Semi-solid hydrophobic bioerodible poly (ortho ester) for potential application in glaucoma filtering surgery

Merkli, Alain; Heller, Jorge; Tabatabay, C.; Gurny, Robert

doi:10.1016/0168-3659(94)90126-0

Cited by 40 publications

(15 citation statements)

References 16 publications

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“…18 On the basis of these initial results, the new hydrophobic substituted polylactides could be favorable and interesting for applications as injectable semisolid materials for drug delivery comparable to the reported hydrophobic poly (ortho esters). 21,22 Moreover, the increased hydrophobicity of these PLA-polymers could lead to further interesting properties in colloidal systems, for example, in terms of encapsulation efficiency and release of hydrophobic drugs. Our initial studies showed that nanoparticles can be obtained from these new polymers by the nanoprecipitation technique.…”

Section: Introductionmentioning

confidence: 99%

Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

Trimaille

Gurny

Möller

2006

J Biomedical Materials Res

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Poly(hexyl-substituted lactides) (PHLA) as new hydrophobic polyesters with controlled molecular weights and narrow distributions were synthesized by ring-opening polymerization (ROP) using tin(II) 2-ethylhexanoate (Sn(Oct) 2 ) and benzyl alcohol as catalyst and initiator. Glass transition temperatures (T g ) and zero shear viscosities (g 0 ) at 258C could be modulated from T g ¼ À428C to À108C and 40 to 4850 Pa s, respectively, by varying the polymer molecular weight and the number of hexyl groups along the polymer chain. Degradation studies were performed in terms of both mass and molecular weight loss in the course of time. The degradation mechanism is shown to be of the ''bulk erosion'' type, and comparable to standard poly(D,L-lactide) (PLA). Despite the increased steric hindrance in the poly(monohexyl-substituted lactide) (PmHLA) due to the hexyl side groups, its degradation rate at pH 7.4 and 378C was found to be slightly higher than observed for the analogue standard PLA. This could be attributed to the flexible rubbery state of the hexyl-substituted polymer (T g *À158C) at the physiological temperature, which is favoring the degradation in comparison to the rigid and glassy standard PLA (T g *408C). In contrast, degradation studies performed at 608C, where both polymers are above their glass transition temperature, confirmed that the degradation rate is lower for the sterically more hindered PmHLA. The degradation products were analyzed by ESI-MS. Hydrolysis lead first to the corresponding oligo-ester fragments and finally to the nontoxic 2-hydroxyoctanoic acid and lactic acid. Tetracycline was tested as a model drug for release studies. This drug was found to be released faster and in higher amounts in its active form from the PHLA matrix than from standard PLA. The results presented in this work demonstrate the potential of these hydrophobic polylactide-based semisolid materials as an alternative to conventional PLA/PLGA for injectable drug delivery systems. 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A: [55][56][57][58][59][60][61][62][63][64][65] 2007

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Section: Introductionmentioning

confidence: 99%

Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

Trimaille

Gurny

Möller

2006

J Biomedical Materials Res

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“…1,2 Glaucoma filtration surgery is realized by creating a fistula between the anterior chamber of the eye and the subconjunctival space, allowing the drainage of aqueous humor to reduce the intraocular pressure and preserve vision in patients suffering from severe glaucoma. 3 Inhibition of subconjunctival fibrosis is desired, and the surgical procedure fails when the scarred conjunctiva adheres to the episcleral tissue and the bulbar sclera.…”

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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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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“…In vitro drug release was conducted in specially thermostated cells at 37°C circulated with phosphate buffer. 26 The amount of drug released was measured by high-performance liquid chromatography (HPLC) using the method described previously. 25 …”

Section: Methodsmentioning

confidence: 99%

Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: Preliminary trial in humans

Schwach-Abdellaoui

Loup

Vivien-Castioni

et al. 2002

AAPS J

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The semisolid consistency of poly(ortho esters) (POEs) containing tetracycline free base allows direct injection in the periodontal pocket and shows sustained and almost constant in vitro release in phosphate buffer, pH 7.4 at 37°C, for up to 14 days. Total polymer degradation concomitant with drug release was obtained. Formulations containing 10% or 20% (wt/wt) tetracycline were evaluated in a panel of 12 patients suffering from severe and recurrent periodontitis. In the first trial including 6 patients, singlerooted teeth and molar teeth with furcations were treated immediately after scaling and root planing. Patients tolerated both formulations well, experienced no pain during application, and showed no signs of irritation or discomfort during the observation period. However, retention of the formulation was minimal in this first study. An improved clinical protocol followed in the second study (stopping bleeding after scaling and root planning) prolonged the retention of the formulations in the inflamed periodontal pockets. For up to 11 days, tetracycline concentrations in the gingival crevicular fluid were higher than the minimum inhibitory concentration of tetracycline against most periodontal pathogens.

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Semi-solid hydrophobic bioerodible poly (ortho ester) for potential application in glaucoma filtering surgery

Cited by 40 publications

References 16 publications

Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

Poly(hexyl‐substituted lactides): Novel injectable hydrophobic drug delivery systems

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

Bioerodible injectable poly(ortho ester) for tetracycline controlled delivery to periodontal pockets: Preliminary trial in humans

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