10^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems March 13-15, 2017 London, UK

Yoshihiro Takatsu has completed his Ph.D. at Hokkaido University. After working for Takeda Pharmaceutical Company Limited as a principal research scientist for 9 years, he moved to Seikagaku Corporation and has been developing ChonylationTM technology as a associate chief researcher at Glyco Research Department in Central Research Laboratory.

PEG has become the gold standard polymer extending the circularly stability of conjugated therapeutics. However, repeated administration of PEGylated proteins to animals has in some cases been associated with cellular vacuolation of macrophages, histiocytes, renal tubular cells and choroid plexus ependymal cells. In addition, immune responses to PEG itself have been recognized and have caused a loss of therapeutic efficacy. CH is the naturally-occurring biodegradable sugar chain which consists of repeated disaccharide units of D-glucuronic acid and N-acetyl-D-galactosamine. We found that i.v.-injected CH circulated surprisingly for a long period as well as PEG in mice. Consequently, we have been developing ChonylationTM technology comprising conjugation of CH to protein and peptide therapeutics. CH-conjugated asparaginase (CH-Asp) showed a good pharmacokinetic profile (T1/2 = 35.2 hours, MRT = 48.7 hours) although asparaginase (Asp) itself disappeared from the circulation within 24 hours. Similarly, ChonylationTM improved pharmacokinetics of various kinds of protein and peptide, including ovalbumin, interferon α, growth hormone, GLP-1, and insulin. To evaluate the influence of ChonylationTM to the immunogenesity of foreign protein, Asp, PEGylated Asp (Oncaspar®) and CH-Asp were repeatedly injected via the intramuscular route. Asp-treated group induced high immune responses against Asp. Oncaspar®-treated group induced immune responce to PEG but not to Asp. In contrast, CH-Asp induced no immune responces, neither to Asp nor to CH. ChonylationTM technology will be a new generation drug delivery system for protein and peptide therapeutics with significantly improved pharmacological profiles.

Shayan F. Lahiji has completed his education at Yonsei University (South Korea) with outstanding contributions to science and novel drug delivery systems. Due to his various achievements in science, Dr. Lahiji was invited to a wide range of conferences and congresses around the world to participate, present his scientific findings and share his knowledge of novel drug delivery systems with other scientists. So far he has been awarded for “the best researcher”, “the best research awards”, “the best poster presentation”, “the best academic poster” and more. Beside the high impact papers he published over the past few years in reputed journals, he has few patents related to novel drug delivery as well.

Lipophilic drugs require hazardous organic solvents for their solublization which makes it difficult to produce a non-toxic drug for pharmaceutical market. Therefore, recently there were various researches regarding solvent free systems. In this study we developed a solvent-free lipophilic drug delivery system via creating nano-sized colloidal structures and fabrication of dissolving microneedles (DMNs). DMNs are currenly bein used in various research fields such as vaccine delivery, cosmetic application and biological drug delivery. This delivery system provides advantages over topical application as well as hypodermic drug delivery systems, Here, we investigated effects of capsaicin on the mice with rheumatic arthritis by comparing DMN based solvent-free lipophilic delivery system and solvent-based system. Results showed a promising potential of our newly developed system compared with conventional systems used for solvent-free lipophilic drug delivery.

Chrow Khurshid has her master degree in biochemistry field; she started her PhD in biomedical and cancer research department at school of Environment and Life Science University of Salford Manchester in 2013. She gained experiences in biochemistry, biomedical and cell culture labs during her project, demonstrations for undergraduate students, training courses and collaboration with other scientist inside UK and US.

Marine biology is an exceptional rich source of many biological and chemical active compounds; they have important values in pharmaceutical industry, nutrition, cosmetic and medical fields as alternative source for the treatment of many diseases. Almost each class revels individually unique structure from other kinds or species. Approximately 24 percent from opisthobranch molluscs has been isolated, with focusing on invertebrate phyla that have soft bodies, researchers reported of almost 10 percent increase in new found compounds per year. In this project, identification of novel structure of GAG polysaccharide and tumour regulatory sequences within GAG chains extracted from an invertebrate belonging to mollusc family is addressed, this involved the examination of their activity as anticancer bioactive compounds, following by structure elucidation using enzymatic degradation and structural analysis of the sulphated oligosaccharide chains. This process produced complex mixtures of GAG derived oligosaccharides, which can be evaluated to identify the minimal binding sequences required for anticancer activity. Variety of cancer cell lines including triple negative breast cancer cell lines are used as in vitro model to identify the anti-cancer activity of GAG- derived oligosaccharides. Understanding the cellular mechanism by which GAG- derived cause apoptosis in breast cancer is exclusively exanimated by advanced proteomics LC-MS/MS technologies and pathway analysis

Stephen Rumbelow is the Research and Technology Manager for Croda Inc., managing research programs in Health Care and Analytical Chemistry. He developed his expertise, through providing claims substantiation data supporting the development of high performance excipients for the pharmaceutical industry. In this role, Stephen is responsible for developing an integrated R&D program provide timely data, technical support, and industry presence advancing Croda’s reputation within the Pharmaceutical Industry. The integration of both teams facilitates the selection, development and application of new methods and measurement techniques critical to value creation and retention.

