Efficient and Economic Heparin Recovery from Porcine Intestinal Mucosa Using Quaternary Ammonium-Functionalized Silica Gel

Abstract

Heparin, usually isolated from porcine intestinal mucosa, is an active pharmaceutical ingredient of great material value. Traditionally, diverse types of commercial resins were employed as an adsorbent for heparin retrieval from biological samples. However, more recent years have encouraged the advent of new cost-effective adsorbents to achieve enhanced heparin retrieval. Inexpensive cationic ammonium-functionalized silica gels, monodispersed with larger surface area, porosity, and higher thermal stability, were chosen to evaluate the heparin recovery yield from porcine intestinal mucosa. We demonstrated that higher positively charged and less bulky quaternary modified silica gel (e.g., QDASi) could adsorb ~28% (14.7 mg g−1) heparin from the real samples. In addition, we also determined suitable surface conditions for the heparin molecule adsorption by mechanistic studies and optimized different variables, such as pH, temperature, etc., to improve the heparin adsorption. This is going to be the first reported study on the usage of quaternary amine-functionalized silica gel for HEP uptake.

Modified Diatomaceous Earth in Heparin Recovery from Porcine Intestinal Mucosa

“…Also, the value of S* equal to 0.227 indicates the proper stick of heparin molecules on the surface of the adsorbent [59][60][61][62]. [11]. Specifically, it achieved an adsorption efficiency of approximately 31% and a capacity of 16.4 mg•g −1 under the optimized conditions.…”

“…3.1.2. Methyl Iodide Treatment of Amine-Functionalized DEs [11,37] Different volumes of methyl iodide (1.0, 1.5, and 2.0 mL) were added individually to the Milli-Q water solutions (12.5 mL) of MADE, DADE, and TADE (1 g per material), respectively, at pH ~6.0. An excessive amount of methyl iodide (CH 3 I) was employed for the synthesis.…”

“…). By plotting Lnη rel C against the concentration (C), we obtained the necessary data [11,65]. Finally, the molecular weight (Mw) of the heparin was calculated using the Mark-Houwink-Sakurada equation ([η]= K.M α w ).…”

“…Besides heparin, this digestion mixture contains nucleic acids, proteins, and other biochemicals. The next step of the heparin extraction process involves several adsorption-desorption steps [7][8][9][10][11][12]. This complex and labor-intensive process makes the extraction unviable and only very low concentrations (0.01% w/w) of heparin are isolated from enzymatically digested natural tissue [13].…”

“…Therefore, it is highly desirable to conduct research to develop new adsorbents. Adsorbent surface area, porosity, surface chemistry/properties, and chemical stability, along with thermodynamic stability, are some of the crucial parameters for the maximum extraction of heparin [11,16].…”