Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids

Abstract

Two polysaccharide-based hydrogels made of only kcarrageenan (4%; w/v) or of a mixture of methylcellulose:kcarrageenan (2%; w/v) were used to encapsulate cationic nioplexes. These vesicular particles were made of a synthetic aminolipid and polysorbate-80 (Tween-80), as a non-ionic surfactant agent. According to oscillatory rheological measurements, the presence of nioplexes did not compromise the mechanical integrity of the gels. In vitro niosomal release experiments demonstrated the liberation of nioplexes up to 24 h, and the curves were fitted according to Higuchi, Korsmeyer-Peppas and Weibull equation models, which indicated Fickian-diffusion controlled mechanisms. Besides nioplexes, cervical cancer cells were also entrapped within the biohydrogels. Cell release confirmed that these materials did not affect the cell viability, allowing cells to spread and proliferate after 24 h. The applicability of these biocompatible hydrogels was also extended to gene delivery. In this regard, the best silencing activities were found when cationic niosomes were complexed with antisense oligonucleotides in KC hydrogels. Nioplexes were able to release through the hydrogel and promoted silencing of luciferase expression in the presence of serum without using commercially available cationic lipids. Overall, the formation of such hybrid materials by integrating cationic nioplexes within biodegradable hydrogels provides a new perspective for the delivery of macromolecular therapeutics.

Niosomes encapsulated in biohydrogels for tunable delivery of phytoalexin resveratrol

“…4). The observed increase in PDI aer hydrogel degradation is in agreement with our previous observations 49 and could be attributed to non-specic intermolecular interactions between the functional groups of the biopolymers and the niosomes affecting to some extent the supramolecular organization of the dynamic vesicles.…”

“…Similar destabilization was previously observed in gel networks made of k-C and methylcellulose. 49 Finally, DTS (dynamic time sweep) measurements conrmed the temporal stability of the hydrogels within the linear viscoelastic regime (1 Hz frequency, 0.1% strain) (ESI, Fig. S2 †).…”

“…The average diameter of the vesicles slightly increases (<10 nm) aer gel network degradation. 49 Similarly, the structural integrity of niosomes entrapped in the hydrogel made of k-C : gelatin (1 : 1 mass ratio, 4% w/v) was conrmed using dynamic light scattering (DLS) and emission eld scanning electron microscopy (FE-SEM). Hydrogel degradation was induced by diluting the hydrogel to achieve a gelator concentration below the critical gelation concentration (i.e., <2% w/v in the mixture k-C : gelatin 1 : 1 mass ratio) and incubating the sample 24 h at 37 C to trigger erosion and liberate the corresponding niosomes into the receptor phase.…”

Hyaluronic acid hydrogel scaffolds loaded with cationic niosomes for efficient non-viral gene delivery

“…In addition, cationic nioplexes have also been successfully encapsulated in polysaccharide-based hydrogels made of κ-carrageenan and of a mixture of methylcellulose and κ-carrageenan. 18 However, despite the fast development of niosome formulations in the field of gene delivery, their applicability for encapsulation in HA hydrogel scaffolds has not yet been studied.…”

It’s All in the Delivery: Designing Hydrogels for Cell and Non-viral Gene Therapies

“…121 Furthermore, the development of hypoxia-inducible promoters to control gene expression in ischemic environments is particularly relevant to tissue regeneration applications. 122,123 Cell-or tissue-specific promoters may also be considered, especially with respect to the types of cells infiltrating the scaffold or being transplanted with the scaffold. Lastly, post-regulatory elements, such as woodchuck hepatitis virus (WHP) posttranscriptional regulatory element (WPRE), can also be added to the expression cassette to enhance mRNA stabilization to result in enhanced and longer expression; however, this effect is strongly dependent on the promoter and cell line used.…”