MALDI-MS imaging has been successfully applied to demonstrate its utility of this technique for developing claims substantiation data on targeted drug delivery studies via topical applications. Data from Trans-epithelial Permeation (TEP) assays and microscopy demonstrated that Super-Refined Oleic Acid caused significantly less damage and disruption to human skin, compared to its standard grade counterpart, which was attributed to it containing significantly less potentially harmful impurities (eg aldehydes). The aim of this study was to see whether the reduction in degree of disruption to the skin structure impacted upon the permeation of an antifungal agent (terbinafine hydrochloride) using MALDI-MSI. Good quality ‘heat map’ images showing the degree of penetration of API into human skin (previously treated with solutions in two grades of excipient) were generated by MALDI MSI. This active could be detected with both excipients, even at low concentrations. Moreover, no significant difference was observed in the degree of penetration between the two grades of Oleic Acid. This data further supports the use of Super-Refined Oleic acid in topical applications, in demonstrating the benefits of minimising skin irritation without negatively impacting its permeation properties. Furthermore, additional studies in which penetration/permeation studies are combined with this imaging technique and histological measurements on potential changes to skin surface structure would also provide further insights into how different excipient/active combinations achieve effective penetration and permeation.

Yuhong Jiang is a PhD student from Institute for Molecular Bioscience (IMB), The University of Queensland. She majored in pharmaceutics, and main research focused on immunity and targeting gene/drug delivery system during three-year Master period. She got lots of valuable results and publications in adenoviral vector-based drug delivery. In 2014, she started her PhD study in Institute for Molecular Bioscience involves collaboration in diverse fields, such as chemistry, biology, immunology and pharmacology, which deeply inspire me. Her previous project is mainly on signalling pathway of a class of GPCR—PAR2, relevant functions and diseases in cancer. Currently, she has submitted PAR2 paper as first author to ACS journal.

Protease activated receptor 2 (PAR2) has been reported as a viable drug target as it is associated with many diseased states including inflammatory diseases, obesity, cancer and others. Cleavage of the N-terminus of PAR2 by different proteases at divergent sites has generated tethered ligands with distinct signaling profiles upon PAR2 activation, known as biased signaling, that can affect specific physiological functions in diseases. Structure-function profiling has now revealed two novel, small peptidic, biased agonists for PAR2. DF253 triggers calcium release (EC50 2.0 μM) in CHO-hPAR2 cells but does not induce ERK1/2 phosphorylation (EC50 > 100 μM). On the other hand, AY254 activates ERK1/2 phosphorylation (EC50 2 nM) more effectively than calcium signaling (EC50 80 nM). This different signaling bias leads to different functional responses in human colorectal carcinoma cells (HT29). AY254, but not DF253, attenuates cytokine-induced caspase 3/8 activation and promotes wound healing via PAR2-ERK1/2 signaling. These compounds and their analogues identify key molecular determinants responsible for specific PAR2 functions and represent new tools for interrogating PAR2 functions in physiology and disease. Further development of such potent small-molecule biased agonists/antagonists could lead to a selective PAR2-targeting Medicine.

Krisztian KVELL MD PhD has primary expertise in immunology and biotechnology. He works in the field of immune senescence and its relation to steroid compounds. Currently he is working at the Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, at the University of Pecs, Hungary. He is currently involved in interdisciplinary research utilizing steroid compounds and nanoparticles. This hot field encouraged the collaborative research team to develop novel drug delivery strategies of steroid treatment, to allow for targeted steroid treatment with potent anti-inflammatory effect, yet with reduced level side effects.

Statement of the Problem: Steroids are acknowledged anti-inflammatory drugs used in multiple conditions, including autoimmune disease. Steroids provide strong suppression of inflammation, however, their long-term utilization triggers numerous adverse effects including obesity, diabetes, osteoporosis, edema retention etc. As a result, only inflammatory flares are treated with steroid compounds, for short term. Methodology & Theoretical Orientation: Our collaborative research team has produced nanoparticles of specific size harboring steroid compounds. In theory, due their specific size steroid-harboring nanoparticles trigger phagocytosis in monocytes and macrophages, but leave other (non-phagocytic) cells unaltered. Findings: Our human in vitro data indicate that steroid particles show potent anti-inflammatory effect on monocytes / macrophages, equivalent to that of steroid solution. However, their adverse effects are reduced using non-phagocytic cells. Liver cells, for example, show increased viability with steroid particles as opposed to steroid solution (see image on right). Conclusion & Significance: Our working hypothesis was that steroid-particles of a specific size range can preferentially target monocytes / macrophages, the major mediators of inflammation. Other (non-phagocytic) cell types shall largely be unaltered by steroid particles, as opposed to steroid solution. This is confirmed by our data. Our technology allows for the production of regular steroid compounds with significantly reduced side effects, with the promise of long-term use in human.

Zhuangzhi Zhu graduated with a bachelor of bioengineering in School of Biopharmaceutics, China Pharmaceutical University in 2006, and received his doctoral degree in pharmaceutics (supervised by Prof. Hao Wang) from National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry in 2015. His research focuses on transdermal delivery system, especially in microneedles for biomacromolecules delivery and transcutaneous vaccination. He is now also focusing on novel solid oral drug delivery systems.

