Dietrich Scheglmann

Analytik Jena AG, Jena, Thuringia, Germany

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Publications (10)44.18 Total impact

  • Francesca Moret, Dietrich Scheglmann, Elena Reddi
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    ABSTRACT: The folate receptor (FR) is over-expressed in many human tumours and is being intensively studied also in the field of nanomedicine as a target to enhance the selectivity of drug delivery to cancer cells by using nanocarriers bearing folic acid (FA) on their surface. In this study we report the encapsulation of the photosensitizer (PS) meta-tetra(hydroxyphenyl)chlorin (m-THPC) in FA-targeted PEGylated liposomes used as a novel drug delivery system for photodynamic therapy (PDT) of cancer. Our in vitro investigations revealed that only a modest fraction of targeted liposomes were internalized by specific endocytosis in FR-positive KB cells. However, FA-liposomes doubled the uptake of the entrapped m-THPC with respect to un-targeted liposomes and enhanced the photo-induced cytotoxicity in KB cells. In contrast, in FR-negative A549 cells FA-targeted or un-targeted liposomes exhibited a very similar extent of internalization and as a consequence the same photo-killing efficiency.
    Photochemical and Photobiological Sciences 02/2013; · 2.92 Impact Factor
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    ABSTRACT: In this study we evaluated temoporfin-loaded polyethylene glycol (PEG) Poly-(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) as a new formulation for potential use in cancer treatment. NPs were characterized for their photophysical properties, temoporfin release, cellular uptake and intracellular localization, and dark and photocytotoxicities of temoporfin by using A549, MCF10A neoT and U937 cell lines. In vivo imaging was performed on athymic nude-Foxn1 mice. Temoporfin was highly aggregated within the NPs and the release of temoporfin monomers was faster from PEGylated PLGA NPs than from non-PEGylated ones. PEGylation significantly reduced the cellular uptake of NPs by the differentiated promonocytic U937 cells, revealing the stealth properties of the delivery system. Dark cytotoxicity of temoporfin delivered by NPs was less than that of free temoporfin in standard solution (Foscan(®), Biolitec AG [Jena, Germany]), whereas phototoxicity was not reduced. Temoporfin delivered to mice by PEGylated PLGA NPs exhibits therapeutically favorable tissue distribution. These encouraging results show promise in using PEGylated PLGA NPs for improving the delivery of photosensitizers for photodynamic therapy.
    Nanomedicine 05/2012; 7(5):663-77. · 5.26 Impact Factor
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    ABSTRACT: Pegylated liposomal nanocarriers have been developed with the aim of achieving improved uptake of the clinical PDT photosensitiser, m-THPC, into target tissues through increased circulation time and bioavailability. This study investigates the biodistribution and PDT efficacy of m-THPC in its standard formulation (Foscan®) compared to m-THPC incorporated in liposomes with different degrees of pegylation (FosPEG 2% and FosPEG 8%), following i.v. administration to normal and tumour bearing rats. The plasma pharmacokinetics were described using a three compartmental analysis and gave elimination half lives of 90 h, 99 h and 138 h for Foscan®, FosPEG 2% and 8% respectively. The accumulation of m-THPC in tumour and normal tissues, including skin, showed that maximal tumour to skin ratios were observed at ≤ 24 h with FosPEG 2% and 8%, whilst skin photosensitivity studies showed Foscan® induces more damage compared to the liposomes at drug-light intervals of 96 and 168 h. PDT treatment at 24h post-administration (0.05 mg kg⁻¹) showed higher tumour necrosis using pegylated liposomal formulations in comparison to Foscan®, which is attributed to the higher tumour uptake and blood plasma concentrations. Clinically, this improved selectivity has the potential to reduce not only normal tissue damage, but the drug dose required and cutaneous photosensitivity.
