Modeling nanoparticle delivery of TB drugs to granulomas.
TL;DR: This study analyzes drug delivery to granulomas by means of a nanoparticle delivery system and reveals significant differences in drug concentrations between the plasma and macrophages.
About: This article is published in Journal of Theoretical Biology.The article was published on 2016-01-07. It has received 12 citations till now. The article focuses on the topics: Drug delivery & Granuloma.
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TL;DR: In this article, the authors discuss Mtb phenotypic and genotypic changes driving resistance, including changes in cell envelope components, as well as recently described intrinsic and extrinsic factors promoting resistance emergence and transmission.
Abstract: In the last two decades, multi (MDR), extensively (XDR), extremely (XXDR) and total (TDR) drug-resistant Mycobacterium tuberculosis (Mtb) strains have emerged as a threat to public health worldwide, stressing the need to develop new tuberculosis (TB) prevention and treatment strategies It is estimated that in the next 35 years, drug-resistant TB will kill around 75 million people and cost the global economy $167 trillion Indeed, the COVID-19 pandemic alone may contribute with the development of 63 million new TB cases due to lack of resources and enforced confinement in TB endemic areas Evolution of drug-resistant Mtb depends on numerous factors, such as bacterial fitness, strain's genetic background and its capacity to adapt to the surrounding environment, as well as host-specific and environmental factors Whole-genome transcriptomics and genome-wide association studies in recent years have shed some insights into the complexity of Mtb drug resistance and have provided a better understanding of its underlying molecular mechanisms In this review, we will discuss Mtb phenotypic and genotypic changes driving resistance, including changes in cell envelope components, as well as recently described intrinsic and extrinsic factors promoting resistance emergence and transmission We will further explore how drug-resistant Mtb adapts differently than drug-susceptible strains to the lung environment at the cellular level, modulating Mtb-host interactions and disease outcome, and novel next generation sequencing (NGS) strategies to study drug-resistant TB
66 citations
TL;DR: A first-time comprehensive review of work on within-host TB models that describe the immune response of the host to infection, including the formation of lung granulomas, to suggest future directions to impact this global disease.
55 citations
01 Feb 2015
TL;DR: In this article, a multi-modal mass spectrometry imaging (MSI) and profiling approach has been applied to assess the partitioning of the anti-TB fluoroquinolone levofloxacin into pulmonary lesions.
Abstract: A multi-modal mass spectrometry imaging (MSI) and profiling approach has been applied to assess the partitioning of the anti-TB fluoroquinolone levofloxacin into pulmonary lesions. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and a commercial liquid microjunction surface sampling technology (LMJ-SSP), or flowprobe, have been used to both spatially profile and image drug distributions in lung tissue sections from TB-infected rabbits following oral administration of a single human-equivalent dose. Levofloxacin levels were highest at 6 h post-dose in normal lung, cellular granuloma, and necrotic caseum compartments. The drug accumulated in the cellular granuloma regions with lower amounts partitioning into central caseous compartments. Flowprobe imaging at 630 μm (limited by the probe tip diameter) enabled visualization of drug distribution into lesion compartments, including limited differentiation of relative drug abundance in cellular versus caseous regions of the lesions. MALDI-MSI analysis at 75 μm provided more detailed drug distribution, which clearly accumulated in the cellular region immediately surrounding the central caseum core. Imaging and profiling data acquired by flowprobe and MALDI-MSI were validated by quantitative LC/MS/MS analysis of lung and granuloma homogenates taken from the same animals. The results of the investigation show flowprobe imaging and sampling as a rapid and sensitive alternative to MALDI-MSI for profiling drug distributions into tissues when spatial resolution of data below the threshold of the probe diameter is not required.
43 citations
TL;DR: This review aims to compile the recent innovations of inhalable polymeric dry powder systems for the delivery of anti-TB drugs exploring the methods of production, aerodynamic characterization and the efficacy of targeted drug delivery systems using in vitro and in vivo models of the disease.
22 citations
01 Sep 2019
TL;DR: This review discusses the application of the various forms of nanomedicine towards targeting of Mtb, which offers the potential for specific disease targeting, dosage reduction, and intracellular drug delivery.
Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), causes the most human deaths than any other diseases from a single infectious agent. Treatments are long and costly and have many associated side effects. Intracellular bacilli are slow growing and difficult to target, which is augmenting the emergence of multi‐drug resistance. A hallmark trait of TB is the formation of granulomas, chronic cellular aggregates, which limit bacterial growth but provides a survival reservoir where bacilli may disseminate from. Targeting intracellular Mtb is challenging, but nanomedicine may offer a solution. Nanomedicine is a significantly growing research area and offers the potential for specific disease targeting, dosage reduction, and intracellular drug delivery. This review discusses the application of the various forms of nanomedicine towards targeting of Mtb.
21 citations
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1,286 citations
"Modeling nanoparticle delivery of T..." refers background in this paper
...50 liters per minute (Brown et al., (1997); Leggett et al....