Recent large outbreaks of hand-foot-and-mouth disease (HFMD) have seriously affected the health of young children. Enterovirus 71 (EV71) is the main causative agent of HFMD. Herein, for the first time, rapidly dissolvable microneedles (MNs) loaded with EV71 virus-like particles (VLPs) were evaluated whether they could induce robust immune responses that confer protection against EV71 infection. The characteristics of prepared MNs including hygroscopy, mechanical strength, insertion capacity, dissolution profile, skin irritation and storage stability were comprehensively assessed. EV71 VLPs remained morphologically stable during fabrication. The MNs made of sodium hyaluronate maintained their insertion ability for at least 3 h even at a high relative humidity of 75%. With the aid of spring-operated applicator, EV71 MNs (approximately 500 μm length) could be readily penetrated into the mouse skin in vivo, and then rapidly dissolved to release encapsulated antigen within 2 min. Additionally, MNs induced slight erythema that disappeared within a few hours. More importantly, mouse immunization and virus challenge studies demonstrated that MNs immunization induced high level of antibody responses conferring full protection against lethal EV71 virus challenge that were comparable to conventional intramuscular injection, but with only 1/10th of the delivered antigen (dose sparing). Consequently, our rapidly dissolving MNs may present as an effective and promising transcutaneous immunization device for HFMD prophylaxis among children.

My main research is the fabrication, evaluation and application of environment-friendly agricultural inputs. The aim of the research was to improve the properties of agricultural input, including formulation function, efficacy, duration and environmental friendliness. (1) Construction of water-based delivery systems by increasing surface area of agricultural inputs to avoid using harmful solvent and enhance solubility, dispersibility and bioavailability of products. (2) Construction of controlled release systems of agricultural inputs using environment-friendly materials as carriers to extend duration and decrease usage of agrochemical like pesticides, fungicides, herbicides.The solid microemulsions of emamectin benzoate with the same content of surfactants were prepared in a self-emulsifying method. Emulsifier 600# and 700# (3/2, w/w) screened from eleven kinds of commonly used surfactants displayed great emulsifying properties. The re-dispersed solution of the solid microemulsion presented aqueous microemulsion characteristic. The mean particle size and polydispersity index were 10.34 ± 0.10 nm and 0.283 ± 0.013, respectively. The solid microemulsion showed excellent storage stability and the bioassay compared with water dispersible granules against diamondback moths provided a proof of its improved biological activities. This formulation could significantly reduce surfactants and is perspective in plant protection for improving bioavailability and environmental friendliness.

The solid microemulsions of emamectin benzoate with the same content of surfactants were prepared in a self-emulsifying method. Emulsifier 600# and 700# (3/2, w/w) screened from eleven kinds of commonly used surfactants displayed great emulsifying properties. The re-dispersed solution of the solid microemulsion presented aqueous microemulsion characteristic. The mean particle size and polydispersity index were 10.34 ± 0.10 nm and 0.283 ± 0.013, respectively. The solid microemulsion showed excellent storage stability and the bioassay compared with water dispersible granules against diamondback moths provided a proof of its improved biological activities. This formulation could significantly reduce surfactants and is perspective in plant protection for improving bioavailability and environmental friendliness.

SunChangjiao has got her Master Degree from Graduate School of Chinese Academy of Agricultural Sciences in 2010. Then she began to work in the Institute of Environment and Sustainable Development in Agriculture as a research assistant. Her main research area is the application of nanotechnology in agriculture. She has her expertise in characterization and evaluation of nano-delivery system. She established a method for the evaluation of the UV degradation and controlled release properties of the nano formulation. And she also established a method for evaluating the effect of surface groups of the carriers on drug loading.

The spiraling whitefly (Aleurodicusdispersus Russell) is an invasive and dangerous pest to agriculture and forestry which has invaded Taiwan and Hainan provinces. Due to the lack of effective ecological and physical control methods, chemical control is still an important mean for controlling the pest. In addition, the generation and resistance development of spiraling whitefly has become an important and unavoidable issue during the process of chemical control. The LC50 values of spiraling whitefly populations to pyrethroids were tested by Potter spray method. Those populations fed on different host plants were collected from different geographic regions. This study is aimed at understanding the resistance risk to pesticides, and further controlling the occurrence and development of resistance in field populations of spiraling whitefly

Yan Wang has her expertise in the fabrication of environment-friendly agricultural inputs. She is searching for the improvement of agricultural input formulation with perfect properties of water dispersion, chemical stability, efficacy, duration and degradation with small size, big surface area and target modification. Her research involves the construction of controlled release systems of agricultural inputs using environment-friendly materials as carriers, including porous structure, encapsulated structure, emulsive structure, etc.

Pesticide is the foundation for preventing major biological disasters and the safeguard of national food security. However, conventional pesticide formulation process has presented some serious disadvantages, such as use of harmful solvent, poor dispersion, dust drift, etc. Also, pesticide loss of up to 70-90% in the field spraying process has caused some serious social concerns in food safety and ecological environment. Therefore, developing an efficient, safe, and green pesticide formulation process has become a national and strategic need to protect the national food and ecological security through nano-delivery system of pesticides with nanotechnology to improve the efficacy and safety of pesticides. Advance of nanotechnology offers some new approaches for the pesticide development：1） developing novel formulations of high efficacy and safety pesticide；2）developing sustainable agriculture system；and 3）controlling pesticide food residues and environmental pollution. The pesticide nano-delivery systems will be comprehensively introduced with perfect properties of water dispersion, chemical stability，efficacy duration and degradation.

