Preparation and in vivo and in vitro Characteristic Evaluation of Ligustrazine Ophthalmic Liposome Thermosen- sitive Gel
- VernacularTitle:川芎嗪眼用脂质体温敏凝胶的制备及体内外特性评价
- Author:
Wei LI
1
;
Liang CHEN
1
,
2
;
Dan YIN
1
,
3
;
Hao YANG
1
;
Jiayi ZHOU
1
;
Yu SONG
4
;
Yan ZHANG
1
;
Liang ZOU
4
Author Information
1. Basic Medical School，Chengdu University，Chengdu 610106，China
2. College of Pharmacy，Chengdu University of TCM，Chengdu 611137，China
3. College of Pharmacy，Chengdu University，Chengdu 610052，China
4. Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs，Chengdu University，Chengdu 610106，China
- Publication Type:Journal Article
- Keywords:
Ligustrazine opthalmic liposome;
Thermosensitive gel;
Preparation technology;
in vitro drug release;
Human
- From:
China Pharmacy
2021;32(3):320-327
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To prepare Liguatrazine opthalmic liposome therm osensitive gel ，and to investigate its in vivo and in vitro characteristics. METHODS ：The ammonium sulfate gradient method was used to prepare Liguatrazine liposomes. The preparation technology was optimized by using orthogonal test. Using poloxamer P 407 as gel matrix ，Liguatrazine liposomes were prepared into thermosensitive gel. A membraneless model was used to study the dissolution and in vitro drug release of the gel. The modified Franz diffusion cell was used to investigate corneal permeability and further determine corneal hydration value. The effects of the gel on the proliferation of human corneal epithelial cell HCE-T. HE staining and Draize test were used to investigate the stimulatory effects of the gel on corneal cells of the rabbit ，and the histological changes of the eyes were observed. RESULTS ：The optimal preparation technology of Liguatrazine liposome was drug-lipid ratio of 1 ∶ 10（m/m），the ammonium sulfate concentration of 0.2 mol/L，phospholipid-cholesterol ratio of 4∶1（m/m），incubation temperature of 45 ℃. Then ligustrazine opthalmic liposome thermosensitive gel was prepared with 23％ poloxamer P 407 as gel matrix. The gel had good gelatinization temperature. The in vitro drug release and dissolution showed zero-order kinetic characteristics ，and in vitro drug release of the gel was mainly related to dissolution （R2＝0.993 4）. The cumulative transcorneal permeability of the gel was 43.3％ within 6 hours and corneal hydration value was 72.98％. Low and medium concentrations （1，5 mg/L）of Ligustrazine opthalmic liposome thermosensitive gel had no obvious proliferation toxicity to HCE-T cells ，but it showed cytotoxicity at high concentration （10 mg/L）. The mean Draize eyeirritation score of the gel on rabbit cornea was within non-stimulation，and there was no abnormal change in rabbit （No.2018001） corneal histology. CONCLUSIONS ： Prepared Ligustrazine opthalmic liposome thermosensitive gel has a suitable phase transition temperature ，good corneal permeability ，and low corneal irrit ation.
