Modification of zein functional drug-loaded microsphere with TRIS 2018-11-02 15:48:03

As a common biological buffer, Tris(Hydroxymethyl)Aminomethane (TRIS) is not only widely used as a solvent for nucleic acids and proteins, but also as one of the main components of protein electrophoresis buffers. It can also produce a variety of chemicals and pesticides, pharmaceutical products, and it is an important intermediate for the preparation of surfactants, vulcanization accelerators and some drugs. This article will introduce another role of TRIS——modified zein functional drug-loaded microspheres.

As a natural hydrophobic macromolecule, zein has a wide range of sources, it is non-toxic, non-immunogenic, and has good biocompatibility and biodegradability. It is one of the few hydrophobic biopolymers that are allowed to be taken orally by the FDA:

(1) Its amino acid composition is very special, the proportion of non-polar amino acids is more than 50%. It can embed various substances such as polysaccharides. DNA, RNA, proteins, metal nanoparticles, quantum dots, oil droplets, and hydrophobic drugs;

(2) The amino acid residues on zein carry certain polar groups (such as ‐SH, ‐COOH, ‐NH3, and ‐OH), it provides the possibility to graft various functional molecules for chemical reaction sites and adapt to the complex and varied human environment.

Therefore, zein is an advantageous drug carrier material. However, the proportion of sulphur-containing amino acids in zein is only 2.8%, the ratio of basic amino acids is only 2.9%, and the proportion of hydroxyamino acids is 13.4%, which limits the selection of functional molecules and the effect of modification. To improve this, the researchers modified it with TRIS, including the following steps [1]:

(1) The zein and the amino protecting agent di-tert-butyl dicarbonate are dissolved in a specific dimethyl sulfoxide or ethanol aqueous solution at a mass ratio of 1:1~1.5:1, and protected from light at 25~40°C. The reaction is carried out for 12~24 hours to obtain a zein protection solution;

(2) Under the protection of nitrogen, add carbodiimide salt, N-hydroxysuccinimide and TRIS (CAS 77-86-1) to the zein protection solution, and avoid the light reaction at 25-40°C for 12~24 hours. To obtain a TRIS-zein solution;

(3) under the protection of nitrogen, adding concentrated hydrochloric acid to the tris-zein solution, and avoiding light reaction at 25-40°C for 6-8h;

(4) adjusting the pH to 5.0~6.0, transferring to a dialysis bag, centrifuging the retained solution in the dialysis bag, and lyophilizing to obtain TRIS-zein;

(5) Dissolving the hydrophobic drug and the lyophilized TRIS -zein in an aqueous solution of ethanol at a mass ratio of 1:1 to 1:10; and injecting hydrochloric acid having a pH of 2.5 to 4.5 under magnetic stirring. In the aqueous solution, after stabilization, the supernatant is centrifuged to obtain a drug-loaded microsphere;

(6) Functional modification of drug-loaded microspheres: separately prepare solutions containing different functional molecules, disperse the drug-loaded microspheres into a solution containing functional molecules, stir the reaction, centrifuge to remove the supernatant, and obtain functional drug carrying microsphere. The drug microspheres have a particle size of 100~300 nm and a drug-loading efficiency of 81.48~86.01%, and the grafting amount of the functional molecules is 1.72~1.94 times that of the unmodified zein microspheres.

The coupling of TRIS to zein significantly improves the physicochemical properties of zein. The prepared microspheres have good sphericity, uniform particle size distribution, high drug-loading efficiency, and are suitable for in vivo delivery. This research expands the application of zein in drug delivery systems and has a good application prospect in the field of medicine.


[1] Jiang Yanbin, Pang Jiafeng, Lu Shan, Li Zhixian, Trimethylolamine modified zein functional drug-loaded microspheres and preparation method. 2018, CN108403662A.

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