Xiang Zhao has his expertise in “The novel transformation platform technology using the magnetic nanoparticles as DNA carriers”. He has provided an important experimental basis for the application of MNPs for effective magnetofection and applications in the genetic transformation of plants and animals.

Modified magnetic nanoparticles are used as non-viral gene carriers in biological applications. To achieve successful gene delivery, it is critical that nanoparticles effectually assemble with nucleic acids. However, relatively little work has been conducted on the assemble mechanisms between nanoparticles and DNA, and its effects on transfection efficiency. Using biophysical and biochemical characterization, along with Atomic force microscopy (AFM) and Transmission electron microscopy (TEM), we investigate the morphologies, assembling structures and gene delivering abilities of the PEI modified magnetic nanoparticles (MNPs) gene delivery system. In this gene delivery system, MNP/DNA complexes are formed via binding of DNA onto the surface of MNPs. MNPs are favorable to not only increase DNA concentration but also prevent DNA degradation. Magnetofection experiments showed that MNPs has low cytotoxicity and introduces highly stable transfection in mammalian somatic cells. In addition, different binding ratios between MNPs and DNA result in various morphologies of MNP/DNA complexes and have an influence on transfection efficiency. Dose–response profile indicated that transfection efficiency positively correlate with MNP/DNA ratio. Furthermore, intracellular tracking demonstrate that MNPs move though the cell membranes, deliver and release exogenous DNA into the nucleus.

Melania F. MUNTEANU has completed his PhD at the age of 34 years from University of Medicine and Pharmacy Targu Mures (Romania). She is a Assoc prof of “Vasile Goldis” West University Arad (Romania), Health and environmental Chemistry discipline – Pharmacy Dept. She has published more than 20 papers in reputed journals.

Cardiovascular disease is the first cause of death; it kills more people than the next four causes of death summed every year (around 17 million deaths worldwide). It was proven that almost 80 % of heart diseases can be prevented if you pay attention to diet and the lifestyle that could favor the onset of these disorders. Spices like chilli pepper, cinnamon, ginger, garlic etc. can be ofen used to reduce LDL cholesterol and triglyceride levels, to dissolve blood clots, to purify the blood and to reduce the risk of irregular heart rhythms. Unfortunately, people rarely consume these spices due to their health problems (stomach ulcers or ulcerative colitis) or to the unpleasant odor which is known as 'garlic breath'. In this study, bioresorbable structures based on poly(ester-ether urethane) were synthesized using poly(epsilon-caprolactone)-poly(ethylene oxide) and hexamethylene diisocyanate as raw materials; ginger and/or hot pepper extracts were used as active substances. These polymer structures, a possible application as drug delivery system, were characterized by HPLC/MS analysis for determination of yield of encapsulation, thermal analysis for evaluation of products’ stability, Zetasizer analysis for determination of structures sizes and in vivo evaluations of skin parameters (erythema and transepidermal water loss) were done using SKH1 mice to observe the irritation potential of products. The results suggest that were been obtained non-irritative structures with sizes between 97 and 139 nm, almost homogeneous, with an important stability between 30 and 300 oC.

TBU

The objective of this work is to explore application of ultrasound energy for compression of a poorly compressible model molecule paracetamol. A static cell was designed for ultrasound irradiation of the samples. The effect of variables such as power and sonication time on the properties of the obtained paracetamol tablets was investigated. A paracetamol/PEG tablet with increased hardness and thickness was achieved as the sonication time increased; the PEG decreased the rate of drug release, which is advantageous for drug delivery.

Wooseong kim is a researcher with expert knowledge of inflammatory bowel disease (IBD) and colorectal cancer. He published several academic studies through the IBD model using rodent. His main field of interest is the cause and treatment of IBD. Through his research and training, he has the knowledge and experience of chemical knowledge and experimental techniques, biological research techniques and even animal experiments. With all of this, he is now challenging the development of new IBD treatments.

To improve the anticolitic efficacy of 5-aminosalicylic acid (5-ASA), a colon-specific mutual prodrug of 5-ASA was designed. 5-ASA was coupled to procainamide (PA), a local anesthetic, via an azo bond to prepare 5-(4-{[2-(diethylamino)ethyl]carbamoyl}phenylazo)salicylic acid (5-ASA-azo-PA). 5-ASA-azo-PA was cleaved to 5-ASA and PA up to about 76% at 10 h in the cecal contents while remaining stable in the small intestinal contents. Oral gavage of 5-ASA-azo-PA and sulfasalazine, a colon-specific prodrug currently used in clinic, to rats showed similar efficiency in delivery of 5-ASA to the large intestine, and PA was not detectable in the blood after 5-ASA-azo-PA administration. Oral gavage of 5-ASA-azo-PA alleviated 2,4,6-trinitrobenzenesulfonic acid-induced rat colitis. Moreover, combined intracolonic treatment with 5-ASA and PA elicited an additive ameliorative effect. Furthermore, combined treatment with 5-ASA and PA additively inhibited nuclear factor-kappaB (NFκB) activity in human colon carcinoma cells and inflamed colonic tissues. Finally, 5-ASA-azo-PA administered orally was able to reduce inflammatory mediators, NFκB target gene products, in the inflamed colon. 5-ASA-azo-PA may be a colon-specific mutual prodrug acting against colitis, and the mutual anticolitic effects occurred at least partly through the cooperative inhibition of NFκB activity.

