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Evaluating the Immunogenicity Risk of Protein Therapeutics by Augmenting T Cell Epitope Prediction with Clinical Factors.

AAPS J

January 2025

Department of BioAnalytical Sciences, Genentech Inc, South San Francisco, California, USA.

Protein-based therapeutics may elicit undesired immune responses in a subset of patients, leading to the production of anti-drug antibodies (ADA). In some cases, ADAs have been reported to affect the pharmacokinetics, efficacy and/or safety of the drug. Accurate prediction of the ADA response can help drug developers identify the immunogenicity risk of the drug candidates, thereby allowing them to make the necessary modifications to mitigate the immunogenicity.

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Valsartan (VST) is an angiotensin II receptor antagonist with low oral bioavailability. The present study developed a solid self-nanoemulsifying drug delivery system (S-SNEDDS) to enhance the oral absorption and bioavailability of VST. VST-loaded liquid SNEDDS (VST@L-SNEDDS) was prepared by investigating the solubility of VST and constructing the pseudo-ternary phase diagrams.

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Chamuangone, a compound extracted from the leaves of Garcinia cowa, exhibits various biological activities. Yet, its absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile as well as anti-inflammatory effects in macrophages remain unexplored. In this study, we employed a computational tool to predict the ADMET profile of chamuangone and performed molecular docking simulations to assess its interactions with key proteins involved in inflammatory pathways.

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The repercussions of hormone replacement therapy (HRT) and bisphosphonates pose serious clinical challenges and warrant novel therapies for osteoporosis in menopausal women. To confront this issue, the present research aimed to design and fabricate daidzein (DZ); a phytoestrogen-loaded hydroxyapatite nanoparticles to mimic and compensate for synthetic estrogens and biomineralization. Hypothesizing this bimodal approach, hydroxyapatite nanoparticles (HAPNPs) were synthesized using the chemical-precipitation method followed by drug loading (DZHAPNPs) via sorption.

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The opioid crisis, driven by synthetic opioids like fentanyl, demands innovative solutions. The opioid antidote naloxone has a short action ( ~ 1 hour), requiring repeated doses. To address this, we present a new and simple naloxone prodrug delivery system repurposing a hydrophilic derivative of acoramidis, a potent transthyretin ligand.

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