Gelation Kinetics‐Structure Analysis of pH‐triggered Low Molecular Weight Hydrogelators

Lakshminarayanan, Vasudevan; Chockalingam, Cindhuja; Mendes, Eduardo; Esch, Jan H. van

doi:10.1002/cphc.202100276

Cited by 7 publications

(6 citation statements)

References 26 publications

(67 reference statements)

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“…To understand the effect of doxorubicin conjugation on the formation of the CTH – BzPEG network, we fitted the oscillatory rheology time sweep profiles with a model based on the Avrami equation (eq ). , The slope of the first transition in the time sweep correlates with the nucleation and fractal growth of the nanofiber network described by analyzing the fractal dimension, D f . The CTH – BzPEG gel in the absence of doxorubicin possesses a D f value of 2.07, confirming the fractal-like growth of the fibers into a continuous network.…”

Section: Resultsmentioning

confidence: 88%

“…60,61 The slope of the first transition in the time sweep correlates with the nucleation and fractal growth of the nanofiber network described by analyzing the fractal dimension, D f . 62 The CTH−BzPEG gel in the absence of doxorubicin possesses a D f value of 2.07, confirming the fractal-like growth of the fibers into a continuous network. Incubation of doxorubicin with CTH and delaying BzPEG addition resulted in decreased D f values of 1.51 (0 h), 1.46 (1 h), 1.47 (2 h), 1.56 (4 h), 1.27 (8 h), and 1.34 (24 h).…”

Section: Preparation Of Cth−bzpeg Gels Under Physiologicalmentioning

confidence: 81%

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Switching the Mode of Drug Release from a Reaction-Coupled Low-Molecular-Weight Gelator System by Altering Its Reaction Pathway

et al. 2022

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Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an L-histidine methyl ester catalyst to prepare the drugloaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer−Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery.

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Section: Resultsmentioning

confidence: 88%

Section: Preparation Of Cth−bzpeg Gels Under Physiologicalmentioning

confidence: 81%

Switching the Mode of Drug Release from a Reaction-Coupled Low-Molecular-Weight Gelator System by Altering Its Reaction Pathway

et al. 2022

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“…However, this rapid assembly may represent a kinetically trapped state, and a more idealized thermodynamic product with different material properties could be attainable. Assembly pathway complexity and kinetics are increasingly appreciated in the supramolecular literature, − and a deeper study of these phenomena is sure to aid in the development of functional sPDC materials.…”

Section: Results and Discussionmentioning

confidence: 99%

Iterative Design Reveals Molecular Domain Relationships in Supramolecular Peptide–Drug Conjugates

Sis,

Liu,

Allen

et al. 2024

Biomacromolecules

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Supramolecular peptide−drug conjugates (sPDCs) are prepared by covalent attachment of a drug moiety to a peptide motif programmed for one-dimensional self-assembly, with subsequent physical entanglement of these fibrillar structures enabling formation of nanofibrous hydrogels. This class of prodrug materials presents an attractive platform for mass-efficient and sitespecific delivery of therapeutic agents using a discrete, singlecomponent molecular design. However, a continued challenge in sPDC development is elucidating relationships between supramolecular interactions in their drug and peptide domains and the resultant impacts of these domains on assembly outcomes and material properties. Inclusion of a saturated alkyl segment alongside the prodrug in the hydrophobic domain of sPDCs could relieve some of the necessity for ordered, prodrug−produg interactions. Accordingly, nine sPDCs are prepared here to iterate the design variables of amino acid sequence and hydrophobic prodrug−alkyl block design. All molecules spontaneously formed hydrogels under physiological conditions, indicating a less hindered thermodynamic path to self-assembly relative to previous prodrug-only designs. However, material studies on the supramolecular arrangement, formation, and mechanical properties of the resultant sPDC hydrogels as well as their drug release profiles showed complex relationships between the hydrophobic and peptide domains in the formation and function of the resulting assemblies. Together, these results indicate that sPDC material properties are intrinsically linked to holistic molecular design with coupled contributions from their prodrug and peptide domains in directing properties of the emergent materials.

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“…While altering the final gel properties by changing the gelation trigger, changing the solvent mixtures, 51,52 and controlling the gelation kinetics has been extensively studied, [52][53][54][55][56][57] changing the pre-gelled solution before triggering gelation is rarely discussed. There are many advantages of altering the pre-gelled solution to alter the gel properties.…”

Section: Emily R Drapermentioning

confidence: 99%

Methods of changing low molecular weight gel properties through gelation kinetics

Ginesi,

Draper

2024

Soft Matter

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Gelation Kinetics‐Structure Analysis of pH‐triggered Low Molecular Weight Hydrogelators

Cited by 7 publications

References 26 publications

Switching the Mode of Drug Release from a Reaction-Coupled Low-Molecular-Weight Gelator System by Altering Its Reaction Pathway

Switching the Mode of Drug Release from a Reaction-Coupled Low-Molecular-Weight Gelator System by Altering Its Reaction Pathway

Iterative Design Reveals Molecular Domain Relationships in Supramolecular Peptide–Drug Conjugates

Methods of changing low molecular weight gel properties through gelation kinetics

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