Seongkeun Jeong is an expert of inflammatory bowel disease (IBD) with pathological knowledge and medication. He has studied in the field of medicinal chemistry & pharmacology for a decade. He has now researched in drug delivery and repositioning of several kinds of drug candidates for the treatment of IBD with using rodent model. He is especially interested in colon-targeted drug delivery by adopting unique strategies to minimize unwanted side effects and increase large intestine drug accumulation for intensifying therapeutic effectiveness. With all of this, he is now challenging the development of new IBD treatments.

Celecoxib is a selective cyclooxygenase-2 inhibitor applied to the treatment of arthritis. Repositioning the anti-inflammatory drug as an anti-inflammatory bowel disease drug has obstacles such as controversial anti-colitic efficacy and potential side effects. We examined whether colonic delivery of celecoxib could circumvent the therapeutic limitations. N-succinylglutam-1-yl celecoxib (SG1C), a colon-specific prodrug of celecoxib), was administered orally to rats with colitis and the anti-inflammatory activity and pharmacologic mechanisms were investigated. SG1C alleviated the colonic injury and lowered myeloperoxidase activity in the inflamed colonic tissues much more effectively than conventional celecoxib. While suppressing expression of pro-inflammatory nuclear factor kappaB gene products including cyclooxygenase-2, SG1C elevated an anti-inflammatory nuclear factor-erythroid 2 p45 (NF-E2)-related factor 2 (Nrf2) and its target gene product heme oxygenase (HO)-1 in the inflamed colon. In contrast, no significant molecular effects were observed with conventional celecoxib. Unlike conventional celecoxib, SG1C did not lower the serum level of 6-keto-PGF1α, an inverse indicator of cardiovascular adverse effects. Collectively, colonic delivery of celecoxib, likely improving therapeutic and toxicological properties of celecoxib, may be a feasible pharmaceutical strategy to therapeutically switch celecoxib to an anti-colitic drug.

Dohoon Kim is a researcher with knowledge based on Chemistry and Biology. He is researching and studying about prodrugs which is targeting to large intestine and cause and treatment of intestinal bowel disease(IBD). He has the experiences of chemical and biological knowledge and experimental techniques through his research. He is now keep studying and researching to extend chemical and biological knowledge and experimental techniques.

Metronidazole (MTDZ), the drug of choice for the treatment of protozoal infections such as luminal amebiasis, is highly susceptible to colonic metabolism, which may hinder its conversion from a colon-specific prodrug to an effective anti-amebic agent targeting the entire large intestine. Thus, in an attempt to control the colonic distribution of the drug, a polymeric colon-specific prodrug, MTDZ conjugated to dextran via a succinate linker (Dex-SA-MTDZ), was designed. Upon treatment with dextranase for 8 h, the degree of Dex-SA-MTDZ depolymerization (%) with a degree of substitution (DS, mg of MTDZ bound in 100 mg of Dex-SA-MTDZ) of 7, 17, and 30 was 72, 38, and 8 respectively, while that of dextran was 85. Depolymerization of Dex-SA-MTDZ was found to be necessary for the release of MTDZ, because dextranase pretreatment ensures that de-esterification occurs between MTDZ and the dextran backbone. In parallel, Dex-SA-MTDZ (DS 17) was found not to release MTDZ upon incubation with the contents of the small intestine and stomach of rats, but released MTDZ when incubated with rat cecal contents (including microbial dextranases). Moreover, Dex-SA-MTDZ exhibited prolonged release of MTDZ, which contrasts with drug release by small molecular colon-specific prodrugs, MTDZ sulfate and N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-D,L-glycine. These prodrugs were eliminated very rapidly and no MTDZ was detected in the cecal contents. Consistent with these in vitro results, we found that oral gavage of Dex-SA-MTDZ delivered MTDZ [as MTDZ conjugated to (depolymerized) dextran] to the distal colon. However, upon oral gavage of the small molecular prodrugs, no prodrugs were detected in the distal colon. Collectively, these data suggest that dextran conjugation is a potential pharmaceutical strategy to control the colonic distribution of drugs susceptible to colonic microbial metabolism.

Yejin Yang belongs to the laboratory of bio-medicinal chemistry at Pusan National University in South Korea. She has studied in the field of colon-associated diseases such as colitis, colon cancer and inflammatory bowel diseases (IBD). She is trying to collect data through various experiments for the treatment of IBD with using rodent. She is to develop colon-targeted drug delivery by adjusting unique strategies to minimize unwanted side effects and increase therapeutic effects. She keeps studying to develop useful IBD treatments.

Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.