    Journal of Controlled Release 01/2012; 157(2):196-205. · 7.63 Impact Factor
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    ABSTRACT: We studied the effects of density and thickness of PEG coating on in vitro cellular uptake, and dark- and photo-toxicity of liposomal formulations (Fospeg) of the photodynamic agent meta-tetrahydroxyphenyl chlorin (m-THPC). The cellular uptake of various Fospeg formulations was determined by flow cytometry in CCD-34Lu human normal fibroblasts and A549 lung cancer cells. Dark and light-induced cytotoxicity was measured by MTS assay after exposure to increasing concentrations of Fospeg only and followed by irradiation with red light. Intracellular localization of m-THPC delivered by Fospeg was determined by fluorescence microscopy. The studies were carried out in comparison with m-THPC delivered by the standard solvent. In the dark all Fospeg formulations were less cytotoxic than m-THPC in standard solvent (ethanol/poly(ethylene glycol 400/water; 20 : 30 : 50 by vol.) and cytotoxicity decreased by increasing PEGylation. m-THPC delivered as Fospeg was internalised by endocytosis and localised mainly in the Golgi apparatus and endoplasmic reticulum. The efficiency of cellular uptake of Fospeg was reduced by 30-40% with respect to m-THPC in standard solution causing a slight reduction of the phototoxicity but without serious impairment of the efficacy of the treatment. Our study suggests that PEGylated liposomes are promising nanocarriers for the delivery of photosensitisers for photodynamic therapy because they reduce dark cytotoxicity while preserving therapeutic efficacy.
    Photochemical and Photobiological Sciences 08/2011; 10(11):1751-9. · 2.92 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the influence of membrane-softening components (terpenes/terpene mixtures, ethanol) on fluidity of phospholipid membranes in invasomes, which contain besides phosphatidylcholine and water, also ethanol and terpenes. Also mTHPC was incorporated into invasomes in order to study its molecular interaction with phospholipids in vesicular membranes. Fluidity of bilayers was investigated by electron spin resonance (ESR) using spin labels 5- and 16-doxyl stearic acid and by differential scanning calorimetry (DSC). Addition of 1% of a single terpene/terpene mixture led to significant fluidity increase around the C16 atom of phospholipid acyl chains comprising the vesicles. However, it was not possible to differentiate between the influences of single terpenes or terpene mixtures. Incorporation of mTHPC into the bilayer of vesicles decreased fluidity near the C16 atom of acyl chains, indicating its localization in the inner hydrophobic zone of bilayers. These results are in agreement with DSC measurements, which showed that terpenes increased fluidity of bilayers, while mTHPC decreased fluidity. Thus, invasomes represent vesicles with very high membrane fluidity. However, no direct correlation between fluidity of invasomes and their penetration enhancing ability was found, indicating that besides fluidity also other phenomena might be responsible for improved skin delivery of mTHPC.
    International Journal of Pharmaceutics 06/2011; 412(1-2):85-94. · 3.99 Impact Factor
  • Photodiagnosis and Photodynamic Therapy - PHOTODIAGNOSIS PHOTODYN THER. 01/2011; 8(2):195-195.
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    ABSTRACT: Undesired alterations of the blood clotting balance may follow the intravascular injection of nanotherapeutics/diagnostics. Here, we tested the procoagulant activity of synthetic amorphous silica (SAS) and organically modified silica (ORMOSIL) nanoparticles (NPs) and whether a high-density polyethylene glycol coating minimizes these effects. Hageman factor- and tissue factor-dependent activation of human blood/plasma coagulation, and binding to human monocytes, endothelial cells and platelets were quantified in vitro using naked and PEGylated ORMOSIL-NPs. Their effects were compared with those of SAS-NPs, present in many industrial products, and of poly(lactic-co-glycolic acid)- and small unilamellar vesicles-NPs, already approved for use in humans. Both SAS-NPs and ORMOSIL-NPS presented a significant procoagulant activity. However, highly PEGylated ORMOSIL-NPs were particularly averse to the interaction with the soluble factors and cellular elements that may lead to intravascular blood coagulation. Stealth, highly PEGylated ORMOSIL-NPs with a poor procoagulant activity can be used as starting blocks to design hemocompatible nanomedical-devices.
