Polycarbonate-Based Copolymer Micelles as Biodegradable Carriers of Anticancer Podophyllotoxin or Juniper Extracts.

Podophyllotoxin (PPT) is used in the industrial production of efficient anticancer, antiviral and other drugs. Sinopodophyllum hexandrum or Podophyllum peltatum are natural sources of PPT, but at present they are considered as endangered species. Their PPT content is variable, depending on the growing conditions. Searching for new sources of PPT, some representatives of the genus Juniperus were found to exhibit efficient PPT biosynthesis. However, PPT is highly toxic and poorly soluble in water compound, which limits its clinical applications. In this connection, amphiphilic polymer micelles are considered to be suitable PPT carriers, aimed at increase in water solubility and decrease in toxicity. The present research deals with the evaluation of MPEG-polycarbonate block copolymer micelles loaded with PPT or juniper extracts. The active component-loaded polymer nanocarriers were characterized by dynamic and electrophoretic light scattering, as well as by transmission electron microscopy. The active component loading efficiency and loading capacity were also determined. Highly efficient antiproliferative activity of the loaded micelles was determined in a panel of cancer cell lines. The obtained amphiphilic nanocarriers, loaded with PPT-containing bioactive components, have application in future in vivo preclinical trials of their pharmacokinetics and pharmacodynamics as potential therapeutical agents in the prospective nanomedicine.

Increasing the Accuracy of the Characterization of a Thin Semiconductor or Dielectric Film on a Substrate from Only One Quasi-Normal Incidence UV/Vis/NIR Reflectance Spectrum of the Sample.

OEMT is an existing optimizing envelope method for thin-film characterization that uses only one transmittance spectrum, T(λ), of the film deposited on the substrate. OEMT computes the optimized values of the average thickness, d¯, and the thickness non-uniformity, Δd, employing variables for the external smoothing of T(λ), the slit width correction, and the optimized wavelength intervals for the computation of d¯ and Δd, and taking into account both the finite size and absorption of the substrate. Our group had achieved record low relative errors, <0.1%, in d¯ of thin semiconductor films via OEMT, whereas the high accuracy of d¯ and Δd allow for the accurate computation of the complex refractive index, N˙(λ), of the film. In this paper is a proposed envelope method, named OEMR, for the characterization of thin dielectric or semiconductor films using only one quasi-normal incidence UV/Vis/NIR reflectance spectrum, R(λ), of the film on the substrate. The features of OEMR are similar to the described above features of OEMT. OEMR and several popular dispersion models are employed for the characterization of two a-Si films, only from R(λ), with computed d¯ = 674.3 nm and Δd = 11.5 nm for the thinner film. It is demonstrated that the most accurate characterizations of these films over the measured spectrum are based on OEMR.

Anticancer Podophyllotoxin Recovery from Juniper Leaves at Atmospheric and High Pressure Using Eco-Friendly Solvents.

Podophyllotoxin (PPT) is a precursor for the synthesis of drugs against cancer and other diseases. The present sources of PPT (Sinopodophyllum hexandrum and Podophyllum peltatum) are endangered species, with PPT production highly dependent on their growing conditions. In connection with the identification of new sources of PPT, the present study aimed to recover PPT from Juniperus virginiana leaves via atmospheric or high pressure extraction methods with a focus on using eco-friendly solvents. PPT quantification was determined by UHPLC/HRMS/MS. A thorough study of conventional extraction was carried out to reveal the optimal conditions (solvent ethyl acetate at room temperature and a duration of 1 h) for maximizing the PPT recovery (about 30 mg/g of dry extract and 3 mg/g of dry initial plant material). Peleg's equation was applied for process kinetics modeling. The best PPT content in the final dry extract (42-45 mg/g of dry extract) was obtained by high pressure methods under supercritical (scCO2 with ethanol or ethyl acetate, 30 MPa, 50 °C and 100 min) or accelerated solvent extraction conditions (solvent ethyl acetate, 10.35 MPa, 20 °C and 3 cycles for 15 min). Seasonal stability and storage stability of the raw material were also determined. The present results have potential applications in the pharmacy for the delivery of PPT from juniper leaves.

Hybrid Dispersion Model Characterization of PAZO Azopolymer Thin Films over the Entire Transmittance Spectrum Measured in the UV/VIS/NIR Spectral Region.