TBA

Background We have identified a novel peptide, derived from a cell matrix protein, which inhibits multiple receptors known to be up regulated in tissues from a wide variety of cancers. While the peptide inhibits tumour growth in vivo, it is not cytotoxic and eventually the tumours regrow. In order to increase the therapeutic efficacy of the peptide, we aimed to exploit this receptor specificity to target PEGylated liposomes containing the cytotoxic drug, doxorubicin (Doxil®) to tumour tissue. Method Azide functionalised, FITC-Labelled-peptide with a polyethylene glycol (PEG12) spacer was conjugated to dibenzocyclooctyl (DBCO) functionalised Doxil® by click chemistry and coupling determined by flow cytometry. Binding of the product (Doxil-Peptide) to primary human dermal microvascular endothelial cells (HDMEC), and human (MCF-7) and mouse breast tumour (4T1) cell lines, was determined by flow cytometry and internalisation of both peptide and doxorubicin determined by confocal microscopy. The effect of increasing concentrations of peptide alone, Doxil or Doxil-Peptide on the viability of MCF-7, HDMEC and 4T1 cells was assessed by cytotoxicity (MTS) assay. Result The peptide was efficiently coupled to Doxil®. Doxil-Peptide retained its receptor binding profile. In contrast to Doxil alone, it was rapidly internalized by mouse (4T1) and human (MCF7) breast cancer cells with Doxil-Peptide showing an approximately 100-fold increase in uptake relative to Doxil alone. Internalisation by normal human dermal microvascular vascular endothelial cells was much lower than cancer cells. Furthermore, this enhanced uptake increased the sensitivity of breast cancer cells to Doxil. Conclusion Conjugating this novel peptide to Doxil® greatly increases internalisation of the cytotoxic drug, potentially resulting in increased tumour specificity which should, in turn, decrease off target effects.

Sophie Franceschi has her expertise in “Chemical and physicochemical studies of organized molecular systems for drug delivery and material applications”. She has 20 years of experience in Research and Teaching. She completed her Graduation and PhD at Paul Sabatier University of Toulouse (France) in 1997 and completed her Master’s Degree in Molecular and Supramolecular Chemistry. Currently, she is a Researcher in SMODD group in the IMRCP laboratory at Paul Sabatier University of Toulouse and also a teacher at Paul Sabatier University.

In recent years, a growing interest has emerged in the development of semi-solid colloidal careers for the delivery of water-insoluble drugs. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Careers (NLC) are example of such systems. As an alternative to SLN, we propose the use of an original family of organogel nanoparticles. Organogels are semi-solid materials in which an organic solvent (e.g., vegetable oil) is entrapped in the three-dimensional fibrous network formed by self-aggregation of a low molecular mass organic gelator (12-hydroxystearic acid). The preparation process of the gelled oil nanoparticles is based on the sol-gel phase transition of the organogel obtained by hot emulsification (T°>T°gel) in presence of an aqueous solution of stabilizing agent (polyvinyl alcohol 80), leading to a stable semi-solid dispersion after cooling (T°

Nachal Subramanian has a PhD in Chemical Engineering with major areas of specialization being catalysis, materials synthesis & characterization, surface science, and reaction kinetic studies. She has five years of postdoctoral experience and is currently the Scientist-Business Development for UK and Benelux regions at Surface Measurement Systems Ltd, UK. SMS develops and engineers innovative experimental techniques and instrumentation for physico-chemical characterization of complex solids, namely, Dynamic Vapor Sorption (DVS) and Inverse Gas Chromatography – Surface Energy Analyzer (iGC-SEA) techniques.

Dynamic Vapour Sorption (DVS) has been widely used for investigating the interaction of water vapour with active pharmaceutical ingredients (API’s), excipients and pharmaceutical formulations. The moisture sorption properties of these materials are recognized as critical factors in determining their storage, stability, processing and application performance [1]. A few pharmaceutical-related applications of DVS include hygroscopicity, moisture content, moisture-induced phase transitions, hydrate formation/loss, and amorphous content. DVS is a well-established method for the determination of vapour sorption isotherms. It is based on a highly sensitive gravimetric system, which measures the adsorption and desorption of extremely small amounts of probe molecule. The ability to use organic vapours besides water allows the DVS instrument to be used for some unique applications. The instrument also has the ability to couple in-situ video microscopy and spectroscopy (Raman and/or Near-IR) with the gravimetric sorption measurements which allows for the investigation of vapour-induced morphological and structural changes in the material. The presentation will describe the operation of the DVS and show some applications to illustrate how the DVS technology could be applied to a wide range of pharmaceutical materials and drug delivery.

Dr Rana M. Obaidat is the vice dean of faculty of pharmacy at Jordan University of Science and Technology. She has her expertise in the area of pharmaceutical technology. Her research focused on preparation of sustained release formulations, preparation of buccal and transdermal patches, enhancement of dissolution of class II drugs, physicochemical characterizations, polymorphism, and solid state stability. She is working currently in the area of supercritical fluid technology with focus on pharmaceutical applications of this technology such as preparation of pulmonary drug carriers using supercritical fluid technology.

