[Experimental study of low molecular weight heparin drug delivery system for prevention of posterior capsular opacification in rabbit eyes].
OBJECTIVE
To investigate the safety and efficacy of low-molecular-weight heparin drug delivery system (LMWH DDS) for prevention of posterior capsular opacification (PCO) in rabbit eyes.


METHODS
(1) To prepare the LMWH DDS by freeze-drying way with Polylactic-co-glycolic acid (PLGA) as the carrier, and evaluate its release properties in vitro. (2) Fifty New Zealand albino rabbits (50 eyes) undergoing phacoemulsification were equally divided into five groups: receiving normal saline eye drops (group A), 3 different dose (1 mg, 0.5 mg and 0.25 mg) of LMWH DDS respectively implanted into the posterior chamber (group B, C and D), and a carrier DDS implanted into the posterior chamber (group E). All the 50 eyes were examined by slit-lamp microscopy. The low-molecular-weight heparin levels in aqueous humor were measured, and the wet posterior capsules were weighed.


RESULTS
The LMWH DDS prepared with a freeze-dried way has high encapsulation efficiency, and the equation of 49-day release curve fitting in vitro were were similar to zero order. The fibrin exudation in group B, C and D were lower than in Group A and E during the first postoperative day. There were 10, 2, 3, 9 and 10 eyes that developing PCO in the group A, B, C, D and E, respectively. The mean wet-weight of the posterior capsule were (114.59 +/- 14.58) mg, (24.14 +/- 6.08) mg, (39.23 +/- 17.13) mg, (99.35 +/- 29.37) mg, (115.29 +/- 19.87) mg respectively in 5 trial groups. There were stable and high concentration of low molecular weight heparin in aqueous of group B and C during the 4 weeks (> 20 mg/L), while a instable and lower concentrations in group D. The result of optical microscopy and electron microscopy examination indicated that fibroblast proliferation was quite active in groups A, D and E, but inactive in group B and C. Neither infiltration of inflammatory cells at the cornea, iris, trabecular meshwork and ciliary body nor retinal degeneration or necrosis was found in any group at 12 weeks. There was no intraocular bleeding in all the five groups in the following 12 weeks.


CONCLUSIONS
The LMWH DDS prepared by freeze-drying way with PLGA as the carrier has good slow-release and biological tolerance. Implantation of LMWH DDS into the posterior chamber of experimental animals can significantly reduce postoperative fibrin exudation, and can safe and effective prevent the occurrence of PCO, and also there were some dose-effect relationship.
Dai
Yun-Hai
YH
State Key Laboratory Cultivation Base, Shandong Eye Institute, Qingdao 266071, China.
Xie
Li-Xin
LX
Wu
Xiang-Gen
XG
Huang
Yu-Sen
YS
Gong
Hua-Qing
HQ
Yin
Hong-Mei
HM
D000818:Animals; D002386:Cataract / Q000517:prevention & control*; D016503:Drug Delivery Systems; D005612:Freeze Drying; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000627:therapeutic use; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011446:Prospective Studies; D011817:Rabbits
D006495:Heparin, Low-Molecular-Weight; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid