that PAMAM dendrimer increased the corneal permeation of puerarin mainly by altering the corneal barrier.

Preparation and characterization of puerarin-dendrimer complexes as an ocular drug delivery system.

OBJECTIVE: The aim of this study was to prepare and characterize the complex of puerarin and poly(amidoamine) (PAMAM) dendrimers and to evaluate the complex as an ocular drug delivery system. METHODS: The complexes of puerarin and PAMAM dendrimers were prepared at various puerarin-to-dendrimer ratios. The physicochemical properties of the complexes were characterized by differential scanning calorimetry and Fourier transform infrared spectroscopy. The in vitro release studies were performed by dialysis. Corneal permeation was evaluated by Valia-Chien diffusion cell with excised corneas and ocular residence time in rabbits. RESULTS: The results showed that puerarin-dendrimer complexes formed primarily by hydrogen-bonding interactions. Typically, 43, 56, 125, and 170 molecules of puerarin could be incorporated into G3.5, G4, G4.5, and G5 PAMAM dendrimer molecule. Puerarin was released more slowly from puerarin-dendrimer complexes than free puerarin in deionized water and phosphate buffer solution (pH 6.8). The in vitro release rate of puerarin complexed with full generation dendrimers was lower than that with half generation dendrimers. Furthermore, puerarin-dendrimer complexes produced longer ocular residence times in rabbits compared with puerarin eye drops. No damages to the epithelium or endothelium were observed after the PAMAM dendrimer administration in this corneal permeation study. CONCLUSIONS: Puerarin-dendrimer complexes represent a potential ocular drug delivery system to improve the efficacy of drug treatment.