In vitro toxicity assessment of crosslinking agents used in hyaluronic acid dermal filler

Jeong, Chang Hee; Kim, Do Hyun; Yune, Jong Hyeok; Kwon, Hyuk-Cheol; Shin, Dong-Min; Sohn, Hyejin; Lee, Keyong Ho; Choi, Bokryul; Kim, E Sle; Kang, Ju Hee; Kim, Eun Kyoung; Han, Sung Gu

doi:10.1016/j.tiv.2020.105034

Cited by 49 publications

(29 citation statements)

References 35 publications

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“…The new CS/PVA-based hydrogels were successfully obtained, from diluted solutions of PVA, by combining two cross-linking techniques: (a) in the first stage, the covalent cross-linking of the CS chains was performed at RT with EGDGE or BDDGE, known to have low toxicity [ 48 , 49 ]; (b) in the second stage, the physical cross-linking of the PVA chains was achieved by the freeze–thaw cycles [ 33 ]. With the aim to obtain a hydrogel with optimal properties, the influence of synthesis parameters on the hydrogel characteristics was studied ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Dual Cross-Linked Chitosan/PVA Hydrogels Containing Silver Nanoparticles with Antimicrobial Properties

Suflet¹,

Popescu²,

Pelin³

et al. 2021

Pharmaceutics

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Stable chitosan/PVA-based hydrogels were obtained by combining covalent and physical cross-linking methods. As covalent cross-linkers, epoxy agents with different chain lengths were used, while freeze–thaw cycles were applied for additional physical cross-linking. The chemical structure of the hydrogel was examined by FTIR spectroscopy whereas the morphology was analyzed by SEM, showing well-defined pores with dimensions of around 50 μm in diameter. It was proved that gel fraction and the network morphology were deeply influenced by the synthesis conditions. Chitosan/PVA hydrogel showed a relative high swelling rate, reaching equilibrium in the first hour. The values obtained for the elastic modulus were relatively low (3–30 kPa); as a result, these hydrogels are soft and very flexible, and are ideal candidates for medical applications as wound or oral dressings. In addition, the natural antimicrobial activity of chitosan was enhanced by in situ generation of silver nanoparticles (AgNPs) under UV irradiation. The total amount of Ag from hydrogel was determined by elemental analyses and its crystalline state was confirmed by XRD. The CS/PVA hydrogels entrapped with AgNPs exhibited high inhibitory activity against S. aureus and K. pneumonia. The vitality tests confirmed the lack of cytotoxicity of CS/PVA hydrogels without and with AgNPs.

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Section: Resultsmentioning

confidence: 99%

Dual Cross-Linked Chitosan/PVA Hydrogels Containing Silver Nanoparticles with Antimicrobial Properties

Suflet¹,

Popescu²,

Pelin³

et al. 2021

Pharmaceutics

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“…Sodium hydroxide was used to catalyze the crosslinking mechanism between levan derivatives and BDDE. 44,45…”

Section: Resultsmentioning

confidence: 99%

Synthesis and characterization of levan hydrogels and their use for resveratrol release

Selvi

Hasköylü

Genç

et al. 2021

Journal of Bioactive and Compatible Polymers

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Considering the need for systematic studies on levan based hydrogels to widen their use in drug delivery systems and biomedical applications, this study is mainly focused on the synthesis and comprehensive characterization as well as drug release properties of hydrogels based on Halomonas levan (HL) and its chemical derivatives. For this, hydrolyzed and phosphonated HL derivatives were chemically synthesized and then cross-linked with 1,4-Butanediol diglycidyl ether (BDDE) and the obtained hydrogels were characterized in terms of their swelling, adhesivity, and rheological properties. Both native and phosphonated HL hydrogels retained their rigid gel like structure with increasing shear stress levels and tack test analysis showed superior adhesive properties of the phosphonated HL hydrogels. Moreover, hydrogels were loaded with resveratrol and entrapment and release studies as well as cell culture studies with human keratinocytes were performed. Biocompatible and adhesive features of the hydrogels confirmed their suitability for tissue engineering and drug delivery applications.

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“…For example, BDDE induced contact allergy in a patch test and acted as an allergen in brush factory workers [14,15]. In contrast, PEGDE-treated human keratinocyte cells and human dermal fibroblast cells exhibited higher levels of cell viability, lower extent of cell membrane disruption, lower levels of cellular oxidative stress, and more muted inflammatory response than BDDE-treated cells [16]. This previous study provided in vitro evidence that PEGDE induces lower levels of dermal toxicity than BDDE.…”

Section: Introductionmentioning

confidence: 82%

Toxicity Assessment of a Single Dose of Poly(ethylene glycol) Diglycidyl Ether (PEGDE) Administered Subcutaneously in Mice

Kim

Han

Kwon

et al. 2021

Toxics

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Poly(ethylene glycol) diglycidyl ether (PEGDE) is widely used to cross-link polymers, particularly in the pharmaceutical and biomaterial sectors. However, the subcutaneous toxicity of PEGDE has not yet been assessed. PEGDE samples (500–40,000 μg/mouse) were subcutaneously injected into the paraspinal dorsum of BALB/c male mice. Cage-side observations were carried out with measurement of organ weight, body weight variation, and feed intake, as well as histopathological characterization on day 28 post-exposure. Mice that received 40,000 μg of PEGDE showed severe toxic response and had to be euthanized. Subcutaneous injection of PEGDE did not alter feed intake and organ weight; however, the body weight variation of mice injected with 20,000 μg of PEGDE was significantly lower than that of the other groups. Exposure to 10,000 and 20,000 μg of PEGDE induced epidermal ulcer formation and hair loss. The histology of skin tissue in mice administered with 20,000 μg of PEGDE showed re-epithelialized or unhealed wounds. However, the liver, spleen, and kidneys were histologically normal. Collectively, PEGDE, particularly above 10,000 μg/mouse, caused subcutaneous toxicity with ulceration, but no toxicity in the other organs. These results may indicate the optimal concentration of subcutaneously injected PEGDE.

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In vitro toxicity assessment of crosslinking agents used in hyaluronic acid dermal filler

Cited by 49 publications

References 35 publications

Dual Cross-Linked Chitosan/PVA Hydrogels Containing Silver Nanoparticles with Antimicrobial Properties

Dual Cross-Linked Chitosan/PVA Hydrogels Containing Silver Nanoparticles with Antimicrobial Properties

Synthesis and characterization of levan hydrogels and their use for resveratrol release

Toxicity Assessment of a Single Dose of Poly(ethylene glycol) Diglycidyl Ether (PEGDE) Administered Subcutaneously in Mice

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