Challenges in delivering therapeutic peptides and proteins: A silk-based solution

Wu, Junqi; Sahoo, Jugal Kishore; Li, Yamin; Xu, Qiaobing; Kaplan, David L.

doi:10.1016/j.jconrel.2022.02.011

Cited by 51 publications

(28 citation statements)

References 168 publications

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“…We present here a silk fibroin based drug delivery system to address the stability limitations of PAL. Regenerated silk fibroin, a natural protein derived from the cocoons of Bombyx mori silkworms, is biocompatible and biodegradable and can be used to stabilize biomolecules, which makes it a good carrier for intrinsically labile molecules such as PAL. − In this study, we show that silk fibroin can preserve the bioactivity of PAL at room temperature when it is embedded in solid film formats. These films allowed for the stabilization of the enzyme for over a month without the need for refrigeration.…”

Section: Introductionmentioning

confidence: 74%

A Silk-Based Platform to Stabilize Phenylalanine Ammonia-lyase for Orally Administered Enzyme Replacement Therapy

et al. 2022

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Phenylalanine ammonia-lyase (PAL) has gained attention in recent years for the treatment of phenylketonuria (PKU), a genetic disorder that affects ~1 in 15,000 individuals globally. However, the enzyme is easily degraded by proteases, unstable at room temperature, and is currently administered in PKU patients as daily subcutaneous injections. We report here the stabilization of the PAL from Anabaena variabilis, which is currently used to formulate pegvaliase, through incorporation in a silk fibroin matrix. The combination with silk stabilizes PAL at 37 C. In addition, in vitro studies showed that inclusion in a silk matrix preserves the biological activity of the enzyme in simulated intestinal fluid, enabling the oral administration of pegvaliase for the treatment of PKU.

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Section: Introductionmentioning

confidence: 74%

A Silk-Based Platform to Stabilize Phenylalanine Ammonia-lyase for Orally Administered Enzyme Replacement Therapy

et al. 2022

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“…Fibroin is insoluble in water and is a nontoxic, hydrophobic and histocompatible glycoprotein [ 72 ]. Moreover, silk-based DDSs can promote drug delivery through the mucus layer by increasing particle residence time and, therefore, improving drug efficacy [ 74 ]. It was first used by Kim et al .…”

Section: Mps Based On Proteinsmentioning

confidence: 99%

Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations

Knap

Kwiecień

Reczyńska-Kolman

et al. 2022

Regenerative Biomaterials

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Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases. Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution, leading to a more effective therapy with reduced required doses and side effects. On the other hand, there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical, aerodynamic, and biological properties, which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result. Therefore, we focused on powders consisting of polysaccharides, lipids, proteins, or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers. We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms. This review paper addresses the most common manufacturing methods with novel modifications, pros and cons of different materials, drug loading capacities with release profiles, and biological properties such as cytocompatibility, bactericidal, or anticancer properties.

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“…Silk fibroin (SF), domesticated from the Bombyx mori cocoons, finds significant applications in different biomedical advances because of its biocompatibility, impressive mechanical properties, tunable rates of biodegradation, and aqueous processability. − SF-based hydrogels have been fabricated using different physical (e.g., temperature, pH, ultrasound, vortexing) and chemical (e.g., photochemistry, Fenton reaction , ) treatments. Most hydrogels prepared by physical cross-linking result in stable and mechanical robust hydrogels but also tend toward brittle behavior.…”

Section: Introductionmentioning

confidence: 99%

Horseradish Peroxidase Catalyzed Silk–Prefoldin Composite Hydrogel Networks

Sahoo

Falcucci

et al. 2022

ACS Appl. Bio Mater.

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Protein-based hydrogel biomaterials provide a platform for different biological applications, including the encapsulation and stabilization of different biomolecules. These hydrogel properties can be modulated by controlling the design parameters to match specific needs; thus, multicomponent hydrogels have distinct advantages over singlecomponent hydrogels due to their enhanced versatility. Here, silk fibroin and γ-prefoldin chaperone protein based composite hydrogels were prepared and studied. Different ratios of the proteins were chosen, and the hydrogels were prepared by enzyme-assisted cross-linking. The secondary structure of the two proteins, dityrosine bond formation, and mechanical properties were assessed. The results obtained can be used as a platform for the rational design of composite thermostable hydrogel biomaterials to facilitate protection (due to hydrogel mechanics) and retention of bioactivity (e.g., of enzymes and other biomolecules) due to chaperone-like properties of γ-prefoldin.

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Challenges in delivering therapeutic peptides and proteins: A silk-based solution

Cited by 51 publications

References 168 publications

A Silk-Based Platform to Stabilize Phenylalanine Ammonia-lyase for Orally Administered Enzyme Replacement Therapy

A Silk-Based Platform to Stabilize Phenylalanine Ammonia-lyase for Orally Administered Enzyme Replacement Therapy

Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations

Horseradish Peroxidase Catalyzed Silk–Prefoldin Composite Hydrogel Networks

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