Inhibition of Cell Proliferation by Mitomycin C Incorporated into P(HEMA) Hydrogels

Blake, Diane A.; Şahiner, Nurettin; John, Vijay T.; Clinton, A.D.; Galler, K.E.; Walsh, Molly M.; Arosemena, Analisa; Johnson, Pamela Y.; Ayyala, Ramesh S.

doi:10.1097/01.ijg.0000212236.96039.9c

Cited by 28 publications

(18 citation statements)

References 15 publications

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“…In the GH-MMC group, the exposed concentration for the initial 3 days was 2 lg MMC in 0.0375 mL (0.0375 g) solution, 0.054 mg/g MMC per day, which was higher than 0.04 mg/g, the minimum concentration needed for inhibiting conjunctival fibroblast proliferation in vitro. 24 Taken together, the amount of MMC released from the GH in the present study should be effective for suppressing scar formation after glaucoma surgery and should induce less toxicity to the conjunctiva.…”

Section: Discussionmentioning

confidence: 61%

Effects of Gelatin Hydrogel Loading Mitomycin C on Conjunctival Scarring in a Canine Filtration Surgery Model

Kojima

Sugiyama

Jin

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 61%

Effects of Gelatin Hydrogel Loading Mitomycin C on Conjunctival Scarring in a Canine Filtration Surgery Model

Kojima

Sugiyama

Jin

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…4,5 In 2002, we initiated studies to incorporate the antifibrotic drug mitomycin C into a poly(2-hydroxyethyl methacrylate) (P[HEMA])-based drug-release device. 6 The P(HEMA) polymer was washed to remove low-molecular-weight toxicants that remained after polymerization, and the mitomycin C was subsequently loaded into the matrix using a novel mechanism. This polymer enabled release of the drug on contact with water.…”

mentioning

confidence: 99%

“…The results demonstrated that the P(HEMA) polymer enabled release of mitomycin C and inhibited the proliferation of fibroblasts in a dose-dependent manner. 6 The objectives of the present study were (1) to develop techniques for preparation and standardization of P(HEMA) disks loaded with mitomycin C; (2) to demonstrate that the device released mitomycin C both in vitro and in vivo when attached to a commercially available flexiplate silicone Ahmed glaucoma valve (AGV) (model FP7; New World Medical, Inc, Rancho Cucamonga, California); and 3to determine the effects of the modified device after implantation in a rabbit model.…”

mentioning

confidence: 99%

Creation of a Drug-Coated Glaucoma Drainage Device Using Polymer Technology

Şahiner

Kravitz²,

Qadir³

et al. 2009

Arch Ophthalmol

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To create and test a slow-release antifibrotic drug-coated glaucoma drainage device using in vitro and in vivo experiments. Methods: A slow-release device incorporating mitomycin C in poly(2-hydroxyethyl methacrylate) disks was developed using redox-polymerization techniques. A standardized preparation of this drug delivery device was attached to the Ahmed glaucoma valve (model FP7; New World Medical, Inc, Rancho Cucamonga, California). Semicircular disks (5ϫ6 mm) of P(HEMA)-mitomycin C containing varying concentrations of mitomycin C per gram dry weight of the gel were attached to the lower half of an Ahmed glaucoma valve plate. Water was pumped through the modified Ahmed glaucoma valve at a rate comparable to that of aqueous humor outflow, and mitomycin C release was measured. Modified and unmodified Ahmed glaucoma valves were implanted in a rabbit model, and drug release and fibrosis were assessed after 3 months. Results: The P(HEMA)-mitomycin C device released mitomycin C in vitro over 1 to 2 weeks. Studies in rabbits revealed that mitomycin C was released from the disks during the 3-month implantation. Histologic analysis demonstrated a significant reduction in inflammatory reaction and fibrosis in the resulting blebs. Conclusion: Our slow-release drug-coated glaucoma drainage device decreased fibrosis and inflammation in the resulting bleb in a rabbit model. Clinical Relevance: This device could reduce the failure rate of glaucoma drainage devices.

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“…In a recent example, it was shown that long-term mitomycin C release could be measured up to 3 months postoperatively but was associated with retinal impairment in rabbit models in vivo [25,46]. Hydrogels and non-degradable polymers as well as biodegradable polymers have been used as antifibrotic drug delivery systems in animal studies [25,47,48]. …”

Section: Discussionmentioning

confidence: 99%

Development of a biodegradable antifibrotic local drug delivery system for glaucoma microstents

et al. 2018

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To prevent implant failure due to fibrosis is a major objective in glaucoma research. The present study investigated the antifibrotic effects of paclitaxel (PTX), caffeic acid phenethyl ester (CAPE), and pirfenidone (PFD) coated microstent test specimens in a rat model. Test specimens based on a biodegradable blend of poly(4-hydroxybutyrate) biopolymer and atactic poly(3-hydroxybutyrate) (at.P(3HB)) were manufactured, equipped with local drug delivery (LDD) coatings, and implanted in the subcutaneous white fat depot. Postoperatively, test specimens were explanted and analyzed for residual drug content. Fat depots including the test specimens were histologically analyzed. In vitro drug release studies revealed an initial burst for LDD devices. In vivo, slow drug release of PTX was found, whereas it already completed 1 week postoperatively for CAPE and PFD LDD devices. Histological examinations revealed a massive cell infiltration in the periphery of the test specimens. Compact fibrotic capsules around the LDD devices were detectable at 4–36 weeks and least pronounced around PFD-coated specimens. Capsules stained positive for extracellular matrix (ECM) components. The presented model offers possibilities to investigate release kinetics and the antifibrotic potential of drugs in vivo as well as the identification of more effective agents for a novel generation of drug-eluting glaucoma microstents.

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Inhibition of Cell Proliferation by Mitomycin C Incorporated into P(HEMA) Hydrogels

Abstract: This study demonstrates that a slow release form of MMC can inhibit cell proliferation in vitro. Future experiments will focus upon the efficacy of this polymer-bound form during in vivo wound healing.

Cited by 28 publications

References 15 publications

Effects of Gelatin Hydrogel Loading Mitomycin C on Conjunctival Scarring in a Canine Filtration Surgery Model

Effects of Gelatin Hydrogel Loading Mitomycin C on Conjunctival Scarring in a Canine Filtration Surgery Model

Creation of a Drug-Coated Glaucoma Drainage Device Using Polymer Technology

Development of a biodegradable antifibrotic local drug delivery system for glaucoma microstents

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