22^nd International Conference and Exhibition on Pharmaceutical Formulations July 04-06, 2019 Valencia, Spain

Luis F. Bravo-Duque has exposed interest for Pharmaceutical Technology, Physical Chemistry, Cancer Research, and Drug Delivery System research. He has collaborated in both, privet investment and academic institution, research projects to develop Drug Delivery Systems. One of them was the development and manufacture of an oral polymeric multiparticle system, for the release of a chronic use drug against obesity. Also, he was teacher assistant in the Pharmaceutical Technology Laboratory at the Faculty of Chemistry, where he supported in the realization of experimental practices, focused on the integration of knowledge of sterile liquid pharmaceutical forms and modified release systems. Currently he is studding a Science Master at the National Autonomous University of Mexico.

Multiparticle polymer systems (nano or micrometric) have gained great importance within the development of drug delivery systems (DDS), due to their great versatility and biocompatibility. Conventional manufacturing techniques are generally based on the formation of simple or multiple emulsions to use the drops as a template. The polymer particles prepared by these conventional methods exhibit a great variation between batch and batch in their physicochemical properties, such as average particle size, size distribution, surface charge and release profile. A manufacturing alternative is the miniaturization of the emulsification process by using microchannels to control the droplet size and their size distribution. The handling of fluids with microchannels is also called Microfluidics. The aim of this project is developed a multifunctional system for a more efficient treatment of tumors, obtained with a robust manufacturing process to control the physicochemical properties of the particles and thus reduce the variation in the manufacturing batches. We have obtained a multiparticle polymeric system with magnetic properties for the treatment of tumors, manufactured with microfluidic devices. This system consists of magnetic iron oxide nanoparticles embedded in porous polymer microparticles of poly-ε-caprolactam (PCL) and coated with a temperature- sensitive co-polymer of poly-N-isopropylacrylamide (pNIPAM), N,N′-Methylenebisacrylamide (MBA) and methacrylc acid (MA). The polymer coat has a transition phase temperature around 43°C where the polymer collapse and the microparticle inside is exposed. We pretend load Methotrexate (MTX) within the particles pores and by applying an alternating magnetic field (AMF), the nanoparticles will generate an increase in the temperature of the system resulting in the MTX release. The magnetic nanoparticles will also serve to do an in vivo monitoring of the system and tumor by Magnetic Resonance Imaging (MRI).

Sofía N. Casillas-Popova studied a Bachelor of Chemical Pharmaceutical Biology in the National Autonomous University of Mexico, now she is a master student in the Chemical Sciences Program of the National Autonomous University of Mexico. During the bachelor she studied the influence of gene transcription and protein translation in the prefrontal cortex and hippocampus in forgetting during consolidation and recovery of information in animals trained in the autoshaping task, through pharmacological manipulation. Now she is working on her master´s project, which involved the synthesis of magnetoelectric nanoparticles as new nanocarriers for the treatment of cancer

Statement of the Problem: In the recent years, pharmaceutical sciences have been quickly developed, so it´s easy to forget that no many years ago there weren´t available, effective and safety treatments for common diseases. Despite the advances in the pharmaceutical sciences, nowadays there are still inefficiently treated diseases that remain a challenge, therefore the development of new systems is crucial for the improvement of current therapies. The magnetoelectric nanocarriers are nanoparticles composed by magnetoelectric materials, a subgroup of multiferroic compound that exhibit the magnetoelectric effect, a phenomenon in which a magnetic field can induce an electrical polarization or vice versa. The coating of magnetoelectric nanoparticles with materials that respond dynamically to stimuli in the cellular environment provides a way to control the release of the drug inside the target cells. The aim of this study is to design, elaborate and characterize magnetoelectric core-shell nanoparticles coated with a thermoresponsive polymer for their application in drug release and cellular nanoelectroporation. Methodology & Theoretical Orientation: The coprecipitation method was used to the synthesis of the magnetic core of the nanoparticles, which then were coated with a ferroelectric material by sol gel method. Finally, the magnetoelectric nanoparticles were coated with PNIPAm via radical polymerization. The nanoparticles where characterized by several method as X-ray, electronic microscopy, IR, DSC, among others. Findings: The methodology employed in this study allowed the synthesis of the core-shell nanoparticles which now are subject of in vitro release studies. Conclusion & Significance: This new nanocarriers promises to improve the treatment of diseases which remain a cause of premature death. In the case of cancer, they promise to overcome one of the main challenges, the delivery and specifically release of drugs into tumoral cells without effecting healthy cells.

