MASS BALANCE OF NEBULIZED DRUG DELIVERY: RESIDUAL DRUG LEVELS AND THE EFFECTS OF AN ALTERNATIVE AIR HUMIDIFICATION METHOD

2008 ◽  
Vol 18 (6) ◽  
pp. 495-510
Author(s):  
Corinne S. Lengsfeld ◽  
Benjamen A. Filas
Keyword(s):  
Drug Delivery ◽  
Mass Balance ◽  
Drug Levels ◽  
Air Humidification

scholarly journals The Development of an ex vivo Flow System to Assess Acute Arterial Drug Retention of Cardiovascular Intravascular Devices

2021 ◽  
Vol 3 ◽  
Author(s):  
Kathryn Cooper ◽  
Claire V. Cawthon ◽  
Emily Goel ◽  
Marzieh Atigh ◽  
Uwe Christians ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Carotid Arteries ◽  
Tissue Concentration ◽  
Ex Vivo ◽  
Drug Levels ◽  
Liquid Chromatography Tandem Mass ◽  
Bioreactor System ◽  
Intravascular Devices ◽  
Drug Coated Balloon

Purpose: The goal of this study was to develop an ex vivo system capable of rapidly evaluating arterial drug levels in living, isolated porcine carotid arteries.Methods: A vascular bioreactor system was developed that housed a native porcine carotid artery under physiological flow conditions. The ex vivo bioreactor system was designed to quantify the acute drug transfer of catheter-based drug delivery devices into explanted carotid arteries. To evaluate our ex vivo system, a paclitaxel-coated balloon and a perfusion catheter device delivering liquid paclitaxel were utilized. At 1-h post-drug delivery, arteries were removed, and paclitaxel drug levels measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Parallel experiments were performed in a pig model to validate ex vivo measurements.Results: LC-MS/MS analysis demonstrated arterial paclitaxel levels of the drug-coated balloon-treated arteries to be 48.49 ± 24.09 ng/mg and the perfusion catheter-treated arteries to be 25.42 ± 9.74 ng/mg at 1 h in the ex vivo system. Similar results were measured in vivo, as arterial paclitaxel concentrations were measured at 59.23 ± 41.27 ng/mg for the drug-coated balloon-treated arteries and 23.43 ± 20.23 ng/mg for the perfusion catheter-treated arteries. Overall, no significant differences were observed between paclitaxel measurements of arteries treated ex vivo vs. in vivo.Conclusion: This system represents the first validated ex vivo pulsatile system to determine pharmacokinetics in a native blood vessel. This work provides proof-of-concept of a quick, inexpensive, preclinical tool to study acute drug tissue concentration kinetics of drug-releasing interventional vascular devices.

NIMG-75. ANALYZING THE INTERFACE BETWEEN MRI AND DRUG DISTRIBUTION USING ORTHOTOPIC GBM-DERIVED XENOGRAFT (PDX) MODELS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi146-vi146
Author(s):  
Sameer Channar ◽  
Sara Ranjbar ◽  
Pamela Jackson ◽  
Leland Hu ◽  
Michael Regan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cell Lines ◽  
Mean Squared Error ◽  
Drug Distribution ◽  
Normal Brain ◽  
Imaging Features ◽  
Visible Image ◽  
Drug Levels ◽  
Mri Features ◽  
Pdx Models

