A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506)

Tajdaran, Kasra; Shoichet, Molly S.; Gordon, Tessa; Borschel, Gregory H.

doi:10.1002/bit.25598

Cited by 63 publications

(69 citation statements)

References 44 publications

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“…This work focuses on development of a fibrin gel based drug delivery system (DDS) containing drug loaded poly(lactic‐ co ‐glycolic acid) (PLGA) microspheres (MS). This system is a surgically implantable hydrogel designed for localized and sustained release of drugs and therapeutic proteins such as glial cell line‐derived neurotrophic factor (GDNF) to the injured peripheral nerve . In this study, the free GDNF in a solubilized form contained within fibrin gel was released rapidly (∼7 days) in vitro [Fig.…”

Section: Discussionmentioning

confidence: 99%

An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair

Tajdaran

Gordon

Wood

et al. 2015

J Biomedical Materials Res

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Localized drug delivery strategies could greatly benefit patients with peripheral nerve injury and could be easy for surgeons to implement. We developed a local drug delivery system (DDS) using drug-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) embedded in a fibrin gel. In an in vitro study, we investigated the biocompatibility of this DDS by performing a toxicity assay in which we incubated PC-12 cells with the medium released from the DDS in vitro. In an in vivo study, this DDS was applied at the rat common peroneal (CP) nerve injury site to deliver exogenous glial cell line-derived neurotrophic factor (GDNF) to the regenerating axons after delayed nerve repair. In vitro, PC-12 cells incubated with released media samples from the DDS had similar viability to control cells cultured with normal media, demonstrating that the DDS was not toxic. In vivo, the numbers of motor and sensory neurons that regenerated their axons with empty MS treatment were the same as when there was no MS treatment. The DDS increased the numbers of regenerating motor- and sensory neurons to levels indistinguishable from those observed with immediate nerve repair. The DDS increased neuron regeneration to levels double those observed with negative control groups. This biocompatible, nontoxic, fibrin gel-based DDS enhances outcomes following severe peripheral nerve injuries.

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Section: Discussionmentioning

confidence: 99%

An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair

Tajdaran

Gordon

Wood

et al. 2015

J Biomedical Materials Res

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“…Also, additional non‐FDA‐approved preclinical and clinical uses have been reported. These applications include providing seals and adhesion in fistula closure (Chung et al , ), preventing seroma formation (Ruggiero et al , ), delivering drugs and genes to target tissues (Schillinger et al , ; Wilems and Sakiyama‐Elbert, ; Tajdaran et al , ) and enhancing cell retention and implantation in tissue‐engineering approaches (Garcia‐Olmo et al , ; Gasparotto et al , ; Germain et al , ).…”

Section: Fibrin: Back To the Futurementioning

confidence: 99%

Fibrin, the preferred scaffold for cell transplantation after myocardial infarction? An old molecule with a new life

Roura

Gálvez‐Montón

Bayés‐Genís

2016

J Tissue Eng Regen Med

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Fibrin is a topical haemostat, sealant and tissue glue, which consists of concentrated fibrinogen and thrombin. It has broad medical and research uses. Recently, several studies have shown that engineered patches comprising mixtures of biological or synthetic materials and progenitor cells showed therapeutic promise for regenerating damaged tissues. In that context, fibrin maintains cell adherence at the site of injury, where cells are required for tissue repair, and offers a nurturing environment that protects implanted cells without interfering with their expected benefit. Here we review the past, present and future uses of fibrin, with a focus on its use as a scaffold material for cardiac repair. Fibrin patches filled with regenerative cells can be placed over the scarring myocardium; this methodology avoids many of the drawbacks of conventional cell-infusion systems. Advantages of using fibrin also include extraction from the patient's blood, an easy readjustment and implantation procedure, increase in viability and early proliferation of delivered cells, and benefits even with the patch alone. In line with this, we discuss the numerous preclinical studies that have used fibrin-cell patches, the practical issues inherent in their generation, and the necessary process of scaling-up from animal models to patients. In the light of the data presented, fibrin stands out as a valuable biomaterial for delivering cells to damaged tissue and for promoting beneficial effects. However, before the fibrin scaffold can be translated from bench to bedside, many issues must be explored further, including suboptimal survival and limited migration of the implanted cells to underlying ischaemic myocardium. Copyright © 2016 John Wiley & Sons, Ltd.

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“…33,34) Although the encapsulation efficiency appeared to decrease as the ratio of drug to polymer increased, the LC (16.81±0.37%) was superior to other reported methods. 4,6,7,[35][36][37] X-Ray Diffraction Pattern The X-ray diffraction pattern of TAC revealed characteristic peaks of the drug, most prominently at 2θ value of 10-25°, which indicates high crystalline nature of the drug. The disappearance of these characteristic peaks in the drug-loaded formulations suggests that the drug was molecularly dispersed or was present in amorphous state within the microspheres (Fig.…”

Section: )mentioning

confidence: 99%

Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-<i>co</i>-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method

et al. 2016

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Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres (TAC-PLGA-M) can be administered for the long-term survival of transplanted organs due to their immunosuppressive activity. The purpose of our study was to optimize the parameters of the electrospray method, and to prepare TAC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. In vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Drug-loading efficiency was greater than 80% in all formulations with a maximum loading capacity of 16.81 0.37%. XRD and DSC studies suggested that the drug was incorporated in an amorphous state or was molecularly dispersed in the microspheres. The in vitro release study showed prolonged release patterns. TAC-PLGA-M with enhanced drug loading and prolonged-release patterns were successfully prepared using the electrospray method.Key words electrospray; microsphere; poly(lactic-co-glycolic acid); prolonged release; tacrolimus Tacrolimus (TAC), a potent immunosuppressant drug, is primarily used to increase the survival time of transplanted organs.1) The immunosuppressive activity of tacrolimus is mediated through the inhibition of calcineurin, which is a protein phosphatase found in the cytoplasm of T-cells, and the subsequent blockage of interleukin-2 production, leading to a decrease in T cell proliferation.2) In clinical practice, tacrolimus is administered as a twice-daily dosing regimen. Modified-release tacrolimus with once daily administration has also been used safely.3) There are no reports regarding the use of prolonged release formulations of tacrolimus in clinical practice, although some polymer-based formulations for longterm delivery of tacrolimus have been used in animal model studies. As has been previously reported, a single dose of the new type of tacrolimus with biodegradable microspheres could keep the plasma concentration steady for two weeks, suggesting that immunosuppressive activity could be achieved with the use of polymer-based formulations.4,5) Subcutaneous injection of tacrolimus pellets, which could give a plasma concentration within the desired therapeutic window, provided effective immunosuppression for more than three months in rat model studies.6) Likewise, tacrolimus-loaded biodegradable microspheres reportedly achieved sustained release over a long period, giving flat parallel concentration profiles for 10 d from the first day after a single subcutaneous administration in liver-transplanted rats. 7)Long-term controlled delivery of drugs has been accomplished by the use of biodegradable polymeric particulate systems.8) Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer that undergoes hydrolysis in the body to produce two monomers: lactic acid and glycolic acid. The rate of degradation of PLGA and the release profile of drugs from PLGAbased formulations depend on the mole...

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A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506)

Cited by 63 publications

References 44 publications

An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair

An engineered biocompatible drug delivery system enhances nerve regeneration after delayed repair

Fibrin, the preferred scaffold for cell transplantation after myocardial infarction? An old molecule with a new life

Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-<i>co</i>-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method

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