Ocular Pharmacokinetic Study Using T1 Mapping and Gd-Chelate- Labeled Polymers

Shi, Xianfeng; Liu, Xin; Wu, Xueming; Lü, Zheng Rong; Li, S. Kevin; Jeong, Eun Kee

doi:10.1007/s11095-011-0507-5

Cited by 7 publications

(10 citation statements)

References 32 publications

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“…54 By using MR imaging, the authors calculated the half-life using T1-mapping. They followed the contrast agents for approximately two days, showing the feasibility of using the noninvasive technique of MRI in monitoring the biodistribution and clearance of the macromolecules.…”

Section: Discussionmentioning

confidence: 99%

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Dynamic MR Imaging, Biodistribution and Pharmacokinetics of Polymer Shelled Microbubbles Containing Spion

Barrefelt

Paradossi

Asem

et al. 2014

NANO

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Magnetic Resonance Imaging (MRI) is a noninvasive diagnostic method that provides information on morphological and physiological changes of the internal organs over time. Imaging and measurements can be repeated on the same subject, thereby reducing inter-individual variability effects and hence the number of subjects required. A potential MRI contrast agent consisting of microbubbles embedded with superparamagnetic iron oxide nanoparticles (SPION) in the shell (SPION MBs) was injected intravenously into rats to determine their biodistribution and pharmacokinetics using MR imaging. Agarose phantoms containing SPION MBs were scanned using 3 T MRI to construct a standard curve. Rats were injected with SPION MBs, free SPION or plain MBs and scanned dynamically at 3 T using a clinical MR scanner. The relaxation rate (R2*) was studied over time as a measure of the iron oxide concentrations to enable calculation of the pharmacokinetic parameters. The kinetics of SPION MBs in the liver was fitted to a one-compartment model. Furthermore, the biological fate of SPION MBs was examined via a histological survey of tissue samples using Perls' Prussian blue staining and immunohistochemistry (IHC). 1.2 h after injection of SPION MBs, T2* of the liver had decreased to its minimum. The elimination half-life of SPION MBs was 598.2 ± 97.3 h, while the half-life for SPION was 222.6 ± 26.4 h. Moreover, our study showed that SPION MBs were taken up by the macrophages in the lungs, spleen and liver. MBs labeled with SPION can be used for MR imaging. Moreover, MRI is a reliable and noninvasive tool that can be utilized in pharmacokinetic investigations of future contrast agents using SPION MBs and SPION in the rat.

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Section: Discussionmentioning

confidence: 99%

“…They followed the contrast agents for approximately two days, showing the feasibility of using the noninvasive technique of MRI in monitoring the biodistribution and clearance of the macromolecules. 54 Altogether, the half-life of SPION varies considerably depending on the formulation and coating.…”

Section: Discussionmentioning

confidence: 99%

Dynamic MR Imaging, Biodistribution and Pharmacokinetics of Polymer Shelled Microbubbles Containing Spion

Barrefelt

Paradossi

Asem

et al. 2014

NANO

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“…Short retention of free drug in the anterior chamber typically occurs due to the aqueous humor turnover and clearance system (rate ≈0.18 mL h −1 ) . Therefore, it is highly desirable to investigate whether only 5% of total dose released from delivery carrier during the later follow‐up time points (day 20–day 84) is sufficient to reach therapeutic drug level (i.e., >10 µg mL −1 ) in the ocular anterior chamber.…”

Section: Resultsmentioning

confidence: 99%

Dendritic Effects of Injectable Biodegradable Thermogels on Pharmacotherapy of Inflammatory Glaucoma‐Associated Degradation of Extracellular Matrix

