Dataset Information

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

ABSTRACT:

Purpose

The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney.

Methods

We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injection of placebo and rapamycin monodisperse microspheres (monospheres) was compared to subcutaneous injection, mimicking systemic administration.

Results

We did not find any adverse effects related to the delivery method. Irrespective of the injection site, a similar low dose of rapamycin was present in the circulation. However, only local intrarenal delivery of rapamycin from monospheres led to decreased macrophage infiltration and a significantly lower amount of myofibroblasts in the kidney, where systemic administration did not. Local delivery of rapamycin did cause a transient increase in the deposition of collagen I, but not of collagen III.

Conclusions

We conclude that therapeutic effects can be increased when rapamycin is delivered subcapsularly by monospheres, which, combined with low systemic concentrations, may lead to an effective intrarenal delivery method.

SUBMITTER: Zandstra J

PROVIDER: S-EPMC4577552 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

Zandstra Jurjen J van Beuge Marike M MM Zuidema Johan J Petersen Arjen H AH Staal Mark M Duque Luisa F LF Rodriguez Sergio S Lathuile Audrey A R AA Veldhuis Gert J GJ Steendam Rob R Bank Ruud A RA Popa Eliane R ER

Pharmaceutical research 20150509 10

<h4>Purpose</h4>The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney.<h4>Methods</h4>We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injectio ...[more]

PMID: 25957099

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Project description:BackgroundBecause orthodontic tooth movement is dependent upon osteoclast-mediated resorption of alveolar bone adjacent to the pressure side of tooth roots, biologic mediators that regulate osteoclasts can be utilized to control tooth movement.ObjectivesTo develop a novel method to locally enhance orthodontic anchorage.MethodsWe encapsulated osteoprotegerin (OPG) in polymer microspheres and tested the effectiveness of microsphere encapsulated versus non-encapsulated OPG for enhancing orthodontic anchorage in a rodent model of tooth movement. A single injection of 1 mg/kg non-encapsulated or microsphere encapsulated OPG was delivered into the palatal mucosa mesial to the first maxillary molar 1 day prior to tooth movement. A positive control group received injections of 5 mg/kg non-encapsulated OPG every 3 days during tooth movement. After 28 days of tooth movement, hemi-maxillae and femurs were dissected. Molar mesial and incisor distal tooth movement was measured using stone casts that were scanned and magnified. Local alveolar, distant femur bone, and tooth root volumes were analyzed by micro computed tomography. Serum OPG levels were measured by ELISA. Osteoclast numbers were quantified by histomorphometry.ResultsThe single injection of microsphere encapsulated OPG significantly enhanced orthodontic anchorage, while the single injection of non-encapsulated OPG did not. Injection of encapsulated OPG inhibited molar mesial movement but did not inhibit incisor tooth movement, and did not alter alveolar or femur bone volume fraction, density, or mineral content. Multiple injections of 5 mg/kg non-encapsulated OPG enhanced orthodontic anchorage, but also inhibited incisor retraction and altered alveolar and femur bone quality parameters. Increased OPG levels were found only in animals receiving multiple injections of non-encapsulated 5 mg/kg OPG. Osteoclast numbers were higher upon tooth movement in animals that did not receive OPG. Osteoclast numbers in OPG injected animals were variable within groups.ConclusionsMicrosphere encapsulation of OPG allows for controlled drug release, and enhances site-specific orthodontic anchorage without systemic side effects. With additional refinements, this drug delivery system could be applicable to a broad array of potential biologic orthodontic therapeutics.

Dataset Information

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

Purpose

Methods

Results

Conclusions

Publications

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury.

Similar Datasets

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