Dataset Information

Layer-by-Layer Fabrication of Hydrogel Microsystems for Controlled Drug Delivery From Untethered Microrobots.

ABSTRACT: Targeted drug delivery from untethered microrobots is a topic of major interest in current biomedical research. The possibility to load smart materials able to administer active principles on remotely in vivo guidable microdevices constitutes one of the most attractive opportunities to overcome the drawbacks of classical untargeted delivery methodologies. Hydrogels, in particular, are ideal candidates as drug-carrying materials due to their biocompatibility, low cost, and ease of manufacturing. On the other hand, these polymers suffer from poor control over release rate and overall released amount. Starting from these premises, the present article demonstrates the possibility to tune the release of hydrogels applied on magnetically steerable microrobots by fabricating microsystems via layer-by-layer self-assembly. By doing this, the diffusion of chemicals from the hydrogel layers to the external environment can be optimized and the phenomenon of burst release can be strongly limited. The microrobotic platforms employed to transport the hydrogel active material are fabricated by employing 3D printing in combination with wet metallization and present a gold layer on their surface to enhance biocompatibility. The maneuverability of microdevices coated with both thin and thick multilayers is investigated, individuating optimized parameters for efficient actuation.

SUBMITTER: Bernasconi R

PROVIDER: S-EPMC8548779 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Layer-by-Layer Fabrication of Hydrogel Microsystems for Controlled Drug Delivery From Untethered Microrobots.

Bernasconi Roberto R Pizzetti Fabio F Rossetti Arianna A Butler Brendan B Levi Marinella M Pané Salvador S Rossi Filippo F Magagnin Luca L

Frontiers in bioengineering and biotechnology 20211013

Targeted drug delivery from untethered microrobots is a topic of major interest in current biomedical research. The possibility to load smart materials able to administer active principles on remotely <i>in vivo</i> guidable microdevices constitutes one of the most attractive opportunities to overcome the drawbacks of classical untargeted delivery methodologies. Hydrogels, in particular, are ideal candidates as drug-carrying materials due to their biocompatibility, low cost, and ease of manufact ...[more]

PMID: 34722474

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Project description:Microneedle-based drug delivery offers an attractive and minimally invasive administration route to deliver therapeutic agents through the skin by bypassing the stratum corneum, the main skin barrier. Recently, hydrogel-based microneedles have gained prominence for their exceptional ability to precisely control the release of their drug cargo. In this study, we investigated the feasibility of fabricating microneedles from triblock amphiphiles with linear poly(ethylene glycol) (PEG) as the hydrophilic middle block and two dendritic side-blocks with enzyme-cleavable hydrophobic end-groups. Due to the poor formation and brittleness of microneedles made from the neat amphiphile, we added a sodium alginate base layer and tested different polymeric excipients to enhance the mechanical strength of the microneedles. Following optimization, microneedles based on triblock amphiphiles were successfully fabricated and exhibited favorable insertion efficiency and low height reduction percentage when tested in Parafilm as a skin-simulant model. When tested against static forces ranging from 50 to 1000 g (4.9-98 mN/needle), the microneedles showed adequate mechanical strength with no fractures or broken segments. In buffer solution, the solid microneedles swelled into a hydrogel within about 30 s, followed by their rapid disintegration into small hydrogel particles. These hydrogel particles could undergo slow enzymatic degradation to soluble polymers. In vitro release study of dexamethasone (DEX), as a steroid model drug, showed first-order drug release, with 90% released within 6 days. Eventually, DEX-loaded MNs were subjected to an insertion test using chicken skin and showed full penetration. This study demonstrates the feasibility of programming hydrogel-forming microneedles to undergo several mesophase transitions and their potential application as a delivery system for self-administration, increased patient compliance, improved efficacy, and sustained drug release.

Project description:A two-component injectable hydrogel was suitably prepared for the encapsulation and prolonged release of tilorone which is an antimuscular atrophy drug. The rapid (7-45 s, depending on the polymer concentration) in situ solidifications of the hydrogel were evoked by the evolving Schiff-base bonds between the aldehyde groups of modified PVA (4-formyl benzoate PVA, PVA-CHO, 5.9 mol% functionalization degree) and the amino groups of 3-mercaptopropionate chitosan (CHIT-SH). The successful modification of the initial polymers was confirmed by both FTIR and NMR measurements; moreover, a new peak appeared in the FTIR spectrum of the 10% w/v PVA-CHO/CHIT-SH hydrogel at 1647 cm-1, indicating the formation of a Schiff base (-CH=N-) and confirming the interaction between the NH2 groups of CHIT-SH and the CHO groups of PVA-CHO for the formation of the dynamic hydrogel. The reaction between the NH2 and CHO groups of the modified biopolymers resulted in a significant increase in the hydrogel's viscosity which was more than one thousand times greater (9800 mPa·s) than that of the used polymer solutions, which have a viscosity of only 4.6 and 5.8 mPa·s, respectively. Furthermore, the initial chitosan was modified with mercaptopropionic acid (thiol content = 201.85 ± 12 µmol/g) to increase the mucoadhesive properties of the hydrogel. The thiolated chitosan showed a significant increase (~600 mN/mm) in adhesion to the pig intestinal membrane compared to the initial one (~300 mN/mm). The in vitro release of tilorone from the hydrogel was controlled with the crosslinking density/concentration of the hydrogel; the 10% w/v PVA-CHO/CHIT-SH hydrogel had the slowest releasing (21.7 h-1/2) rate, while the 2% w/v PVA-CHO/CHIT-SH hydrogel had the fastest releasing rate (34.6 h-1/2). Due to the characteristics of these hydrogels, their future uses include tissue regeneration scaffolds, wound dressings for skin injuries, and injectable or in situ forming drug delivery systems. Eventually, we hope that the developed hydrogel will be useful in the local treatment of muscle atrophy, such as laryngotracheal atrophy.

Dataset Information

Layer-by-Layer Fabrication of Hydrogel Microsystems for Controlled Drug Delivery From Untethered Microrobots.

Publications

Layer-by-Layer Fabrication of Hydrogel Microsystems for Controlled Drug Delivery From Untethered Microrobots.

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