Electron spin resonance studies of the effects of sterilization on poly(ethylene glycol) hydrogels

Kanjickal, Deenu; Lopina, Stephanie T.; Evancho-Chapman, M. Michelle; Schmidt, Steven; Inbaraj, Johnson J.; Cardon, Thomas B.; Lorigan, Gary A.

doi:10.1002/jbm.a.31717

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…A sustained release of CyA was achieved with the release lasting for ∼30 days. It was concluded that gamma sterilization was the preferred method of sterilization based on the tests conducted in this study and an earlier study conducted on PEG hydrogels 22, 23. Histological findings of gamma‐sterilized polymeric ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device.…”

Section: Resultsmentioning

confidence: 51%

Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia

Kanjickal

Lopina

Evancho-Chapman

et al. 2009

J Biomedical Materials Res

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The long-term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:877-887). However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of CyA from a polymeric vascular wrap would prevent the development of IH. To test this hypothesis, we developed a controlled release polymeric ring that could be placed around anastomotic sites to deliver therapeutic drugs locally. The ring is a composite polymeric device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres embedded in a poly(ethylene glycol) hydrogel. Several in vitro studies were conducted to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice for this device. In vivo studies were conducted on a swine model to evaluate the biocompatibility of the ring. The histological findings of the ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device.

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Section: Resultsmentioning

confidence: 51%

Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia

Kanjickal

Lopina

Evancho-Chapman

et al. 2009

J Biomedical Materials Res

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“…The presence of the peroxy radical in a segmented polyurethane has been shown in other studies too 31, 33–35. The readers are also referred to a previous work that studied the evolution of free radicals over time for unsterilized and sterilized PEG‐hydrogel sheets 36…”

Section: Resultsmentioning

confidence: 58%

Effects of sterilization on poly(ethylene glycol) hydrogels

Kanjickal

Lopina

Evancho-Chapman

et al. 2008

J Biomedical Materials Res

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The past few decades have witnessed a dramatic increase in the development of polymeric biomaterials. These biomaterials have to undergo a sterilization procedure before implantation. However, many sterilization procedures have been shown to profoundly affect polymer properties. Poly(ethylene glycol) hydrogels have gained increasing importance in the controlled delivery of therapeutics and in tissue engineering. We evaluated the effect of ethylene oxide (EtO), hydrogen peroxide (H(2)O(2)), and gamma sterilization of poly(ethylene glycol) hydrogels on properties relevant to controlled drug delivery and tissue engineering. We observed that the release of cyclosporine (CyA) (an immunosuppressive drug that is effective in combating tissue rejection following organ transplantation) was significantly affected by the type of sterilization. However, that was not the case with rhodamine B, a dye. Hence, the drug release characteristics were observed to be dependent not only on the sterilization procedure but also on the type of agent that needs to be delivered. In addition, differences in the swelling ratios for the sterilized and unsterilized hydrogels were statistically significant for 1:1 crosslinked hydrogels derived from the 8000 MW polymer. Significant differences were also observed for gamma sterilization for 1:1 crosslinked hydrogels derived from the 3350 MW polymer and also the 2:1 crosslinked hydrogels derived from the 8000 MW polymer. Atomic force microscopy (AFM) studies revealed that the roughness parameter for the unsterilized and EtO-sterilized PEG hydrogels remained similar. However, a statistically significant reduction of the roughness parameter was observed for the H(2)O(2) and gamma-sterilized samples. Electron spin resonance (ESR) studies on the unsterilized and the sterilized samples revealed the presence of the peroxy and the triphenyl methyl carbon radical in the samples. The gamma and the H(2)O(2)-sterilized samples were observed to have a much higher concentration of the radical pecies when compared with the EtO and the unsterilized samples.

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“…PEG is a common component of many polymer hydrogels, including drug and cell delivery systems. Sterilization methods for PEG hydrogels require consideration of potential reactions of the polyethylene backbone as well as the crosslinks . The polyether backbone of PEG hydrogels is stable to most chemical and heat sterilization methods but susceptible toward free radicals from peroxides and gamma radiation.…”

Section: Resultsmentioning

confidence: 99%

Autoclave sterilization of tetra‐polyethylene glycol hydrogel biomaterials with β‐eliminative crosslinks

Henise

Yao

Ashley

et al. 2020

Engineering Reports

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Sterilization of degradable polymeric biomaterials intended for injection presents a formidable challenge. Often, either the polymer backbone or labile crosslinks controlling degradation are adversely affected by commonly used sterilization methods. The purpose of this work was to develop an approach to sterilize tetra-polyethylene glycol hydrogel microspheres (MSs) with -eliminative crosslinks that are destined to be carriers for drug delivery. The approach taken was to acidify the medium to compensate for the base-catalyzed cleavage of linkers at high temperatures. We determined that rates of linker cleavage at pH 4 or below were sufficiently slow as to allow autoclaving and showed that precursor amine-derivatized MSs could withstand autoclaving at pH 4 for at least four cycles of 20 minutes each at 121 • C. Thus, amine-MSs need not be prepared aseptically, but instead can be prepared in a low bioburden environment, and then sterilized by autoclaving before drug attachment. K E Y W O R D Sbiodegradable hydrogel, drug delivery, half-life extension, microspheres, tetra-polyethylene glycol INTRODUCTIONWe have developed a general approach for half-life extension of therapeutics, in which a drug is covalently tethered to a long-lived carrier by a linker that slowly cleaves by -elimination to release the native drug (Scheme 1). 1 The cleavage rate of the linker is controlled by the nature of an electron-withdrawing "modulator" (Mod) attached to a carbon containing an acidic C-H bond. After rate-determining proton removal, the intermediate rapidly collapses to provide the free drug. These linkers are not affected by enzymes and are stable for years when stored at low pH and temperature. One carrier we use is a large-pore tetra-polyethylene glycol (PEG) hydrogel polymer. 2-4 These hydrogels-fabricated as uniform 50-μm microspheres (MSs)-are injected subcutaneously (SC) or locally through a small-bore needle where they serve as a depot to slowly release the drug. Importantly, a slower cleaving -eliminative linker is incorporated in crosslinks of these polymers, so gel degradation occurs after drug release. 3,5 Fabrication of tetra-PEG hydrogel MS-drug conjugates is achieved in two stages (Scheme 2). 3,4 Stage 1 involves preparation of amine-derivatized MSs. Here, equimolar amounts of an 8-arm PEG containing 4 amine-and 4 azido-linker end groups and a 4-arm PEG containing cyclooctyne end groups are mixed in a droplet forming device. The azide (A) and cyclooctyne (B) end groups of the PEG prepolymers react within the droplets by strain-promoted alkyne-azide cycloadditions (SPAAC) to form 1,2,3-triazoles and provide homogeneous amine-derivatized tetra-PEG

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Electron spin resonance studies of the effects of sterilization on poly(ethylene glycol) hydrogels

Cited by 12 publications

References 32 publications

Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia

Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia

Effects of sterilization on poly(ethylene glycol) hydrogels

Autoclave sterilization of tetra‐polyethylene glycol hydrogel biomaterials with β‐eliminative crosslinks

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