Inter-Grade and Inter-Batch Variability of Sodium Alginate Used in Alginate-Based Matrix Tablets

Shao, Fu; Buckner, Ira S.; Block, Lawrence

doi:10.1208/s12249-014-0154-3

Cited by 8 publications

(2 citation statements)

References 15 publications

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“…Although they are of natural origin, cost‐effective for simple preliminary mobility studies, and contain a variety of native‐similar functional groups, these systems do not meet all the requirements of a high‐fidelity native ECM model for research. High batch‐to‐batch variations of the component biomolecules must be taken into account . In addition, due to the diverse compositions of such multicomponent networks, experimental setups are difficult to compare.…”

Section: In Vitro Models For Native Ecmmentioning

confidence: 99%

Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix

Tomasetti

Breunig

2017

Adv Healthcare Materials

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Although nanosized drug delivery systems are promising tools for the treatment of severe diseases, the extracellular matrix (ECM) constitutes a major obstacle that endangers therapeutic success. Mobility of diffusing species is restricted not only by small pore size (down to as low as 3 nm) but also by electrostatic interactions with the network. This article evaluates commonly used in vitro models of ECM, analytical methods, and particle types with respect to their similarity to native conditions in the target tissue. In this cross-study evaluation, results from a wide variety of mobility studies are analyzed to discern general principles of particle-ECM interactions. For instance, cross-linked networks and a negative network charge are essential to reliably recapitulate key features of the native ECM. Commonly used ECM mimics comprised of one or two components can lead to mobility calculations which have low fidelity to in vivo results. In addition, analytical methods must be tailored to the properties of both the matrix and the diffusing species to deliver accurate results. Finally, nanoparticles must be sufficiently small to penetrate the matrix pores (ideally R < 0.5; d = particle diameter, p = pore size) and carry a neutral surface charge to avoid obstructions. Larger (R >> 1) or positively charged particles are trapped.

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Section: In Vitro Models For Native Ecmmentioning

confidence: 99%

Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix

Tomasetti

Breunig

2017

Adv Healthcare Materials

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“…[19] Biologically derived hydrogels (e.g., collagen, hyaluronic acid, matrigel, and calcium-alginate) can also suffer batch-to-batch variability and present biochemical cues, confounding the effects of viscoelastic mechanical properties on chondrocyte secretory properties and tissue regeneration. [20–23]…”

Section: Introductionmentioning

confidence: 99%

Hydrazone covalent adaptable networks modulate extracellular matrix deposition for cartilage tissue engineering

et al. 2019

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Cartilage tissue engineering strategies often rely on hydrogels with fixed covalent crosslinks for chondrocyte encapsulation; yet the resulting material properties are largely elastic and can impede matrix deposition. To address this limitation, hydrazone crosslinked poly(ethylene glycol) hydrogels were formulated to achieve tunable viscoelastic properties and to study how chondrocyte proliferation and matrix deposition vary with the time-dependent material properties of covalent adaptable networks. Hydrazone equilibrium differences were leveraged to produce average stress relaxation times from hours (4.01×103s) to months (2.78×106s) by varying the percentage of alkyl-hydrazone (aHz) to benzyl-hydrazone (bHz) crosslinks. Swelling behavior and degradation associated with adaptability was characterized to quantify temporal network changes that can influence the behavior of encapsulated chondrocytes. After four weeks, mass swelling ratios varied from 36±3 to 17±0.4 and polymer retention ranged from 46±4% to 92±5%, with higher aHz content leading to loss of network connectivity with time. Hydrogels were formulated near the Flory-Stockmayer bHz percolation threshold (17% bHz) to investigate chondrocyte response to distinct levels of covalent architecture adaptability. Four weeks post-encapsulation, formulations with average relaxation times of 3 days (2.6×105s) revealed increased cellularity and an interconnected articular cartilage-specific matrix. Chondrocytes embedded in this adaptable formulation (22% bHz) deposited 190±30% more collagen and 140±20% more sulfated glycosaminoglycans compared to the 100% bHz control, which constrained matrix deposition to pericellular space. Collectively, these findings indicate that incorporating highly adaptable aHz crosslinks enhanced regenerative outcomes. However, connected networks containing more stable bHz bonds were required to achieve the highest quality neocartilaginous tissue.

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The Role of Excipients in Quality by Design (QbD)

Carlin

2018

Pharmaceutical Quality by Design

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Inter-Grade and Inter-Batch Variability of Sodium Alginate Used in Alginate-Based Matrix Tablets

Cited by 8 publications

References 15 publications

Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix

Preventing Obstructions of Nanosized Drug Delivery Systems by the Extracellular Matrix

Hydrazone covalent adaptable networks modulate extracellular matrix deposition for cartilage tissue engineering

The Role of Excipients in Quality by Design (QbD)

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