Supercritical fluid technology (SFT) method offered many advantages in the pharmaceutical area for heat sensitive materials, drying process and preparation of carriers and recently for solid dispersions. The aim of this study was enhancement of dissolution for Atorvastatin as class II model drug. SFT was employed in sample preparation. Selected polymers were polyvinylpyrrolidine (PVP K30), polyethylene glycol (PEG 6000), Soluplus®, and chitosan. Full physicochemical characterizations including in-vitro release were performed. The drug was mixed physically with one of the polymers (PVP K30, PEG 6000, soluplus or chitosan carrier) to produce mixture of drug to polymer in ratio of (1: 9). Then it was processed by SFT apparatus. The overall loading efficiency for all prepared SDs were very good with values higher than 59%. Enhancement of rate of dissolution was achieved in the prepared dispersions. The drug was precipitated as crystalline form in all prepared dispersion. Drug peaks appeared in FTIR for all PMs and SDs indicating absence of chemical interaction between the drug and the polymers though weakening of (N-H stretching bond) indicated possibility of interaction between atorvastatin with Soluplus®. SEM analysis for PVPK30, and PEG 6000 dispersions suggested deposition of the drug particles on the surface of the polymer. On the other hand, SD prepared using Soluplus® shows that the surface of the polymer has been foamed and bubbles have been formed. While the particles of the drug were observed clearly in porous structure of chitosan carrier with powder X-ray diffraction indicating the crystalline nature of the drug. All prepared dispersions showed chemical stability except for PVP dispersions which formed stick paste. In conclusions, enhancement of dissolution was achieved through preparation of solid dispersions using SFT solvent free method.

Mai Khanfar has her expertise in the formulation and enhancement of solubility of poorly soluble drugs. She has many publications on the enhancement of solubility of drugs using many methods like liquisolid method, surfactant use and the use of silica polymers and inulin to enhance the solubility.

Introduction: Liquisolid technique is a powdered solution technology used to convert a liquid medicament into an acceptably flowing & compressible powder by physical blending with selected excipients (1). Methods and Materials: In this study the Ezetimibe will be used with new co-processed excipients (compacted Chitin Magnesium silicate and/or Mannitol & their physical mixtures) & compared to Avicel® PH101 & Aerosil®200 that were used in the original mathematical method of Spireas et.al (1998) with the aim of having a novel multifunctional excipient that act as carrier, coating, disintegrant at the same time, thus reducing cost & drug excipient interactions. Results and Discussion: Compacted powder blends containing different ratios of Chitin, Magnesium silicate & /or Mannitol were prepared using roller compacter and tested for their surface area, particle size & flowability to be compared with Avicel and then liquisolid compacts were prepared according to Spireas . For all prepared liquisolid formulation, interactions between the drug & selected excipients had been detected by a lot of techniques. Co- processing of excipients using roll compactor has a remarkable improve in the flowability, and compressibility of the powder. Conclusion: The best dissolution profile was achieved by using the compacted Chitin: Mannitol (20:80)

I graduated from Ege University Faculty of Science Department of Chemistry. I did my master degree in Ege University Faculty of Pharmacy Department of Pharmaceutical Technology. I conducted my graduate thesis on Aristotle University (October 2014- December 2014) for development micro/ nano emulsification’s pellet formulation. I was scholarship student of the project from “THE SCIENTIFIC AND TECHNOLOGICAL RESEARCH COUNCIL OF TURKEY (TUBİTAK). I’m currently working in drug development and research center called ARGEFAR in Ege Univesity as a Chemist and drug development researcher and doing pH.D. studies in Ege University Faculty of Pharmacy Department of Pharmaceutical Technology. Working in ARGEFAR; Mastersizer, Zetasizer, spray dryer, microfludics, TGA, DSC, dissolution , HPLC.

Atorvastatin Calcium (AtrCa) is a BCS class 2 classification group and displays low resolution with high permeability. AtrCa has almost 14 % bioavability absolutely. The aim of this study is to development and validate an analytical method for oral delivery of AtrCa in pharmaceutical dosage form. The HPLC system consisted of a gradient pump, thermostable column department and a UV detector supplied by Agilent 1100. The column was a C18 column (5µm, 150x4,6mm) (ACE). All UV-Vis spectrums were moniterized between 200-400 nm and quantification was performed at 238 nm. The injection volume was 20µL and the retention time of AtrCa was about 7.1 min. The mobil phase was mixture of acetonitrile and 0.1 M sodium dihydrogen phosphate (55:45) (v/v) and adjusted to pH 3 with trifluoroacetic acid (1 mL) pumped at 1 mL/min. The HPLC method was validated partially with respect to linearity, limit of detection (LOD) and quantitation (LOQ), precision and accuracy. The linearity between peak area and concentration was analyzed using three calibration curves obtained in the different days with standard solutions of AtrCa at eleven different concentrations ranging from 0.065 to 20 ppm for AtrCa. Data indicate that AtrCa peak area is linear over concentration range of 0.065-20 ppm. The R2 for regression line is 0.999 with slope of 61.428 and y + intercept of 15.33. LOD was found 0.429 µg /mL and LOQ was found 1.30 µg/mL. In conclusion, an efficient high performance liquid chromatographic method was developed and validated method described is suitable for oral delivery of AtrCa.

