Two-component cross-linkable gels for fabrication of solid oral dosage forms

Croitoru-Sadger, Tsuf; Yogev, Sivan; Shabtay-Orbach, Ayelet

doi:10.1016/j.jconrel.2019.04.021

Cited by 10 publications

(6 citation statements)

References 45 publications

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“…[31] Moreover, a higher amount of NHS end groups has also been associated with increased cross-linking density and improved structural integrity gels, which can also explain the better resistance to burst pressure. [32] Swelling and degradation of the cross-linked system were evaluated by immersing 30 mg of each mixture in 30 mL artificial pancreatic juice (pH 8) at 37°C. This media was chosen since sealants started swelling immediately upon immersion, reaching a maximum weight after approximately 1 h. The 1:1 mixture swelled slightly more than the 9:1 mixture (131% vs 111%, respectively).…”

Section: Resultsmentioning

confidence: 99%

Liquid Copolymers as Biodegradable Surgical Sealant

Shimony

Shagan

Eylon

et al. 2021

Adv Healthcare Materials

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Surgical sealants are widely used to prevent seepage of fluids and liquids, promote hemostasis, and close incisions. Despite the remarkable progress the field of biomaterials has undergone, the clinical uses of surgical sealants are limited because of their short persistence time in vivo, toxicity, and high production costs. Here, the development of two complementary neat (solvent-free) prepolymers, PEG 4 -PLGA-NHS and PEG 4 -NH 2 , that harden upon mixing to yield an elastic biodegradable sealant is presented. The mechanical and rheological properties and cross-linking rate can be controlled by varying the ratio between the two prepolymers. The tested sealants show a longer persistence time compared with fibrin glue, minimal cytotoxicity in vitro, and excellent biocompatibility in vivo. The neat, multiarmed approach demonstrated here improves the mechanical and biocompatibility properties and provides a promising tissue sealant solution for wound closure in future surgical procedures.

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Section: Resultsmentioning

confidence: 99%

Liquid Copolymers as Biodegradable Surgical Sealant

Shimony

Shagan

Eylon

et al. 2021

Adv Healthcare Materials

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“…These smaller macromonomers and their derivatives are liquid even at room temperature, which is a tremendous advantage for drug delivery systems since they allow for direct injection into the organism requiring only minimally invasive surgery . Moreover, due to the absence of evaporating solvents, implants can also be prepared by 3D printing . Kelmansky et al have already shown that “neat biogels” can be prepared in a water-free manner through cross-linking with amine- and succinimidyl carbonate-functionalized 4armPEG2k precursors at 37 °C. , However, their material contained succinimidyl carbonate groups, that covalently bound to the tissue after injection.…”

Section: Introductionmentioning

confidence: 99%

Injectable Anhydrous Poly(ethylene glycol) Polymer Liquids Form Protein Depot for Extended Controlled Release Applications Via Rapid In Situ Gelation

et al. 2023

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Water-free preparation of protein delivery systems has the potential to overcome the limitations of hydrogel depot systems such as off-target reactions, functional group hydrolysis, and limited loading capacity. However, a major roadblock in the development and use of these systems is administration as implantation is often required. In this study, we developed a biodegradable and water-free injectable protein delivery system via inverse electron demand Diels−Alder reaction between norbornene-and tetrazine-functionalized four-armed poly(ethylene glycol) macromonomers. 1:1 mixtures of these precursors gelled rapidly in situ, taking less than 11 s to reach their gelation point. Methyl substitution of tetrazine slowed the gelation time and increased the cross-linking density, whereas oxygen incorporation into norbornene changed the mechanical properties. Introduction of hydrolytically cleavable groups enabled biodegradability. Using phenyl carbamate and phenyl carbonate ester groups, we could tune the stability. Controlled release of the protein surrogate glucose oxidase was achieved over a period of 500 days. The novel preparation method presented here is a promising step toward the development of water-free injectable protein depots for controlled drug delivery.

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“…To be suitable for injection and administration through minimally invasive devices, these copolymers should have appropriate viscosity. The viscosity values of the copolymers are comparable to or lower than some other injectable systems, including in drug delivery hydrogels, 26 injectable scaffolds in tissue engineering, 27 3D printing ink 28 and medical tissue adhesives 29 …”

Section: Resultsmentioning

confidence: 95%

Liquid PEG₄‐PLLA copolymers: Effect of chirality and molecular weight on mechanical properties

Galperin

Eylon

Mizrahi

2022

Polymers for Advanced Techs

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The mechanical properties of polylactic acid (PLA), largely determined by its molecular weight and tacticity, can be modified by copolymerization and multi-armed structure, among other things. A series of liquid PEG 4 -PLA copolymers bearing various PDLLA or PLLA of increasing molecular weights was synthesized and characterized.The glass transition temperature and viscosity gradually increased with the molecular weight and the optical purity of the copolymer's PLA segment. The release profiles of two model drugs, bupivacaine HCl and bovine serum albumin were comparable, and controlled by the molecular weight and dissolution of the polymeric carrier. These findings can help in the development of new applications in biomedicine in which viscosity plays a significant role.

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Two-component cross-linkable gels for fabrication of solid oral dosage forms

Cited by 10 publications

References 45 publications

Liquid Copolymers as Biodegradable Surgical Sealant

Liquid Copolymers as Biodegradable Surgical Sealant

Injectable Anhydrous Poly(ethylene glycol) Polymer Liquids Form Protein Depot for Extended Controlled Release Applications Via Rapid In Situ Gelation

Liquid PEG₄‐PLLA copolymers: Effect of chirality and molecular weight on mechanical properties

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Two-component cross-linkable gels for fabrication of solid oral dosage forms

Cited by 10 publications

References 45 publications

Liquid Copolymers as Biodegradable Surgical Sealant

Liquid Copolymers as Biodegradable Surgical Sealant

Injectable Anhydrous Poly(ethylene glycol) Polymer Liquids Form Protein Depot for Extended Controlled Release Applications Via Rapid In Situ Gelation

Liquid PEG4‐PLLA copolymers: Effect of chirality and molecular weight on mechanical properties

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Liquid PEG₄‐PLLA copolymers: Effect of chirality and molecular weight on mechanical properties