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• W4200356737 abstract "Positively charged drug carriers are rapidly emerging as a viable solution for long-standing challenges in delivery to dense, avascular, negatively charged tissues. These cationic carriers have demonstrated especially strong promise in targeting drugs to articular cartilage for osteoarthritis (OA) treatment. It is critical to evaluate the dose-dependent effects of their high intratissue uptake levels on charge-shielding of anionic matrix constituents, and the resulting changes in tissue osmotic swelling and mechanical integrity.We use the ideal Donnan osmotic theory to derive a model for predicting intracartilage swelling pressures as a function of net charge (z) and equilibrium uptake of short-length, arginine-rich, multivalent, cationic peptide carriers (cationic peptide carriers [CPCs], z varied from +8 to +20) in cartilage samples with varying arthritic severities and fixed charge density (FCD). We use this model to determine the dose-dependent influence of CPCs on both physiological osmotic swelling pressures and compressive electrostatic moduli of cartilage in healthy and arthritic states.Under physiological conditions, the Donnan model predicted carrier-induced reductions in free swelling pressure between 8 and 29 kPa, and diminished compressive modulus by 20-68 kPa, both dependent on the net charge and uptake of CPCs. The magnitudes of deswelling and stiffness reduction increased monotonically with carrier uptake and net charge. Furthermore, predicted levels of deswelling by CPC charge shielding were amplified in tissues with reduced FCD (which model OA). Finally, the Donnan model predicted markedly higher reductions in tissue compressive modulus in hypotonic bathing salinity compared with physiological and hypertonic conditions.This analysis demonstrates the importance of considering charge shielding as a likely adverse effect associated with uptake of cationic drug carriers into negatively charged tissues, especially in the case of damaged tissue. The simple modeling approach and principles described herein can inform the design of cationic drug delivery carriers and their clinical treatment regimens." @default.
• W4200356737 created "2021-12-31" @default.
• W4200356737 creator A5029967749 @default.
• W4200356737 date "2022-12-01" @default.
• W4200356737 modified "2023-09-29" @default.
• W4200356737 title "Modeling Electrostatic Charge Shielding Induced by Cationic Drug Carriers in Articular Cartilage Using Donnan Osmotic Theory" @default.
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• W4200356737 doi "https://doi.org/10.1089/bioe.2021.0026" @default.
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• W4200356737 hasPublicationYear "2022" @default.
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