Irfan Akartas was graduates in Hacettepe University Faculty of Pharmacy in Ankara. He has started PhD in Ege University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry in Izmir. He has studying about polymeric micelles with Cisplatin for the treatment of ovarian cancer with his Phd thesis.

Surfactant solutions which are prepared by different concentrations, could show rapid changes of its osmotic pressure, conductivity, turbidity and surface tension at higher concentrations. McBain associated these rapid changes with the formation of micelles or aggregates. The lyphophyllic hydrocarbon chains which have hydrophyllic groups that interacts with water phase, move to the inner part of the micelles. The critical micelle concentration (CMC) is defined as the concentration of surfactants above which micelles form and all additional surfactants added to the system go to micelles. The aim of this study is determination of critical micelle concentration of lipid based system with cisplatin by surface tension method. Isopropyl myristate was used as the oil phase, Kolliphor were used as the surfactant, propylene glycol was used as the co-surfactan to produce lipid based system. Surface tension is typically measured in dynes/cm, the force in dynes required to break a film of length 1 cm. There are several methods to measure the surface tension such as Wilhelmy plate, capillary rise method, drop weight method. In this study Traube Stalogmometre is used for drop weight method. Water, HCl buffer with pH 1,2 and phosphate buffer with pH 6,8 were used as solvents. 0.24x10-3, 1.2x10-3, 2x10-3, 4x10-3 ve 6x10-3 g/ml concentrations of smedds with cisplatin are prepared to measure surface tension in these solvents.

Salma Mohyeldin is interested in pharmaceutical nanotechnology and non-invasive drug delivery systems with a particular emphasis on tailoring liposomes and nano-carriers for various drugs through different routes of administration. I’m highly experienced in elaboration and appraisal procedures and techniques of nano- and micro-sized pharmaceutical carriers among them; nanoliposomes, nanoparticles, nanocrystals, nanocapsules, microporous silica and micelles. Mathematical optimization and assessment of delivery systems covers various routes of administration such as oral, transdermal and pulmonary are considered an area of my specialty.

The present chapter aimed to elaborate novel self-assembled liquid crystalline nanoparticles (LCNPs) for management of hormonal disturbances following non-invasive transdermal delivery of progesterone. The LCNPs bearing progesterone were prepared via a simple processing technique utilizing different glyceryl monoglycerides. Fabrication and optimization of progesterone-loaded LCNPs were assessed via a quality by design approach based on 23 full factorial design. The design includes the functional relationships between independent processing variables and dependent responses of particle size, polydispersity index, zeta potential, % cumulative drug release after 24 h and ex-vivo transdermal steady flux. Morphological elucidation of the prepared novel system was examined using transmission electron microscopy. The developed nanocarrier was subjected to a stability study within a period of 3 months at different storage temperatures. The cubic phase of LCNPs was successfully prepared using GMO (glyceryl monooleate) via the emulsification technique. Based on the factorial design, the independent operating variables significantly affected the five dependent responses. The diameters of the prepared cubosomes were in the nanometric range (101-386 nm) with a narrow particle size distribution, high negative zeta potential ≥ -30 mV and entrapment efficiency ≥ 94%. The LCNPs succeeded in sustaining the drug release for almost 24 h, following a non-Fickian transport of drug diffusion mechanism. Ex-vivo study revealed a significant enhancement up to 6 folds in the transdermal permeation of progesterone-loaded LCNPs compared to the aqueous drug suspension. The optimized LCNPs exhibited a high physical stability profile while retaining the cubic structure for at least 3 months. In conclusion, a quality by design approach successfully accomplished a predictable mathematical model permitting the development of novel LCNPs for transdermal delivery of progesterone with the benefit of reducing its oral route hazards.

Mohd Basyaruddin Abdul Rahman has completed his PhD at the age of 25 years from University of Southampton and postdoctoral studies from Institute of Structural and Molecular Biology, University of Edinburgh. He was the director of Malaysia Genome Institute, and currently the Deputy Dean of Faculty of Science, Universiti Putra Malaysia. His research areas include biocatalysis, protein chemistry, nanobiotechnology and computational chemistry. He has published more than 200 papers in reputed journals and filed more than 20 patents. He is the Fellow of Royal Society of Chemistry and Fellow of Academy of Sciences Malaysia.

Quercetin is a hydrophobic drug commonly studied and used to treat lung cancer. However, poor hydrophilicity leads to low solubility and hinders its application in water-based formulation. Oil-in-water (o/w) nanoemulsion is capable of delivering poorly water-soluble drugs. D-optimal mixture design was used to optimize the particle size of quercetin (QT) nanoemulsions for lung cancer by aerosols delivery. A very small droplet size of emulsion can provide an effective encapsulation for delivery system in the body. The formulation was carried out using low and high pressure homogenizer. The effects of palm oil esters:ricinoleic acid, lecithin, Tween 80, glycerol, and water on the droplet size as a response were studied. Under optimum formulation, the corresponding predicted response value for droplet size was 109.05 nm, excellent agreement with the actual value (109.12 nm) with residual standard error, 0.06%. Volume median diameter of nanoemulsion was 4.907 ± 0.067 μm. These results suggest that quercetin nanoemulsion in this study is ideal for pulmonary delivery.