Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 10th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems London, UK.

Day 3 :

Keynote Forum

Olivia Merkel

Ludwig-Maximilians-Universit√§t M√ľnchen, Germany

Keynote: In-Situ Forming Gel Devices as Local Depot Therapeutic for Rheumatoide Arthritis

Time : 09:30-10:10

Pharmaceutica 2017 International Conference Keynote Speaker Olivia Merkel photo

Olivia Merkel, is a Professor of Drug Delivery in the Department of Pharmacy at LMU Munich. From 2011 until 2016 she was an Assistant Professor of Pharmaceutics and an Associate Faculty Member of Oncology at Wayne State University and Barbara Ann Karmanos Cancer Institute in Detroit. She became a Registered Pharmacist in 2005. In 2006, she received a MS in Pharmaceutics from Martin-Luther-Universität Halle-Wittenberg, and a PhD in Pharmaceutics from Philipps-Universität Marburg in 2009. She received several awards, including an ERC Starting Grant, the Galenus Foundation Technology Award, the Wayne State College of Pharmacy Young Investigator Award, the European Federation for Pharmaceutical Science Young Pharmaceutical Investigator Award, an invitation to the Lindau Nobel Laureates Meeting, the Carl-Wilhelm-Scheele-Award by the German Pharmaceutical Society (DPhG) and the award for the best PhD thesis at Philipps-Universität Marburg. Currently Prof. Merkel’s research focuses on targeted siRNA delivery in cancer and inflammatory diseases


Statement of the Problem: More efficient anti-inflammatory therapies with reduced side effects are needed to treat Rheumatoid arthritis (RA), a chronic and disabling autoimmune condition that affects about 1% of the population in developed countries. Even though a multitude of cell types is involved, macrophages play a central role in the pathophysiology of RA. Locally implantable, targeted, macrophage-specific RNA interference (RNAi)-based therapies could therefore revolutionize RA therapy.

Methodology: Three-layered micelles (3LM) encapsulating nucleic acids were formed from triblock copolymers of PLLA-PEI-PLLA and PLLA-PEG-PLLA in a three-step procedure. Their structure and DNA entrapment in the core was determined by TEM. Hydrodynamic diameters and zeta potentials were measured by dynamic light scattering. DNA release in neutral and acidic pH was detected by modified SYBR Gold assays. For targeting of activated macrophages, folic acid (FA) was attached to the PEG-chain of a PLLA-PEG diblock affording PLLA-PEG-FA. Subsequently, 3LM were formed with PLLA-PEG-FA in the outer polymer shell. RAW264.7 cells were activated with LPS or left resting. Primary macrophages were isolated after in vivo activation. One day later, the cells were transfected with targeted and non-targeted 3LM, and GFP expression was quantified by flow cytometry. Thermoresponsive hydrogels were obtained by stereocomplexing 3LM which contain PLLA-PEG-PLLA in the outer core with PDLA-PEG-PDLA.

Conclusion & Significance: The core-corona structure and efficient DNA entrapment in the core were confirmed by TEM. Sizes were found to be less than 200 nm, and the encapsulation efficiency of DNA was optimized. 3LM were stable at neutral pH but released DNA in an acidic environment. 3LM were efficiently targeted to activated macrophages by blending PLLA-PEG-FA in the outer layer, while non-targeted micelles or PEI polyplexes were not efficiently taken up. Stereocomplexes of 3LM formed hydrogels above their phase transition temperature and released 3LM in acidic environment that efficiently transfected primary macrophages.