Nguyen

Luo

Lai

2019

Adv Healthcare Materials

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111.8 million people worldwide by 2040. [1] High intraocular pressure (IOP) has been considered the major indicator for diagnosing glaucoma, and the reduction of elevated IOP is the current clinical approach used to prevent disease progression. [2] Several models of glaucoma have indicated that inflammatory components can directly link elevated IOP with retinal degeneration. [3][4][5][6] As a result, the expression of inflammatory molecules, including nitric oxide, [7] interleukins (ILs), [8] p38 MAPK, [9] and prostaglandin E2 (PGE2), [10] are increased in progressive glaucoma. Furthermore, inflammatory progression is also associated with the increased expression of matrix metalloproteinases (MMPs), [11] which consequently induce the degradations of extracellular matrix (ECM) components such as stromal collagen [12] and retinal laminin. [13] It is noteworthy that ECM possesses adhesive characteristics that can regulate cell function and survival; changes in composition and status of ECM components can result in disruptions of cell-cell and cell-ECM interactions, consequently inducing cell apoptosis. [14][15][16] Therefore, it is highly imperative to develop new therapies for effectively attenuating the upregulation of inflammatory molecules as well as the degradation of stromal collagen and retinal laminin in glaucoma.Dendrimers, which are synthetic macromolecules with well-defined 3D shapes that contain a central core, repeating branched units, and dense shells with terminal functional groups, have been emerging in polymeric architecture in biomedical engineering. These macromolecules can increase the water solubility, bioavailability, and biocompatibility of pharmaceutical agents and show promise for practical use as drug carriers. [17] More interestingly, dendrimers can also be exploited as a key component that regulates the encapsulation and release of other carriers to achieve improved drug delivery. For example, the interior cavities of polyamidoamine (PAMAM) dendrimers can entrap drug molecules, while their amine-terminated surface groups are available for crosslinking with poly(ethylene glycol) mono/diacrylate to generate hydrogel materials with the ability to release drugs in a sustained manner through a twostage process, which involves the release of drug-entrapping dendrimers from degradable hydrogels and the release of drug The development of advanced drug delivery systems with extensively sustained release and multiple functions is highly imperative for effective attenuation of the degradation of ocular extracellular matrix that is associated with inflammatory glaucoma. Here, the generation of amine-terminated polyamidoamine dendrimers in an injectable biodegradable thermogel is demonstrated to be important for achieving prolonged drug release profiles and potent anti-inflammatory effects. Among various generations (Gx, x = 0, 1, 3, 5), third-generation G3 is proved as the most effective material for optimizing the synergistic effects of gelatin and poly(N-isopropylacrylamide) and generating a thermo...

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“…In addition, MRI was not able to visualize the clearance pathways from the subconjunctival space, except an increase in the contrast signal at the buccal lymph node, possibly due to the contrast agent concentration in and the dimensions of the blood and lymph vessels 2. In MRI studies of intravitreal injection4,8,9 and intraocular implant,2,11 contrast agents were not detected at the level that can be quantified in the anterior chamber with the MRI techniques. There was also no identifiable elimination pathway from the vitreous after intravitreal administration, probably due to the limitations of the MRI studies as described above.…”

Section: Introductionmentioning

confidence: 93%

“…Magnetic resonance imaging (MRI) is a noninvasive method and can be used to study the mechanisms of ocular drug delivery. Previous studies have demonstrated the utility of MRI to characterize the routes of penetration and ocular barriers such as the dynamic barriers, least resistive route of transscleral penetration, drug delivery flux‐enhancing mechanisms, locations of periocular and intraocular depots, and release kinetics from these depots (or ocular implants) in periocular, intrascleral, suprachoroidal, and intravitreal delivery 2–10. Such information would be difficult to obtain in traditional pharmacokinetic studies involving the dissection of the eye in ocular delivery research.…”

Section: Introductionmentioning

confidence: 99%

MRI Study of Subconjunctival and Intravitreal Injections

Hao

Liu

et al. 2012

Journal of Pharmaceutical Sciences

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Previous magnetic resonance imaging (MRI) studies to investigate the routes of penetration and barriers in ocular delivery have provided insights into the mechanisms of transscleral and intraocular drug delivery. The objective of the present study was to investigate ocular penetration and clearance after subconjunctival and intravitreal injections using a contrast agent at concentrations higher than those in the previous studies. This high concentration approach was hypothesized to allow the visualization of the contrast agent in the eye that could not be achieved previously. Subconjunctival and intravitreal injections of contrast agent Magnevist, a model hydrophililc probe, were performed in rabbits, and the distribution and clearance of the probe after the injections were examined by MRI. After subconjunctival injection in vivo, significant contrast agent penetration into the anterior chamber was observed but not into the vitreous. A clearance pathway of the hydrophilic probe from the subconjunctival depot to the regions near the periocular fat behind the eye was found. After intravitreal injection in vivo, the contrast agent was observed in the anterior chamber, optic nerve, and tissues surrounding the eye during clearance. MRI continues to provide insights into the transport barriers and clearance pathways of hydrophilic molecules in ocular delivery.

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Ocular Pharmacokinetic Study Using T1 Mapping and Gd-Chelate- Labeled Polymers

Cited by 7 publications

References 32 publications

Dynamic MR Imaging, Biodistribution and Pharmacokinetics of Polymer Shelled Microbubbles Containing Spion

Dynamic MR Imaging, Biodistribution and Pharmacokinetics of Polymer Shelled Microbubbles Containing Spion

Dendritic Effects of Injectable Biodegradable Thermogels on Pharmacotherapy of Inflammatory Glaucoma‐Associated Degradation of Extracellular Matrix

MRI Study of Subconjunctival and Intravitreal Injections

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