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Yun Liu,1,2 Timo Hamm,3 Thomas Ralf Eichinger,3 Walter Kamm,3 Heike Andrea Wieland,3 Brigitta Loretz,1 Anna KH Hirsch,2,4 Sangeun Lee,1,2 Claus-Michael Lehr1,2 1Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany; 2Department of Pharmacy, Saarland University, Saarbrücken, Germany; 3Department of Research and Development, Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany; 4Department of Drug Design and Optimisation, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, GermanyCorrespondence: Claus-Michael Lehr, Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany, Tel +49 681 98806-1000, Fax +49 681 98806 1009, Email Claus-Michael.Lehr@helmholtz-hips.de Sangeun Lee, Department of Pharmacy, Saarland University, Saarbrücken, Germany, Tel +49 681 302 4764, Fax +49 681 302 2028, Email Sangeun.Lee@uni-saarland.deBackground: Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of protein release pose significant challenges due to the extensive range of physicochemical properties inherent to proteins. The development of a comprehensive protein delivery strategy becomes imperative accounting for the diverse nature of therapeutic proteins.Methods: Biodynamers are amphiphilic proteoid dynamic polymers consisting of amino acid derivatives connected through pH-responsive dynamic covalent chemistry. Taking advantage of the amphiphilic nature of the biodynamers, PNCs and DEs were possible to be prepared and investigated to compare the delivery efficiency in drug loading, stability, and cell uptake.Results: As a result, the optimized PNCs showed 3-fold encapsulation (< 90%) and 5-fold loading capacity (30%) compared to DE-NPs. PNCs enhanced the delivery efficiency into the cells but aggregated easily on the cell membrane due to the limited stability. Although DE-NPs were limited in loading capacity compared to PNCs, they exhibit superior adaptability in stability and capacity for delivering a wider range of proteins compared to PNCs.Conclusion: Our study highlights the potential of formulating both PNCs and DE-NPs using the same biodynamers, providing a comparative view on protein delivery efficacy using formulation methods. Keywords: amphiphilic polymer, nanocomplex, double emulsion, pH-responsive, protein delivery, dynamic covalent chemistry

Ahmad Haffar,1 Alexander Hirsch,1 Christian Morrill,1 Adelaide Garcia,1 Zachary Werner,2 John P Gearhart,1 Chad Crigger1 1Robert D. Jeffs Division of Pediatric Urology, James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Johns Hopkins Medical Institutions, Charlotte Bloomberg Children’s Hospital, Baltimore, MD, USA; 2West Virginia University School of Medicine, Department of Urology, Division of Pediatric Urology, Morgantown, WV, USACorrespondence: Ahmad Haffar, The Johns Hopkins University School of Medicine, The James Buchanan Brady Urological Institute, Robert D. Jeffs Division of Pediatric Urology, Charlotte Bloomberg Children’s Center, Baltimore, MD, 21287, USA, Tel +1 (304) 993-2237, Email ahaffar1@jh.eduPurpose: This study examines the readability of online medical information regarding cloacal exstrophy (CE). We hypothesize that inappropriate levels of comprehension are required in these resources, leading to poor understanding and confusion amongst caregivers.Methods: The Google and Bing search engines were used to search the terms “cloacal exstrophy” and “cloacal exstrophy treatment”. The first 100 results for each were collected. Each webpage was analyzed for readability using four independent validated scoring systems: the Gunning-Fog index (GFI), SMOG grade (Simple Measure of Gobbledygook), Dale-Chall index (DCI), and the Flesch-Kincaid grade (FKG).Results: Forty-seven unique webpages fit the inclusion criteria. Mean readability scores across all websites were GFI, 14.6; SMOG score, 10.8; DCI, 9.3; and FKG, 11.8, correlating to adjusted grade levels of college sophomore, 11th grade, college, and 11th grade, respectively. There were significant differences across all readability formulas. Non-profit websites were significantly less readable than institutional and commercial webpages (GFI p = 0.012, SMOG p = 0.018, DCI p = 0.021, FKG p = 0.0093).Conclusion: Caregiver-directed health information regarding CE and its treatment available online is written at the 11th grade reading level or above. Online resources pertaining to CE must be simplified to be effective.Plain Language Summary: Cloacal exstrophy is a rare severe birth defect that does not always show up in prenatal screening. Parents are often unfamiliar with this disease and must learn about the disease, procedures, and outcomes their child may have in a short amount of time. Online medical information has been recommended to be written at a 6th grade reading level so that the general public may understand. The authors of this study wanted to investigate if average websites that parents might find using common search engines would be easily understood. The authors used different search phrases on Google and Bing search engines, and used them to look at the top 100 search results for each. The text from each page was graded based on 4 different readability scoring systems. The authors found 47 unique webpages that matched the criteria and found that most pages had reading levels of about 11th grade-college level. Due to its rarity, the information available about cloacal exstrophy are similar and would likely be poorly understood by most parents. Hospital institutions and non-profit exstrophy programs need to make a concerted effort to work together to develop simple yet helpful information regarding this disease.Keywords: cloacal exstrophy, readability, online health information, exstrophy treatment