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TL;DR: This critical review will present the role of nanoparticles (NPs) in the directions that are vital to the new field of nanomedicine, including imaging and drug delivery, and review recent advances in major NP based biomedical applications.
Abstract: This critical review will present the role of nanoparticles (NPs) in the directions that are vital to the new field of nanomedicine, including imaging and drug delivery. We reflect on the physical properties that make NPs advantageous for in vivo efficacy, and review recent advances in major NP based biomedical applications. Critical questions of transport, uptake, and clearance will be discussed and illustrated through the success and opportunities of NP imaging and therapy on a photodynamic therapy (PDT) based NP system that has been developed in our lab over the past decade (540 references).
925 citations
TL;DR: Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone.
Abstract: CONTEXT Despite potentially curative resection of stomach cancer, 50% to 90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) have compared surgery alone with adjuvant chemotherapy, but definitive evidence is lacking. OBJECTIVES To perform an individual patient-level meta-analysis of all RCTs to quantify the potential benefit of chemotherapy after complete resection over surgery alone in terms of overall survival and disease-free survival, and to further study the role of regimens, including monochemotherapy; combined chemotherapy with fluorouracil derivatives, mitomycin C, and other therapies but no anthracyclines; combined chemotherapy with fluorouracil derivatives, mitomycin C, and anthracyclines; and other treatments. DATA SOURCES Data from all RCTs comparing adjuvant chemotherapy with surgery alone in patients with resectable gastric cancer. We searched MEDLINE (up to 2009), the Cochrane Central Register of Controlled Trials, the National Institutes of Health trial registry, and published proceedings from major oncologic and gastrointestinal cancer meetings. STUDY SELECTION All RCTs closed to patient recruitment before 2004 were eligible. Trials testing radiotherapy; neoadjuvant, perioperative, or intraperitoneal chemotherapy; or immunotherapy were excluded. Thirty-one eligible trials (6390 patients) were identified. DATA EXTRACTION As of 2010, individual patient data were available from 17 trials (3838 patients representing 60% of the targeted data) with a median follow-up exceeding 7 years. RESULTS There were 1000 deaths among 1924 patients assigned to chemotherapy groups and 1067 deaths among 1857 patients assigned to surgery-only groups. Adjuvant chemotherapy was associated with a statistically significant benefit in terms of overall survival (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.90; P < .001) and disease-free survival (HR, 0.82; 95% CI, 0.75-0.90; P < .001). There was no significant heterogeneity for overall survival across RCTs (P = .52) or the 4 regimen groups (P = .13). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy. CONCLUSION Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone.
710 citations
"Modeling nanoparticle delivery of T..." refers background in this paper
...1 Author of correspondence e-mail: hviljoen1@unl.edu; tel: (402)472-9318; fax: (402)472-6989 TB (Azarmi et al., (2008), Khar and Vyas, (2002), Paoletti et al. (2012), Clemens et al. (2012), He et al. (2013))....
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...The drug concentration in the blood has a maximum value of and the maximum in the macrophages is (This is a reasonable match with the peak values of Pienaar et al. (2015), (see their Fig....
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TL;DR: Research performed over the last decades on the application of nanoparticles administered via different routes of administration for treatment or diagnostic purposes, including targeted nanoparticle delivery to the lungs is reviewed.
382 citations
"Modeling nanoparticle delivery of T..." refers background in this paper
...TB (Azarmi et al., (2008), Khar and Vyas, (2002), Paoletti et al....
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...TB (Azarmi et al., (2008), Khar and Vyas, (2002), Paoletti et al. (2012), Clemens et al. (2012), He et al. (2013)). Zhan et al (2014) modeled drug delivery to a heterogeneously vascularized liver and showed that significant disparities in drug concentration exist between regions with good and poor blood supply....
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TL;DR: The current paper reviews the relevance of this intimate hepatic blood flow regulatory system in health and disease and exclusively focuses on the endogenous interrelationship between the hepatic arterial and portal venous inflow circuits in liver resection and transplantation, as well as inflammatory and chronic liver diseases.
Abstract: The interest in the liver dates back to ancient times when it was considered to be the seat of life processes. The liver is indeed essential to life, not only due to its complex functions in biosynthesis, metabolism and clearance, but also its dramatic role as the blood volume reservoir. Among parenchymal organs, blood flow to the liver is unique due to the dual supply from the portal vein and the hepatic artery. Knowledge of the mutual communication of both the hepatic artery and the portal vein is essential to understand hepatic physiology and pathophysiology. To distinguish the individual importance of each of these inflows in normal and abnormal states is still a challenging task and the subject of ongoing research. A central mechanism that controls and allows constancy of hepatic blood flow is the hepatic arterial buffer response. The current paper reviews the relevance of this intimate hepatic blood flow regulatory system in health and disease. We exclusively focus on the endogenous interrelationship between the hepatic arterial and portal venous inflow circuits in liver resection and transplantation, as well as inflammatory and chronic liver diseases. We do not consider the hepatic microvascular anatomy, as this has been the subject of another recent review.
377 citations