Investigation of macromolecular transport through tunable collagen hyaluronic acid matrices.

Autor: Hakim MH; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA., Jun BH; School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA., Ahmadzadegan A; School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA., Babiak PM; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA., Xu Q; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA., Buno KP; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA., Liu JC; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA., Ardekani AM; School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA., Vlachos PP; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA. Electronic address: pvlachos@purdue.edu., Solorio L; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, USA. Electronic address: lsolorio@purdue.edu.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2023 Feb; Vol. 222, pp. 113123. Date of Electronic Publication: 2023 Jan 03.
DOI: 10.1016/j.colsurfb.2023.113123
Abstrakt: Therapeutic macromolecules possess properties such as size and electrostatic charge that will dictate their transport through subcutaneous (SC) tissue and ultimate bioavailability and efficacy. To improve therapeutic design, platforms that systematically measure the transport of macromolecules as a function of both drug and tissue properties are needed. We utilize a Transwell chamber with tunable collagen-hyaluronic acid (ColHA) hydrogels as an in vitro model to determine mass transport of macromolecules using non-invasive UV spectroscopy. Increasing hyaluronic acid (HA) concentration from 0 to 2 mg/mL within collagen gels decreases the mass transport of five macromolecules independent of size and charge and results in a maximum decrease in recovery of 23.3% in the case of bovine immunoglobulin G (IgG). However, in a pure 10 mg/mL HA solution, negatively-charged macromolecules bovine serum albumin (BSA), β-lactoglobulin (BLg), dextran (Dex), and IgG had drastically increased recovery by 20-40% compared to their performance in ColHA matrices. This result was different from the positively-charged macromolecule Lysozyme (Lys), which, despite its small size, showed reduced recovery by 3% in pure HA. These results demonstrate two distinct regimes of mass transport within our tissue model. In the presence of both collagen and HA, increasing HA concentrations decrease mass transport; however, in the absence of collagen, the high negative charge of HA sequesters and increases residence time of positively-charged macromolecules and decreases residence time of negatively-charged macromolecules. Through our approach, ColHA hydrogels serve as a platform for the systematic evaluation of therapeutic macromolecule transport as a function of molecular characteristics.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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