Preparation of podophyllotoxin nanostructured lipid carriers and its effects on immortalized human cervical epithelial cells with HPV infection in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of podophyllotoxin nanostructured lipid carriers (POD-NLC) on immortalized human cervical epithelial cells (H8) infected with HPV in vitro.</p><p><b>METHODS</b>POD-NLC was prepared by emulsion evaporation method and characterized using transmission electron microscopy, Zetasizer analyzer and high-performance liquid chromatography (HPLC). H8 cells were treated with different concentrations (0.0001-1 µg/ml) of POD-NLC, free POD, or blank nanostructured lipid carriers (NLC), and the cell proliferation was assessed using MTT assay to evaluate the cytotoxic effects. The changes of cell morphology were observed using fluorescence microscopy, and the cell cycle changes and cell apoptosis were analyzed using flow cytometry.</p><p><b>RESULTS</b>POD-NLC showed a spherical or elliptical shape with good stability in vitro. The average particle size of POD-NLC was 85.6∓10.25 nm, with a Zeta potential of 26.2∓4.1 mV and entrapment efficiency of POD of (88.56∓3.1)%. POD-NLC caused a significant inhibition of H8 cell proliferation in a concentration- and time-dependent manner. At an equivalent concentration, POD-NLC produced a stronger inhibitory effect on cell proliferation than POD. The inhibition rate of H8 cells after a 48-h exposure to POD-NLC and POD reached 95.8% and 65.6%, respectively, and at the highest concentration of 1 µg/ml, the IC(50) of POD-NLC and POD was 0.015 µg/ml and 0.13 µg/ml, respectively. Blank NLC did not obviously affect the proliferation of H8 cells. POD-NLC and POD both caused obvious increases in G(2)/M phase cell percentages and induced typical apoptotic changes of the cells, and their effects were comparable (P>0.05).</p><p><b>CONCLUSION</b>Compared with POD, POD-NLC has more potent effect in inhibiting H8 cell proliferation and inducing cell apoptosis, suggesting its potential in the treatment of cervical HPV infection.</p>

Preparation of lidocaine nanoemulsion and its transdermal absorption by rat skin ex vivo / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare lidocaine nanoemulsion and investigate its transdermal delivery ability in vitro.</p><p><b>METHODS</b>The optimal Km (surfactant/cosurfactant) value and the component proportion were determined by pseudoternary phase diagrams combined with Origin software analysis. The diameter and distribution range were detected by Zeta particle size analysis instrument, and the morphology of the nanoemulsion was observed by electron microscope. The permeation flux of lidocaine was determined in vitro using the modified Franz diffusion cell combined with HPLC, and the cumulative transdermal absorption amount and the apparent skin transdermal velocity were compared among nanoemulsion, gel and tincture containing 5% lidocaine. The permeation mode of lidocaine nanoemulsion was analyzed.</p><p><b>RESULTS</b>The average drop size of lidocaine nanoemulsion was 29.8-/+14.4 nm, and 98% of the drop sizes ranged from 15.1 to 45.5 nm and 2% from 77.9 to 261.3 nm. The nanoemulsion drop showed a spherical morphology in a polydisperse system. The Kp value of the nanoemulsion (3.07-/+0.74 cm/h) was significantly higher than that of gel (1.27-/+0.35 cm/h) and tincture (0.97-/+0.18 cm/h), and the permeation rate of the nanoemulsion was 69.82-/+7.48 microg x cm(-2) x h(-1), which fitted the the Zero-order release dynamic procedure.</p><p><b>CONCLUSIONS</b>The component proportion of lidocaine nanoemulsion can be conveniently obtained through pseudoternary phase diagrams and Origin software analysis, and the drop size, distribution, morphology and system type can be determined by Malvern Zetasizer combined with electron microscopy. The results also indicate that the nanoemulsion system with high permeation rate may provide a new promising means for local anesthesia.</p>

The histological changes of diabetic rats' skin and the effects on the percutaneous absorption of glucocorticoid / 药学学报

To examine the histological changes of diabetic rats' skin and the effects on the percutaneous absorption of hydrocortisone (HC, a glucocorticoid), male Wistar rats were randomly divided into five groups: control group, diabetes one-week group (W1), two-week group (W2), three-week group (W3), and four-week group (W4), while each group contained 6 rats. Diabetes mellitus (DM) rat model was prepared with the method of streptozocin (STZ, 40 mg x kg(-1)) intraperitoneal injection. Abdominal skin was cut to carry out an in-vitro penetration experiment on an improved Franz diffusion cells, and phosphate buffer (PBS, pH 7.4) was used as receptor solution. The solution was analyzed with HPLC, and then the penetrating rate can be calculated. Meanwhile, rats' abdominal skins of different DM periods were HE stained and made into tissue slices to find if any histological changes occurred. The penetrating rate of control, W1, W2, W3, and W4 groups were 2.39 +/- 1.25, 3.22 +/- 1.72, 3.02 +/- 1.89, 3.63 +/- 2.02 and 5.00 +/- 3.36 microg x h(-1) x cm(-2), respectively. There was significant difference between the control and the W4 group (P < 0.05), but no significant differences were found between any other two groups (P > 0.05). The tissue slices showed that compared to the normal rats' skin, little change was observed in one-week DM rats' skin, but the skin of one-month DM rats' skin was observed thinner, and it became much thinner than that of rats with two-month diabetes, especially the epidermis. After making a rat into diabetic, the rats' skin goes through a pathological change, and this change is closely interrelated with the increase of the permeation of HC. Therefore, it is necessary to adjust the dose while some drug was applied on the skin in case of diabetes mellitus.

Effects of podophyllotoxin solid lipid nanoparticles on proliferation and apoptosis of cervical carcinoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the anti-proliferative and apoptosis-inducing effect of podophyllotoxin solid lipid nanoparticles (PDP-SLN) in human cervical carcinoma cells in vitro.</p><p><b>METHODS</b>Hela cells were treated with PDP and PDP-SLN at different concentrations (0.0005-5 micromol/L), and the proliferation of the cells was assessed using MTT assay and the apoptotic index was determined by flow cytometry.</p><p><b>RESULTS</b>Both PDP and PDP-SLN showed obvious inhibitory effect on the cell proliferation in a dose- and time-dependent manner. At the same concentration, PDP-SLN produced stronger inhibitory effect on the cells than PDP, with IC50 24, 48, and 72 h after the cell exposure to PDP-SLN and PDP of 4.10, 0.65, 0.20 micromol/L and 9.2, 4.0, 1.3 micromol/L, respectively. Both PDP and PDP-SLN significantly induced the apoptosis of the Hela cell, and the apoptosis rates of the cells incubated in the presence of 0.5 micromol/L PDP-SLN reached 90.8% at 24 h and 94.2% at 72 h, significantly higher than the rate of cells incubated with PDP (64.1% at 24 h and 68.4% at 72 h, P<0.01).</p><p><b>CONCLUSION</b>PDP-SLN can effectively suppress the proliferation and induce apoptosis of Hela cells in vitro.</p>

Comparison of transdermal permeation in vitro of lidocaine tincture and microemulsion / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare lidocaine tincture and microemulsion for their transdermal permeation.</p><p><b>METHODS</b>The experimental model for percutaneous administration of lidocaine preparations in vitro was prepared using modified Franz diffusion cell.</p><p><b>RESULTS</b>The accumulated infiltration amount of lidocaine microemulsion in unit area was higher than that in its cream or tincture preparations.</p><p><b>CONCLUSION</b>The transdermal permeation of lidocaine microemulsion in vitro can be more efficient than that of the tincture preparation, and the permeation is linearly dependent on the dose administered within a certain range.</p>

Treatment of recurrent condyloma acuminatum with solid lipid nanoparticle gel containing podophyllotoxin: a randomized double-blinded, controlled clinical trial / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the clinical efficacy and safety of podophyllotoxin delivered via solid lipid nanoparticle gel for topic treatment of recurrent condyloma acuminatum.</p><p><b>METHODS</b>In a randomized double-blinded study, podophyllotoxin solid lipid nanoparticles gel and routine podophyllotoxin gel preparation was applied respectively for treatment of 97 volunteer patients with recurrent condyloma acuminatum. The therapeutic effect, condyloma acuminatum relapse following the treatment and adverse effect were evaluated.</p><p><b>RESULTS</b>The wart clearance rate in the condyloma acuminatum patients in the first treatment course with podophyllotoxin solid lipid nanoparticle gel reached 97.1%, close to that with the routine preparation of 90.6%, but the nanoparticle preparation significantly reduced the recurrence rate and adverse effect (P<0.01).</p><p><b>CONCLUSION</b>Podophyllotoxin delivered via solid lipid nanoparticle gel can effectively clear condyloma acuminatum and reduce its recurrence rate with only mild, tolerable adverse effect.</p>

Preparation and electron microscopic observation of lidocaine microemulsion / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare and determine the proportion of the components of lidocaine microemulsion.</p><p><b>METHODS</b>Pseudoternary phase diagrams of the prepared lidocaine microemulsion with different Km (surfactant/cosurfactant) were generated to determine the optimal Km according to the size of the microemulsion area. The diameter and its distribution range, viscosity, electric conductivity and refractivity of lidocaine microemulsion drop was determined, and the appearance and system type of the microemulsion was observed using electron microscope. RESULTS; Maximum microemulsion area in the pseudoternary phase diagrams was obtained with the Km of 3, and the drop size of the microemulsion averaged 29.8+/-14.4 nm (with up to 98% of the drop size ranging between 15.1-45.5 nm and 2% between 77.9-261.3 nm). At 25 degrees C, the viscosity, electric conductivity and refractivity of the microemulsion was 25 mPa.S, 130 micros/cm and 1.473, respectively, and the lidocaine microemulsion was identified to belong to O/W type. The microemulsion drop appeared in spherical shape of heterogeneous sizes in a multi-disperse system.</p><p><b>CONCLUSION</b>The optimal proportion of the components in lidocaine microemulsion can be obtained by analyzing pseudoternary phase diagrams, and the drop size, distribution, shape and system type can be determined or observed through Maerwen Zetasizer combined with electron microscopic observation.</p>