Monticelli Damiano, Martina Virginia, Mocchi Roberto, Rauso Raffaele, Zerbinati Umberto, Cipolla Giovanna, Zerbinati Nicola
University of Insubria, Department of Science and High Technology, Como, Italy.
MatexLab S.p.a., Department of Research and Development, Brindisi, Italy.
Open Access Maced J Med Sci. 2019 Apr 14;7(7):1077-1081. doi: 10.3889/oamjms.2019.279. eCollection 2019 Apr 15.
Hyaluronic acid (HA) based hydrogels for esthetic applications found widespread use. HA should be crosslinked for this application to achieve the correct viscoelastic properties and avoid fast degradation by the hyaluronidase enzyme naturally present in the skin: these properties are controlled by the amount of crosslinker and the fraction that is effectively crosslinked (i.e. that binds two HA chains).
Crosslinking by polyethylene glycol diglycidyl ether (PEGDE) has been more recently introduced and showed attractive features in terms of viscoelastic properties and reduced biodegradation. Aim of this paper is to define a method for the determination of the crosslinking properties of these recently introduced fillers, method that is lacking at the moment.
The percentage of crosslinker and the fraction that is effectively crosslinked were determined by proton Nuclear Magnetic Resonance (1H NMR) and by 13C NMR, respectively. The filler were preliminarily washed with acetonitrile to remove residual PEG and then digested by hyaluronidase to obtain a sample that can be analysed by NMR.
The crosslinking parameters were determined in four samples of NEAUVIA PEG-crosslinked dermal fillers (produced by MatexLab S.p.A., Italy). The percentage of crosslinker was between 2.8% and 6.2% of HA, whereas the effective crosslinker ratios were between 0.07 and 0.16 (ratio between the moles of effectively crosslinked PEG and total moles of PEG). Moreover, a digestion procedure alternative to enzymatic digestion, based on acidic hydrolysis, was successfully tested for the determination of crosslinker percentage.
The proposed method successfully determined the two crosslinking parameters in PEG-crosslinked dermal fillers. The estimated percentage of crosslinker is similar to previously reported data for other crosslinkers, whereas the effective crosslinker ratio is lower for PEG crosslinked hydrogels.
用于美容应用的基于透明质酸(HA)的水凝胶得到了广泛应用。为此应用,HA应进行交联以获得正确的粘弹性特性,并避免被皮肤中天然存在的透明质酸酶快速降解:这些特性由交联剂的量和有效交联的部分(即连接两条HA链的部分)控制。
最近引入了聚乙二醇二缩水甘油醚(PEGDE)交联方法,该方法在粘弹性特性和降低生物降解方面显示出有吸引力的特征。本文的目的是定义一种用于测定这些最近引入的填充剂交联特性的方法,目前该方法尚不存在。
交联剂的百分比和有效交联的部分分别通过质子核磁共振(1H NMR)和13C NMR测定。填充剂先用乙腈初步洗涤以去除残留的PEG,然后用透明质酸酶消化以获得可通过NMR分析的样品。
在四个NEAUVIA PEG交联的真皮填充剂样品(由意大利MatexLab S.p.A.生产)中测定了交联参数。交联剂的百分比在HA的2.8%至6.2%之间,而有效交联剂比率在0.07至0.16之间(有效交联的PEG摩尔数与PEG总摩尔数之比)。此外,基于酸性水解的酶消化替代消化程序已成功测试用于测定交联剂百分比。
所提出的方法成功地测定了PEG交联真皮填充剂中的两个交联参数。估计的交联剂百分比与先前报道的其他交联剂数据相似,而PEG交联水凝胶的有效交联剂比率较低。