Concomitant and controlled release of dexamethasone and 5-fluorouracil from poly(ortho ester)

Einmahl, Suzanne; Zignani, M.; Varesio, Emmanuel; Heller, Jorge; Veuthey, Jean‐Luc; Tabatabay, C.; Gurny, Robert

doi:10.1016/s0378-5173(99)00149-0

Cited by 58 publications

(25 citation statements)

References 13 publications

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“…27 This is explained by the stabilization of POE by the basic nature of DEX, as described in an in vitro study. 19 The in vivo prolonged presence of polymer containing DEX could also result from a reduced inflammatory cell infiltration, notably a decreased accumulation of macrophages, due to the anti-inflammatory properties of DEX. In fact, the interfacial pH between macrophages and the biodegradable polymer surface may be as low as 3, and an acidic environment is known to increase POE degradation rate.…”

Section: Discussionmentioning

confidence: 99%

“…17 Kinetics of drug release from POE, as well as polymer degradation rate, can be controlled by many factors such as polymer molecular weight and physicochemical properties of the excipients and drugs incorporated, 1 notably their water solubility, hydrophilic/hydrophobic balance, and acidobasicity. 18,19 The use of acids leads to a fast polymer degradation and drug release because ortho ester bonds are sensitive to acid catalysis. POE containing basic excipients such as magnesium hydroxide and sodium acetate or drugs such as dexamethasone sodium phosphate is stabilized and the release rate is sustained.…”

Section: Introductionmentioning

confidence: 99%

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A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application

Einmahl

Behar‐Cohen

Tabatabay

et al. 2000

J. Biomed. Mater. Res.

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The biocompatibility of a viscous, hydrophobic, bioerodible poly(ortho ester) (POE) intended for intraocular application was investigated. POE was evaluated as a blank carrier and as containing modulators of degradation. Each formulation was injected intracamerally and intravitreally in rabbit eyes, and clinical and histological examinations were performed postoperatively for 2 weeks. In the case of intracameral injections, polymer biocompatibility appeared to depend on the amount injected in the anterior chamber. When 50 microL was administered, the polymer degraded within 2 weeks, and clinical observations showed good biocompatibility of POE with no toxicity to the ocular tissues or increase in intraocular pressure. The injection of a larger volume, 100 microL, of POE, appeared inappropriate because of direct contact of polymeric material with the corneal endothelium, and triggered reversible edema and inflammation in the anterior chamber of the eye that regressed after a few days. After intravitreal administration, POE was well tolerated and no inflammatory reaction developed during the observation period. The polymer degraded slowly, appearing as a round whitish bubble in the vitreous cavity. The presence of modulators of degradation both improved POE biocompatibility and prolonged polymer lifetime in the eye. POE appears to be a promising biomaterial for clinical intraocular application.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application

Einmahl

Behar‐Cohen

Tabatabay

et al. 2000

J. Biomed. Mater. Res.

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“…In particular, biodegradable polymeric materials have been extensively investigated for ocular drug delivery systems for the past two decades [55]. Although we described mainly drug delivery systems with use of PLA or PLGA, new biodegradable polymers such as polyanhydrides [20, 21, 22, 23, 24, 25]and poly(ortho esters) [26, 27]also have been evaluated for ophthalmic use. Polymeric drug delivery systems will likely increase bioavailability of the drug and decrease its side effects.…”

Section: Resultsmentioning

confidence: 99%

“…PLA, PGA, and PLGA are the most popular polymers that undergo the bulk erosion process. Polymers such as polyanhydride [20, 21, 22, 23, 24, 25]or poly(ortho ester) [26, 27]that undergo a surface erosion process have been investigated. The most commonly used polyanhydride for drug delivery is a copolymer of bis( p -carboxyphenoxy) propane and sebacic acid.…”

Section: Fundamentals Of Polymers In Controlled Release Systemsmentioning

confidence: 99%

Biodegradable Polymers for Ocular Drug Delivery

2001

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A variety of ocular drug delivery systems, including a controlled release of the drug, drug targeting, and penetration enhancement of the drug, have been investigated. Biodegradable polymers have been widely used as the drug carrier for controlled-release systems. Biodegradable polymers release the drug as they themselves degrade and are finally absorbed within the body. Several ocular drug delivery systems using different kinds of biodegradable polymers have been studied. In this article, we describe the fundamental mechanisms of drug delivery systems, polymer erosion and drug release, and then review those systems using the most popular biodegradable polymers, poly(lactic acid) and poly(lactic-glycolic acid).

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“…POE has investigated as a sustained drug release system for an ophthalmic application in intraocular proliferative disorders. The combination of wound healing modulators such as 5-fl uorouracil and dexamethasone has advantage, since these drugs act at different stages of these diseases [ 114 ].…”

Section: Polyorthoestersmentioning

confidence: 99%