• Crossing biological barriers for advanced drug delivery.

      Schneider, Marc; Windbergs, Maike; Daum, Nicole; Loretz, Brigitta; Collnot, Eva-Maria; Hansen, Steffi; Schaefer, Ulrich F; Lehr, Claus-Michael (2013-06)
      This special issue compiles invited and contributed papers of the 9th International Conference and Workshop "Biological Barriers", 29 February-9 March 2012 at Saarland University, Saarbrücken Germany.
    • Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application.

      Nnamani, Petra O; Hansen, Steffi; Windbergs, Maike; Lehr, Claus-Michael (2014-12-30)
      NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750mg). ART-loaded NLCs were stable (-22 to -40mV), polydispersed (0.4-0.7) with d90 size distribution range of 247-530nm without microparticles up to one month of storage. The encapsulation efficiency (EE%) for ART in the NLC was concentration independent as 250mg of ART loading achieved ∼61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028J/g). Ex vivo study showed detectable ART amounts after 20h which gradually increased over 48h achieving ∼26% cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART.
    • Improved input parameters for diffusion models of skin absorption.

      Hansen, Steffi; Lehr, Claus-Michael; Schaefer, Ulrich F; Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz-Center for Infection Research (HZI), Saarbruecken, Germany. Steffi.hansen@helmholtz-hzi.de (2013-02)
      To use a diffusion model for predicting skin absorption requires accurate estimates of input parameters on model geometry, affinity and transport characteristics. This review summarizes methods to obtain input parameters for diffusion models of skin absorption focusing on partition and diffusion coefficients. These include experimental methods, extrapolation approaches, and correlations that relate partition and diffusion coefficients to tabulated physico-chemical solute properties. Exhaustive databases on lipid-water and corneocyte protein-water partition coefficients are presented and analyzed to provide improved approximations to estimate lipid-water and corneocyte protein-water partition coefficients. The most commonly used estimates of lipid and corneocyte diffusion coefficients are also reviewed. In order to improve modeling of skin absorption in the future diffusion models should include the vertical stratum corneum heterogeneity, slow equilibration processes, the absorption from complex non-aqueous formulations, and an improved representation of dermal absorption processes. This will require input parameters for which no suitable estimates are yet available.
    • Modeling the human skin barrier--towards a better understanding of dermal absorption.

      Hansen, Steffi; Lehr, Claus-Michael; Schaefer, Ulrich F (2013-02)
    • Particle based vaccine formulations for transcutaneous immunization.

      Mittal, Ankit; Raber, Anne S; Hansen, Steffi; Biopharmaceutics and Pharmaceutical Technology; Saarland University; Saarbruecken, Germany. (2013-06-18)
      Vaccine formulations on the basis of nano- (NP) or microparticles (MP) can solve issues with stabilization, controlled release, and poor immunogenicity of antigens. Likewise transcutaneous immunization (TCI) promises superior immunogenicity as well as the advantages of needle-free application compared with conventional intramuscular injections. Thus the combination of both strategies seems to be a very valuable approach. However, until now TCI using particle based vaccine formulations has made no impact on medical practice. One of the main difficulties is that NPs and MPs cannot penetrate the skin to an extent that would allow the application of the required dose of antigen. This is due to the formidable stratum corneum (SC) barrier, the limited amount of antigen in the formulation and often an insufficient immunogenicity. A multitude of strategies are currently under investigation to overcome these issues. We highlight selected methods presenting a spectrum of solutions ranging from transfollicular delivery, to devices disrupting the SC barrier and the combination of particle based vaccines with adjuvants discussing their advantages and shortcomings. Some of these are currently at an experimental state while others are already in clinical testing. All methods have been shown to be capable of transcutaneous antigen delivery.