Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5915_Библиотеки_им_академика_М_И_Перельмана

Several preliminary studies have reported the use of POE as a delivery vehicle for 5-fluorouracil (Einmahl et al. 1999, 2001; Bernatchez et al. 1994). Einmahl and colleagues investigated an injectable, sustained-release POE-based 5-fluorouracil ointment in an experimental glaucoma filtration model in rabbits. The ointment significantly decreased intraocular pressure and led to persistence of the filtering bleb at days 9–28 after trabeculectomy (Einmahl et al. 2001). Corneal toxicity with the POE ointment was significantly lower as compared with conventional 5-fluo­rouracil tamponade. Histopathologic analysis indicated that POE was well toler­ated and did not lead to fibrosis. The same research group also developed a POE-based ointment capable of delivering dexamethasone and 5-fluorouracil con­comitantly for the potential treatment of intraocular proliferative disorders (Einmahl et al. 1999). A POE-based 5-chlorouracil drug delivery system has also been devel- oped and its performance was evaluated in a glaucoma filtration surgery model in rabbits (Polak et al. 2008).

Jampel and associates developed biodegradable subscleral PAH-based discs (a copolymer of 25:75 1,3-bis[p-carboxyphenoxy] propane and sebacic acid) for the delivery of various antiproliferative agents and evaluated their effects in vitro and in a primate glaucoma filtration surgery model (Jampel et al. 1990, 1991, 1993; Uppal et al. 1994). PAH discs impregnated with 5-fluorouridine inhibited fibroblast prolif­eration in vitro, provided sustained drug delivery for at least 16 days in vivo, and prolonged the duration of intraocular pressure reduction following filtration surgery (Jampel et al. 1990). PAH discs were also developed to provide sustained delivery of the antiproliferative agents taxol and etoposide (VP-16) (Jampel et al. 1991). In vitro, the discs delivered taxol for 100 days and at concentrations exceeding taxol’s ID50 threefold for fibroblast proliferation (3 ng/mL). PAH discs with etoposide provided sustained release for 31 days (Jampel et al. 1991). PAH discs impregnated with taxol (50 mg) or etoposide (1 mg) have been investigated as an adjunct to filtration surgery in monkeys (Jampel et al. 1993). PAH disks containing taxol, but not etoposide, had a marked beneficial effect on intraocular pressure and bleb appearance postsurgically. Etoposide-PAH discs (1 mg) placed subconjunctivally in healthy rabbit eyes provided a nearly linear rate (30 mg/day) of drug release over 12 days, except for a burst occurring between days 6 and 7. Steady-state drug levels were 89 ng/mg in the conjunctiva and sclera, 195 ng/mL in the vitreous, and 29 ng/mL in serum; these levels were deemed sufficient to reduce fibroblast prolif­eration after glaucoma surgery (Uppal et al. 1994).

Additional strategies for ocular drug delivery that have been investigated in pre­clinical studies include biodegradable injectable polymeric particulates (micro/ nano particles, spheres), drug-polymer gels, and drug-eluting polymer-based contact lenses.