Combination of calcipotriol and methotrexate in nanostructured lipid carriers for topical delivery

The combination of calcipotriol with methotrexate can strengthen the topical therapy for psoriasis. The aim of the present study was to evaluate the potential of nanostructured lipid carriers (NLCs) loaded with lipophilic calcipotriol and hydrophilic methotrexate as topical therapy. NLCs composed of Precirol ATO 5 with various amounts of squalene as the liquid lipid were prepared. The particle size, surface charge, molecular environment, drug permeation, and skin irritation of the carriers were assessed. Hyperproliferative skin was also used as a permeation barrier in this study. It was found that variations in the Precirol®/squalene ratio had profound effects on the physicochemical characteristics of the NLCs. The range of particle size of the NLC preparations was 270 to 320 nm, with vehicles containing a higher Precirol amount exhibiting a larger diameter. NLCs with a higher Precirol/squalene ratio also showed greater polarity in their molecular environment. Calcipotriol-loaded NLC systems provided drug fluxes of 0.62 to 1.08 μg/cm2/h, which were slightly higher or comparable to the 30% ethanol vehicle (control, 0.72 μg/cm2/h). The methotrexate amount permeating the skin was 2.4 to 4.4-times greater using NLCs compared to that with the control. Dual drug-loaded NLCs exhibited reduced skin permeation of calcipotriol but not methotrexate. The in vivo topical delivery examined by confocal laser scanning microscopy (CLSM) showed a good correlation with the in vitro results. These two drugs with extremely different polarities can successfully be combined in NLCs. Results suggest that NLCs may have the potential to serve as delivery carriers for antipsoriatic drugs because of enhanced drug permeation and limited skin irritation

Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology

Squalene is a triterpene that is an intermediate in the cholesterol biosynthesis pathway. It was so named because of its occurrence in shark liver oil, which contains large quantities and is considered its richest source. However, it is widely distributed in nature, with reasonable amounts found in olive oil, palm oil, wheat-germ oil, amaranth oil, and rice bran oil. Squalene, the main component of skin surface polyunsaturated lipids, shows some advantages for the skin as an emollient and antioxidant, and for hydration and its antitumor activities. It is also used as a material in topically applied vehicles such as lipid emulsions and nanostructured lipid carriers (NLCs). Substances related to squalene, including β-carotene, coenzyme Q10 (ubiquinone) and vitamins A, E, and K, are also included in this review article to introduce their benefits to skin physiology. We summarize investigations performed in previous reports from both in vitro and in vivo models

A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2

In the early 1990s, 9-(+)-C-11-dihydrotetrabenazine (9-(+)-C-11-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-C-11-DTBZ analog, 10-(+)-C-11-DTBZ, as a vesicular monoamine transporter2 (VMAT2) imaging agent and compare it with 9-(+)-C-11-DTBZ. 10-(+)-C-11-DTBZ was obtained by C-11-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 +/- 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-C-11-DTBZ (30.5 +/- 2.3%). MicroPET studies showed that 10-(+)-C-11-DTBZ had a striatum-to-cerebellum ratio of 3.74 +/- 0.21 at 40 min post-injection, while the ratio of 9-(+)-C-11-DTBZ was 2.50 +/- 0.33. This indicated that 10-(+)-C-11-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-C-11-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-C-11-DTBZ to include dynamic brain distribution in rat brains

A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2.

In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-11C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-11C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ to include dynamic brain distribution in rat brains

Radiochemical synthesis of 9-(+)-¹¹C-DTBZ and 10-(+)-¹¹C-DTBZ.

<p>Radiochemical synthesis of 9-(+)-¹¹C-DTBZ and 10-(+)-¹¹C-DTBZ.</p

Time-activity curves of (A) 9-(+)-¹¹C-DTBZ and (B) 10-(+)-¹¹C-DTBZ in normal Sprague Dawley rat brains.

<p>PET data were collected for 90 min. Regions of interest (cerebellum, striatum, cortex and hippocampus) were identified according to the stereotaxic atlas, and the radioactivities were plotted against the time post-injection. Each value represents the mean ± SD (n = 3).</p

The chemical structure of TBZ and its derivatives.

<p>The chemical structure of TBZ and its derivatives.</p

The SUR comparison of 9-(+)-¹¹C-DTBZ and 10-(+)-¹¹C-DTBZ in a rat brain.

<p>The SUR comparison of 9-(+)-¹¹C-DTBZ and 10-(+)-¹¹C-DTBZ in a rat brain.</p

Semi-preparative HPLC purification chromatograms of 10-(+)-¹¹C-DTBZ (Waters XTerra, 10 x 150 mm, 50 mM NH₄OAc adjusted to pH = 4.5 with acetic acid/ethanol, 90/10, v/v, 6 mL/min), panel A: UV detection at 280 nm, panel B: radioactivity.

<p>The product fraction was collected at 9.6 to 10.6 min.</p