Mayra Martínez-Peláez is dedicated at the design and development of novel drug delivery systems. Because of her knowledge in chemistry, pharmacology and pharmacokinetics, she has experience in preformulation and formulation of drugs, but also, she is familiar with regulatory and marketing affairs. She was graduated with honors by the Universidad Autonoma de Mexico in Mexico City and right now she is about to obtain a chemistry master’s degree.

Statement of the Problem: Rheumatoid arthritis is a chronic, autoimmune and inflammatory disease that affects almost 1.0% of the world population.1 The current treatment used is based on the administration of Disease-Modifying Antirheumatic Drugs (DMARDs) like methotrexate (MTX), which is the first-choice medication.2 Unfortunately, DMARDs based therapies aren´t satisfactory, because of the kidney and medullar damage they cause,3 associated with the non- specificity of the drugs to a target tissue.4 Here, it is proposed the development of a targeted, pH and thermosensitive nanogel5 that ensure MTX´s delivery only at arthritic joints. Methodology. Nanogel particles were made by the radical polymerization of N-isopropylacrylamide, 1- vinylimidazole and N’N-methylenebisacrylamide in water. The obtained system was coated with a hyaluronic acid film in order to get an active target mechanism. An amount of MTX was loaded at the coated nanogel particles by physical adsorption. The system´s structure was characterizated by FTIR and NMR. The size and morphology of the particles were studied with DLS and SEM (Figure 1). The thermo and pH sensibility of the system were getting by turbidimetry techniques. An in vitro drug delivery was made to quantify the MTX´s delivery. Results. It was found that 90.5% of NIPAM, 7.5% of VI and 2% of MBA are required to obtain stable nanogel particles that swell at 36.5°C at pH 7 and at 42°C at pH 5 (Figure 2). It was demonstrated the adsorption of a therapeutic amount of MTX according a Langmuir- Freundlich isotherm. In vitro essays show that MTX loaded is delivered at arthritic joints conditions in 10 hrs., whereas at physiological health conditions, it is required more than 36 hrs. for its complete delivery (Figure 3). Conclusion and Significance. The obtained system has special characteristics to deliver MTX specifically at arthritic joints, so it could help to reduce the adverse effects that affect the life condition of patients.

Leticia Antonio is a student of the master’s in chemicals sciences of the National Autonomous University of Mexico, UNAM. Her investigation project is focused on the study of magnetic molecularly imprinted polymers as a drug delivery system for the treatment of cancer. In order to improve the efficiency in the coating, she is evaluating a new method of synthesis using the magnetic hyperthermia.

Statement of the problem: Cancer is an illness present in the whole world, only in 2015, it registered 8,8 million people died because of this disease.1 Nowadays the chemotherapeutic remains like the most popular treatment. However, it is not selective and usually, bring with its multifold side effects which decrease the patient’s quality of life. For this reason, is searched to develop drug delivery systems which let the drug release in the target site decreasing in this form dose and side effects.2,3 One of the most promising drug delivery systems are the systems based on the hybrid of molecularly imprinted polymers (MIP´s) with magnetic nanoparticles as magnetite (Fe3O4).4,5 The magnetic molecularly imprinted polymers (MMIP´s) combine the magnetic properties from nanoparticles with the high capacity of recognize from MIP´s in an only hybrid structure functional which let to obtain a system whose drug delivery is only in the target site improving the drug efficiency and resulting in a reduction of the side effects on normal tissues. In this work is presented the synthesis and characterization of a magnetic MIP system for the selective recognition of the antitumoral drug 6-mercaptopurine and its evaluation as a drug delivery system. Methodology: The synthesis of magnetite nanoparticles has been carried out by the coprecipitation method. The particles were coated with the polymer by non-covalent molecularly imprinted technique, four different functional monomers were evaluated. The systems were characterized and carried it out the adsorption studies. Finally, the in vitro release of 6-mercaptopurine was studied evaluating the effect of the magnetic hyperthermia with alternating magnetic field. Conclusion: the magnetic nanoparticles were successfully coated with different polymers. Differences in the amount of drug adsorbed were observed in the different systems showing all these Isotherms like Langmuir-Freundlich. The evaluation of drug release showed differences when the systems were exposed under an alternate magnetic field.