Abstract INTRODUCTION Glioblastoma (GBM) is a diffusely invasive primary brain tumor with significant spread of tumor cells to the periphery of visible image abnormality. Enhancement of Gadolinium (Gd) contrast agent on magnetic resonance imaging (MRI) has historically been considered a confirmation of local breakdown of the blood brain barrier (BBB) and sufficient drug delivery to the bulk of tumors. In this work, we used GBM-derived xenograft (PDX) models to compare drug delivery in GBM brain for high and low BBB-permeable drugs. MATERIALS AND METHODS Five patient-derived orthotopic xenograft models from two GBM cell lines (GBM39 and GBM12) were co-dosed with erlotinib and osimertinib, two drugs with low and high BBB-permeability, respectively. T1Gd and T2-weighted MRIs were acquired from all animals prior to model sacrifice. Tumors were manually segmented on denoised and standardized MRIs and intensity patterns were captured using first and second order statistical features in the moving 3x3 kernel. We compared drug levels found in Matrix Assisted Laser Desorption Ionization (MALDI) in T1Gd enhancement, T2 enhancement, and normal brain. We also performed linear regression modeling to predict drug levels using MRI features. Model performance was measured using root mean squared error (RMSE). RESULTS Our analysis showed correlations between imaging features and MALDI drug levels. Osimertinib had a uniform distribution across the brain for all animals and all cell lines, consistent with our expectation for a high BBB-penetrant drug. Erlotinib showed the highest drug levels in T2 for GBM39 and in T1Gd for GBM12. Regression models showed promising results for predicting Erlotinib with a low RMSE of 0.037. CONCLUSION Our preliminary results suggest MRI can be predictive of drug levels for low-BBB penetrant drugs. Understanding the relationship between MRIs and drug distribution in diffuse tumors can be beneficial to developing effective treatment.

scholarly journals Immunohistological observations in rat kidney allografts after local steroid administration.

1987 ◽  
Vol 166 (5) ◽  
pp. 1205-1220 ◽  
Author(s):  
T J Ruers ◽  
W A Buurman ◽  
C J van Boxtel ◽  
C J van der Linden ◽  
G Kootstra
Keyword(s):  
Drug Delivery ◽  
Immunosuppressive Therapy ◽  
Graft Survival ◽  
Mhc Class Ii ◽  
Graft Rejection ◽  
Rat Kidney ◽  
Class Ii ◽  
Regulatory Mechanisms ◽  
Drug Levels ◽  
Systemic Drug

In this report we investigated local regulatory mechanisms in graft rejection and their response to local immunosuppressive therapy. For this purpose local immunosuppression was induced in rat kidney allografts by intrarenal infusion of prednisolone. Intrarenal drug delivery resulted in high drug levels within the graft and low systemic drug levels. Systemic drug levels were by themselves not sufficiently immunosuppressive to induce graft survival, and local prednisolone levels within the graft proved to be responsible for prolongation of graft survival. During intrarenal drug delivery, systemic responsiveness to the renal allograft proved normal, since intrarenally treated grafts were infiltrated by MHC class II-positive host cells and, except for a somewhat lower percentage of macrophages, cellular infiltration in intrarenal treated grafts was comparable to untreated grafts. However, T cells and macrophages present in intrarenally treated grafts were not able to destroy the grafted tissue. Local immunosuppressive therapy resulted in inhibition of IL-2-R expression, absence of IFN-gamma, and prevention of MHC class II induction on grafted tissue. These observations strongly indicate the presence of local regulatory mechanisms in graft rejection. The experimental model described can be used for further analysis of these intragraft events. Moreover, the results demonstrate that local immunosuppressive therapy can contribute to effective inhibition of cellular immune response in graft rejection.

scholarly journals Chemotherapeutic Potential of Orally Administered Poly(Lactide-Co-Glycolide) Microparticles Containing Isoniazid, Rifampin, and Pyrazinamide against Experimental Tuberculosis

2003 ◽  
Vol 47 (9) ◽  
pp. 3005-3007 ◽  
Author(s):  
Qurrat ul-Ain ◽  
Sadhna Sharma ◽  
G. K. Khuller
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Drug Delivery ◽  
Relative Bioavailability ◽  
Oral Drug ◽  
Experimental Tuberculosis ◽  
Drug Levels ◽  
Oral Drug Delivery System

ABSTRACT Poly(lactide-co-glycolide) (PLG) microspheres (diameter, less than 3 μm) containing isoniazid, rifampin, and pyrazinamide were used in a sustained oral drug delivery system to treat murine tuberculosis. Drug levels above the MIC were observed up to 72 h in plasma and for 9 days in various organs. Relative bioavailability of encapsulated drugs was greater than that of free drugs. Chemotherapy results showed better or equivalent clearance of bacilli in the PLG-drug-administered group (weekly) than with free drugs (daily).

