Liposome-Cross-Linked Hybrid Hydrogels for Glutathione-Triggered Delivery of Multiple Cargo Molecules

Abstract

Novel, liposome-cross-linked hybrid hydrogels cross-linked by the Michael-type addition of thiols with maleimides were prepared via the use of maleimide-functionalized liposome cross-linkers and thiolated polyethylene glycol (PEG) polymers. Gelation of the materials was confirmed by oscillatory rheology experiments. These hybrid hydrogels are rendered degradable upon exposure to thiol-containing molecules such as glutathione (GSH), via the incorporation of selected thioether succinimide cross-links between the PEG polymers and liposome nanoparticles. Dynamic light scattering (DLS) characterization confirmed that intact liposomes were released upon network degradation. Owing to the hierarchical structure of the network, multiple cargo molecules relevant for chemotherapies, namely doxorubicin (DOX) and cytochrome c, were encapsulated and simultaneously released from the hybrid hydrogels, with differential release profiles that were driven by degradation-mediated release and Fickian diffusion, respectively. This work introduces a facile approach for the development of advanced, hybrid drug delivery vehicles that exhibit novel chemical degradation.

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

“…[189] Although GAG-based hydrogels have been employed for the parallel release of multiple growth factors, studies have shown that the sequential delivery of multiple growth factors would better mimic the temporal profile of the natural healing process. [190] Motivated by recent advances in hierarchically structured, multicomponent hydrogels and orthogonal degradation chemistries, GAG-based hydrogels with sequential release characteristics could be designed by incorporating a secondary nanoparticle domain (e.g., liposomes or PLGA nanoparticles) [191] into a GAG-based network and introducing multiple degradable linkages (e.g., wavelength-selective photocleavable units) [192] into the precursors. Combined with the inherent biological activities of GAGs, such GAG-based materials could provide physiologically relevant release profiles and spatial gradients of multiple growth factors, with the potential to improve tissue regeneration.…”

Mechanical Deformation Mediated Transmembrane Transport

“…[1,2] Naturally, molecules pass across biological membranes by either active transport [3][4][5][6] or passive diffusion. [19][20][21][22][23][24][25][26][27][28] However, artificial membrane channels created so far mainly rely on complicated chemical synthesis and are inefficient to dynamically control the transport process. [19][20][21][22][23][24][25][26][27][28] However, artificial membrane channels created so far mainly rely on complicated chemical synthesis and are inefficient to dynamically control the transport process.…”

“…[7][8][9] With the advent of new methods capable of mimicking and regulating transmembrane transport, [10][11][12][13][14][15][16][17][18] various biosensors, separation membranes, and drug carriers have been developed for diagnosis and treatments. [19][20][21][22][23][24][25][26][27][28] However, artificial membrane channels created so far mainly rely on complicated chemical synthesis and are inefficient to dynamically control the transport process. [29,30] showed that LLHs fully embedded with homogeneously distributed liposomes in an average size of 184 ± 41 nm ( Figure 2c).…”

50th Anniversary Perspective: Polymeric Biomaterials: Diverse Functions Enabled by Advances in Macromolecular Chemistry

“…153 The enhanced stability permits release of encapsulated cargo molecules over longer timescales (ca. 3–6 days), 153, 154 demonstrating significant promise for tailoring therapeutic release within tumor microenvironments.…”