scholarly journals Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1677
Author(s):  
Hesham A. Saafan ◽  
Kamilia M. Ibrahim ◽  
Yasmeena Thabet ◽  
Sara M. Elbeltagy ◽  
Rana A. Eissa ◽  
...  

Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Nicholas M Boulis

Abstract INTRODUCTION Oral riluzole is the only approved treatment known to improve survival in patients with amyotrophic lateral sclerosis (ALS), with modest efficacy and dosing limited by hepatic toxicity and asthenia. We postulated that a continuous intrathecal (IT) delivery of low daily doses of riluzole could elevate spinal cord (SC) concentrations well above those achievable with oral treatment alone, without increasing side-effects. METHODS A 6-wk and a 24-wk GLP study were conducted to evaluate the safety of IT riluzole in purpose-bred hound dogs. Oral riluzole, equivalent to 50 mg BID in humans, was administered in combination with one of 3 IT doses given through continuous infusion. Plasma, SC, and brain concentrations of riluzole were measured, along with assessments of safety and tolerability. RESULTS In the 6-wk study, when combining the oral and IT routes, IT infusion significantly increased SC concentrations well above those achieved with oral drug administration alone, without increasing brain concentrations. All IT doses in combination with oral administration were well tolerated by the animals. In the 6-mo study, the lowest dose used in the 6-wk study was dropped and a higher dose was added. This highest dose of IT riluzole was not tolerated by the dogs and yielded SC and brain concentrations significantly higher than achieved in any of our previous studies. CONCLUSION Continuous IT administration of riluzole when combined with oral administration can increase the SC concentration of riluzole above those achievable with oral therapy, without increasing the risk for adverse events associated with systemic drug exposure or off-target side-effects in the brain. Therefore, IT riluzole infusion when used in conjunction with oral therapy may safely enhance lower motor neuron neuroprotection and improve the survival benefit of the drug through enhanced SC delivery, and, with a careful selection of IT doses, it could be implemented in patients with ALS.


1988 ◽  
Vol 6 (1) ◽  
pp. 158-162 ◽  
Author(s):  
B Reichman ◽  
M Markman ◽  
T Hakes ◽  
N Kemeny ◽  
D Kelsen ◽  
...  

In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting.


2019 ◽  
Vol 2019 ◽  
pp. 1-3 ◽  
Author(s):  
Amerigo Giudice ◽  
Francesco Liborio ◽  
Fiorella Averta ◽  
Selene Barone ◽  
Leonzio Fortunato

Oral lichenoid reactions (OLR) can be caused by systemic drug exposure. To the best of our knowledge, this is the second report describing a case of OLR induced by rituximab administration in a patient with a diagnosis of non-Hodgkin B-cell lymphoma. After 5 doses of rituximab, a typical pattern of OLP was identified with bilateral and symmetrical lesions on the buccal mucosa and on the right lingual margin. This temporal relationship suggested a probable association between oral lesions and drug therapy. The clinical diagnosis of a rituximab-induced OLR was confirmed by an incisional biopsy reporting a histopathological result of lichenoid mucositis consistent with oral lichen planus. Because of the increasing use of rituximab, it is necessary to know and recognize this uncommon side effect.


1993 ◽  
Vol 33 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Steven A. Curley ◽  
Diana L. Stone ◽  
George M. Fuhrman ◽  
David C. Hohn ◽  
Zahid H. Siddik ◽  
...  

2019 ◽  
Vol 12 (8) ◽  
pp. e230077 ◽  
Author(s):  
Virginia Cabrera Hernandez ◽  
Monica Gonzalez Afonso ◽  
Ariel Callero Viera ◽  
Lidon Martin-Fernandez Martin

Systemic drug exposure can produce a skin reaction consisting of symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) occurs after systemic exposure to a drug in which the patient was not previously sensitised, either in the first dose or after several doses. The mechanism of SDRIFE is unknown but is hypothesised to be the result of a delayed hypersensitivity response resulting in a cutaneous eruption some days after the exposure to the drug. The diagnosis should be clinical, based on the history and examination, but skin tests can also be performed to confirm sensitisation. But, as always, the gold-standard test is oral provocation. It is important to know this clinical entity to prevent re-exposure to the responsible allergen in the future.


2017 ◽  
Vol 4 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Sujit K. Debnath ◽  
Saisivam Srinivasan ◽  
Monalisha Debnath

Objective:The objective of the present work was to formulate Prothionamide (PTH) nanoparticles using Poly lactic co-glycolic acid (PLGA), optimized by Box-Behnken Design and further modification to dry powder inhaler followed byin-vivostudy.Methods:Poly-lactic co-gycolic acid (PLGA), a biodegradable polymer was used to coat Prothionamide by solvent evaporation technique. Formulation was optimized using Box-Behnken Design. Response surface curve and desirability factors helped in the selection of optimum formulation of PTH nanoparticles. Dry powder inhaler was prepared by adding inhalable grade lactose to optimize PTH nanoparticles. Mass median aerodynamic diameter (MMAD) was carried out using Andersen Cascade Impactor (ACI) to demonstrate its suitability in the pulmonary administration.In-vitrodrug release of dry powder inhaler was carried out in simulated lungs fluid. Correlationin-vitrotoin-vivowas established after performing animal experiment.Results:FTIR study reveals no chemical interaction between PTH, lactose and PLGA as the principle peaks was retained with same intensity in the physical mixture. Scanning electron microscope showed the spherical shape and aerodynamic particle size was found to be 1.69µm. Drug release study showed initial burst release followed by zero order release.In-vivomodel confirmed the presence of PTH after 24h. Aerodynamic particle size and the release profile revealed the suitability of PTH loaded nanoparticles containing dry powder inhaler for the pulmonary administration.Conclusion:Prepared DPI containing PTH nanoparticles can improve in the management of tuberculosis by increasing PTH residency in the lungs tissue for prolong period of time.


2008 ◽  
Vol 18 ◽  
pp. S337-S338
Author(s):  
A. Rakic Ignjatovic ◽  
B. Miljkovic ◽  
D. Todorovic ◽  
I. Timotijevic ◽  
M. Pokrajac

Sign in / Sign up

Export Citation Format

Share Document