Notwithstanding the significant optical applicability of PAZO polymer films, there are no accurate data about their optical characteristics. To remedy this shortcoming, in this study three PAZO polymer thin films are characterized, with dissimilar thicknesses, on glass substrates using only one UV/VIS/NIR transmittance spectrum T(λ) per sample and an original hybrid dispersion model (HDM). HDM is based on the Tauc-Lorentz model, the new amorphous dispersion formula, the Tauc-Lorentz-Urbach model of Foldyna and the Tauc-Lorentz-Urbach model of Rodriguez. HDM with two oscillators is employed in characterizations of the PAZO polymer films in the range [300, 2500] nm, whereby the root-mean-square deviation (RMSD) of the fitted transmittance spectrum with respect to T(λ) does not exceed 1.6 × 10-3. Decreasing RMSD by 2.3% to 94.4% is demonstrated by employing HDM compared with the above mentioned four popular dispersion models, for each one of the studied films. HDM is applicable to amorphous films independent of their thickness as well as to cases of non-transparent substrate.

Junipers of Various Origins as Potential Sources of the Anticancer Drug Precursor Podophyllotoxin.

Juniper representatives are natural sources of plenty of bioactive metabolites and have been used since ancient times as folk remedies against tapeworms, warts, cancer, etc. The antiproliferative activities of junipers are attributed to podophyllotoxin (PPT), which is a precursor for the synthesis of efficient anticancer drugs. However, the natural sources of PPT, Sinopodophyllum hexandrum (Royle) T. S. Ying and Podophyllum peltatum L., are already endangered species because of their intensive industrial exploitation. Therefore, identification of other sources of PPT is necessary. This study is a broad comparative investigation of junipers, for which original sources have been accessed from different continents of the world. The present research is aimed at the identification of species, producing PPT and other lignans at concentrations that are sufficient for the high antiproliferative activity of the corresponding extracts. Cytotoxic juniper leaf extracts demonstrated a broad spectrum of activity on a panel of cancer cell lines. The antiproliferative properties of junipers were attributed to the combined activity of great diversity of lignans (podophyllotoxin, deoxypodophyllotoxin, ß-peltatin, yatein, matairesinol, anhydropodorhizol, etc.), detected by UHPLC-HRMS and LC-ESI-MS/MS in the corresponding extracts. Several species of the genus Juniperus L. were outlined as perspective sources of drug precursors with potential pharmaceutical applications.

Further Increasing the Accuracy of Characterization of a Thin Dielectric or Semiconductor Film on a Substrate from Its Interference Transmittance Spectrum.

Three means are investigated for further increasing the accuracy of the characterization of a thin film on a substrate, from the transmittance spectrum T(λ) of the specimen, based on the envelope method. Firstly, it is demonstrated that the accuracy of characterization, of the average film thickness d¯ and the thickness non-uniformity ∆d over the illuminated area, increases, employing a simple dual transformation utilizing the product T(λ)xs(λ), where Tsm(λ) is the smoothed spectrum of T(λ) and xs(λ) is the substrate absorbance. Secondly, an approach is proposed for selecting an interval of wavelengths, so that using envelope points only from this interval provides the most accurate characterization of d¯ and ∆d, as this approach is applicable no matter whether the substrate is transparent or non-transparent. Thirdly, the refractive index n(λ) and the extinction coefficient k(λ) are computed, employing curve fitting by polynomials of the optimized degree of 1/λ, instead of by previously used either polynomial of the optimized degree of λ or a two-term exponential of λ. An algorithm is developed, applying these three means, and implemented, to characterize a-Si and As98Te2 thin films. Record high accuracy within 0.1% is achieved in the computation of d¯ and n(λ) of these films.

Optical Characterization of AsxTe100-x Films Grown by Plasma Deposition Based on the Advanced Optimizing Envelope Method.

Three AsxTe100-x films with different x and dissimilar average thickness are characterized mainly from one interference transmittance spectrum T(λ = 300 to 3000 nm) of such film on a substrate based on the advanced optimizing envelope method (AOEM). A simple dual transformation of T(λ) is proposed and used for increasing the accuracy of computation of its envelopes T+(λ) and T-(λ) accounting for the significant glass substrate absorption especially for λ > 2500 nm. The refractive index n(λ) of As40Te60 and As98Te2 films is determined with a relative error <0.30%. As far as we know, the As80Te20 film is the only one with anomalous dispersion and the thickest, with estimated = 1.1446 nm, ever characterized by an envelope method. It is also shown and explained why the extinction coefficient k(λ) of any of the three AsxTe100-x films is computed more accurately from the quantity Ti(λ) = [T+(λ)T-(λ)]0.5 compared to its commonly employed computation from T+(λ). The obtained results strengthen our conviction that the AOEM has a capacity for providing most accurate optical characterization of almost every dielectric or semiconductor film with > 300 nm on a substrate, compared to all the other methods for characterization of such films only from T(λ).