Natalia Skinder is a Master student completing her project in the Department of Protein Engineering at the University of Wroclaw. The research she is involved in currently is focusing on development of anticancer targeted therapies using cytotoxic conjugates as basis for the treatment.

Fibroblast growth factor receptors, involved in progression and development of certain types of cancer, are currently being targeted by multitude of different anticancer therapies. The goal of our project is to develop cytotoxic conjugates, in a format of peptibody conjugated with monomethylauristatin E (MMAE), that would target FGFR-expressing cancer cells. The natural ligands of FGF receptors – FGFs – are screened in this project to isolate binding regions interacting with receptor and minimize these regions down to linear peptides, which will be then reformatted into Fc-fusions, ie. peptibodies. Peptibodies showing FGFR-dependent internalization will be conjugated with the cytotoxic drug and tested for the FGFR-specific cytotoxic effect on cells. We have already shown that two of the FGF2 sequence-derived peptibodies are internalized into FGFR-expressing cells and, after conjugation with the cytotoxic drug, decrease their viability down to 20%. The peptibody conjugated with a drug functions as a selective drug-delivery system that shows a potential to reach its target without harming the neighboring cells. The results we show indicate that this format can work as a basis for targeted therapies aiming at cancer cell with the overexpression or malfunctioning of the FGFRs.

Natalie Perraudeau is an experienced Team Leader within Protagen Protein Services (PPS), a world leading CRO and recognized expert for analytical services in protein science. Ms Perraudeau is an immunologist and applied biology scientist by training and serves as a specialist for protein analysis regarding higher order structure, glycosylation, charge variants and protein stability. Together with her team she offers a broad range of services, from drug discovery and development, to release testing and regulatory compliance applying CD, DSC, Edman, HILIC, IEX analysis methods and ELISA tests.

Protagen Protein Services (PPS) is a world leading CRO and recognized expert for protein analytical services in the biopharmaceutical field. With two sites in Germany and since very recently a third site in Boston US we have more than 20 years’ experience in supporting customers in the biopharmaceutical, biotech and life science industry. We are partnering them throughout the entire process ranging from candidate selection to development and further to approval and GMP compliant release testing. The integrity of an API is essential for its required efficacy and safety. This integrity depends on the stability, secondary and tertiary structure, aggregation behavior and concentration of the developed molecule, factors which are highly influenced by the formulation of the API. We address such critical quality attributes by applying state of the art analysis techniques: During formulation studies orthogonal methods are used: To address aspects of higher order structure we apply orthogonal methods like FT-IR analysis in aqueous solution, CD analysis and fluorescence scan. Stability is elucidated by DSC equipped with autosampler, enabling high throughput screening. To assess aggregation behavior, we use highly sensitive DLS and AUC methods as well as SEC-methods equipped with MALLS detection and AF4-MALLS providing a broad range of orthogonal methods for detailed characterization. To precisely determine concentration, we offer AAA or HPLC and photometric techniques. As an expert in all these methods PPS is constantly extending its method portfolio and expertise to steadily improve our support in the formulation field for our sponsors. The poster presentation will illustrate the broad portfolio of methods available at PPS for formulation studies. If you are searching a partner in this field, please contact us. We are delighted to find the right answers to your questions in biopharmaceutical formulation analysis.