Pharmaceutical Research & Development (Track)


Xingyi Li and Hao Chen

Wenzhou Medical College, School of Optometry and Ophthalmology and Eye Hospital, China



To develop a novel injectable small molecular hydrogel (Triamcinolone acetonide (TA) and rapamycin (RA)) for ocular drug delivery applications.


Synthesis of TA/RA-SA

A mixture of TA or RA 0.13 g (0.3 mmol) and succinic anhydride 0.09 g (0.9 mmol) were dissolved in pyridine (2.5 mL) and stirred for 3 h at room temperature, evaporated the solution to dryness in vacuo. Water (50 ml) was added into the residue slowly, stirring for 20 min, and the solution was placed on ice statically. Finally, the fine crystals were collected through centrifuging and lyophilized by lyophilizer.

Synthesis of TA/RA hydrogel

TA/RA-SA (53.4 mg, 0.1 mmol) was dissolved in CH2Cl2 (20 mL) followed by addition of N-hydroxysuccinimide (12.7 mg , 0.11 mmol) and dicyclohexylcarbodiimide (24.7 mg, 0.12 mmol). The reaction was strirred for 3 h at room temperature and in dark, the precipitation was filtered and washed with CH2Cl2 , and the organic solution was removed under reduced pressure to give a intermediate. The intermediate was dissolved in DMF (10 mL), and then FA-K-ss-EE (159.3 mg, 0.15 mmol) and DIEA (99μL, 0.6mmol) were added. The mixture was stirred at room temperature and in dark for 24 h. The reaction mixture was purified by preparative HPLC, yield 118 mg of title product (74.9%).


We have developed molecular hydrogels of TA and RA derivatives and demonstrated that FA might be a versatile molecule to construct molecular gelators through conjugation to hydrophobic therapeutic agents. The hydrogels were stable at room temperature for more than 5 months and TAgel could gradually adsorb/degrade after sub-Tenon injection in rabbit eye in a 60 days experimental period. The in vivo compatibility results indicated that TAgel showed no obvious toxicity to rabbit eye, which suggested its big potential as a long acting drug delivery system for the treatment of eye diseases.

Keywords: Small molecuar hydrogel, ocular drug delivery.