In the lung aerosol cyclosporine provides a regional concentration advantage over intramuscular cyclosporine

Mitruka, Surindra N.; Won, Alvina; McCurry, Kenneth R.; Zeevi, Adriana; McKaveney, Teresa P.; Venkataramanan, Raman; Iacono, Aldo; Griffith, Bartley P.; Burckart, Gilbert J.

doi:10.1016/s1053-2498(00)00176-5

Cited by 21 publications

(14 citation statements)

References 20 publications

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“…The difference in lung tissue levels after inhalation and oral administration (lung targeting index) were 7-to 14-fold higher in this study in than in earlier studies by Blot et al 15 and Mitruka et al, 29 which may have been due to the different administration method used in our study. Both Blot et al and Mitruka et al used nose-only exposure to the aerosol, whereas, in our study, insufflation was used.…”

Section: Discussioncontrasting

confidence: 71%

Efficacy of a New Pulmonary Cyclosporine A Powder Formulation for Prevention of Transplant Rejection in Rats

Zijlstra

Wolting

Prop

et al. 2009

The Journal of Heart and Lung Transplantation

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Section: Discussioncontrasting

confidence: 71%

Efficacy of a New Pulmonary Cyclosporine A Powder Formulation for Prevention of Transplant Rejection in Rats

Zijlstra

Wolting

Prop

et al. 2009

The Journal of Heart and Lung Transplantation

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“…[1][2][3] In addition, CsA has therapeutic effects on the prevention of allograft rejection after lung transplantation. 4,5 The systemic effects associated with CsA are substantial, including hypertension and most notably renal toxicity. 6 Local noninvasive administration of CsA as aerosols may reduce the incidence of toxic complications associated with systemic administration of CsA, increase the therapeutic availability of CsA for localized immunosuppression, and provide a high pulmonary concentration.…”

Section: Introductionmentioning

confidence: 99%

Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

Wu¹,

Zhang²,

Hayes³

et al. 2013

IJN

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Abstract:In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug -cyclosporine A -for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero-3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters.

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“…Previous investigations in animal lung transplant models demonstrated that aerosol cyclosporin produces higher concentrations of cyclosporin in lung tissue than does systemic administration and also decreases allograft inflammation associated with rejection [26][27][28][29][30]. The present authors have used aerosol cyclosporin to treat lung recipients with refractory rejection since 1991 [31].…”

mentioning

confidence: 99%

“…It blocks lymphocyte activation by inhibiting transcription of cytokine genes in a dose-dependent manner [22,23]. Cyclosporin also exerts an antifibrotic effect by inhibiting alveolar macrophage function and suppressing collagen deposition by lung fibroblasts [24,25].Previous investigations in animal lung transplant models demonstrated that aerosol cyclosporin produces higher concentrations of cyclosporin in lung tissue than does systemic administration and also decreases allograft inflammation associated with rejection [26][27][28][29][30]. The present authors have used aerosol cyclosporin to treat lung recipients with refractory rejection since 1991 [31].…”

mentioning

confidence: 99%

Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans

et al. 2004

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The majority of patients who develop bronchiolitis obliterans, after lung transplantation, die within 2-3 yrs after onset since treatment with conventional immunosuppression is typically ineffective. A case/control study was conducted in lung transplant recipients with biopsy-documented bronchiolitis obliterans to determine whether aerosol cyclosporin use contributed to increased survival.The cases comprised 39 transplant recipients who received open-label aerosol cyclosporin treatment in addition to conventional immunosuppression. The controls were transplant recipients treated with conventional immunosuppression alone. There were 51 controls from the University of Pittsburgh Medical Center and 100 from a large multicentric database (Novartis Lung Transplant Database).Forced expiratory volume in one second expressed as a percentage of the predicted value was an independent predictor of survival in all patients with bronchiolitis obliterans. Cox proportional-hazards analysis revealed a survival advantage for aerosol cyclosporin cases compared to the Pittsburgh control group. A survival advantage was also seen when comparing study cases to multicentric controls.Aerosol cyclosporin, given with conventional immunosuppression to lung transplant recipients with bronchiolitis obliterans, provides a survival advantage over conventional therapy alone. The 3-yr survival after lung transplantation is 55% [1]. More than half of all lung transplant recipients who survive o1 yr develop chronic allograft rejection that is associated with bronchiolitis obliterans [2][3][4][5]. The development of bronchiolitis obliterans has a negative impact on long-term survival. No immunosuppressive regimen has been shown to prevent this complication or improve survival once it occurs [6][7][8].Bronchiolitis obliterans is thought to be a consequence of immunological lung injury [9][10][11]. An inflammatory cascade directed against allograft bronchiolar epithelial and endothelial cells is initiated by T-lymphocytes, as demonstrated in animals [12][13][14] and human subjects [15,16]. Alloreactive lymphocytes are found in bronchoalveolar lavage fluid, and selective T-cell clones are expanded during bronchiolitis obliterans [17]. Myriad cytokines and lymphocyte gene expression induce small airway inflammation, leading to myofibroblast-like cell proliferation and ingrowth of small airway granulation tissue, and resulting in occlusion of the airway lumen [18][19][20][21]. A cascade of injury and remodelling triggers a fibroproliferative process responsible for bronchiolar scarring and graft failure.Cyclosporin is one of the mainstays of maintenance immunosuppression after transplantation; however, it has a narrow therapeutic index when given systemically [22]. It blocks lymphocyte activation by inhibiting transcription of cytokine genes in a dose-dependent manner [22,23]. Cyclosporin also exerts an antifibrotic effect by inhibiting alveolar macrophage function and suppressing collagen deposition by lung fibroblasts [24,25].Previous inves...

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In the lung aerosol cyclosporine provides a regional concentration advantage over intramuscular cyclosporine

Cited by 21 publications

References 20 publications

Efficacy of a New Pulmonary Cyclosporine A Powder Formulation for Prevention of Transplant Rejection in Rats

Efficacy of a New Pulmonary Cyclosporine A Powder Formulation for Prevention of Transplant Rejection in Rats

Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans

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