scholarly journals Microspheres for the Drug Delivery Applications

2014 ◽  
Vol 1 (1) ◽  
pp. 9
Author(s):  
Hafiz Shoaib Sarwar ◽  
Muhammad Hanif ◽  
Aamir Jalil ◽  
Malik Suleman Haider ◽  
Fahad Naeem ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Loading ◽  
Short Interval ◽  
Dosage Forms ◽  
Plasma Drug ◽  
Drug Levels ◽  
Plasma Drug Levels ◽  
Sustained Drug Delivery ◽  
Hydrophobic Polymers

Conventional dosage forms provide a sharp increase in plasma drug levels that falls below the therapeutic range after short interval of time until the re-administration of drug. There is a need of such dosage forms which provide not only sustained drug delivery but also reduce the plasma drug levels fluctuations. Microspheres used in drug delivery systems due to their ability to sustain the drug release, their biodegradability and compatibility and targeted drug delivery. In this review different types of microspheres their methods for the preparation with different hydrophilic and hydrophobic polymers, drug loading capacities will be discussed. Different characterizations like SEM, FTIR, XRD, DSC, rheological properties and invitro drug release are successfully described.

Photophysical and Photobiological Studies of a Silicon Tribenzonaphthoporphyrazinato Incorporated into Liposomes for Photodynamic Therapy Use

2008 ◽  
Vol 8 (6) ◽  
pp. 3208-3215 ◽  
Author(s):  
Andreza R. Simioni ◽  
Marcelo M. M. Pelisson ◽  
Milton Beltrame ◽  
Antonio C. Tedesco
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Flash Photolysis ◽  
Laser Flash Photolysis ◽  
Photophysical Properties ◽  
Laser Flash ◽  
Time Resolved Fluorescence ◽  
Time Resolved ◽  
Drug Levels

Nanostructured drug delivery systems (NDDS), such as liposomes, represent a growing area in biomedical research. These microheterogeneous media can be used in many biological systems to provide appropriate drug levels with a specific biodistribution. The photophysical properties of a silicon derivative of tribenzonaphthoporphyrazinato (Si-tri-PcNc) incorporated into liposome were studied by steady-state techniques, time-resolved fluorescence and laser flash photolysis. All the spectroscopy measurements performed allowed us to conclude that Si-tri-PcNc in liposome is a promising NDDS for PDT. The in vitro experiments with liposomal NDDS showed that the system is not cytotoxic in darkness, but exhibits a substantial phototoxicity at 1 μM of photosensitizer concentration and 10.0 J/cm2 of light. These conditions are sufficient to kill about 80% of the cells.

Techniques For The Preparation of Tissue Samples Containing Injectable Polymer Microcapsules

1985 ◽  
Vol 43 ◽  
pp. 710-711
Author(s):  
G.E. Visscher ◽  
R. L. Robison ◽  
G. J. Argentieri
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Gastrocnemius Muscle ◽  
Degradation Process ◽  
Delivery Systems ◽  
Tissue Reaction ◽  
Electron Microscopic ◽  
Tissue Samples ◽  
Injectable Polymer ◽  
Microscopic Techniques

The use of various bioerodable polymers as drug delivery systems has gained considerable interest in recent years. Among some of the shapes used as delivery systems are films, rods and microcapsules. The work presented here will deal with the techniques we have utilized for the analysis of the tissue reaction to and actual biodegradation of injectable microcapsules. This work has utilized light microscopic (LM), transmission (TEM) and scanning (SEM) electron microscopic techniques. The design of our studies has utilized methodology that would; 1. best characterize the actual degradation process without artifacts introduced by fixation procedures and 2. allow for reproducible results.In our studies, the gastrocnemius muscle of the rat was chosen as the injection site. Prior to the injection of microcapsules the skin above the sites was shaved and tattooed for later recognition and recovery. 1.0 cc syringes were loaded with the desired quantity of microcapsules and the vehicle (0.5% hydroxypropylmethycellulose) drawn up. The syringes were agitated to suspend the microcapsules in the injection vehicle.

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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