Optimization of a novel bioerodible device based on auto-catalyzed poly(ortho esters) for controlled delivery of tetracycline to periodontal pocket

Schwach-Abdellaoui, Khadija; Monti, Alessio; Barr, John T.; Heller, Jorge; Gurny, Robert

doi:10.1016/s0142-9612(00)00327-6

Cited by 35 publications

(19 citation statements)

References 27 publications

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“…Recently, Heller and Gurny successfully applied it in the hydrophobic semisolid poly(ortho esters) (POE) for injectable drug-delivery systems for the treatment of periondontal diseases. 22,30 Here, investigations with tetracycline hydrochloride (TH) should facilitate easy comparison with our previous data from the POE studies and check on similarities and differences for these two kinds of hydrophobic polymers.…”

Section: Tetracycline Releasementioning

confidence: 99%

“…It was previously reported that TH degraded quickly in acidic conditions leading to about 50% of the epimer form. 22 Therefore, it is probable that also here TH is degraded inside the polymer matrix, which has an acidic environment while polymer degradation takes place. The released proportion of the medical active TH compared to 4-epitetracycline was systematically much higher for PmHLA than for the standard PLA.…”

Section: Tetracycline Releasementioning

confidence: 99%

“…Interestingly, the TH release profile from PmHLA is with 45% better than that reported for commercial Actisite fibers, which is loaded with 25% TH and releases about 30% active TH within 14 days. 22 Actual molecular weights are peak molecular weights plus atomic weight of one proton (negative polarization). …”

Section: Tetracycline Releasementioning

confidence: 99%

“…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%

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

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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: Tetracycline Releasementioning

confidence: 99%

Section: Tetracycline Releasementioning

confidence: 99%

Section: Tetracycline Releasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

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Gurny

Möller

2006

J Biomedical Materials Res

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“…25 TB incorporated into these materials was released within 10 to 14 days depending on polymer structure. Increase in lactic acid content in the polymer tended to increase the drug release rate and to reduce the initial lag time.…”

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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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Ocular biocompatibility of a poly(ortho ester) characterized by autocatalyzed degradation

Einmahl

Ponsart

Bejjani

et al. 2003

J Biomedical Materials Res

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The biocompatibility of autocatalyzed poly(ortho ester) (POE(70)LA(30)), a viscous, hydrophobic, bioerodible polymer, was investigated. POE(70)LA(30) was synthesized, sterilized by gamma irradiation, and injected in rabbit eyes at adequate volumes through subconjunctival, intracameral, intravitreal, and suprachoroidal routes. Clinical examinations were performed postoperatively at regular time points for 6 mo, and histopathologic analysis was carried out to confirm tissular biocompatibility. After subconjunctival injection, the polymer was well tolerated and persisted in the subconjunctival space for about 5 weeks. In the case of intracameral injections, polymer biocompatibility was good; the POE(70)LA(30) bubble was still present in the anterior chamber for up to 6 mo after injection. No major histopathologic anomalies were detected, with the exception of a localized Descemet membrane thickening. After intravitreal administration, POE(70)LA(30) biocompatibility was excellent, and no inflammatory reaction could be detected during the observation period. The polymer was degraded in approximately 3 mo. Suprachoroidal injections of POE(70)LA(30) were reproducible and well tolerated. POE(70)LA(30) triggered a slight elevation of the retina and choroid upon clinical observation. The polymer was detectable in the suprachoroidal space for about 6 mo. No inflammatory reaction and no major retinal anomalies could be detected by histology. In conclusion, POE(70)LA(30) appears to be a promising biomaterial for intraocular application, potentially providing sustained drug delivery over an extended period of time, with a good tolerance.

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Optimization of a novel bioerodible device based on auto-catalyzed poly(ortho esters) for controlled delivery of tetracycline to periodontal pocket

Cited by 35 publications

References 27 publications

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

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

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

Ocular biocompatibility of a poly(ortho ester) characterized by autocatalyzed degradation

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