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Shayak Samaddar, Joshua Mazur, Devin Boehm, David H Thompson Department of Chemistry, Purdue University, Bindley Bioscience Center, West Lafayette, Indiana 47906, USACorrespondence: David H ThompsonDepartment of Chemistry, Purdue University, Bindley Bioscience Center, 1203 W. State St., West Lafayette, Indiana 47906, USATel +1 765-494-0386Email davethom@purdue.eduBackground: Bladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site.Materials and methods: A dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI2.5kD) followed by coating of the polyplex using lipid membranes. The resulting lipid-coated polyplex (LCP) formulations are targeted to bladder cancer cells by employing a bacterial adhesive peptide sequence, RWFV, that targets the LCP to the tumor stroma for efficiently delivering reporter plasmid, EGFP-NLS and a model small molecule drug, pyrene, to the cancer cells.Results: Encapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 μg/mL, whereas the empty and non-targeted formulations did not result any significant cell death.Conclusion: These results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.Keywords: dual delivery, bladder cancer, gene therapy

Jennifer L Ridgeway,1,2 Jason S Egginton,1,2 Kristina Tiedje,3 Mark Linzer,4,5 Deborah Boehm,4 Sara Poplau,6 Djenane Ramalho de Oliveira,7 Laura Odell,8 Victor M Montori,2,9 David T Eton1,2 1The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 2Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 3Department of Anthropology, Université Lumière Lyon 2, Lyon, France; 4Division of General Internal Medicine, Hennepin County Medical Center, 5University of Minnesota Medical School, 6Minneapolis Medical Research Foundation, Minneapolis, MN, USA; 7Department of Social Pharmacy, Universidade Federal de Minas Gerais, Brazil; 8Pharmacy Services, 9Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA Purpose: Patients with multiple chronic conditions (multimorbidity) often require ongoing treatment and complex self-care. This workload and its impact on patient functioning and well-being are, together, known as treatment burden. This study reports on factors that patients with multimorbidity draw on to lessen perceptions of treatment burden. Patients and methods: Interviews (n=50) and focus groups (n=4 groups, five to eight participants per group) were conducted with patients receiving care in a large academic medical center or an urban safety-net hospital. Interview data were analyzed using qualitative framework analysis methods, and themes and subthemes were used to identify factors that mitigate burden. Focus groups were held to confirm these findings and clarify any new issues. This study was part of a larger program to develop a patient-reported measure of treatment burden. Results: Five major themes emerged from the interview data. These included: 1) problem-focused strategies, like routinizing self-care, enlisting support of others, planning for the future, and using technology; 2) emotion-focused coping strategies, like maintaining a positive attitude, focusing on other life priorities, and spirituality/faith; 3) questioning the notion of treatment burden as a function of adapting to self-care and comparing oneself to others; 4) social support (informational, tangible, and emotional assistance); and 5) positive aspects of health care, like coordination of care and beneficial relationships with providers. Additional subthemes arising from focus groups included preserving autonomy/independence and being proactive with providers. Conclusion: Patients attempt to lessen the experience of treatment burden using a variety of personal, social, and health care resources. Assessing these factors in tandem with patient perceptions of treatment burden can provide a more complete picture of how patients fit complex self-care into their daily lives. Keywords: adherence, patient-centered, minimally disruptive medicine, patient preferences

Bromodomains are conserved protein modules of ~110 amino acids that bind acetylated lysine residues in histone and non-histone proteins. Bromodomains are present in many chromatin-associated transcriptional regulators and have been linked to diverse aspect