Bioengineered robust hybrid hydrogels enrich the stability and efficacy of biological drugs

Gil, Moon Soo; Cho, Jinhwan; Thambi, Thavasyappan; Phan, Vu To-Anh; Kwon, Inchan; Lee, Sang Soo

doi:10.1016/j.jconrel.2017.04.009

Cited by 42 publications

(25 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, our results showed that, for a small protein (sfGFP, 28 kDa), PA conjugation does not compromise the binding of FcRn to serum albumin in vitro or the serum half-life extension in vivo regardless of linker length. Combined with the previous results for a large protein (Uox, 140 kDa) [24], our results supported that the protein size in the fatty acid-protein conjugate is an important factor for effective binding of FcRn with serum albumin leading to prolonged serum half-life in vivo. We believe our findings can contribute to the successful design of other fatty acid-conjugated therapeutic proteins for serum half-life extension.…”

Section: Discussionsupporting

confidence: 88%

See 1 more Smart Citation

The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension

et al. 2020

Self Cite

View full text Add to dashboard Cite

Conjugation of serum albumin or one of its ligands (such as fatty acid) has been an effective strategy to prolong the serum half-lives of drugs via neonatal Fc receptor (FcRn)–mediated recycling of albumin. So far, fatty acid (FA) has been effective in prolonging the serum half-lives for therapeutic peptides and small proteins, but not for large therapeutic proteins. Very recently, it was reported a large protein conjugated to FA competes with the binding of FcRn with serum albumin, leading to limited serum half-life extension, because primary FA binding sites in serum albumin partially overlap with FcRn binding sites. In order to prevent such competition, longer linkers between FA and the large proteins were required. Herein, we hypothesized that small proteins do not cause substantial competition for FcRn binding to albumin, resulting in the extended serum half-life. Using a small protein (28 kDa), we investigated whether the intramolecular distance in FA-protein conjugate affects the FcRn binding with albumin and serum half-life using linkers with varying lengths. Unlike with the FA-conjugated large protein, all FA-conjugated small proteins with different linkers exhibited comparable the FcRn binding to albumin and extended serum half-life.

show abstract

Section: Discussionsupporting

confidence: 88%

“…Despite the numerous reports of serum half-life extension via fatty acid conjugation, its molecular mechanism was not yet fully revealed. It is noteworthy that fatty acid conjugation was effective for serum half-life extension of therapeutic peptides and small proteins (less than 28 kDa) [17,[19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, it is a challenge to create hyperuricemic models in mice, because in rodents, uricase oxidizes UA to allantoin which is highly soluble in water and excreted unchanged in the urine, but not in humans [24]. As potassium oxonate (PO) can block uricase, and hypoxanthine (HX) is the precursor of UA which is finally oxidized into UA by xanthine oxidase, combination of PO and HX has been widely used to induce HUA in rodents [25][26][27]. As our data indicated, we successfully induced HUA in KK-Ay mice by combination of peritoneal injection of PO and intragastric administration of HX.…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin Attenuates Hyperuricemia by Upregulation of ABCG2 via AMPK/AKT/CREB Signaling Pathway in Type 2 Diabetic Mice

Lu¹,

Chang²,

Li³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Hyperuricemia (HUA) is a metabolic disease characterized by elevated serum uric acid (SUA). Empagliflozin, a kind of sodium-glucose cotransporter 2 inhibitors, has recently emerged as a new antidiabetic agent by facilitating glucose excretion in urine. Moreover, there was evidence of SUA reduction following treatment with empagliflozin in addition to glycaemic control, while the molecular mechanisms remain unknown. To investigate the potential mechanisms, the model of type 2 diabetes (T2DM) with HUA was established by combination of peritoneal injection of potassium oxonate and intragastric administration of hypoxanthine in KK-Ay mice. A series of method such as RT-PCR, western blot, immunochemistry, immunofluorescence were conducted to explore the mechanism. Our results showed that empagliflozin significantly ameliorated the levels of SUA and blood glucose in T2DM mice with HUA. Furthermore, in both kidney and ileum, empagliflozin obviously promoted protein expression of uric acid (UA) transporter ABCG2, p-AMPK, p-AKT and p-CREB. The same trend was observed in human tubular epithelial (HK-2) cells. Additionally, through application of an AMPK inhibitor (Compound C), it was further confirmed empagliflozin exerted its anti-hyperuricemic effects in an AMPK dependent manner. Meanwhile, with the help of ChIP assay and luciferase reporter gene assay, we found that CREB further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Taken together, our study demonstrated that empagliflozin treatment played an essential role in attenuating HUA by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway.

show abstract

“…Further versatile hydrogel printing applications can be developed as hydrogels are already in use for different kinds of experimental approaches. For example, the entrapment of biopharmaceutical proteins in hydrogel structures is part of investigations into a new methodology of drug release . Furthermore, the encapsulation or even immobilization of enzymes in and on hydrogels is of huge interest as reusable matrix in biocatalysis or analytical applications .…”

Section: Introductionmentioning

confidence: 99%

“…For example, the entrapment of biopharmaceutical proteins in hydrogel structures is part of investigations into a new methodology of drug release. [32][33][34] Furthermore, the encapsulation or even immobilization of enzymes in and on hydrogels is of huge interest as reusable matrix in biocatalysis or analytical applications. 35 Functional biological composite materials can be incorporated in microreactors and microfluidic devices, [36][37][38] biosensors 39,40 or as beads in diverse applications.…”

Section: Introductionmentioning

confidence: 99%

The Biomaker: an entry‐level bioprinting device for biotechnological applications

Radtke

Hillebrandt

Hubbuch

2017

J of Chemical Tech & Biotech

View full text Add to dashboard Cite

BACKGROUND 3D printing and bioprinting in particular are emerging technologies in the field of biotechnology. The developments of bioprinters and applications lie mostly in the highly observed working fields of tissue engineering and regenerative medicine. Until now only little attention has been paid to the application of 3D bioprinting for the investigation of hydrogel–liquid phase interactions in biotechnological applications. This can mostly be attributed to the need for complex and expensive equipment. RESULTS In this work, an entry‐level bioprinter on the base of a commercially available Fused‐Filament‐Fabrication 3D printer and an easy to handle user interface was designed. This newly developed bioprinter allowed the structuring of bioinks and hydrogels in microwell plates and even complex models were printed. The applicability of the presented printer setup in the field of biotechnology was shown by the encapsulation of β‐galactosidase (EC 3.2.1.23) in poly(ethylene glycol) diacrylate based hydrogels. Subsequently, an automated screening of the biocatalytic conversion of the substrate ONPG by the encapsulated enzyme was executed on a liquid handling station. Under varied pH conditions in the surrounding liquid phase highest substrate turnover rates were detected at pH 3 and pH 5 which is in good accordance with previously reported pH optima of β‐galactosidase. CONCLUSION This approach shows an easy access to 3D bioprinting in the field of biotechnology and the implementation of 3D printed hydrogels in high‐throughput experimentation. © 2017 Society of Chemical Industry

show abstract

Bioengineered robust hybrid hydrogels enrich the stability and efficacy of biological drugs

Cited by 42 publications

References 49 publications

The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension

The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension

Empagliflozin Attenuates Hyperuricemia by Upregulation of ABCG2 via AMPK/AKT/CREB Signaling Pathway in Type 2 Diabetic Mice

The Biomaker: an entry‐level bioprinting device for biotechnological applications

Contact Info

Product

Resources

About