    Nanomedicine 08/2010; 5(6):881-96. · 5.26 Impact Factor
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    ABSTRACT: The aim of this study was to develop ethanol-containing (3.3-20%, w/v) liposomes loaded with temoporfin (mTHPC), which presents a highly hydrophobic photosensitizer with low percutaneous penetration, and to investigate their skin penetration enhancing effect. Characterization parameters of liposomes were measured by photon correlation spectroscopy, lamellarity was analyzed by cryo-electron microscopy and mTHPC-content in formulations was determined spectrofotometrically. In order to assess the stability of mTHPC-liposomes at 4 and 23 degrees C, at predetermined time intervals characterization parameters and mTHPC-content were measured. The in vitro skin penetration of mTHPC was investigated using human abdominal skin mounted in Franz cells. The results indicated that mTHPC-liposomes were of a small particle size, small polydispersity index, negative surface charge, unilamellar or oligolamellar, and of a spherical or oval shape. All liposomes were stable during 12 months' storage at 4 degrees C. Increasing the amount of ethanol in mTHPC-liposomes the skin deposition of mTHPC increased also. Liposomes without ethanol delivered the lowest amount of mTHPC into the skin, while liposomes containing 20% ethanol showed the highest penetration enhancement. In conclusion, mTHPC-liposomes containing 20% ethanol could be a promising tool for delivering temoporfin to the skin, which would be beneficial for the photodynamic therapy of cutaneous malignant or non-malignant diseases.
    Colloids and surfaces B: Biointerfaces 08/2009; 74(1):114-22. · 4.28 Impact Factor
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    ABSTRACT: A previous study revealed that the invasome dispersion containing 3.3% (w/v) ethanol and 1% (w/v) of the terpene mixture (cineole:citral:d-limonene=45:45:10, v/v=standard mixture) could significantly enhance skin penetration of the highly hydrophobic photosensitizer temoporfin (mTHPC). Invasomes enhanced mTHPC-deposition in stratum corneum (SC) compared to liposomes without terpenes and conventional liposomes, and they were efficient in delivering mTHPC to deeper skin layers [J. Control. Release 127 (2008) 271-280]. The aim of this study was to develop new mTHPC-loaded invasomes in order to further enhance the drug penetration. The ratio between d-limonene, citral and cineole was varied in the standard terpene mixture and also single terpenes were used. As a result new mTHPC-loaded invasome dispersions were prepared, characterized and investigated for stability and in vitro penetration of mTHPC into abdominal human skin using Franz diffusion cells. Invasomes were of a small particle size (<150nm), high homogeneity (<0.3), mostly unilamellar and spherical, but also deformed vesicles were detected. Invasomes containing 1% (w/v) cineole provided the highest skin penetration enhancement of mTHPC, i.e. they provided high amounts of mTHPC in the SC and deeper skin layers, indicating that also incorporation of a single terpene into invasomes could provide efficient nanocarriers of mTHPC. These invasomes could be considered as a promising tool for delivering the photosensitizer mTHPC to the skin. However, in contrast to most invasomes, being effective nanocarriers of mTHPC, there were also formulations less effective than liposomes containing 3.3% (w/v) ethanol and one formulation was less efficient than conventional liposomes.
    Colloids and surfaces B: Biointerfaces 12/2008; 70(2):198-206. · 4.28 Impact Factor
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    ABSTRACT: Temoporfin (mTHPC) is a highly hydrophobic second generation photosensitizer with low percutaneous penetration. In order to enhance its percutaneous penetration it was necessary to develop a mTHPC-loaded drug carrier system for enhanced skin delivery. mTHPC-loaded invasomes were developed, characterized and investigated for the in vitro percutaneous penetration of mTHPC into abdominal human skin using Franz diffusion cells. mTHPC-loaded invasomes were prepared using non-hydrogenated soybean lecithin (10% w/v), ethanol (3.3% w/v) and a mixture of terpenes (0.5 and 1% w/v). The invasomes obtained were of a sufficiently small particle size (<150 nm) and polydispersity index (<0.3). The particle size of invasomes increased following an increase in the amount of terpenes in the invasomes. All invasomes possessed a negative surface charge. The vesicles appeared to be unilamellar and oligolamellar, spherical and oval in shape. An interesting phenomenon was the finding that with increasing the amount of terpenes, the number of deformed vesicles in the dispersion increased. In vitro skin penetration data revealed that the invasome dispersion with 1% of the mixture of terpenes showed a significantly enhanced deposition (p<0.05) of the drug in the SC compared to liposomes without terpenes and the ethanolic solution.
    Journal of Controlled Release 05/2008; 127(1):59-69. · 7.63 Impact Factor